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Mini-Reviews

“Heat of the Moment: The Overlooked Key to Cartilage Engineering’’
Theofanis Stampoultzis - ,
Yanheng Guo - , and
Dominique P. Pioletti *
This publication is Open Access under the license indicated. Learn More
Articular cartilage’s limited regenerative capacity is compounded by the overlooked thermomechanical factors critical to its function. Recent studies emphasize the importance of cartilage self-heating, arising predominantly from energy dissipation under physiological loading, in maintaining an optimal environment for chondrocyte activity. This thermal dimension, integral to cartilage homeostasis, is absent in traditional tissue engineering approaches, which may explain their limited success. A deeper integration of thermomechanical cues into regenerative strategies could thus be pivotal for advancing articular cartilage repair. Incorporating thermomechanical cues into regenerative strategies offers a practical pathway to revolutionize cartilage repair and regeneration. By mimicking the physiological environment through dynamic thermal and mechanical stimulation within bioreactors, these approaches hold promise for advancing tissue engineering models and optimizing in vitro culture conditions tailored to the complexities of cartilage regeneration. This Mini-Review aims to highlight the need for a paradigm shift in cartilage regeneration, advocating for approaches that incorporate dynamic thermal and mechanical stimuli to enhance therapeutic outcomes.
Reviews

Biobased Food Packaging Systems Functionalized with Essential Oil via Pickering Emulsion: Advantages, Challenges, and Current Applications
Patrícia Marques De Farias - ,
Roberta Vieira De Sousa - ,
Bianca Chieregato Maniglia - ,
Melvin Pascall - ,
Julia Matthes - ,
Anna Sadzik - ,
Markus Schmid *- , and
Ana Elizabeth Cavalcante Fai *
This publication is Open Access under the license indicated. Learn More
The development of innovative active food packaging is a promising strategy to mitigate food loss and waste while enhancing food safety, extending shelf life, and maintaining overall quality. In this review, Pickering emulsions with essential oils are critically evaluated as active additives for sustainable food packaging films, focusing on their antimicrobial and antioxidant properties, stabilization mechanisms, and physicochemical performances. A bibliometric approach was used to contextualize the current research landscape and new trends. Data were collected from the Web of Science and Scopus databases to find studies published between 2020 and 2024. The analysis of 51 articles shows that cinnamon, clove, and oregano are the most used essential oils, while cellulose and chitosan are the predominant polymer matrices. Pickering emulsions as stabilizers in food science represent a step forward in sustainable emulsion technology. The incorporation of essential oils into biobased films via Pickering emulsions can improve the mechanical and barrier properties, antimicrobial and antioxidant activities, and shelf life of foods. This approach offers a natural, environmentally friendly alternative to conventional materials and is in line with the 2030 Agenda goals for sustainability and responsible consumption. Recent advances show that composite particles combining polysaccharides and proteins have higher stability and functionality compared to single particles due to their optimized interactions at the interfaces. Future research should focus on developing scalable, cost-effective production methods and conducting comprehensive environmental testing and regulatory compliance, particularly for nanotechnology-based packaging. These efforts will be crucial to drive the development of safe and effective biobased active food packaging.

Advancements in Breathomics: Special Focus on Electrochemical Sensing and AI for Chronic Disease Diagnosis and Monitoring
Nikini Rashmithara Subawickrama Mallika Widanaarachchige - ,
Anirban Paul - ,
Ivneet Kaur Banga - ,
Ashlesha Bhide - ,
Sriram Muthukumar - , and
Shalini Prasad *
This publication is Open Access under the license indicated. Learn More
This Review examines the potential of breathomics in enhancing disease monitoring and diagnostic precision when integrated with artificial intelligence (AI) and electrochemical sensing techniques. It discusses breathomics’ potential for early and noninvasive disease diagnosis with a focus on chronic kidney disease (CKD), chronic obstructive pulmonary disease (COPD), and lung cancer, which have been well studied in the context of VOC association with diseases. The noninvasive nature of exhaled breath analysis can be advantageous compared to traditional diagnostic methods for CKD, which often rely on blood and urine testing. VOC analysis can enhance spirometry and imaging methods used in COPD diagnosis, providing a more comprehensive picture of the disease’s progression. Breathomics could also provide a less intrusive and potentially earlier diagnostic approach for lung cancer, which is now dependent on imaging and biopsy. The combination of breathomics, electrochemical sensing, and AI could lead to more personalized and successful treatment plans for chronic illnesses using AI algorithms to decipher complicated VOC patterns. This Review assesses the viability and effectiveness of combining breathomics with electrochemical sensors and artificial intelligence by synthesizing recent research findings and technological developments.

A Review on Perception of Binding Kinetics in Affinity Biosensors: Challenges and Opportunities
Benjamin McCann - ,
Brandon Tipper - ,
Sepeedeh Shahbeigi - ,
Morteza Soleimani - ,
Masoud Jabbari - , and
Mohammad Nasr Esfahani *
This publication is Open Access under the license indicated. Learn More
There are challenges associated with design and development of affinity biosensors due to the complicated multiphysics nature of the system. Understanding the binding interaction between target molecules and immobilized receptors and its kinetics is a crucial step to develop robust and reliable biosensor technologies. Evaluation of binding kinetics in biosensors becomes more important and challenging for clinical samples with a complex matrix. Despite drastic advancements in biosensor technologies, having a practical perception of the binding kinetics has remained a critical bottleneck due to limited fundamental understanding. This Review aims to provide a comprehensive discussion on concepts and advances developed so far for the perception of binding kinetics in affinity biosensors. Here, modeling approaches and measurement techniques are presented to characterize the binding interactions in biosensor technologies, while the effect of fouling and secondary factors in the binding interactions will be discussed in the concept of kinetics. This Review will investigate the existing research gaps and potential opportunities in the perception of binding kinetics and challenges to develop robust and reliable biosensors.
Articles

Experimental Study on Key Parameters of Pulsating Water Injection for Coal Seam Damage
Jianqiang Chen - ,
Enmao Wang *- ,
Bo Chang - ,
Gang Wang - ,
Xudong Liu - , and
Shuliang Xie
This publication is Open Access under the license indicated. Learn More
Coal mine dust is one of the most severe hazards that threaten underground coal mining, and it can be effectively controlled and prevented by coal seam water injection. However, with the progress of coal mining, the excavation advances to the deep horizontal levels, where the coal seam porosity is smaller due to the increased crustal stress. The static pressure coal seam water injection becomes insufficient for dust control, which has urged the development of pulsating water injection that can realize coal seam damage and wetting simultaneously by the pressure pulse effect. In the present study, the damage law of coal seam caused by pulsating water injection was explored experimentally using a triaxial pulsating seepage device and taking the Wudong coal mine in Xinjiang, China, as the research background. The following conclusions have been obtained. ① Pulsating water injection can effectively damage the coal seam, increase its permeability coefficient, and promote its wetting effect. ② The permeability coefficients of coal treated with pulsating water injection in different pulse waveforms are in the order of rectangular waveform > sinusoidal waveform = triangular waveform > constant pressure under the lower and upper pressure limits of 5–8 MPa, in the order of sinusoidal waveform > rectangular waveform > triangular waveform > constant pressure under the lower and upper pressure limits of 4–9 MPa, and in the order of sinusoidal waveform > rectangular waveform = triangular waveform > constant pressure under the lower and upper pressure limits of 3–10 MPa. ③ Under the experimental variable conditions of this study, the optimal pulsating water injection parameter is determined to be a sine waveform, the upper pressure limit is 10 MPa, and the lower limit is 3 MPa. ④ The optical microscopy and scanning electron microscopy imaging of the coal sample before and after water injection verifies that pulsating water injection can damage the coal seam, expand its pores and fractures, and enhance its wetting effect.

Spontaneous Formation of Micelles and Vesicles in Langmuir Monolayers of Heneicosanoic Acid
Martha I. Escamilla-Ruiz - ,
Moises G. Zarzoza-Medina - ,
Maricarmen Ríos-Ramírez - ,
Pablo L. Hernández-Adame *- , and
Jaime Ruiz-García *
This publication is Open Access under the license indicated. Learn More
In Langmuir monolayers of heneicosanoic acid (C21H42O2), at low temperature, in the L′2 and CS crystalline phases, a blinking phenomenon occurs at the same positions of the monolayer, which is called localized oscillations (LO), but its origin has not been clarified. In this study, the LO phenomenon was correlated with the ejection of material out of the monolayer which was analyzed to understand this phenomenon. The techniques used for this purpose were pressure–area isotherms on a Langmuir balance and simultaneous observation of the monolayer by Brewster angle microscopy (BAM). Subsequently, using the Langmuir–Blodgett technique, the monolayers were transferred using freshly cleaved mica substrates for analysis by atomic force microscopy (AFM). Our results showed that the origin of the LO is related to a spontaneous formation of micelles and vesicles, since in AFM images these structures were observed in a size range from 4 to 16 nm. In addition, the AFM images showed that the difference between the heights of the L′2 and CS crystalline phases ranges from 13 to 15 Å.

Stability and Bonding Analyses of Heteronuclear 1,2-Dichloro-Silylene-Germylenes Supported by Homo/Heterobileptic Donor Base Ligands
Maria Francis - ,
Farsana Abdul Salam - , and
Sudipta Roy *
This publication is Open Access under the license indicated. Learn More
Herein, we depict the detailed computational studies on the stability and chemical bonding of heteronuclear 1,2-dichloro-silylene-germylenes [(Cl)SiGe(Cl)] supported by homoleptic [L = L′ = cAACMe; NHCMe; and PMe3] and heterobileptic [L, L′ = cAACMe; NHCMe; cAACMe, PMe3; NHCMe; and PMe3] donor base ligands with the general formula (L)(Cl)SiGe(Cl)(L′) having tunable binding energies. The bonding of the corresponding didehalogenated analogue, (L)SiGe(L′) has been also investigated to explore the possibility of multiple bonding between the two-coordinate heteroatoms, Si and Ge. Our studies employing density functional theory, atoms in molecules analysis, and energy decomposition analysis coupled with natural orbitals for chemical valence (EDA-NOCV) unveiled the synthetic viability of the hypothetical compounds in the presence of phosphines and/or stable singlet carbenes, e.g., cyclic alkyl(amino) carbenes (cAACs), and N-heterocyclic carbenes (NHCs) as the suitable ligands. Comparison of the computed bond parameters of the presently hypothesized molecules with those of the relevent experimentally isolated molecules could rationalize the feasibility of the future isolation of the predicted compounds.

Morphology-Driven Bifunctional Activity of Layered Birnessite-Based Materials toward Oxygen Electrocatalysis
Rajesh K. Behera - ,
Alaka P. Sahoo - ,
Debidutta Das - ,
Amarendra Nayak - ,
Sikha Sayantani - ,
Debasis Jena - ,
Swarna P. Mantry - , and
Kumar S. K. Varadwaj *
This publication is Open Access under the license indicated. Learn More
The chemical, structural, and morphological diversity of birnessite, a 2D layered MnO2, has opened avenues for its application as an electrocatalyst toward both the oxygen reduction reaction (ORR) and the oxygen evolution reaction (OER). Among pristine birnessites prepared by different methods, the freestanding flakes (primary structure) obtained from molten salt (MS-KMnO) showed remarkable bifunctional activity as compared to samples with thicker plates or a hierarchical honeycomb-like (type-I secondary structure) morphology. While the ORR onset potential (Eonset) and halfwave potential (E1/2) for MS-KMnO were recorded at 0.89 and 0.81 V vs RHE, respectively, the OER overpotential (η) was found to be 300 mV. We demonstrated heat-induced secondary structure evolution by modification of the molten salt method, which led to a decrease in activity. In contrast to previous studies, the Co-doped birnessite (Co-KMnO) prepared in molten salt showed lower bifunctional activity (ORR, E1/2 = 0.72 V; OER, η= 460 mV) as compared to MS-KMnO. Co-KMnO showed an interwoven wrinkled sheet-like (type-II secondary structure) morphology, with Co3+ present in both the in-layer and the interlayer. However, in Co-KMnO/360 prepared at a lower reaction temperature, the areal coverage of the type-II structure reduces, leading to an increase in ORR (E1/2 = 0.76 V) and OER (η = 440 mV) activity. The chronopotentiometry for 100 h at a constant OER current of 50 mA cm–2 showed an increase in potential from 1.62 to 1.89 V and the characterization of the sample post-treatment showed degradation of the layered structure in MS-KMnO. The samples obtained after 1000 CV cycles in both the ORR and the OER regions showed the formation of secondary structures with a substantial decrease in the Mn3+/Mn4+ ratio. This study demonstrates that morphology tuning within the 2D birnessite system has a marked effect on its bifunctional activity.

Phytoconstituents of Hericium erinaceus Exert Benefits for ADHD Conditions by Targeting SLC6A4: Extraction, Spectroscopic Characterization, Phytochemical Screening, In Vitro, and Computational Perspectives
Kamalaharshini Mohan - ,
Nandhakumar Ravichandran - ,
Harish Rajendran - ,
Jency Roshni - ,
Mahema Sivakumar - ,
Janakiraman Velayudam - ,
Sheikh F. Ahmad - ,
Haneen A. Al-Mazroua - , and
Shiek SSJ Ahmed *
This publication is Open Access under the license indicated. Learn More
Attention-deficit/hyperactivity disorder (ADHD) is a persistent neurodevelopmental disorder. Despite pharmacological interventions, there is a need for effective lead molecules and therapeutic targets. Recently, Hericium erinaceus (HE) has been traditionally reported to treat various diseases. Herein, we aimed to explore the noncytotoxic properties, phytochemical composition, and spectroscopic characterization of HE aqueous extract. Additionally, we used computational workflows to identify key therapeutic targets for ADHD and assess HE extract phytoconstituents for potential targeting. Initially, the HE aqueous extract was obtained using Soxhlet extraction, and its cytotoxicity was assessed on SH-SY5Y cells using MTT assays. FTIR spectroscopy characterized the extract’s functional groups, while biochemical methods and GC–MS identified its phytochemical constituents. A protein–protein interaction network identified ADHD targets, and molecular docking, dynamics, and QM/MM calculations were used to find potential drug candidates from the HE extract. As a result, the HE extract exhibited no cytotoxicity in SH-SY5Y cells across concentrations (0.625 to 10 μg/mL) after 24 h. FTIR spectroscopic analysis detected 13 different functional groups that hold diverse biological importance. Qualitative phytochemical screening revealed the presence of carbohydrates, flavonoids, anthocyanins, tannins, alkaloids, saponins, steroids, and phenolic compounds. GC–MS profiling identified 17 diverse metabolites. Simultaneously, ADHD-related genes and known therapeutic protein targets were integrated into a network, identifying SLC6A4 as a hub target. Molecular docking of HE extract compounds showed myo-inositol’s high binding efficiency (−6.53 kcal/mol). Dynamic simulations demonstrated stable interactions, and QM/MM analysis confirmed myo-inositol’s ability to transfer electrons, reinforcing its interaction potential. Overall, the HE aqueous extract shows a potent nontoxic profile and contains phytoconstituents like myo-inositol, offering promising therapeutic potential by targeting SLC6A4 for ADHD.

Ni-W Catalysts Supported on TiO2-Al2O3 for Efficient Green Diesel Production: “Standard” vs “Keggin” Comparison
Ricardo Rivera-Guasco - ,
Acela López-Benítez - , and
Alfredo Guevara-Lara *
This publication is Open Access under the license indicated. Learn More
In order to obtain an efficient Ni-W catalyst for green diesel production, a new preparation method based on Keggin-type polyoxotungstates supported on TiO2-Al2O3 was developed. The as-obtained catalyst (NiPW/TiO2-Al2O3) was compared to a conventionally synthesized catalyst (NiW/TiO2-Al2O3) during each step of the catalyst preparation. Depending on the preparation method, different Ni-W species were formed. Afterward, the catalysts were sulfided, and the Lewis and Brønsted acid concentrations were determined. Finally, all catalysts were tested in the hydroprocessing of soybean oil. The results show a direct correlation between hydroprocessing activity and Lewis/Brønsted acidity. The NiPWS/TiO2-Al2O3 catalyst presents the highest value of Lewis acid sites (227 μmol/g). Consequently, this catalyst shows deoxygenation activity values 10 and 55% higher than those for NiWS/TiO2-Al2O3 and NiWS/Al2O3-reference, respectively. The NiPWS/TiAl catalyst exhibits the highest selectivity to C18 among all of the catalysts studied, producing green diesel with the highest added value.

Fluence and Dose Distribution Modeling of an Ultraviolet Light Disinfection Process for Pathogen Inactivation Efficiency Evaluation
Tamás Dóka *- and
Péter Horák
This publication is Open Access under the license indicated. Learn More
This study addresses the need to utilize bench-scale experimental results for ultraviolet (UV) light disinfection on solid food surfaces by proposing a novel framework to evaluate the fluence rate field of arbitrarily placed UV sources to ensure proper disinfection in industrial-scale food processing. Despite extensive research establishing UV fluence values for disinfection of various food types, industrial applications often face challenges due to nonhomogeneous UV distribution. This study introduces a method capable of determining the fluence distribution on solid food and food contact surfaces in both static and moving environments. Additionally, it aids in selecting the appropriate light sources and irradiation times. Our model leverages UV radiation models from different engineering disciplines to determine the UV fluence and dose distribution on the surface of convex objects. This helps to understand and optimize processes for proper decontamination, improved food quality, and a longer shelf life for processed products.

Alginate Beads Encapsulated Auxin-Producing PGPR as a Biofertilizer Promotes Triticum aestivum Growth
Nimra Mushtaq - ,
Atia Iqbal *- ,
Shumaila Batool - ,
Sara Janiad - ,
Mehboob Ahmed - ,
Fahad Al-Asmari - ,
Muhammad Abdul Rahim *- ,
Mohamed Fawzy Ramadan - , and
Eliasse Zongo *
This publication is Open Access under the license indicated. Learn More
Plant growth-promoting rhizobacteria (PGPR) can be utilized to enhance plant growth and production. The use of efficient PGPR is one of the effective ways to improve Triticum aestivum (wheat) growth and nutrition. The exploration of native rhizobacterial strains as biofertilizers with suitable carriers in immobilized form is an alternative way to prevent soil ecosystem pollution. In order to evaluate the potential of biofertilizers and multiple plant growth-promoting attributes, numerous experiments were conducted on isolated strains. The impact of auxin-producing rhizobacterial strains (APRS) on various growth parameters of wheat was examined through laboratory and field experiments. This study aimed to investigate the potential of rhizobacteria (isolated from various crop types) to encourage wheat growth by immobilization in alginate beads. The PGPR, obtained from different rhizospheric soils, were identified based on their colony morphology and biochemical characteristics. In addition, they were evaluated for their ability to produce indole-3-acetic acid (IAA), hydrogen cyanide (HCN), ammonia (NH3), and siderophores. The 16S rRNA-based identification revealed that auxin-producing rhizobacterial strains showed homology to various genera, including Bacillus, Brevundimonas, and Exiguobacterium spp. Selected strains showed plant growth-promoting (PGP) attributes and hydrolytic enzyme-producing abilities. Most of the strains had multifaceted plant growth-promoting attributes. Growth potential, assessed under laboratory and natural environments, confirmed the efficacy of bacterial strains as alginate beads biofertilizers. Encapsulation with alginate beads showed a 70–80% improvement in seed germination and a 60–70% enhancement in root and shoot length than control. The results revealed that the selected strain can be used as biofertilizers. Screening and the application of efficient PGPR encapsulation with alginate beads can be a better option to promote the production and yield of wheat.

Quantification of Antiretroviral Drug Emtricitabine in Human Plasma by Surface Enhanced Raman Spectroscopy
Marguerite R. Butler - ,
Terry A. Jacot - ,
Sucharita M. Dutta - ,
Gustavo F. Doncel - , and
John B. Cooper *
This publication is Open Access under the license indicated. Learn More
In this study, reproducible label-free detection and quantification of the antiretroviral drug emtricitabine (FTC) down to 78 ng/mL in human plasma by surface enhanced Raman spectroscopy (SERS) is presented. A novel plasma sample pretreatment method using silver nitrate and silver colloidal nanoparticles (Ag CNPs) was used to prepare the plasma samples for analysis. The pretreated plasma samples were evaporated to dryness on an aluminum surface and a computer-controlled Raman scanning system was used to collect spatially resolved SERS spectra of the entire surface. Calibration curves of commercial human plasma samples containing FTC in a concentration range of 5000 to 78 ng/mL were calculated using three different methods. First, a conventional approach was taken, where all the spectra collected for each concentration were averaged, then the SERS intensity of a known FTC peak (792 cm–1) was used for calibrations (total population method). This approach was refined by utilizing a figure-of-merit (FOM) quality index (Qi) to sample spectra from each concentration that contained the highest signal-to-noise (S/N), before averaging and calculating the SERS intensity of the 792 cm–1 FTC peak (Qi sample method). Finally, the distribution of all Qi values for each concentration were modeled using cumulative distribution functions (CDFs) and were used for calibrations (CDF method). The CDF method exhibited the highest analytical sensitivity (slope = 3702.47) compared to the Qi sample method (slope = 1591.05) and the total population method (slope = 754.21). The Qi sample method exhibited the highest linearity (R2 = 0.99) compared to the CDF method (R2 = 0.95) and the total population average (R2 = 0.97). The CDF method exhibited the highest S/N in the concentration range of 5000 to 312 ng/mL (S/N range of 31.5–16.6). The Qi sample method exhibited the highest S/N for concentrations 156 and 78 ng/mL (S/N = 9.7 and 7.4, respectively). These results show that the Qi sample method is advantageous over all other methods when approaching the LOQ while the CDF method is advantageous over all methods at higher concentrations. The LOQ (78 ng/mL) was confirmed by principal component analysis (PCA). Together these results show that statistical treatment of a large population of SERS spectra, where the analyte signal intensity follows an exponential distribution, is superior to standard methods of averaging populations of spectra in terms of analytical sensitivity, linearity, and S/N. Additionally, it was found that the background signal had no interference with the quantitative data calculated for the total population and Qi sample methods after repeating both analyses with baseline-subtracted spectra. The results and methodology presented in this study establish a framework for integrating SERS into drug adherence monitoring for FTC-based treatment and prevention of infections by demonstrating consistent SERS detection and quantification of FTC in human plasma at therapeutically relevant concentrations.

Bimetallic ZIF-8 from Hydroxide Double Salts for Efficient Cu2+ Removal in Wastewater
Yixin Chen - ,
Zexi Chen - , and
Sheng Chu *
This publication is Open Access under the license indicated. Learn More
Metal–organic frameworks (MOFs) hold significant potential for applications in gas adsorption and separation, catalysis, chemical sensing, and drug delivery. Zeolitic imidazolate frameworks (ZIFs) are a type of MOF composed of metal ions and imidazolate ligands, structurally similar to zeolite structures. ZIF-8, a widely studied ZIF material, is composed of zinc ions (Zn2+) and 2-methylimidazole as fundamental building blocks featuring unique porous structures, a high specific surface area, and excellent thermal and chemical stability. This study introduces a rapid room-temperature synthesis method for bimetallic ZIF-8 through the hydroxide double salt (HDS) precursor. Various characterization techniques confirmed that the synthesized bimetallic ZIF-8 exhibits uniform particle size and high crystallinity. Experimental results indicate that the HDS precursor provides numerous active sites, facilitating rapid nucleation and resulting in uniformly sized bimetallic ZIF-8 particles. By optimizing the ultrasonic time of HDS, the concentration of 2-methylimidazole, and the reaction time, the synthesis conditions were refined, producing bimetallic ZIF-8 particles with an average size of 135.0 nm and a minimum polydispersity index (PDI) of 0.024. Additionally, the copper ion adsorption performance was evaluated, with the synthesized bimetallic ZIF-8 showing the highest adsorption capacity of 1196.82 mg/g at pH 6, demonstrating its effectiveness in heavy metal removal.

Structural, CSD, Molecular Docking, Molecular Dynamics, and Hirshfeld Surface Analysis of a New Mesogen, Methyl-4-(5-(4-(octyloxy)phenyl)-1,2,4-oxadiazol-3-yl)benzoate
Pooja Mohandas - ,
Abdul Ajees Abdul Salam *- ,
Thripthi Nagesh Shenoy - ,
Srinivasulu Maddasani *- ,
Santanu Kumar Pal - , and
Channabasaveshwar V. Yelamaggad *
This publication is Open Access under the license indicated. Learn More
1,2,4-Oxadiazoles are well recognized for their exceptional physical, chemical, and pharmacokinetic properties, making them promising candidates for various therapeutic applications. These include treatments for cystic fibrosis, Duchenne muscular dystrophy, Alzheimer’s disease, and a broad spectrum of other therapeutic interventions such as antituberculosis, anticancer, antibiotic, anti-inflammatory, and anticonvulsant activities. In this study, single crystals of a novel 1,2,4-oxadiazole derivative, methyl-4-(5-(4-(octyloxy)phenyl)-1,2,4-oxadiazol-3-yl)benzoate, were grown by a slow evaporation technique. The structural elucidation was performed using X-ray diffraction analysis, confirming the compound’s crystalline structure in the triclinic system. The analysis revealed a linear conformation with bond lengths closely aligned with Cambridge Structural Database (CSD) averages, signifying high precision in the molecular structure. A detailed CSD study identified nine principal configurations of the phenyl octyloxy moiety, underscoring the structural diversity of the compound. Hirshfeld surface analysis highlighted the predominance of C–H···O and C–H···π interactions, with dispersion energy playing a critical role in stabilizing the crystal lattice. Docking studies against key microbial targets, particularly E. coli FabH, demonstrated superior binding energies, suggesting significant antimicrobial potential. The comprehensive suite of structural and computational analyses underscores the potential of the synthesized 1,2,4-oxadiazole derivative, which may be one of the promising candidates for antimicrobial drug development. Future in vitro, in vivo studies will be supportive in optimizing the derivative for enhanced efficacy and further elucidating its pharmacological mechanisms, paving the way for potential clinical applications. This study not only provides insights into the structural and functional properties of a novel 1,2,4-oxadiazole derivative but also highlights its promising role in antimicrobial drug discovery.

Curing and Degradation Kinetics of Phosphorus-Modified Eugenol-Based Epoxy Resin
Danuta Matykiewicz *- and
Beata Dudziec
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Decreasing fossil fuel resources results in a growing demand for polymeric materials obtained from renewable raw materials, such as eugenol. Therefore, this work aimed to assess the kinetics of cross-linking and degradation of epoxy resin obtained from eugenol derivatives and cured with three types of amines: aliphatic: triethylenetetramine (TETA); aromatic: diaminodiphenylmethane (DDM), and cycloaliphatic isophorone diamine (IDA). The product was characterized by 1H, 13C, and 31P NMR as well as ESI MS techniques. The curing kinetics of the biobased resin was studied using differential scanning calorimetry (DSC) at different heating rates. Fourier transform infrared (FTIR) spectroscopy was used to assess chemical changes in bioepoxy monomer after the curing process. The DSC method confirmed the occurrence of an exothermic curing reaction of the tested bioresin for all tested curing agents. The peak temperature Tp and enthalpy ΔH values determined during DSC analysis depended on the type of curing agent. The highest values of Tp (142.6–161.4 °C) and ΔH (28.5–38.3 J/g) were recorded for the TEEP + DDM composition. For the remaining compositions, the values were lower and were as follows: for TEEP + TETA, Tp = 115.0 to 129.9 °C and ΔH = 12.4–26.5 J/g and for TEEP + IDA, Tp = 118.0–137.1 °C and ΔH = 16.3 to 35.5 J/g. According to the Kissinger and Ozawa model, the activation energy of the resin cross-linking process was determined. The calculated activation energies according to Kissinger and Ozawa were 65.38 and 55.90 kJ/mol for TEEP + TETA, 60.09 and 63.84 kJ/mol for TEEP + DDM, and 57.36 and 60.85 kJ/mol for TEEP+IDA, respectively. The kinetics of thermal degradation of the eugenol-based resin were studied by thermogravimetric analysis (TGA) in a nitrogen atmosphere. Moreover, it should be emphasized that compared to commercial resins, bioresin has a much lower maximum degradation rate determined by DTG and a higher amount of char residue after thermal degradation, both in nitrogen and in air.

Synthesis, Biological Properties, In Silico ADME, Molecular Docking Studies, and FMO Analysis of Chalcone Derivatives as Promising Antioxidant and Antimicrobial Agents
Rashedul Ahsan - ,
Sumi Paul - ,
Mohammad Sayed Alam *- , and
A. F. M. Motiur Rahman
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A series of chalcone derivatives were synthesized and characterized using UV–vis, FT-IR, 1H NMR, and mass spectrometry, followed by the evaluation of their antimicrobial and antioxidant properties. In vitro screening against six bacterial strains (Staphylococcus aureus, Bacillus subtilis, Salmonella typhimurium, Escherichia coli, Pseudomonas aeruginosa, and Citrobacter freundii) and two fungal strains (Aspergillus niger and Trichoderma harzianum) revealed outstanding antibacterial activities, particularly with compound 5b, 5d, and 5e against S. aureus, and compounds 5c and 5h against B. subtilis. Notably, compounds 5f and 5g exhibited significant effects against P. aeruginosa, while compound 5b showed the highest antifungal activity against T. harzianum. All compounds demonstrated remarkable antioxidant activities, with 5h (IC50 values of 0.005 μM) and 5c (IC50 values of 0.006 μM) being the most potent, comparable to ascorbic acid (IC50 values of 0.007 μM). In silico evaluations confirmed favorable drug-likeness and pharmacokinetic properties for all analogues, adhering to both Lipinski’s rule of Five and Veber’s rule. Molecular docking studies of potent antibacterial compounds (5e and 5h) indicated strong binding affinities to the PBP-1b receptor in S. aureus, while DFT calculations provided valuable insights into their molecular reactivity and biological properties. Ligand-based enzymatic target predictions indicate that chalcone analogues (5a–m) show potential as inhibitors of oxidoreductases, kinases, enzymes, proteases, or ligands for family A GPCR. These findings position chalcone derivatives as promising candidates for therapeutic applications in combating bacterial infections and oxidative stress.

Novel Triple-Oxygen Isotope Study Indicates Unprecedented Ozone–Particulate Interaction Pathways in Atmospheric Pollution Chemistry
Mao-Chang Liang *- ,
Chao-Hui Huang - ,
Mark Howard Thiemens - ,
Sourendra Kumar Bhattacharya - ,
Sasadhar Mahata - ,
Yu-Jung Chen - , and
Tai-Sone Yih
This publication is Open Access under the license indicated. Learn More
Ozone plays a fundamental role in the chemistry of the atmosphere, mediating oxidation reactions in phases and at phase boundaries. Here, we investigate the least-explored solid-phase heterogeneous processes involving ozone to understand the reaction pathways of O3 with airborne aerosols. Using triple oxygen isotope ratios as tracers, we found that the ozone reaction oxidizes organic particles and produces carbon dioxide, with oxygen atoms largely from O3. Along with the formation of CO2, an equal amount of O2 from water decomposition is inferred. Chemical reaction kinetics, however, is yet to be identified. One hypothetical pathway is through Criegee intermediates, formed by the reaction of ozone with aldehyde/ketone-like organic compounds (unsaturated hydrocarbons) catalyzed by metal oxides. Inclusion of the process in a chemistry-transport model could yield a significant change in the ozone budget. The study shows the importance of ozone-induced heterogeneous chemical reactions on aerosol surfaces occurring in polluted atmospheres.

Investigating Pore Characteristics and Their Dependence on Shale Composition: Case Study from a Permian Basin in India
Saheli Ghosh Dastidar - ,
Kripamoy Sarkar - ,
Debanjan Chandra - ,
Bodhisatwa Hazra - , and
Vikram Vishal *
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Shale reservoirs, often acting as caprocks for conventional hydrocarbon reservoirs, exhibit moderate to high porosity and remarkably low permeability. Organic-rich shales serve as reservoirs for unconventional hydrocarbons. This study focused on evaluating the characteristics of the source rocks and the factors influencing pore parameters in organic-rich shale from a Permian Basin in India, exploring its feasibility as both a CO2 sink and a natural gas source. Experimental techniques were employed to explore the mineral and the organic matter characteristics along with attributes of the pores hosted within them. The investigated shales displayed diverse thermal maturity levels, spanning from that in oil-prone to gas-prone zones, with the total organic carbon content varying from 0.72 to 24.98 wt %, indicating substantial organic richness. Rock-Eval pyrolysis results revealed a range of thermal maturity (Tmax) values between 426 and 474 °C, while X-ray diffraction analysis indicated significant quantities of illite and kaolinite, along with trace amounts of pyrite in certain samples. Field-emission scanning electron microscopy imaging and its detailed interpretation provided valuable insights into the pore structure and arrangement. In our study, we found that both the clay content and the organic matter significantly contribute to gas adsorption. While clay content strongly influences mesopore attributes, the organic matter predominantly affects micropore attributes. Furthermore, a direct relationship among fractal dimension, surface area, and pore volume, indicating increased complexities with these variables. Our examination of mesopore fractal attributes revealed that smaller mesopores exhibit a more convoluted and irregular configuration in comparison to the larger ones. These findings provide significant insights into the pore morphology of the analyzed shale sample.

Hierarchically Porous Anatase Nanoparticles Derived from One-Dimensional Lepidocrocite Titanate for Bisphenol-A Photodegradation
Treesa Reji - ,
Adam D. Walter - ,
Yasunori Hioki - ,
Tracey Curran - ,
Mary Qin Hassig - ,
Hussein O. Badr - ,
Gregory R. Schwenk - ,
Takeshi Torita - ,
Megan A. Creighton - , and
Michel W. Barsoum *
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Herein, we discuss the conversion of one-dimensional lepidocrocite (1DL) titanate nanofilaments to anatase. Upon heating at temperatures >400 °C, the hierarchical 1DLs porous mesostructured particles transform to anatase, while retaining their morphology. These assemblies are characterized via X-ray diffraction, scanning and transmission electron microscopy, Fourier transform infrared spectroscopy, and solid-state ultraviolet absorbance. The assemblies were tested in the photodegradation of a water-soluble, endocrine-disrupting organic compound, bisphenol A (BPA). Using ultraviolet–visible spectroscopy, we show that 95% of BPA is degraded in 1 h under 1 sun of the simulated solar spectrum. Under the same conditions, the total organic carbon of the solution was reduced by 70%.

Spider Webs as Passive Monitors of Microplastic and Its Copollutants in Indoor Environments
Kadamparambil Sivasankaran Aradhana - ,
Vishnu S. Moorchilot - ,
Taiha Joo - ,
Charuvila T. Aravindakumar - , and
Usha K. Aravind *
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Indoor environments are particularly vulnerable to microplastics (MPs) and associated copollutants due to limited air circulation and particulate matter accumulation. Continuous monitoring is essential to evaluate exposure levels and health risks. We propose using indoor spider webs as passive monitors for MPs and their copollutants. MPs were found in both web and dust samples with nonuniform distribution (p < 0.05), indicating contamination hotspots. Web samples had significantly higher MP levels (138–33,570 MPs/g) compared to dust samples (59–9324 MPs/g). A strong positive correlation (r = 0.93, p < 0.05) between MPs in dust and webs suggests that spider webs are effective bioindicators of indoor MP contamination. The study also revealed the presence of Bisphenol A and various phthalic acid esters (PAEs). Co-pollutant concentrations ranged from 52.02–1971.78 μg/kg in webs and 43.18–518.42 μg/kg in dust. Diethyl phthalate (DEP) was more common in webs, while Dibutyl phthalate (DBP) predominated in dust. These findings highlight spider webs’ potential as both effective biomonitoring tools and significant sinks for MPs and their cocontaminants in indoor environments.

Enhanced Cell Proliferation, Migration, and Fibroblast Differentiation with Electrospun PCL–Zinc Scaffolds Coated with Fibroblast-Derived ECM
Alexis Moody - and
Narayan Bhattarai *
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Despite tremendous improvement in the development of tissue-regenerating materials, a promising solution that provides an optimal environment remains to be accomplished. Here, we report a composite nanofiber biomaterial scaffold as a promising solution that closely mimics the extracellular matrix (ECM) to improve cell viability, proliferation, and migration. Initially, nanofiber composites of polycaprolactone (PCL) and zinc (Zn) metal were fabricated by using electrospinning. The resulting PCL–Zn (PZ) nanofibers effectively guided the growth of NIH3T3 fibroblasts for 7 days, forming a fibroblast cell sheet. The PZ fibers were decellularized to remove autologous and allogenic cellular antigens while leaving an intact ECM with structural and functional components. The resulting nanofiber PCL–Zn–ECM (PZE) showcased a natural ECM bonded to the surface, providing a bioactive element to the interconnected fibers. The reseeding of NIH3T3 fibroblasts demonstrated the scaffold’s excellent capacity to direct and support cell proliferation. Furthermore, in vitro cytotoxicity analysis and morphological staining confer the scaffold’s biocompatibility. The PZE scaffold presents a promising development in which these scaffolds can be further used for various regenerative medicine applications including wound healing.

Ammonia (NH3) Production from the Thermal Decomposition of Hydroxylammonium Nitrate (HAN) as a Green Energetic Source for Clean Space
Adil Souagh - ,
Assia Mabrouk - ,
Ahmed Bachar - ,
Seitkhan Azat - , and
Rachid Amrousse *
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Ammonia’s (NH3) high hydrogen concentration and simplicity of storage and transportation have made it a promising energy source, especially for hydrogen production. Using an iridium (Ir)-based catalyst for clean space applications, this study examines the release of NH3 during the thermal decomposition of hydroxylammonium nitrate (HAN), a green energetic propellant. Differential thermal analysis-thermogravimetry in conjunction with mass spectrometry (DTA-TG/MS) was used to examine the thermal decomposition. The generation of NH3 was verified by subsequent fragment analysis. Coupled cluster approaches were utilized to validate NH3 generation and to further clarify the reaction process. Combining the theoretical and experimental methods highlights the feasibility of employing HAN as a precursor for NH3 production, indicating that it can be used as a sustainable energy source for space propulsion systems. The effect of temperature on NH3 production using a coupled cluster is also explored.

Revisiting Water Adsorption on TiO2 and ZnO Surfaces: An SCC-DFTB Molecular Dynamics Study
Yarkın A. Çetin *- ,
Laura Escorihuela - ,
Benjamí Martorell - , and
Francesc Serratosa
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Metal oxides (MOs) are the key materials in applications of biomedicine industrial technologies due to their versatile features. Knowing their possible toxicity level is crucial given some specific environments, particularly in water. We have learned that their reactivity almost depends on the electronic structure on the surface of the MOs. Thus, a detailed understanding of the electronic structure on the surface and its reactivity processes is useful for determining the toxicity in MOs and defining good descriptive parameters. We simulated the interaction of ZnO and TiO2 slab models with water and checked their geometric and electronic structure changes from the bulk of the material to the water interface. To this end, we used the density functional tight binding theory coupled with finite temperature molecular dynamics. We have observed the interaction of water with the MO surface in terms of electronic and geometric parameters for several conditions, such as temperature, hydrogenated or clean, and exposed surface. In doing so, we provide molecular-level insights into topographical and electronic processes on MO surfaces besides finding critical points on the surface that can explain the initialization of dissolution processes. Thus, we reveal information about potential toxicity descriptors in a systematic analysis approach.

Influence of Fuel and Technology on Particle Emissions from Biomass Cookstoves─Detailed Characterization of Physical and Chemical Properties
Robert Lindgren - ,
Natxo García-López - ,
Karin Lovén - ,
Lisa Lundin - ,
Joakim Pagels - , and
Christoffer Boman *
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Globally, 3 billion people rely on solid biomass fuel for their everyday cooking, most often using inefficient cooking practices, leading to high exposure levels of household air pollution. This is subsequently associated with negative health and climate impact. Further, the inefficient use of biomass fuels applies pressure on natural forests, resulting in deforestation, loss of biodiversity, and soil degradation. Improved cookstove technologies and biomass fuels are being promoted to mitigate these issues. However, limited knowledge exists about how the interaction between stove technology and new fuels affects the physical and chemical properties of particulate emissions. In this study, the emission performance of four cookstove technologies in combination with five fuels was evaluated in a laboratory setup, applying a modified water boiling test with a hood dilution system for flue gas sampling. Filter sampling was applied to determine the emissions of fine particulate matter (PM1) and for subsequent analysis of polycyclic aromatic compounds (PAC), organic- and elemental carbon, and inorganic composition. Particle mass size distribution was determined by using a 13-stage low-pressure cascade impactor. Online instruments were used to determine gaseous emissions (e.g., CO, CH4, and BTX) as well as particle number size distribution. The results show that both the stove design and fuel properties influence the total emissions as well as the physiochemical PM characteristics. It was further seen that the impact of fuel on the PM properties did not translate linearly among the different stove technologies. This implies that each stove should be tested with various fuels to determine both the total emissions and fuel suitability.

One-Step Microwave-Assisted Synthesis of MnFe2O4/rGO Nanocomposites and Their Electrochemical Properties in Supercapacitors
Kun-Yauh Shih *- and
Hui-Ying Tseng
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In the pursuit of energy conservation and sustainability, supercapacitors offer high power density, fast charge–discharge rates, and long cycle life, making them ideal for applications in electric vehicles and portable electronics. This study presents the synthesis of MnFe2O4/reduced graphene oxide (rGO) nanocomposites through a rapid, one-pot microwave-assisted hydrothermal method. This approach significantly reduces synthesis time relative to conventional hydrothermal techniques. The nanocomposites were structurally characterized using X-ray diffraction (XRD) and Raman spectroscopy, morphologically examined via transmission electron microscopy (TEM) and Brunauer–Emmett–Teller (BET) analysis, and chemically analyzed through Fourier-transform infrared spectroscopy (FT-IR) and thermogravimetric analysis (TGA). Electrochemical testing revealed a high specific capacitance of 196.6 F/g at 0.5 A/g, with 90.22% retention after 6000 cycles at 10 A/g. The superior performance is attributed to the synergistic effects of MnFe2O4 and rGO, enhancing charge storage and stability. These findings demonstrate the potential of microwave hydrothermal synthesis for scalable production of high-performance electrode materials for supercapacitors.

Toward a Theranostic Approach for the Brain Tumor Toxicity Profile of Polymer-Shelled Microbubbles
Gaio Paradossi *- ,
Fabio Domenici - ,
Francesco Riccitelli - , and
Rachel Grossman *
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The establishment of theranostic devices by combining multimodal real-time intraoperative imaging for brain tumor surgery with targeted drug delivery may provide therapeutic advantages for patients with malignant gliomas. Our group has recently developed a new generation of novel microbubbles (MBs), with an air core and a crosslinked poly(vinyl alcohol) shell, called PVA MBs. The PVA MB surface was engineered to support near-infrared (NIR) imaging with a fluorescence probe (C790) for the surgical microscope. The attachment to a cyclic pentapeptide containing the RGD sequence promotes active adhesion and direct targeting of endothelial tumor integrins. The conjugation of temozolomide (TMZ), an alkylating chemotherapy proven to be effective against malignant gliomas, provides a unique therapeutic advantage. The potential toxicity of this novel technology was assessed in rats by intravenous injections of two doses of naked MBs and MBs equipped with RGD for targeting tumor integrins, NIR fluorescence (CF790) for real-time visualization, and TMZ as a cytotoxic component, at two time points, 10 min and 7 days, for potential acute and chronic responses in rats [(1) MB, (2) MB-C790-RGD, and (3) MB-C790-RGD-TMZ]. No mortality occurred during the 7-day study period in any of the dosing groups. Decreased hemoglobin and hematocrit levels and increased triglyceride levels were noticed in the high-dose naked MBs and MBs-CF790-RGD groups. These findings may be associated with their enlarged spleen and liver, observed during necropsy. Histopathology examination in the high-dose animals showed the development of treatment-related changes seen mostly 7 days post dosing, consisting of granulomatous inflammation and foreign body reaction. Accordingly, we concluded that the low-dose tested items appeared to be safe. The results allow us to proceed with planning for an efficacy study before making the first attempt to use this technology in clinical practice.

Gamma Irradiation Synthesis of Sugar-Derived Carbon-Dot-Functionalized Glutathione for Hg2+ Detection and Antioxidant Activity
Kanokorn Wechakorn - ,
Pacharaphon Khaopueak - ,
Varistha Chobpattana - ,
Natakorn Sapermsap - ,
Sorawis Sangtawesin - , and
Tanagorn Sangtawesin *
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Mercury, a particularly toxic heavy metal from industrial processes, poses significant risks to both people and the environment when it accumulates to dangerous levels, damaging the liver, kidneys, and nervous system. Therefore, fluorescent organic carbon dots (CDs) were developed for detecting Hg2+ ions. These CDs were easily synthesized, chemically stable, biocompatible, low in toxicity, and environmentally friendly. In this work, glutathione-functionalized CDs (CDs-GSH) were produced from sugar using the EDC/NHS coupling method. Gamma irradiation induced the chemical reactions necessary to produce fluorescent CDs. CDs-GSH demonstrated significant selectivity for Hg2+ with an 83% reduction in fluorescence intensity. Additionally, they exhibited a phenolic content of 19.1 μg/mg GAE and strong antioxidant characteristics, with DPPH radical scavenging activity of 63% at 1.0 mg/mL. Due to their stability, selectivity, and antioxidant qualities, high-value CDs can be produced from table sugar using an environmentally friendly synthesis process, offering potential applications in sensing and antioxidant activity.

Synthesis and Characterization of Glycosaminoglycan Mimetic Variants to Promote Chondrogenesis
Richard Vincent - ,
Marcus Foston - ,
Willis B. Hammond - ,
George L. Collins - , and
Treena Livingston Arinzeh *
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Tissue engineering strategies to treat cartilage damage remain inadequate because of the difficulty in regenerating fully functional cartilage tissue. Sulfated glycosaminoglycans (GAGs), which are found in the native extracellular matrix, are known to interact with growth factors and, thus, promote chondrocyte function. Native GAGs have been explored as viable scaffold materials for tissue repair applications. However, it is unclear what structural features in GAGs are critical for promoting chondrogenesis. Therefore, this study generated GAG mimetics that vary in glycosidic linkage geometry and monomer ring substitution and were evaluated for their effect on mesenchymal stem cell (MSC) chondrogenesis and their potential use in cartilage tissue engineering applications. GAG mimetics were synthesized from cellulose (pSC), starch (SS), and chitin (ChS). pSC has beta-glycosidic linkages, SS has alpha-glycosidic linkages, and ChS has beta-glycosidic linkages and monomers that consist of the amide derivative of glucose. Evaluated in soluble form in MSC pellet cultures, pSC and SS enhanced MSC chondrogenic differentiation as measured by the deposition of chondrogenic matrix components, collagen type II and GAG normalized to the cell number, over ChS and the control culture media (without GAG mimetics). The higher degree of sulfation (DOS) in both the pSC and SS also had an effect on the relative collagen type II deposition and GAG production. These data suggest that beta- and alpha-glycosidic linkages are favorable for promoting chondrogenesis. This study demonstrates the potential of semisynthetic GAG mimetics for chondrogenic differentiation, where structural features should be considered for cartilage repair applications.

Synthesis, Characterization, and Effects of Aliphatic and Aromatic Amines on Thermal and Surface Properties of Zwitterionic Amphiphiles
Muhammad Israr - ,
Ahmad Mahboob - ,
Syed Muhammad Shakil Hussain *- ,
Muhammad Shahzad Kamal *- ,
Theis Solling - ,
Mohammed Alotaibi - , and
Mohanad Fahmi
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Solubility and thermal stability of surfactants are the key properties to consider for their possible oilfield applications. Most commercially available surfactants experience hydrolysis under high temperatures, and prolonged heating exacerbates this process, creating significant challenges for the petroleum industry. To address these complications, a novel class of propylamine and pyridinium-based zwitterionic surfactants was prepared, and their structures were confirmed using nuclear magnetic resonance (NMR) and Fourier transform infrared (FT-IR) spectroscopies. Salt tolerance tests were performed in distilled water, seawater, and formation water, while thermal stability was evaluated by using thermogravimetric analysis (TGA). Additionally, surface properties such as critical micelle concentration (CMC) and surface tension at the CMC (γCMC) were measured for these surfactants. The surfactants exhibit remarkable solubility in all types of water without any precipitation or cloudiness. TGA data demonstrated that the thermal decomposition temperatures for all of the newly prepared zwitterionic surfactants were around 300 °C, significantly greater than real reservoir temperatures. The CMC values range from 0.07 to 0.26 mmol L–1, where the surface tension at the CMC (γcmc) ranges from 31.16 to 34.54 mmol/L. Moreover, low CMC values of zwitterionic amphiphiles containing a propylamine group in their core structure signify that they can make more tightly compact micelle structures than zwitterionic amphiphiles with a pyridine ring. This research fills the critical gap concerning the solubility and thermal stability of surfactants under harsh conditions by designing and evaluating these novel zwitterionic amphiphiles. The excellent solubility, thermal stability, and surface properties of the synthesized zwitterionic amphiphiles make them ideal choices for effective applications in challenging reservoir conditions, paving the way for enhanced oil recovery approaches.

Brownian Dynamics Simulation of Microscale Thermophoresis in Liquid
Koki Ide - ,
Tetsuro Tsuji - ,
Takayuki Suzuki - , and
Kenji Setoura *
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Microscale thermophoresis (MST) has garnered significant attention as a manipulation method for chemical species ranging from nanometers to micrometers in liquids. In particular, techniques for manipulating single nanometer-sized objects have been developed by driving MST through laser heating with near-infrared wavelengths focused down to submicron scales or via photothermal conversion of plasmonic nanoparticles. While MST simulations on a macroscopic scale can be addressed by solving the diffusion equation using the finite element method, alternative computational approaches are required to investigate thermophoretic behavior at the single-particle level. For this purpose, we have developed a numerical method for the thermophoresis of individual nanoparticles diffusing in a liquid by combining the finite element method for steady-state heat conduction with Brownian dynamics simulations. The scripts for the finite element method and Brownian dynamics calculations used in the present simulations are uploaded in the Supporting Information and freely available. The numerical results demonstrated satisfactory agreement with the experimental results of laser-induced thermophoresis performed on polystyrene nanoparticles with a diameter of 500 nm in water. This computational method is highly useful for controlling MST at the single-particle level, enabling the design of spatial temperature distributions and the evaluation of thermophoretic forces acting on individual nanoparticles.

Natural-Based Microparticles as Sole Stabilizers of High Internal Phase Pickering Emulsions
Marie Cafiero *- ,
Marie-Noëlle Maillard - ,
Sabrina Maniguet - ,
Valérie de La Poterie - , and
Delphine Huc-Mathis
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Designing a water-reduced emulsion is a technical approach to creating more sustainable cosmetic products and reducing the strain on global water resources. This study explores the structuration of highly concentrated O/W emulsions solely stabilized by particles, also known as “high internal phase Pickering emulsions” (HIPPEs). It focuses especially on particles from natural origins with a micrometric scale instead of the highly modified nanometric ones commonly used (which may raise health issues). Highly concentrated O/W emulsions were formulated with different lipid phases (regarding the chemical nature and polarity) of up to 80%. A comprehensive array of particle natural sources (plant, mineral, etc.), micrometric sizes (from 3 to 45 μm), and geometries were screened. Parameters such as droplet size distribution, microstructure, relative stability (backscatter level changes), and pH were systematically monitored over 2 weeks. An experimental design approach was carried out on three particles to determine their stability domains in various formulation combinations, dissecting complex parameter interactions that pilot emulsion characteristics. Micrometric particles demonstrated excellent efficacy in structuring HIPPEs. A wide spectrum of systems can be engineered, exhibiting a wide range of microstructures (droplets ranging from micrometers to several millimeters), stabilities, and intrinsic properties (with pH values extending from approximately 6 to 10). Emulsions displaying resistance to coalescence in W/O systems were also successfully formulated by using hydrophobic natural particles. Waterless emulsions (less than 20% (w/w) water) stabilized exclusively with naturally derived microparticles represent promising architectures for designing future clean-label cosmetic prototypes. By meticulously selecting particle parameters, including their chemical composition, size, or origin, we can tailor the architecture of HIPPEs to obtain the targeted characteristics and functionalities. Beyond particle constituents, other ingredients influence the structural arrangement such as the lipid phase chemistry.

Cys-tRNAj as a Second Translation Initiator for Priming Proteins with Cysteine in Bacteria
Humbeline Paupelin-Vaucelle - ,
Claire Boschiero - ,
Christine Lazennec-Schurdevin - ,
Emmanuelle Schmitt - ,
Yves Mechulam - ,
Philippe Marlière - , and
Valérie Pezo *
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We report the construction of an alternative protein priming system to recode genetic translation in Escherichia coli by designing, through trial and error, a chimeric initiator whose sequence identity points partly to elongator tRNACys and partly to initiator tRNAfMet. The elaboration of a selection based on the N-terminal cysteine imperative for the function of glucosamine-6-phosphate synthase, an essential enzyme in bacterial cell wall synthesis, was a crucial step to achieve the engineering of this Cys-tRNAj. Iterative improvement of successive versions of Cys-tRNAj was corroborated in vitro by using a biochemical luciferase assay and in vivo by selecting for translation priming of E. coli thymidylate synthase. Condensation assays using specific fluorescent reagent FITC-Gly-cyanobenzothiazole provided biochemical evidence of cysteine coding at the protein priming stage. We showed that translation can be initiated, by N-terminal incorporation of cysteine, at a codon other than UGC by expressing a tRNAj with the corresponding anticodon. The optimized tRNAj is now available to recode the priming of an arbitrary subset of proteins in the bacterial proteome with absolute control of their expression and to evolve the use of xenonucleotides and the emergence of a tXNAj in vivo.

A Note on Enhancing Aeration via a Vortex-Based Cavitation Device
Jagdeep Kumar Nayak - ,
Amol Ganjare - , and
Vivek V. Ranade *
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There is growing interest in generating micro- or nanobubbles for enhancing aeration. Small bubbles not only enhance the interfacial area for gas–liquid mass transfer but also may enhance the equilibrium solubility if the size of the bubbles is small enough. In this note, we demonstrate the use of a vortex-based hydrodynamic cavitation device (VD) for generating small bubbles and enhancing aeration. Experimental results for conventional aeration and aeration with VD operated under three different conditions are presented. A reference case of potential degassing because of the low pressure generated in the cavitation device was also investigated. Experiments were carried out in a bubble column using DI water as the liquid phase. The dissolved oxygen (DO) concentration was measured using a precalibrated dissolved oxygen probe. Measurements of transient profiles of dissolved gas concentrations were carried out under different operating conditions. A generalized framework to analyze mass transfer in the presence of degassing, absorption, and desorption (via top surface or large bubbles) is developed and used for interpreting the experimental data. The per-pass degassing factor of VD was found to increase with the power dissipation [∝ (P–Pc)0.4, where P is power dissipation and Pc is the critical power beyond which degassing starts]. The aeration generated by VD was found to realize 30% higher DO concentration beyond the equilibrium solubility at atmospheric conditions. The bubble sizes estimated from the steady-state DO concentration were in the range from 80 to 200 μm for the operating parameters considered in this work. The presented results demonstrate the effectiveness of VD for enhancing aeration and will be useful for intensifying gas–liquid processes.

UPLC-MS/MS Method for Simultaneous Quantification of Cyclosporine A and Urolithin A in Plasma and Interspecies Analysis Across Mammals Including Humans
Ingrid Marie Heyns - ,
Raghu Ganugula - ,
M. N. V. Ravi Kumar - , and
Meenakshi Arora *
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In the past decade, liquid chromatography–mass spectrometry (LC-MS/MS) has become pivotal in clinical diagnosis, drug discovery, and bioanalytical science due to its high sensitivity and rapid analysis. We have developed an ultrasensitive and robust LC-MS/MS method for the simultaneous detection and quantification of cyclosporine A (CsA) and urolithin A (UA) employing ascomycin (ASC) and naringenin (NAR) as internal standards (ISTDs). The method was validated for clinical use, revealing interspecies differences between human plasma and other mammals (e.g., mouse, rat, feline, canine, and bovine serum). Validation parameters, including accuracy, precision, limits of quantification, specificity, selectivity, carryover, linearity, stability, and recovery, met acceptable ICH standards. Linear regression across the full calibration range (1–250 ng/mL for CsA and 0.5–125 ng/mL for UA) yielded an average R2 ≥ 0.999 in all mammal models. The method achieved a limit of quantification (LOQ) of 1–2.5 ng/mL across all model plasma samples with negligible carryover and demonstrated sample stability up to 96 h intra- and interday and 48 h for bovine serum. The method was successfully applied to quantify CsA and UA in canine samples following oral administration from a previous study. With a rapid run time of 6 min, this method offers high selectivity and precision, making it ideal for analyzing limited sample sizes and addressing regulatory challenges. The ability to simultaneously quantify CsA and UA has significant clinical potential for managing complex immuno-inflammatory diseases, enabling precise dose adjustments, and optimizing treatment outcomes.

Uptake and Release Kinetics Longevity in Stimuli-Responsive Hydrogels for Hydrophilic Drug Therapy
Parker M. Toews - and
Jeffrey S. Bates *
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The uptake and release of target molecules were studied in hydrogels as a function of time over a month to determine what, if any, deviation exists in these properties. Through the use of spectroscopic techniques such as FT-IR and UV–vis–NIR in combination with drug release kinetics and swelling kinetics studies, both the effect of imprinting and the effect of time could be substantially analyzed for hydrogels. Molecular imprinting provides a significant advantage over nonimprinted hydrogel samples through the sustainment of a first-order release profile throughout the month without significant deviations in the releasable concentration, while nonimprinted samples struggle in their capability to be consistently load-cycled. Changes between the imprinted and nonimprinted samples are not evidenced to be significant chemical deviations; rather, they are attributable to functionality differences between the release mechanisms of these hydrogels.

Gold Nanoraspberries for Surface-Enhanced Raman Scattering: Synthesis, Optimization, and Characterization
Megha Mehta - ,
William Skinner - ,
Benjamin Gardner - ,
Sara Mosca - ,
Francesca Palombo - ,
Pavel Matousek - , and
Nick Stone *
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In this work, we demonstrate the synthesis of gold nanoraspberries (AuNRB) using a HEPES buffer at room temperature. The study aimed to identify and compare the physicochemical conditions of the AuNRB and gold nanospheres (AuNS) of similar size to a selected set of reporter molecules. The dispersion stability of shape-controlled and AuNS of similar diameters was investigated in three different physiological media, ultrapure water, phosphate-buffered saline (PBS), and fetal bovine serum (FBS), and compared to understand the effect of NP shape, dispersion stability, and surface-enhanced Raman scattering (SERS) enhancement. We have used two nonresonant reporters, trans-1,2-bis(4-pyridyl) ethylene (BPE) and biphenyl-4-thiol (BPT), and a resonant reporter, IR820 (also known as new indocyanine green), a clinically approved dye for diagnostic studies, to explore the relative benefit of using molecular electronic resonance, i.e., comparing SERS vs surface-enhanced resonance Raman scattering (SERRS) with these nanoparticles. SERS has been explored extensively for biomedical applications, but the synthesis of bright gold nanoparticles and the appropriate Raman label is still challenging. To understand and optimize the SERS process, we have characterized both types of gold nanoparticles, ranging from their average size, ζ-potential, and ultraviolet–visible (UV–vis) absorption. It has been found that AuNRB and AuNS are most stable when dispersed in ultrapure water, while significant aggregation of both types has been observed when dispersed in PBS. With 10% FBS, there was a slight shift and increase in the surface plasmon absorbance peak, which resulted from an increase in particle size due to protein corona formation around the gold nanoparticles. For SERS efficiency, it has been found that AuNRB outperform AuNS with all reporters. Further, the resonant reporter, IR820, has provided a higher SERS signal compared to BPE and BPT and with its FDA approval for clinical use is clearly a strong candidate for future in vivo application.

Advanced One-Pot RPA-CRISPR/Cas12a Reaction with Glycerol and Betaine for High-Sensitivity Diagnosis of mecA-Carrying Strains in Clinical Samples
Jingyuan Wang - ,
Dan Wang - ,
Linlin Fan - ,
Xin Ye - ,
Jian Hu *- , and
Xiaoqin Wang *
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The mecA gene confers methicillin resistance in both MRSA and MR-CoNS by encoding the PBP2a protein and poses a significant public health threat due to its resistance to beta-lactam antibiotics. Rapid and accurate detection of mecA is critical for timely treatment, reducing morbidity, and preventing its spread in healthcare settings. In this study, we developed an advanced one-pot recombinase polymerase amplification (RPA)-CRISPR/Cas12a system, enhanced with glycerol and betaine, for ultrasensitive detection of the mecA gene. Glycerol’s viscosity effect prevents premature interaction between Cas12a and early amplification products, while betaine enhances nucleic acid amplification. The assay demonstrated superior sensitivity, detecting as low as 5 copies/μL of mecA DNA within 60 min. Specificity testing against a panel of bacterial species confirmed the high selectivity of the assay for mecA-carrying strains with negligible cross-reactivity. Furthermore, this method exhibited excellent performance across various clinical samples, including blood, urine, and bronchoalveolar lavage fluid. Our findings underscore the potential of this advanced RPA-CRISPR/Cas12a assay as a powerful diagnostic tool for rapid, cost-effective, and highly sensitive mecA detection, offering a promising solution for clinical diagnostics and infection control.

Polarization Spin Inversion with Nonlinear Plasmon Scattering
Pritam Khan - ,
Grace Brennan - ,
Syed A. M. Tofail - ,
Ning Liu *- , and
Christophe Silien *
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We report on circularly polarized Gaussian beam spin angular momenta that can be inverted upon scattering with quadrupole plasmon modes. The conditions for such conversion are met with high-angle collection, dark-field scattering microscopy on spherical plasmonic particles. We further report that silvered nanoporous silica microparticles exhibit a strong nonlinearity in their scattering, specifically a reverse saturated scattering (RSS), when exposed to high laser power densities on the sample of ca. 5 GW/cm2. Handedness conversion by these microparticles is only observed at wavelengths tuned to the quadrupole modes. Conversely, the scattering remains linear, and the handedness is unchanged, when the same particles are illuminated with low laser power densities of ca. 10 W/cm2. We infer that RSS tuned to the quadrupole modes sufficiently enhances their contribution so that they dominate the high-angle scattering, thereby justifying the light spin inversion. Moreover, the addition of a self-assembled monolayer of ethynylaniline (EA) on the microparticles results in handedness conversion for both low and high incident power, as expected from preferable dipole damping and plasmon mode red shift. This demonstrates that optical nonlinearity in scattering can be exploited for polarization tuning in plasmonic metamaterials.

Improving Spent Coffee Biochar for Effective Organic Contaminant Removal from Aqueous Media
Inga Block *- ,
Harshadrai M. Rawel - ,
Tillmann Klamroth - ,
Christina Günter - ,
Jiyong Kim - ,
Fabian Loepthien - ,
Shashank K. Gahlaut - ,
Ilko Bald - , and
Andreas Taubert *
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The contamination of (waste)water with organic pollutants, such as pharmaceuticals and dyes, is drastically increasing. Their removal process presents several difficulties, and often activated carbon (AC) is used in a filtration step. While commercial AC is often based on fossil resources, in this study, we present a new approach toward biochar from spent coffee (SC). This new AC has considerably enhanced surface areas and porosities, making it suitable for wastewater treatment. Using MgCO3 as an activating agent, a biochar with a significantly enhanced surface area of ∼600 m2/g is produced in a simple but efficient manner. The resulting biochar is effective for the removal of a whole spectrum of organic pollutants in aqueous systems. The dyes methylene blue (MB) and methyl orange (MO), but also the pharmaceuticals diclofenac (DCF) and tetracycline (TET), as well as the xenoestrogen bisphenol A (BPA), are successfully removed by up to 100% from aqueous solutions with the new adsorbents. Removal efficiencies depend on the pH of the solutions. In contaminant mixtures, the biochar shows preferences for adsorption toward some compounds but still shows very high adsorption capacities for all contaminants.

Potential Antibiotic Resurgence: Consecutive Silver Nanoparticle Applications Gradually Increase Bacterial Susceptibility to Antibiotics
Maria Maklakova *- ,
Luis Jesús Villarreal-Gómez - ,
Ekaterina Nefedova - ,
Nikolay Shkil - ,
Roberto Luna Vázquez-Gómez - ,
Alexey Pestryakov - , and
Nina Bogdanchikova *
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The increasing prevalence of resistant bacteria has emerged as a critical public health concern due to their ability to resist multiple antibiotics. This study aimed to investigate whether repeated treatments with silver nanoparticles (AgNPs) could gradually decrease bacterial resistance to antibiotics. The methodology involved three consecutive applications of AgNPs on six bacterial strains, followed by assessing their susceptibility to 38 different antibiotics. To our knowledge, the following three phenomena were observed for the first time. (1) During three consecutive AgNP applications, it was revealed that all the studied bacteria gradually became more susceptible to 38 antibiotics; by the end of the treatments, susceptibility had doubled for five bacteria and tripled for Klebsiella pneumoniae compared to the susceptibility before the first AgNP application. (2) Three consecutive AgNP treatments led to 27–47% restoration of bacterial susceptibility to antibiotics, which had already completely lost their activity before the initial AgNP application. (3) Unlike previous studies, we discovered a novel effect: the repeated AgNP applications increased the susceptibility of Salmonella enteritidis and Staphylococcus aureus to AgNPs themselves. Obtained results suggest that AgNP treatments may offer a new promising strategy to combat antibiotic resistance.

Mechanochemical Thiolation of α-Imino Ketones: A Catalyst-Free, One-Pot, Three-Component Reaction
Srinivasarao Yaragorla *- ,
Mahesh Sulthan - ,
Jagadeshwar Vannada *- , and
Doma Arun
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Herein, we report an efficient mechanochemical synthesis of α,α-amino thioketones involving a one-pot, three-component milling of 2-oxo aldehydes, amines, and thiols. Unlike previous methods, this protocol does not require any catalyst or oxidizing additive. The reaction proceeds through the thiolation of in situ formed α-imino ketones by liquid-assisted grinding. We have successfully extended this protocol to synthesizing benzothiazoles, thiazoles, and quinoxalines, demonstrating its efficiency and potential in the field. Importantly, we have shown the gram-scale synthesis, synthetic applications, and substrate scope of this protocol, instilling confidence in its practicality.

Effect of CH6N4O Additive on Ib-Type Diamond from Ni-Based Alloy under HPHT Conditions
Longsuo Guo *- ,
Shuai Fang *- ,
Jing Zhang - ,
Peipei Sun - ,
Meng Gao - ,
Dongliang Chu *- , and
Xiaopeng Jia
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Natural diamond inclusions comprise elements such as carbon (C), hydrogen (H), oxygen (O), and nitrogen (N), which can be assumed to exist in the natural diamond growth environment. Therefore, the artificial construction of the C–H–O–N system plays an important role in exploring the growth mechanism of natural diamonds. Herein, diamond crystals were successfully synthesized in the NiMnCo–C system by adding carbohydrazide (CH6N4O) as the organic additive at 1280 to 1320 °C and 5.4 GPa–6.0 GPa. The crystals were characterized using various analytical tools. Optical microscopy (OM) showed that the additive caused new extended defects similar to different dislocations. These filiform defects mainly appeared inside the top {111} face of the synthesized diamond and were always perpendicular to the {111} face. Raman spectroscopy and X-ray diffraction (XRD) analysis indicated that the synthesized diamond had high-quality sp3 structures. The Fourier transform infrared spectroscopy (FTIR) spectra showed that under a constant doping concentration, the N content inside the diamond increased with increasing synthesis temperature and constant pressure but decreased with increasing synthesis pressure and constant temperature. X-ray photoelectron (XPS) spectroscopy confirmed that N, O, and H successfully entered the diamond lattice.

Host–Guest Dynamic Behavior of Melatonin Encapsulated in β-Cyclodextrin Nanosponges
Riccardo Ferrero - ,
Stefano Pantaleone - ,
Valentina Brunella - ,
Marta Corno - ,
Gonzalo Jiménez-Osés *- , and
Francesca Peccati *
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Cyclodextrin-based nanosponges are cross-linked polymeric porous nanomaterials obtained by condensation of cyclodextrins with a polyfunctional reagent (cross-linker). Owing to their high surface area, they are attractive for encapsulation applications aimed at increasing the stability, solubility, and bioavailability of drugs. Due to the structural complexity of these emerging materials, computer modeling can provide atomistic-level insights into both the flexibility of nanosponges and their interactions with encapsulated drugs. In this contribution, we focus on nanosponges of β-cyclodextrin cross-linked with citric acid and provide full-atom models for linear and cyclic topologies. We use extensive molecular dynamics (MD) simulations to analyze the flexibility of these constructs and their interactions with encapsulated melatonin, a neurohormone involved in sleep-wake cycle regulation also used as an antioxidant and immunomodulator. We characterize the main interactions responsible for melatonin binding and show that it benefits from multivalence and crowding effects.

Photocatalytic Gas-Phase Hydrogen Sulfide Removal Using Mo Cocatalyst: Implementation of Counter-Poisoning Photocycle
Tomofumi Katayama - and
Morio Nagata *
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Hydrogen sulfide is a toxic gas known for its foul odor and health risks, even at significantly low concentrations. Although its decomposition at high concentrations is common in industrial processes, decomposing it at low concentrations is difficult. One of the difficulties is that sulfate ions generated during the reaction would poison the catalyst and reduce efficiency. Here, we show the gas-phase decomposition of low-concentration hydrogen sulfide using a high-activity photocatalyst, and to counter the poisoning problem, molybdenum is introduced through a novel photosupporting method that utilizes the characteristics of photocatalysts. In this study, we demonstrate a novel molybdenum-loaded catalyst for gas-phase photocatalytic hydrogen sulfide decomposition and its high performance: zero-out of 10 ppm of hydrogen sulfide. Moreover, the catalyst can be regenerated through photocatalytic reduction, keeping decomposing hydrogen sulfide to nearly odorless levels. The study provides a simple and sustainable photocatalytic process for removing low-concentration hydrogen sulfide, effectively preventing catalyst poisoning and enabling catalyst regeneration; thus, this suggests enhancing air quality and reducing health risks associated with this toxic gas in industrial and urban environments.

Computational Screening of Glyme-Based Room-Temperature Aluminum Plating Solutions
Tomoya Kanno - ,
Tsubasa Otsuki - ,
Norio Takenaka *- , and
Atsushi Kitada *
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A computational data-driven approach is applied to the design of liquid electrolyte materials for a complex phenomenon, viz. electrochemical deposition. A protocol for the liquid electrolyte material exploration consists of (i) structure optimization, (ii) reduction mechanism elucidation, and (iii) computational screening. A case study is conducted targeting glyme-based room-temperature aluminum (Al) electroplating solutions, where how to achieve a higher plating speed has been an open issue. The determination of stable Al–Cl–glyme complex structures by density functional theory calculations enables the modeling for molecular dynamics simulations of the bulk electrolytes, namely, aluminum chloride (AlCl3)–diglyme (G2)–cosolvent system. It is shown that a tridentate coordination of diglyme (G2) to [AlCl2]+ is robust against desolvation and one-electron reduction, suggesting that the diffusion coefficients of the [AlCl2]+ cationic complex are an indication of faster plating. Additionally, the calculated diffusion coefficients correlate weakly with the relative permittivity data of cosolvents in their pure state but strongly with viscosity data. This relationship can be used to design Al plating solutions.

Crystallographic Structure and Antiglioma Potential of Centrolobium microchaete Seed Lectin
Benildo Sousa Cavada - ,
Vanir Reis Pinto-Junior - ,
Francisco Edilcarlos Oliveira Lima - ,
Valeria Maria Sousa Ferreira - ,
Messias Vital Oliveira - ,
Vinicius Jose Silva Osterne - ,
Nicole Sartori - ,
Ana Carolina dos Santos - ,
Rodrigo Bainy Leal *- , and
Kyria Santiago Nascimento *
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The genus Centrolobium comprises species of Neotropical trees with seeds that possess medicinal and bioactive applications. Lectins from this genus exhibit anti-inflammatory and immunomodulatory effects, influencing the activation of the immune system. This study focuses on characterizing the structure and carbohydrate-binding properties of the lectin from Centrolobium microchaete (CML) and evaluating its potential against gliomas. The structure of the lectin in complex with methyl-mannose-α1,3-mannose (MDM) was resolved using X-ray crystallography at 1.3 Å resolution, with its interactions further analyzed through molecular dynamics simulations. Structurally, CML adopts a β-sandwich motif and assembles into canonical dimers. In vitro assays revealed that CML reduced the viability of C6 glioma cells, although only at high concentrations, without impacting cell migration or morphology. CML activated autophagic processes, albeit with lower efficacy compared with other mannose-specific lectins. The limited antiglioma activity of CML may be linked to its inability to form tetramers and unusual specificity toward asymmetric glycans, both crucial features for interactions with cellular glycans and the activation of signaling pathways. This study represents the first investigation of the antiglioma potential of a mannose-specific lectin from the Dalbergieae tribe, highlighting both its structural characteristics and functional limitations.

Improving the Activity and Selectivity of a Scorpion-Derived Peptide, A3a, against Acinetobacter baumannii through Rational Design
Dalton S. Möller - ,
Mandelie van der Walt - ,
Carel Oosthuizen - ,
Miruna Serian - ,
June C. Serem - ,
Christian D. Lorenz - ,
A. James Mason *- ,
Megan J. Bester - , and
Anabella R. M. Gaspar *
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The rise in antimicrobial resistance has led to an increased desire to understand how antimicrobial peptides (AMPs) can be better engineered to kill antibiotic-resistant bacteria. Previously, we showed that C-terminal amidation of a peptide, identified in scorpion Androctonus amoreuxi venom, increased its activity against both Gram-positive and -negative bacteria. Here, we incorporate all-atom molecular dynamics (MD) simulations in a rational design strategy to create analogues of A3a with greater therapeutic potential. We discover two novel AMPs which achieve greater potency against, and selectivity toward, Acinetobacter baumannii ATCC 19606 but via two distinct mechanisms and which are effective in Galleria mellonella models of A. baumannii burn wound infection. While CD spectroscopy indicates A3a adopts an α-helix conformation in the presence of models of the Gram-negative bacterial plasma membrane, MD simulations reveal it adopts a hairpin conformation during initial binding. Three different strategies, designed to stabilize this hairpin conformation, produce substantially different outcomes. Deletion of Ile6 and Ile10 restricts conformational flexibility, characteristic of A3a, during membrane binding, prevents adoption of the α-helix conformation in the steady state, and abrogates the antibacterial activity. In contrast, substitution of arginine 7 to lysine (A3a[R7K]) or isoleucine 14 to tryptophan (A3a[I14W]) does not consistently affect peptide conformations. Both of these new analogues are rapidly bactericidal toward A. baumannii ATCC 19606 but A3a[R7K] also causes rapid permeabilization and while the antibacterial potency and selectivity are increased for both peptides, this is greatest for A3a[I14W]. Integration of atomistic MD simulations into a multidisciplinary approach to understanding antimicrobial peptide mechanism of action is a valuable tool for interpreting the effects of rational design strategies.

Confinement-Driven Aggregate Formation of Photoacids within Porous Metal–Organic Frameworks
Markus Rödl - ,
Viktoria Kiefer - ,
Selina Olthof - ,
Klaus Meerholz - ,
Gregor Jung - , and
Heidi A. Schwartz *
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Structurally driven properties of hybrid materials are a fascinating feature of metal–organic framework (MOF) materials that can serve as hosts for various responsive dye molecules. In particular, the formation of aggregates and the related shift of the emission of fluorophors can be tuned as a function of pore confinement. In this work, the fluorosolvatochromic methylated photoacid tris(2,2,2-trifluoroethyl) 8-methoxypyrene-1,3,6-trisulfonate (MePhos) and the free photoacid tris(2,2,2-trifluoroethyl) 8-hydroxypyrene-1,3,6-trisulfonate (Phos) were inserted into various MOF scaffolds, and the resulting emission properties were found to be far beyond the observed red shifts for polar solvents such as methanol or ethanol. Instead of the modulation of the band gap by the local environment given by the physicochemical properties of the MOF pores, there is aggregation of the MePhos molecules depending on the MOF structure, leading either to H- or t o J-like character.

Two-Dimensional Nanofluidic Membranes with Nepenthes-Inspired Superstructures toward Boosting Solar-Driven Ionic Power Generation
You-Peng Fang - ,
Sheng-Hua Liu - ,
Yan-Hong Liu - ,
Ke-Xin Wang - ,
Chun-Kui Hu - ,
Chun-Xin Lu - ,
Rusheng Qian - , and
Xia-Chao Chen *
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Photoinduced transmembrane ion transport in organisms provides a distinctive perspective for exploiting the ocean enriched with both ions and solar energy. Artificial two-dimensional nanofluidic membranes for photothermal-driven ion transport are facing issues such as interrupted nanofluidic transport and much dissipated heat. Peristome surface of Nepenthes enables stable wetting and rapid directional water transport correlated with orientational sophisticated flow-guiding microstructures, inspiring amelioration of these issues by regulating membrane topographies. A conformal layer-by-layer assembly is adopted to construct superstructured positively charged graphene oxide (PGO)/MXene membranes (SGMMs) that differ from topographies. These membranes enable anion-selective transport enhanced by superstructure configurations via providing more and wider nanofluidic channels than planar PGO/MXene membrane (PGMM). SGMMs with orientational superstructures demonstrate superior wetting performance and directional transport of surface microfluidics compared to PGMM, inducing directional ion transport within nanochannels. Additionally, this superstructure design assists SGMMs to outshine PGMM in photothermal evaporation conspicuously, benefiting from an enlarged surface area and well-regulated surface microfluidic distribution. Eventually, SGMMs enable more remarkable photothermal evaporation-driven ion transport facilitated by directional transport of surface microfluidics and efficient photothermal evaporation. This work emphasizes the significance of membrane topography design for nanofluidic transport toward exploiting the ocean including sunlight, water resources, and ionic energy.

Predictive Modeling of Pesticides Reproductive Toxicity in Earthworms Using Interpretable Machine-Learning Techniques on Imbalanced Data
Mihkel Kotli - ,
Geven Piir *- , and
Uko Maran
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The earthworm is a key indicator species in soil ecosystems. This makes the reproductive toxicity of chemical compounds to earthworms a desired property of determination and makes computational models necessary for descriptive and predictive purposes. Thus, the aim was to develop an advanced Quantitative Structure–Activity Relationship modeling approach for this complex property with imbalanced data. The approach integrated gradient-boosted decision trees as classifiers with a genetic algorithm for feature selection and Bayesian optimization for hyperparameter tuning. An additional goal was to analyze and interpret, using SHAP values, the structural features encoded by the molecular descriptors that contribute to pesticide toxicity and nontoxicity, the most notable of which are solvation entropy and a number of hydrolyzable bonds. The final model was constructed as a stacked ensemble of models and combined the strengths of the individual models. Evaluation of this model with an external test set of 147 compounds demonstrated a well-defined applicability domain and sufficient predictive capabilities with a Balanced Accuracy of 77%. The model representation follows FAIR principles and is available on QsarDB.org.

Versatile One-Pot Synthesis of Hydrophobic Tags by Multicomponent Reactions
Federica Carolina Balestrero - ,
Laura Gioiello - ,
Georgia Goutsiou - ,
Sabina Sangaletti - ,
Rita Maria Concetta Di Martino *- ,
Fabrizio Condorelli - ,
Ambra A. Grolla - , and
Tracey Pirali
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Among the various strategies being developed in the field of protein degraders, HyTags remain relatively underexplored, despite their advantages over PROTACs. Their synthesis typically involves multistep procedures, including the use of coupling reagents and protection/deprotection steps. To develop a more sustainable and streamlined approach, we designed a versatile multicomponent platform that generates HyTags with diverse linkers and hydrophobic moieties in high yields. Using (+)-JQ1 as the POI ligand, we synthesized a series of BRD4-targeting HyTags and discovered that compound 23 induces degradation of BRD4 via the autophagy-lysosome pathway through ER stress. This finding further supports the valuable application of this synthetic methodology in the search for effective degraders.

Preparation and Properties of Sodium Carboxymethyl Cellulose Microspheres by Dropping Method
Ling Wang - ,
De-Shuang You - ,
Dan-yan Guo - ,
Xue-Chen Zhuang - ,
Tao Yuan *- , and
Dan Qiu *
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Sodium carboxymethyl cellulose (CMC) is the most extensively utilized derivative of cellulose. In this study, an innovative approach was employed to disperse a CMC aqueous solution into olive oil in the form of liquid droplets, resulting in the direct formation of CMC microspheres after drying. The effects of CMC concentration and needle aperture size on microsphere formation were systematically investigated, showing that the particle size of the microspheres decreased with an increase in CMC concentration and a decrease in needle aperture. The CMC-based microspheres exhibited a consistently uniform spheroid morphology with particle sizes ranging from 1.5 to 2.5 mm, and a three-dimensional uniform polymeric network structure. Furthermore, the drug loading efficiency of the CMC-based olive oil microspheres reached 82.18%, which was markedly superior to that of other cellulose-based microspheres for fat-soluble substances. The CMC-based vitamin C (VC) microspheres exhibited an ultimate drug loading efficiency of approximately 24%, and their maximum encapsulation efficiency was 78.57% at a VC concentration of 30%, which was significantly higher than that of starch-based VC microspheres. Additionally, the CMC-based VC microspheres realized a sustained and stable release rate in ethanol at 30 °C.

Biodistribution of 89Zr-Radiolabeled Nanoassemblies for Monoclonal Antibody Delivery Revealed through In Vivo PET Imaging
Ana M. López-Estévez - ,
Amaia Carrascal-Miniño - ,
Dolores Torres - ,
María José Alonso - ,
Rafael T. M. de Rosales *- , and
Juan Pellico *
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Despite the outstanding performance of monoclonal antibodies (mAbs) in the clinic, their full potential has been hindered due to their inability to cross cell membranes and therefore reach intracellular targets. The use of nanotechnology to deliver mAbs to intracellular domains has been highlighted as a strategy with high potential. Working toward this goal, we have recently developed and validated palmitoyl hyaluronate (HAC16)-based nanoassemblies (HANAs), a novel technology for the intracellular delivery of mAbs in Kirsten Rat Sarcoma Virus (KRAS)-mutated tumors, one of the most prevalent and a challenging intracellular oncoprotein. Despite their success, the pharmacokinetics and biodistribution of these delivery vehicles are still unknown due to their chemical complexity, a challenge common to a large proportion of drug delivery nanomedicines. To support further development and clinical translation, we present an efficient radiolabeling approach with the positron emitter zirconium-89 (89Zr) for the in vivo evaluation of HANAs by whole-body PET imaging. Additionally, we assessed the impact of PEGylation and size modulation on the biodistribution profile of mAbs using 89Zr-radiolabeled PEGylated and non-PEGylated HANAs. Our PET imaging results demonstrated that HANAs significantly modify the pharmacokinetics and biodistribution of the 89Zr-mAb. Furthermore, we established that the biodistribution of HANAs can be conveniently modulated by introducing PEG polymers on the surface, facilitating customization for cancer applications. This versatile radiolabeling strategy provides a facile approach for the in vivo evaluation of complex nanoformulations loaded with mAbs, in a quantitative manner with high sensitivity.

Multifluid Mixture Models for the Binary Mixtures of Trifluoroethene (R-1123) with Difluoromethane (R-32), 2,3,3,3-Tetrafluoroprop-1-ene (R-1234yf), and Propane (R-290)
Ryo Akasaka *- ,
Sho Fukuda - , and
Yukihiro Higashi
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This work presents mixture models for the thermodynamic properties of the mixtures of R-1123 with R-32, R-1234yf, and R-290, which are potential refrigerants for next-generation air conditioning systems. The models are based on the multifluid approximation and employ accurate Helmholtz energy equations of state for the pure fluids. The mixing parameters of the models are determined by fitting experimental data for the (p, ρ, T) behavior and vapor–liquid equilibrium. The range of validity of the models is approximately temperatures from 273 to 400 K and pressures up to 7 MPa. Typical uncertainties (k = 2) in this range are 0.3% for liquid densities, 1.5% for vapor densities, and 1% for bubble-point pressures. The mixture models exhibit qualitatively correct behavior in the critical and extrapolated regions; this is demonstrated by plots of several thermodynamic properties over wide ranges of temperature and pressure.

Synthesis of a Hydroxy-15-Azasterol
Caleb A. H. Jones *- ,
Bruce J. Melancon - , and
Craig W. Lindsley *
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Niemann-Pick type C (NPC) is a lysosomal storage disorder that will cause eventual brain damage with limited treatment options available. Though clinical trials are undergoing with repurposed pharmaceuticals, no novel chemotype exists purely for the treatment of NPC. In 2021, an azasterol was found to bind to both NPC1 and NPC2 proteins and is considered as a cholesterol mimic. A convergent synthesis to obtain a hydroxy-15-azasterol was completed in 12 steps, from 2-oxepanone.

Development of a Multienzyme Cascade for Salvianolic Acid A Synthesis from l-Tyrosine
Mingxi Zhang - ,
Jiayi Zhong - ,
Yuekai Zhang - ,
Weijie Wang - ,
Weirui Zhao *- ,
Sheng Hu - ,
Changjiang Lv - ,
Jun Huang - , and
Lehe Mei *
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Salvianolic acid A (SAA) has an important application value for preventing and treating cardiovascular diseases. In this study, we developed a novel multienzyme cascade system for the efficient biosynthesis of SAA, utilizing l-tyrosine (l-Tyr) as a cost-effective and stable starting material. The cascade system incorporated four enzymes: membrane-bound l-amino acid deaminase from Proteus vulgaris (Pvml-AAD), d-lactate dehydrogenase from Pediococcus acidilactici (Pad-LDH), 4-hydroxyphenylacetate 3-hydroxylase from Escherichia coli (EcHpaBC), and formate dehydrogenase from Mycobacterium vaccae N10 (MvFDH). All reaction steps in the cascade system were thermodynamically favorable. In addition, to avoid generating an unstable intermediate (3,4-dihydroxyphenyl-pyruvate, DHPPA), which was produced owing to the promiscuity of EcHpaBC and Pad-LDH, we performed the cascade system according to the reaction sequence of deamination, chiral reduction, and ortho-hydroxylation. Under optimized conditions, the developed cascade system yielded 81.67 mM SAA from an initial concentration of 100 mM l-Tyr, corresponding to a yield of 81.67%.

Exploring the Stability and Electronic Properties of Janus TMCSe Monolayers via DFT Calculations
Luis Ángel Campos Ortiz - ,
José Israel Paez Ornelas *- ,
Luis Ángel Alvarado Leal - ,
Héctor Noé Fernández Escamilla - ,
Atilano Martinez Huerta - ,
Eduardo Gerardo Pérez Tijerina - , and
Noboru Takeuchi
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Janus monolayers are two-dimensional materials with distinct chemical compositions on their opposing sides, leading to unique properties and potential applications in various fields. Based on density functional theory (DFT) calculations, we have explored the dynamic stability of a family of Janus monolayers with the general formula TMCSe (TM = Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn). Only two explored systems were dynamically and thermal stable: CrCSe and MnCSe, as evidenced by their phonon dispersion curves and molecular dynamics calculations. Their electronic properties and magnetic character have been investigated using their corresponding density of states. The CrCSe monolayer is a 0.4 eV indirect semiconductor, and the magnetic MnCSe monolayer is spin-up metallic and a spin-down semimetal. Electrostatic potential isosurfaces are used to assess the reactivity of the stable monolayers. They indicate that the surfaces of the TMCSe structures are polarized, with the C side exhibiting a strong negative potential and the Se side displaying a more neutral character. This property may lead to applications in many fields, such as Li storage or toxic molecule trapping.

Temperature-Dependent Wax Precipitation Characteristics in Gas Condensates: Composition, Aggregation, and Crystallization Patterns
Lihu Cao - ,
Yongcang Ren - ,
Hongjun Wu - ,
Zhaocai Pan - ,
Zhaomin Li - , and
Chao Zhang *
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This study investigates the characteristics of the wax precipitation activity in the condensates. The patterns of wax precipitation are elucidated by analyzing the composition and amount of precipitate produced at various temperatures, verifying the influence mechanism of factors such as condensate composition and temperature on wax separation. The findings reveal that a decrease in the temperature enhances the contact of wax molecules by reducing their thermal motion, leading to wax particle precipitation. This also weakens the Brownian motion of precipitated wax, further promoting their aggregation and subsequent deposition. Consequently, the amount of wax precipitate increased as the temperature drops. Moreover, an increase in asphaltenes and resins in the condensates raises the critical crystalline radius of wax, making wax precipitation more difficult. Therefore, the amount of wax precipitate decreases as the concentration of asphaltenes and resins in the condensates increases. Additionally, because the solubilities of different hydrocarbon components change at different rates with decreasing temperature, lower carbon number hydrocarbons precipitate more actively in the early stages, with their precipitation rate declining as their concentration in the system diminishes. This relatively increases the precipitation rate of higher carbon number hydrocarbons in the later stage, increasing the proportion of high carbon number components in the composition curve of the wax deposit as the temperature decreases. Finally, the four components of the system─saturated hydrocarbons, aromatic hydrocarbons, asphaltenes, and resins─exhibit different precipitation behaviors as the temperature decreases, and their precipitation proportions show different trends at various temperatures. This study provides data to enrich the theoretical understanding of wax precipitation mechanisms in condensates under well-bore environmental conditions. It can support the development of effective wax blockage prevention strategies in reservoir development.

Nanocarbons Reinforcement Effect into Polyethylene Nanocomposites: γ-Ray Attenuation Potential and Hardness Improvement by the Taguchi Method
Thais Cardoso Oliveira *- ,
Evelyn Alves Nunes Simonetti - , and
Luciana Simone Cividanes
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High-density polyethylene (HDPE) is a light and low-cost polymer widely explored as an excellent barrier material for γ-ray and neutron radiation in situations of high exposure (e.g., aerospace). Nevertheless, this polymer is not a suitable structural material due to its low mechanical resistance. Herein, amino-functionalized carbon nanotubes (CNTs) and graphene oxide (GO) were incorporated into HDPE and statistically studied through a Taguchi design of experiments (DoE) model that investigated their synergistic effect. After incorporating these nanocarbons, microscopy images suggest their homogeneous distribution into HDPE. Furthermore, X-ray diffraction shows that the HDPE crystallinity degree increased due to a nucleation effect caused by the nanofillers. Additionally, all nanocomposites presented improved microhardness resistance (up to 69%), particularly when both nanocarbons were incorporated into the matrix. The nanocomposite with higher microhardness resistance had the γ-ray attenuation potential, exhibiting a similar radiation shielding effect to HDPE, with a linear attenuation coefficient higher than Aluminum, a reference material. Hence, this study shows that the synergy between these nanocarbons can be explored to improve HDPE hardness without negatively affecting its attenuation ability. Therefore, these nanocomposites with improved hardness and γ-ray shielding are potential materials for applications requiring surface durability and radiation resistance, such as in air-/spacecraft systems.

Synthesis and Characterization of a Strontium–Quercetin Complex and Its In Vitro and In Vivo Potential for Application in Bone Regeneration
Israel B. Pimenta - ,
Gildácio Chaves Filho - ,
Elias G. B. Silva - ,
Lucas F. B. Nogueira - ,
Tomaz Santana de Mendonça - ,
Taíssa C. S. Furtado - ,
Paulo Cesar Ferreira GasparNeto - ,
Luis Gustavo Dias - ,
Sandra Yasuyo Fukada - ,
Pietro Ciancaglini - , and
Ana Paula Ramos *
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Progress has been made toward developing therapies to treat bone-related diseases and defects caused by trauma. However, some of these therapies, such as administering strontium ranelate to treat osteoporosis, have significant side effects. In this context, designing new and safer strontium-based materials constitutes an important current challenge. Here, we have used quercetin as a platform to synthesize a new complex based on strontium and evaluate its activity in vitro and in vivo. First, we carried out strontium complexation with quercetin. Then, we employed Fourier transform infrared spectroscopy, nuclear magnetic resonance, and thermal gravimetric analysis to determine the chemical composition of the resulting complex as [(C15H7O7)Sr2]·6(H2O), which was also supported by theoretical calculations. This complex enhanced osteogenic differentiation of a preosteoblastic cell line in vitro, which increased alkaline phosphatase activity and extracellular matrix mineralization. By using a periapical lesion model in mice, we tested whether treatment with this complex could regenerate bone defects in vivo and found that the lesions decreased after 7 days. Together, our data showed that the strontium–quercetin complex synthesized herein is a potential candidate for developing new bone regeneration therapies.

Development of Value-Added Superhydrophobic Fiber as a Highly Selective Oil Filter, Superior Self-Cleaning, and Efficient Oil–Water Separation Material Exhibiting a Significant Number of Life Cycles
Swarna Karthika Thirviyam - and
Selvaraj Vaithilingam *
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The current study attempted to couple acid-treated thermal power station waste fly ash with different weight percentages of phenyltriethoxysilane and deposited on the cotton fabric surfaces in order to get superhydrophobic/superoleophilic materials (TPSWFA/PTES-CF). The contact angle measurements were carried out along with other physiochemical and morphological studies for TPSWFA/PTES-CF materials using a goniometer and showed an average static water angle value of 158.5°. The wetting behavior of corrosive liquids such as coffee, milk, tea, water-dyed methylene blue, strong acids (HCl), strong alkali (NaOH), and saturated salt solution (NaCl) was assessed for the fabricated TPSWFA/PTES-CF superhydrophobic/superoleophilic substrates using an optical contact angle meter. The wash durability, mechanical stability, oil/water separation, and self-cleaning ability through flushed water were also carried out for the newly developed high-value superhydrophobic TPSWFA/PTES-CFS filter and reported. The results obtained from oil–water separation shows exceptional separation efficiency with oil purity of ≥99.97 wt %, and high permeation flux values up to 11,100 ± 22 L m–2 h–1 are observed for surfactant stabilized water-in-oil emulsion using the gravity-driven technique. The developed waste-based cotton showed highly selective oil adsorption, superior self-cleaning property, high value of flux, and efficient oil–water separation with significant cyclic processes.

Optimizing Ethanol–Water Cosolvent Systems for Green Supercritical Carbon Dioxide Extraction of Muscadine Grape Pomace Polyphenols
Arda Tuhanioglu - ,
Sumanjot Kaur - ,
Gabriel Laquete De Barros - ,
Safoura Ahmadzadeh - ,
Renee Threlfall - , and
Ali Ubeyitogullari *
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This study evaluated the ethanol–water modified (50%, v/v) supercritical carbon dioxide (SC-CO2) for the extraction of polyphenols from muscadine grape (Vitis rotundifolia Michgx.) pomace and compared with conventional solvent extractions (ethanol–water and HCl–methanol). The process was optimized with a central composite response surface design consisting of three levels of three independent variables: pressure (20–40 MPa), temperature (40–60 °C), and cosolvent concentration (5–15%) to maximize three responses: total phenolic content (TPC), total flavonoid content (TFC), and resveratrol yields. The optimal conditions were determined as 20 MPa, 60 °C, and 15% cosolvent concentration with TPC, TFC, and resveratrol yields of 2491 mg/100 g, 674 mg/100 g, and 1.07 mg/100 g, respectively. The surface plots indicated that a 15% cosolvent concentration maximized extraction efficiency, producing red-brown colored extracts. In contrast, a 5% cosolvent resulted in poor extractions, yielding yellow-green extracts under all conditions. The yields increased with higher temperatures (i.e., 60 °C) and lower pressures (i.e., 20 MPa). TPC and TFC obtained through cosolvent-modified SC-CO2 were similar to those obtained through conventional extractions. Moreover, the resveratrol yield was lower than the HCl–methanol extraction, even though it was not different from any ethanol–water extractions at any solvent-to-solute ratios. The analysis of antioxidants indicated that the ABTS values of the cosolvent-modified SC-CO2 extract were lower than those of the HCl–methanol extract. However, there were no significant differences in the DPPH values between the two extracts. Thus, this study optimized the sustainable technology of SC-CO2 extraction by employing only food-grade cosolvents─ethanol and water─as a more environmentally friendly method for isolating polyphenols from the underutilized waste product of muscadine grape pomace utilizing statistical methodologies in the extraction process.

Numerical Simulation Study on Hydrogen Accumulation and Explosion in Radioactive Gas Decay Chamber
Shutang Sun - ,
Yuanyuan Li - ,
Ying Ji - ,
Yeming Zhu *- ,
Dong Zhao - ,
Yiren Lian - ,
Yu Rong - ,
Jin Yan - ,
Hongchao Sun - , and
Guoqiang Li
This publication is Open Access under the license indicated. Learn More
During the operation of the reactor, a mixture of oxygen, hydrogen, nitrogen, and radioactive gases is produced and stored under pressure in a decay chamber. This review uses numerical simulation methods to study the accumulation and explosion of hydrogen in these mixed gases during storage. The results show that when the initial volume concentration of hydrogen is 0.2%, the maximum volume concentration of hydrogen in the decay box is about 4% after about 1.61 h, the maximum concentration of hydrogen in the decay box is 30% after about 16.79 h, and the concentration is highest at the top of the decay box. As the operating pressure of the decay chamber increases, the maximum explosion pressure of hydrogen gas significantly increases, reaching up to 7.110 MPa.

TREM-1 as a Potential Coreceptor in Norovirus Pathogenesis: Insights from Transcriptomic Analysis and Molecular Docking
Mike Telemaco Contreras Colmenares - ,
Amanda de Oliveira Matos - ,
Pedro Henrique dos Santos Dantas - ,
José Rodrigues Do Carmo Neto - ,
Bruno Júnior Neves - ,
Luiz Gustavo Araújo Gardinassi - ,
Marcelle Silva-Sales - , and
Helioswilton Sales-Campos *
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Norovirus (NoV) is a major cause of acute diarrheal disease in humans. However, due to complications in cultivating this virus, bioinformatics aids in elucidating the virus–host relationship. One of the molecules that has been associated with the burden of viral diseases is TREM-1, mainly due to its role in amplifying the inflammatory response. Thus, we hypothesized that TREM-1 may be involved in NoV infection. Analysis of public transcriptomic data sets showed an increased expression of Trem1 and Trem3 during murine NoV (MNoV) infection. Then, molecular docking was performed between murine TREM-1 and the P domain of the MNoV VP1 protein. The viral antigenic segment C′–D′ was recognized by the murine TREM-1 CDR1 region. Subsequently, based on phylogenetic criteria, NoV VP1 proteins from the GII.4 genotype sequenced in different years (1987, 2010, 2012, 2014, 2016, and 2019) were modeled. Using docking and molecular dynamics simulations, a stable interaction was observed between the human TREM-1 Ig-like domain and the conserved S and P segments of the NoV VP1 protein. Notably, this interaction was conserved over the years and was mainly dictated by the TREM-1 CDR3 region. Also, coexpression between Trem1 with genes involved in apoptosis and pyroptosis pathways was surveyed during viral infection by MNoV. It was found that Trem1 is primarily expressed with genes from the pyroptosis pathway. These simulations strongly suggest the involvement of TREM-1 in NoV pathogenesis and its potential contribution as a coreceptor.

Efficient and Explainable Virtual Screening of Molecules through Fingerprint-Generating Networks Integrated with Artificial Neural Networks
Rivaaj Monsia - and
Sudeep Bhattacharyya *
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A machine learning-based drug screening technique has been developed and optimized using a novel, stitched neural network architecture with trainable, graph convolution-based fingerprints as a base into an artificial neural network. The architecture is efficient, explainable, and performant as a tool for the binary classification of ligands based on a user-chosen docking score threshold. Assessment using two standardized virtual screening databases substantiated the architecture’s ability to learn molecular features and substructures and predict ligand classes based on binding affinity values more effectively than similar contemporary counterparts. Furthermore, to highlight the architecture’s utility to groups and laboratories with varying resources, experiments were carried out using randomly sampled small molecules from the ZINC database and their computational docking scores against six drug-design relevant proteins. This new architecture proved to be more efficient in screening molecules that less favorably bind to a specific target thereby retaining top-hit molecules. Compared to similar protocols developed using Morgan fingerprints, the neural fingerprint-based model shows superiority in retaining the best ligands while filtering molecules at a higher relative rate. Lastly, the explainability of the model was investigated; it was revealed that the model accurately emphasized important chemical substructures and atoms through the intermediate fingerprint, which, in turn, contributed heavily to the ultimate prediction of a ligand as binding tightly to a certain protein.

Fragment Screening Identifies Novel Allosteric Binders and Binding Sites in the VHR (DUSP3) Phosphatase
Jiaqian Wu - ,
Marek R. Baranowski - ,
Alexander E. Aleshin - ,
Eta A. Isiorho - ,
Lester J. Lambert - ,
Laurent J. S. De Backer - ,
Ye Na Han - ,
Ranajit Das - ,
Douglas J. Sheffler - ,
Andrey A. Bobkov - ,
Alexis M. Lemberikman - ,
Daniel A. Keedy - ,
Nicholas D. P. Cosford - , and
Lutz Tautz *
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The human Vaccinia H1-related phosphatase (VHR; DUSP3) is a critical positive regulator of the innate immune response. Recent studies suggest that inhibiting VHR could be beneficial in treating sepsis and septic shock. VHR belongs to the superfamily of protein tyrosine phosphatases (PTPs), a large class of enzymes that are notoriously difficult to target with small molecules. Fragment-based drug discovery (FBDD) has emerged as an effective strategy for generating potent ligands, even for challenging drug targets. Here, we present a fluorine NMR-based discovery platform for identifying fragments that bind to VHR. This platform encompasses automated library assembly, mixture formation, quantitative material transfer, fluorine NMR screening, and biophysical hit confirmation. We demonstrate that this streamlined, integrated screening workflow produces validated hits with diverse chemical matter and tangible structure–activity relationships (SAR). Crystal structures yielded detailed information on the fragment-protein interactions and provide a basis for future structurally enabled ligand optimization. Notably, we discovered novel ligand binding sites on VHR, distant from the conserved active site, facilitating the generation of selective VHR modulators. This fragment discovery platform can be applied to other PTPs and holds significant potential for identifying potent and selective ligands.

Impedance Spectroscopic Analysis of Methane Sensing Characteristics in Electrospun Tungsten Oxide Nanofibers with Particle Size Heterogeneity
Papot Jaroenapibal - ,
Watchara Sukbua - , and
Napat Triroj *
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The sensing performance of nanostructured metal-oxide-based gas sensors is highly dependent on their morphology, which directly influences sensitivity and response dynamics. This study investigates the impedance characteristics of tungsten oxide (WO3) nanofibers with varying particle sizes, synthesized through electrospinning. By adjusting precursor concentrations and calcination temperatures, nanofibers with an average diameter of 135 ± 29 nm were produced. These nanofibers exhibited particle sizes ranging from 29 to 100 nm, as confirmed by transmission electron microscopy (TEM), and crystallite sizes from 17 to 62 nm, as determined by X-ray diffraction (XRD) analysis. Impedance spectroscopy was employed to analyze electronic conduction and response dynamics, which are critical to the methane (CH4) sensing mechanism. The optimal operating temperature of the sensors was found to be inversely related to particle size. The sensor with the smallest particles (29 nm) exhibited the lowest optimal operating temperature of 200 °C, while sensors with larger particles required higher temperatures, ranging up to 275 °C. Nanofibers with 29 nm particle sizes also demonstrated the highest sensitivity (S = Rair/Rgas) of 2.85 when exposed to 0.1% (1000 ppm) CH4 at 200 °C. Additionally, smaller particle sizes were associated with reduced grain boundary relaxation times, leading to faster sensor responses. The enhanced performance and fast response dynamics of smaller particles are attributed to morphology-induced catalytic effects, which reduce activation energy and improve charge carrier mobility at grain boundaries. This study provides valuable insights into the factors governing the electrical response of nanostructured metal-oxide chemiresistive gas sensors.

Enhanced Piezoresistive Cryogel: MWCNT Nanocomposite-Based Wearable Sensors for Real-Time Human Gait and Exercise Monitoring
Niranjan Deggenahalli Basavaraju - ,
Vaidehi Basavakumar Roopa - ,
Mathew Peter - ,
Jeevan Medikonda - ,
Saumya Bansal - , and
Pramod Kesavan Namboothiri *
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The piezoresistive properties of the modified cryogels were studied. The pressure sensitivity of the cryogel:MWCNT (CG:MWCNT) sensors for different concentrations of MWCNTs are studied. FTIR characterization confirms the formation of CG and CG:MWCNT nanocomposites. Porosity was optimized to enhance the conductivity of the nanocomposite by studying various concentrations. The highly porous structure and the elastic nature of the CG:MWCNT sensors resulted in a change in the electrical percolation even for subtle pressure application, and a linear change in pressure was observed up to 700 kPa. The minimum and maximum pressures detected were 0.4 and 700 kPa, respectively. Electromechanical tests confirm high responsive time and no effect of pore size after stability test, which makes the prepared sensor more span of usage in healthcare conditions. Further, a cryogel:MWCNT wearable wireless sensor module was developed, and the gait signals were acquired wirelessly. The prepared sensor system is able to differentiate between normal, fast, and slow gaits. FFT analysis has been performed to understand the repeatability of signals. Overall, the study emphasizes the potential of the developed sensor system in assisting healthcare professionals, researchers, and individuals in assessing gait characteristics and tracking exercise performance.

Morphological and Electrical Properties of Proteinoid–Actin Networks
Panagiotis Mougkogiannis *- and
Andrew Adamatzky
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Proteinoids, or thermal proteins, are produced by heating amino acids. Proteinoids form hollow microspheres in water. The microspheres produce oscillation of electrical potential. Actin is a filament-forming protein responsible for communication, information processing and decision making in eukaryotic cells. We synthesize randomly organized networks of proteinoid microspheres spanned by actin filaments and study their morphology and electrical potential oscillatory dynamics. We analyze proteinoid–actin networks’ responses to electrical stimulation. The signals come from logistic maps, the Lorenz attractor, the Rossler oscillator, and the FitzHugh–Nagumo system. We show how the networks attenuated the signals produced by these models. We demonstrate that emergent logical patterns derived from oscillatory behavior of proteinoid–actin networks show characteristics of Boolean logic gates, providing evidence for the computational ability to combine different components through architectural changes in the dynamic interface. Our experimental laboratory study paves a base for generation of proto-neural networks and implementation of neuromorphic computation with them.

Octabetaines: a DFT Study of Unexplored Eight-Membered 10π Heterocycles
Christopher A. Ramsden *- and
Wojciech P. Oziminski *
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Eight-membered 10π heterocyclic mesomeric betaines (HMBs) are unusual in that they are associated with two 1,3-dipolar fragments in mutual conjugation; they are conjugated HMBs belonging to Class 1A. Apart from the characterization of five derivatives of the 1,5-dithia-2,4,6,8-tetrazocine ring in the 1980s, this large family of “aromatic” heterocycles has received no attention. The density functional theory (DFT) study reported here investigates the structure, aromaticity, and bonding of representative examples. The parent structures and aza derivatives are planar, and bond lengths are in agreement with a reported crystal structure. Calculated HOMA aromaticity index values and aromatic stabilization energy (ASE) are consistent with high classical aromaticity. Their magnetic aromaticity, measured by the NICS(1)zz index and π electron current density maps, is also high. The introduction of electron-donating ring substituents (Me, OH, and NH2) results in distortion from planarity. The energy values of the frontier orbitals, vertical ionization potentials (VIPs), and vertical electron affinities (VEAs) are reported. Their significant variation with position of aza substitution is rationalized by a perturbation model based on the frontier orbitals of the cyclooctatetraene dianion.

Near-Field Microwave Resonating Sensor for Chronic Bone Assessment through Novel Electromagnetic Band Gap Structures
Karthikeyan Abirami - ,
Rajesh Anbazhagan *- ,
Ravikumar Chinthaginjala - ,
C. Manikandan - ,
Tai-Hoon Kim *- ,
Hamad A. AI-Lohedan - , and
Young Jin Jung *
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Recent advancements in near-field flexible microwave sensor technology have significantly enhanced their capabilities in wearables for noninvasive sensing. This paper aims to evaluate chronic wounds, specifically bone cracks, and their healing processes utilizing near-field microwave sensors for various designs and substrates, as the near-field effect is challenging in assessing chronic bone cracks. The proposed polyamide- and polydimethylsiloxane-based microwave sensor displays novelty in terms of resonating and electromagnetic band gap structures in the FR1 band. The sharp resonance and gain of the sensor make it suitable for wearable bandages in detecting and assessing the percentage of bone cracks. The analysis involves the utilization of tetrad cell electromagnetic band gap structures for crack detection with multiple resonance frequencies at 2.286, 2.35, 3.04, and 3.616 GHz, in which the crack analysis is varied between 0 and 100% noninvasively. The corresponding results are obtained and interpreted through simulations of various resonator use cases for comprehensive chronic bone analysis.

Supersecondary Structure Code for RNA: Trace of Conformational Change on the Mycoplasma pneumoniae Ribosome and the R-Loop Formation of Cas9
Hiroshi Izumi *- ,
Laurence A. Nafie - , and
Rina K. Dukor
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The shape of motifs is important for RNA functions and deeply reflects the structure of RNA at the supersecondary level, an intermediate level between secondary and spatial structure. However, there is currently no standardized classification system for the RNA supersecondary structures. Primary and secondary occupied conformations, accounting for 73% of the nucleic acid backbone units, were found by extending the concept of protein supersecondary structure code (SSSC) combined with the conformational code for organic molecules. The supersecondary structure code for RNA (SSCR) was introduced as a conformational term for each unit of the nucleic acid backbone using the letters P, S, T, and D, denoting respectively the primary occupied conformation (P), the secondary occupied conformation (S), the set of other conformations (T), and disordered residues (D). The alignment of SSCR sequences was used to compare with the different nucleic acid base sequences, depending on the species. SSCR can also trace the conformational change of motifs in RNA molecules such as ribosomal RNA (rRNA) and single-molecule guide RNA (sgRNA) in the R-loop formation process of Cas9. The assignment of supersecondary structure code T using the fuzzy search technique of structural code homology is an effective and quick detection method for motifs with conformational wobbling, such as the relatively rigid TTT motifs of sgRNA with Cas9, streptomycin-binding RNA aptamer, 23S rRNA, 2′-dG-II riboswitch, and human hepatitis B virus ε pregenomic RNA, which work as the scaffold for protein and RNA molecules or as the support stand for small external substrates.

Effects of Dopants on the Structural, Electronic, and Energetic Properties of (ZrO2)16 Clusters
Priscilla Felício-Sousa - ,
Karla F. Andriani - ,
Marcos G. Quiles - , and
Juarez L. F. Da Silva *
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The integration of dopants into ZrO2-based clusters provides the possibility to modulate their physicochemical properties, making small clusters promising candidates for various applications, such as catalysis. However, the synergistic interactions between doping and adsorption of single atoms into ZrO2 remain poorly understood. Therefore, in this study, we investigate the influence of lanthanum (La) doping and rhodium (Rh) single-atom adsorption on the physicochemical properties of (ZrO2)16 clusters using density functional theory calculations combined with data science approaches. We found that both doping and adsorption processes lead to minor local structural changes. La doping induces minimal distortions while preserving the overall stability of the cluster, as evidenced by consistent binding energy values. Rh adsorption has a preference to bind near the O–La moieties. In contrast, the electronic structure is majorly affected by Rh adsorption, by narrowing the HOMO–LUMO energy gap, and enhancing the reactivity of those modified Zr16O32 clusters. Furthermore, Hirshfeld charge analysis reveals a significant charge redistribution following La doping, which is enhanced by the adsorption of a single Rh atom, resulting in localized electronic changes.

Proton Pump Inhibitor Omeprazole Alters the Spiking Characteristics of Proteinoids
Panagiotis Mougkogiannis *- and
Andrew Adamatzky
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This study reveals the significant effect of the proton pump inhibitor omeprazole on the spiking behavior of proteinoids, leading to a transformative shift in the field of unconventional computing. Through the application of different concentrations of omeprazole, we see a notable modification in the spiking characteristics of proteinoids, including significant alterations in amplitude, frequency, and temporal patterns. By using Boolean logic techniques, we analyze the complex dynamics of the proteinoid-omeprazole system, revealing underlying patterns and connections that question our understanding of biological computing. Our research reveals the unexplored potential of proteinoids as a foundation for unconventional computing. Moreover, our research indicates that the electrical spiking observed in proteinoids may be linked to the movement of protons. This discovery offers new insights into the fundamental mechanisms governing the spiking activity of proteinoids, presenting promising opportunities for future research in this area. Additionally, it opens up possibilities of developing new computational models that exploit the inherent nonlinearity and complexity of biological systems. By combining the effects of omeprazole-induced spikes with Boolean logic, a wide range of opportunities arise for information processing, pattern identification, and problem-solving. This pushes the limits of what can be achieved with bioelectronics.

ENO1/Hsp70 Interaction Domains: In Silico and In Vitro Insight for a Putative Therapeutic Target in Cancer
Maria Rita Gulotta - ,
Ugo Perricone - ,
Patrizia Rubino - ,
Angela Bonura - ,
Salvatore Feo - ,
Agata Giallongo *- , and
Giovanni Perconti *
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Alpha-enolase (ENO1) is a multifunctional protein with oncogenic roles. First described as a glycolytic enzyme, the protein performs different functions according to its cellular localization, post-translational modifications, and binding partners. Cell surface-localized ENO1 serves as a plasminogen-binding receptor, and it has been detected in several cell types, including various tumor cells. The plasminogen system plays a crucial role in pathological events, such as tumor cell invasion and metastasis. We have previously demonstrated that the interaction of ENO1 with the multifunctional chaperone Hsp70 increases its surface localization and the migratory and invasive capacity of breast cancer cells, thus representing a novel potential target to counteract the metastatic potential of tumors. Here, we have used computational approaches to map the putative binding region of ENO1 to Hsp70 and predict the key anchoring amino acids, also called hot spots. In vitro coimmunoprecipitation experiments were then used to validate the in silico prediction of the protein–protein interaction. This work outcome will be further used as a guide for the design of potential ENO1/HSP70 inhibitors.

Novel Maleimide Linkers Based on a Piperazine Motif for Strongly Increased Aqueous Solubility
Martijn Dijkstra - ,
Hemma Schueffl - ,
Anja Federa - ,
Caroline Kast - ,
Alexander Unterlercher - ,
Bernhard K. Keppler - ,
Petra Heffeter - , and
Christian R. Kowol *
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Maleimides remain very popular conjugation moieties in the fields of bio(in)organic chemistry and biotechnology. They are particularly interesting for endogenous albumin binding in the bloodstream to exploit the enhanced permeability and retention (EPR) effect and to increase tumor accumulation of anticancer drugs. However, during drug development, insufficient aqueous solubility is frequently a limiting factor. In the present study, four new maleimide linkers were synthesized containing a water-soluble piperazine scaffold. Respective maleimide-platinum(IV)-acetato complexes demonstrated similar hydrolytic stability, albumin-binding kinetics, in vivo serum pharmacokinetics and tissue distribution compared to a reference platinum(IV)-PEG4-maleimide complex. To test the aqueous solubility, platinum(IV)-maleimide complexes containing the highly lipophilic drug ibuprofen were synthesized. Indeed, the compounds containing the new piperazine linkers displayed increased solubility (up to 370 mM) in different aqueous media, whereas the PEG4-maleimide reference was only marginally soluble. Finally, the synthetic toolbox of the new piperazine maleimides was also expanded to pure organic derivatives by conjugation to valine-citrulline-para-aminobenzyl–OH derivatives via peptide and thiourea bonds.

Structural Insights into Ratite Birds and Crocodile Eggshells for Advanced Biomaterials Design
Nerith R. Elejalde-Cadena *- ,
Edilberto Hernández-Juárez - ,
Everardo Tapia-Mendoza - ,
Abel Moreno - , and
Lauro Bucio *
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Detailed analysis of particle size, morphology, elemental composition, crystalline structure, and thermal degradation behavior reveals significant differences between ratite and crocodile eggshells, showing their unique environmental adaptations and biological functions. Ratite eggshells, characterized by smaller particle sizes, present lower thermal degradation and are more suitable for applications requiring flexibility and resilience. In contrast, crocodilian eggshells have more extensive and denser particles, giving them a more uniform structure and therefore contributing to their higher thermal stability and mechanical strength. The variation in activation energy profiles between different parts of the eggshells indicates the complexity of their degradation processes. In this regard, ostrich eggshell presents more complicated, multistage thermal degradation patterns, and may be suitable for layered thermal stability applications. In contrast, the uniform degradation behavior of emu eggshells suggests its utility in systems where consistent thermal performance is essential. Similarly, the stable and predictable degradation profiles of river and swamp crocodile eggshells make them ideal candidates for environments requiring high durability and resistance to thermal cycling. This research highlights the natural design of eggshells and provides valuable guidance for the development of biomimetic materials. By mimicking the structural and thermal properties of these eggshells, it would be useful to create thermally stable and mechanical materials suitable for a wide range of industrial and biomedical applications.

Quantized Inverse Design for Photonic Integrated Circuits
Frederik Schubert *- ,
Yannik Mahlau *- ,
Konrad Bethmann - ,
Fabian Hartmann - ,
Reinhard Caspary - ,
Marco Munderloh - ,
Jörn Ostermann - , and
Bodo Rosenhahn
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The inverse design of photonic integrated circuits (PICs) presents distinctive computational challenges, including their large memory requirements. Advancements in the two-photon polymerization (2PP) fabrication process introduce additional complexity, necessitating the development of more flexible optimization algorithms to enable the creation of multimaterial 3D structures with unique properties. This paper presents a memory efficient reverse-mode automatic differentiation framework for finite-difference time-domain (FDTD) simulations that can handle complex constraints arising from novel fabrication methods. Our method is based on straight-through gradient estimation that enables nondifferentiable shape parametrizations. We demonstrate the effectiveness of our approach by creating increasingly complex structures to solve the coupling problems in PICs. The results highlight the potential of our method for future PIC design and practical applications.

New Antimicrobial Cyclodepsipeptides from a Freshwater Fungus from the Sierra Madre Oriental in Mexico
Itzel Rubí Yeverino - ,
Tania Paola Bocanegra Sosa - ,
Laura Aguilar-Vega - ,
Rodolfo García-Contreras - ,
José L. Magaña-González - , and
Mario Figueroa *
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The Sierra Madre Oriental (SMO) in Mexico is a complex, unexplored geological area with multiple habitats and unique physical, chemical, and biological features. A bioactive-guided study of the organic extract from a solid-state fermentation culture from a taxonomically unidentified fungus isolated from submerged wood in the waterfall “El Caracol”, Nuevo Leon, at the SMO, led to the identification of three new cyclodepsipeptides (1–3) and the known Sch 217048 (4) and Sch 378161 (5). Structures of all compounds were elucidated by spectroscopic and spectrometric methods. The isolated compounds 4 and 5 showed antimicrobial activity against Gram-positive strains and the Gram-negative Acinetobacter baumannii ATCC 17978, including multidrug-resistant clinical strain A564. In addition, the compounds showed no toxic activity in the Galleria mellonella larvae model. Finally, the molecular networking analysis allowed us to annotate all the cyclodepsipeptides in the network. This is the first systematic chemical study of a fungus isolated from the SMO in Mexico.

High-Mobility Electrons in Aqueous Iodide Solutions
Fabio Novelli *- ,
Adrian Buchmann - ,
Iqra Yousaf - ,
Lion-Luca Stiewe - ,
Wibke Bronsch - ,
Federico Cilento - ,
Claudius Hoberg - , and
Martina Havenith *
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The photoexcitation of aqueous iodide solutions is a prototype for the generation of electrons in liquid water. Upon one-photon excitation, the precursors of the solvated electrons are localized states with a radius of a few angstroms. In contrast, with the aid of transient absorption spectroscopy at terahertz, near-infrared, and visible frequencies, we show that the two-photon absorption of ∼400 nm pulses can impulsively generate short-lived (∼250 fs), delocalized electrons that are released tens of angstroms away from the parent ion. We propose that these states can be ascribed to 5p → 6p transitions that, in turn, could be thought of as frustrated Rydberg orbitals or large radius excitons. By capitalizing on the unique capabilities of transient terahertz spectroscopy, we estimate that these delocalized states are characterized by an electronic mobility and diffusivity that are about 500 times greater than those of the fully relaxed electrons.

MultiT2: A Tool Connecting the Multimodal Data for Bacterial Aromatic Polyketide Natural Products
Liangjun Ge - ,
Qiandi Gao - ,
Jiayi He - ,
Xiaoyu Wang - ,
Jiaquan Huang *- ,
Heqian Zhang *- , and
Zhiwei Qin *
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The integration of artificial intelligence (AI) into natural product science is an exciting and rapidly evolving area of research. By combining classical chemistry and biology with deep learning, these technologies have significantly improved research efficiency, particularly in overcoming laborious and time-consuming processes. Recently, there has been growing interest in leveraging multimodal algorithms to integrate biologically relevant yet mathematically disparate data sets in order to reorganize knowledge graphs. However, to the best of our knowledge, no studies have yet applied this approach specifically within the natural product field. This is largely because correlating multimodal natural product data is challenging due to their high degree of fragmentation. Here, we present MultiT2, an algorithm that connects these disparate data from bacterial aromatic polyketides, which form a medically important natural product family, as a showcase. Through a large-scale causal inference process, this approach aims to transcend mere prediction, unlocking new dimensions in the natural product discovery and research domains.

Refinement of Protein Extraction Protocols for Human Peripheral Nerve Tissue
Drifa Frostadottir *- ,
Charlotte Welinder - ,
Raquel Perez - , and
Lars B. Dahlin
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Our aim was to establish an effective method for protein extraction from freshly frozen human peripheral nerves, determine the minimum amount required for consistent protein extraction outcomes, and assess which method produced the highest number of protein identities. Five extraction methods were compared using 8 M urea and Ripa buffer using either the Bullet Blender or Bioruptor. Out of the total 2619 identified proteins, protein extraction using the Ripa buffer combined with either Bioruptor or Bullet Blender resulted in the identification of 1582 (60%) and 1615 (62%) proteins, respectively. In contrast, using 8 M urea and Bioruptor for protein extraction resulted in 1022 proteins (39%), whereas employing Bullet Blender yielded 1446 proteins (55%). Sample amounts, ranging from 0.6 to 10 mg, were prepared with consistent protein extraction outcome obtained for samples ≥1.2 mg. Combining Ripa and 8 M urea with Bullet Blender increased protein identification to 2126 (81%). Proteins were classified by their cell components, molecular functions, and biological processes. Furthermore, a subclassification of proteins involved in the extracellular matrix (ECM) was introduced. We recommend the use of Ripa buffer, in combination with 8 M urea and Bullet Blender for extracting proteins from fresh-frozen human nerves weighing ≥1.2 mg.

Clove and Thyme Essential Oils: From Molecular Docking to Food Application─A Study of Their Preservative Properties in Buttermilk
Mohamed Raafat Atteya - ,
Ramy M Romeilah - ,
Khaled M. A. Ramadan - ,
Hossam S. El-Beltagi *- ,
Ahmed Maher Gaber - ,
Sallah A. Al Hashedi - ,
Nada Ali AboZaid - ,
Mohamed A. A. Mahmoud *- ,
Rania Youssef - ,
Rasha A. Mohamed - , and
Eslam S.A. Bendary
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This study investigates clove (CEO) and thyme (TEO) essential oils as natural preservatives, focusing on their composition, antimicrobial and antioxidant properties, and application in buttermilk. In the first part, GC-MS analysis identified eugenol (73.45%) and thymol (27.53%) as the major bioactive compounds in CEO and TEO, respectively. Antioxidant activity assays revealed strong performance for CEO, with EC50 values of 0.058 mg/mL for H2O2 scavenging and 0.063 mg/mL for DPPH, significantly outperforming TEO (EC50 values of 0.102 and 0.106 mg/mL, respectively). In vitro antibacterial assays demonstrated CEO’s superior efficacy, achieving minimum inhibitory concentrations (MICs) as low as 25 mg/L against Gram-positive bacteria and 50 mg/L against Gram-negative bacteria, while TEO exhibited MICs ranging from 50 to 100 mg/L. Molecular docking highlighted selective binding of eugenol (−6.5 kcal/mol) and thymol (−5.9 kcal/mol) to bacterial enzymes, underpinning their selective antimicrobial mechanisms. In the second part, buttermilk was fortified with CEO and TEO, and sensory analysis revealed that TEO significantly enhanced aroma and taste, achieving a mean score of 7.93 for taste at 100 μg/mL, while CEO exhibited a more neutral sensory impact with a mean score of 6.14 at the same concentration. Additionally, CEO and TEO supplementation promoted LAB growth, sustaining beneficial microbial populations over a 5-day storage period and preserving microbiological quality comparable to untreated samples. These findings highlight CEO and TEO as effective natural preservatives for functional food systems, combining selective antimicrobial, antioxidant, and sensory benefits.
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