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Lipid droplets (LDs) are dynamic organelles that influence intracellular drug disposition, yet their role in modulating therapeutic efficacy remains poorly defined. This study integrates experimental cytotoxicity assays with a mechanistic subcellular pharmacokinetic (PK) model to investigate how LD dynamics affect the distribution and activity of tyrosine kinase inhibitors (TKIs). The model, based on physicochemical parameters including logP, pK a, and protein binding, revealed that increases in LD volume sequester lipophilic drugs such as abemaciclib and lapatinib, reducing their cytoplasmic concentrations and efficacy, whereas low logP compounds like palbociclib remain largely unaffected. TKIs with high pK a values, such as sunitinib, preferentially accumulate in lysosomes, consistent with model predictions and experimental imaging results. Cytotoxicity assays confirmed the predicted bidirectional effects of LD expansion and depletion on drug efficacy. These findings identify LDs as active modulators of subcellular drug PK and suggest that targeting LD dynamics may enhance the therapeutic performance of lipophilic TKIs, especially in cancers with dysregulated lipid metabolism.

With the gradual deployment of integrated wind-solar-to-ammonia projects in China, electrolyzers must track renewable power fluctuations while ensuring economic feasibility for downstream hydrogen production and ammonia synthesis. This dual requirement poses significant challenges for operational strategies. Therefore, this article proposes a collaborative operation strategy for a hybrid electrolyzer fleet (alkaline and proton exchange membrane) that balances renewable power tracking with the economic benefits of green ammonia synthesis. First, a comprehensive mathematical model of the integrated wind-solar-to-ammonia system is constructed. Subsequently, a multiobjective optimization scheme based on an improved knee region (IKR) nondominated sorting genetic algorithm (NSGA-III) is designed to coordinate the multielectrolyzer operation. Finally, operational data from a demonstration project in Da'an City, Jilin Province, China, is utilized for verification. The results demonstrate that the proposed method effectively enhances both the operational efficiency and the economic viability of the system.

Precipitated silica was subjected to a sustainable strategy of surface modification with l-cysteine or functional silanes: 3-aminopropyltriethoxysilane or 3-mercaptopropyltrimethoxysilane (as a reference way), and the effects were compared from the point of view of the degree of coverage and the number of functional groups present on the filler surface. Because the silane coupling agent requires relatively high doses, being additionally hazardous, flammable, susceptible to failure during storage, and has to be incorporated into the organic dispersants and prehydrolysis treatment, the application of more convenient and green modifiers is sought. Infrared spectra and thermogravimetric analysis confirm the effective grafting of silica surface, with the greatest extent observed in the case of l-cysteine. The presence of both amino and thiol groups in the amino acid molecule is likely to be responsible for its much greater degree of adsorption on the filler surface. A greater degree of modification of the silica surface with l-cysteine comes together with better compatibility of the amino acid with natural rubber (NR). Unlike silanes, l-cysteine does not seem to interfere with the sulfur vulcanization process. The proposed modification of silica resulted in an increase in the cross-link density of vulcanizates and a change in the cross-link structure. The replacement of silica-coupling agents with l-cysteine resulted in an improvement in the macrodispersion of filler, represented by the dispersion index and indicated by the Payne effect. The changes in the cross-link density and structure, as well as improved filler dispersion and unchanged bound rubber content, result in an increase in the tensile strength and elongation at break, but contrary to silanization, decreasing stiffness of the vulcanizates. The presented results confirm the possibility of replacing conventional silane compatibilizers with l-cysteine in rubber technology, opening a new direction of research on the application of cheap protein derivatives obtained from recycled natural products.

The stereochemical recognition of the α-methyl group at the d-Ala-d-Ala terminus of peptidoglycan by penicillin-binding proteins (PBPs) has been implicated in shaping the evolutionary divergence of dd-peptidases. Here, we investigate how the β-lactam α-substituent identity influences the conformational dynamics of wild-type Pseudomonas aeruginosa PBP3 using molecular dynamics simulations of covalent acyl-enzyme complexes with CEFacyl (α-hydro) and its α-methyl derivative, MECacyl. Our analysis reveals that the α-methyl group in MEC-PBP3acyl is accommodated within a defined methyl pocket predominantly composed of conserved residues K297, S349, N351, and V333. Hydration network into the buried active site is disrupted in the MEC-PBP3acyl complex, which consequently results to the loss of a deacylation-competent geometry of water at K297 toward the β-lactam acyl carbon required for hydrolytic deactivation. Time-resolved analyses of the CEF-PBP3acyl simulation reveals that the contraction of the active site α-loop is associated with the coupling of water bridge networks that connects the α2 helix active site motif 294 STVK 297 to a distal salt bridge cluster-the "water sink" (R284 α1b, D288 loop, R504 β4, and D525 β5) which corroborates crystal structure evidence (PDB ID: 6R3X) [BelliniD., J. Mol. Biol.2019, 431, 3501-3519]. Pocket-based analyses show that the expansion of the methyl pocket into the STVK motif coincides with active site solvation. These dynamic observations are observed to be associated with the shifting salt bridge interactions of R504 β4 on the α-loop, which may rationalize resistance in R504 mutants. The steric bulk of the α-methyl group in MECacyl toward the K297 α2 side chain disables active site plasticity and consequently impairs the loop mobility required for the influx of water into the active site. These findings provide mechanistic molecular insights into how α-substituent chemistry modulates active site hydration dynamics in PBP3 and support the importance of α-methyl recognition in dd-peptidases. This work also establishes a structural framework for future studies of PBPs and β-lactam drug design relevant to antimicrobial resistance.

We propose a novel two-dimensional (2D) tetrahexagonal NiN2 (tetrahex-NiN2) monolayer, derived through a full Stone-Wales transformation of penta-NiN2, which converts an all-pentagonal lattice into a network of four- and six-membered rings. First-principles calculations confirm that this new phase is dynamically and thermally stable. Tetrahex-NiN2 exhibits pronounced mechanical anisotropy and shortened N-N bonds, indicating significant structural reorganization. Hybrid functional calculations reveal metallic character, with strong hybridization between Ni-d and N-p orbitals near the Fermi level. Furthermore, the material demonstrates broadband and anisotropic optical absorption across the visible spectrum, suggesting promising potential for optoelectronic and photothermal applications. These findings position tetrahex-NiN2 as a stable and tunable 2D nitride and highlight the effectiveness of topological reconstruction as a strategy for engineering novel 2D quantum phases.

Limited aqueous solubility, often associated with low drug bioavailability, represents one of the greatest challenges in the clinical translation of numerous drugs currently on the market or in development. New and safer strategies are needed to unlock the full potential of poorly water-soluble compounds. Here, we report the ability of potato protein isolate (PPI), a valorized side-stream product of the potato starch industry, to arrest precipitation of curcumin in aqueous-based solutions in a concentration-dependent manner, leading to a manifold improvement in the solubility of curcumin as compared to pure water. High concentrations of PPI and presolubilization of curcumin (in pure ethanol) before mixing with the protein isolate were necessary to achieve complete solubilization of 0.1 mg/mL curcumin in 90% (v/v) water. The effect of PPI as a solubility enhancer was found to be limited by its propensity to undergo gel transition when exposed to higher concentrations of ethanol. Finally, PPI was non-toxic to HeLa cells, as demonstrated by an in vitro cell viability study, whereas dispersions of curcumin induced a cytotoxic effect. Our findings highlight the potential of less conventional plant protein isolates, such as PPI, as a strategy to improve the aqueous solubility of poorly water-soluble compounds.

This study explores the corrosion behavior of a nonequiatomic Ni60Cr15Co15Ti5Al2.5Nb2.5 high-entropy alloy (HEA) subjected to thermal aging. Electrochemical testing in 3.5 wt% NaCl solution revealed that short-term aging (≤1 h) induces a loss of passivation (LOP), marked by a corrosion potential drop to -260 mVSCE and an increase in corrosion current density (i corr) to 2.7 μA/cm2. In contrast, prolonged aging (≥10 h) promotes a recovery of passivation (ROP), driven by microstructural elemental redistribution. This recovery is evidenced by a positive shift in corrosion potential to -125 mVSCE, a significant reduction in i corr to 7.1 × 10-2 μA/cm2, and an increase in pitting potential (E pit) from 413 mV to 495 mV. Electrochemical impedance spectroscopy (EIS) further confirmed enhanced passivity through a reduction in effective capacitance (from 3.2 to 2.6 μF/cm2) and an increase in polarization resistance (from 960 to 1084 kΩ·cm2 ). However, excessive aging (>50 h) may trigger a secondary LOP. An optimal aging window (30-50 h) yields a stable and protective passive film.

Antibiotic overuse has driven the development of bacterial drug resistance, highlighting the urgent need for new antimicrobial strategies. Quorum sensing, particularly via autoinducer-2 (AI-2) signal molecules, is a bacterial communication system involved in the development of drug resistance. Our recent work identified AI-2 inhibitors that disrupt biofilm formation in Staphylococcus aureus and Pseudomonas aeruginosa. Here, we investigated the efficacy of the three most promising compounds in modulating bacterial virulence. The compounds strongly impaired the bacterial ability to adhere to human epithelial cells. ELISA-based assays and Western blot analyses revealed the efficacy of the compounds in controlling S. aureus virulence by decreasing the levels of bacterial adhesins, α-hemolysin, and protein SpA. In a co-culture with S. aureus, colorimetric assays revealed the compound efficacy in decreasing P. aeruginosa pyocyanin and elastase production in a dose-dependent manner. Importantly, no cytotoxicity was observed both in vitro (A549 cells) and in vivo (Galleria mellonella model). These results support the potential of our compounds to modulate virulence factor expression consistent with quorum-sensing disruption as promising candidates for the treatment of multidrug-resistant infections.

Poly(vinyl alcohol), PVA, is a molar mass-dependent ice recrystallization inhibitor (IRI), with larger polymers that are more active, similar to antifreeze glycoproteins. Attempts to modulate PVA's IRI activity by side-chain modification or assembly have given limited gains or even a loss of function. Here we take inspiration from antifreeze glycolipids by installing hydrophobic tails at the &#x3b1;-terminus of well-defined PVA derived from RAFT/MADIX photopolymerization, enabled by site-specific capping of the structurally ambiguous &#x3c9;-end chains. Lower molar mass PVAs (<1000 g&#xb7;mol-1) were discovered to have enhanced IRI upon installation of the tails below 0.1 mM, which was more active than small-molecule IRIs of a similar MW. This unlocks new opportunities for IRIs at moderate molar masses and the potential to modulate activity via site-specific end-group chemistry.

Hofmeisteria schaffneri (Asteraceae) is a medicinal plant used in Central Mexico for pain relief. Although thymol- and northymol-derived metabolites contribute to its antinociceptive activity, the low abundance of the latter has limited evaluation. An optimized synthetic route to hofmeisterin I (1) improved yields and reduced reaction times, enabling biological assessment. Hofmeisterin I (1) and derivatives were tested in zebrafish (Danio rerio) and murine formalin models. Halogenated derivatives were toxic and minimally active, whereas the acetylated analogue exhibited higher potency but limited safety. A new nitrogen-containing imide analogue, namely, 1-(2-(5-bromo-2-hydroxy-4-methylphenyl)-2-oxoethyl)-pyrrolidine-2,5-dione (12), exhibited improved efficacy and a safer profile. Mechanistic studies indicated the involvement of TRPV1, CB2, and PPAR&#x3b3; receptors, with modulation by the opioid and serotonergic systems. Collectively, these findings highlight compound 12 as a promising antinociceptive scaffold. X-ray analyses of 1 and 12 are also reported.

In this study, we report a sustainable fabrication strategy for electrothermally active metal yarns using fully recycled polystyrene (re-PS) and polyethylene terephthalate (re-PET) as core materials. Hybrid nanofiber yarns were produced via dual-nozzle electrospinning, combining the processability of re-PS and the mechanical reinforcement of re-PET. Electroless copper plating was subsequently performed under ambient conditions following surfactant-assisted activation and palladium seeding, resulting in uniform and continuous metallic coatings. The Cu-plated hybrid yarns exhibited high electrical conductivity with a resistance of 2.84 &#x3a9; and showed efficient Joule heating, reaching 153.3 &#xb0;C at a low applied voltage of 1.2 V. Stable temperature output (&#x223c;96 &#xb0;C) was maintained during continuous 1 h operation, and rapid heating-cooling response was retained over 300 cycles under both flat and bent configurations, confirming mechanical and thermal durability. This approach presents a scalable method for converting plastic waste into high-performance functional textiles. The fabricated metal yarns are lightweight, flexible, and conductive, showing strong potential for integration into wearable heaters and next-generation smart textile systems.

A fiber-optic visible-near-infrared (vis-NIR) absorption spectroscopy and flow sensor system has been developed for near-real-time tracking of Nd mass in the effluent stream from a column in a fume hood. The approach leverages two unique data streams and a partial least-squares regression (PLSR) model trained on vis-NIR absorption spectra of Nd-(III) (0-1.5 M) in 1 M HNO3. In-line volumetric flow rate and vis-NIR spectra are measured in sequence after a chromatography column. The time stamps from each data stream are then synchronized, which allows integrated volumes to be combined with Nd-(III) molarities predicted by a PLSR model to accurately calculate the Nd mass flowing through the column. This integrated measurement provides instantaneous mass flow and accumulates these data over time to obtain the total mass processed. The methodology developed in this study contributes critical technical infrastructure to improve monitoring capabilities to support chemical separations and the production of strategic materials and isotopes.

Biliary atresia (BA), the most common cause of extrahepatic obstructive jaundice in infants, is a severe infant disease with a poor prognosis and unclear etiology. RNA-binding proteins (RBPs) are key regulators of alternative splicing and are implicated in various liver pathologies. However, whether RBP dysfunction and resultant aberrant splicing contribute to BA pathogenesis remains unknown. We performed an integrated transcriptomic analysis using RNA-seq data from BA patients and normal donor livers (GEO: GSE159720). This encompassed systematic identification of differentially expressed genes (DEGs) and alternative splicing events (ASEs), followed by construction of RBP-ASE coexpression networks to infer underlying regulatory mechanisms. Key bioinformatic predictions were subsequently validated via qRT-PCR in an independent cohort using congenital choledochal cyst (CCC) tissues as controls. Our analysis identified 2022 DEGs and revealed extensive RBP dysregulation, with 135 RBPs showing abnormal expression and 182 exhibiting altered splicing patterns. Notably, 15 RBPs were perturbed at both levels. Coexpression network and functional enrichment analyses demonstrated that RBP-mediated splicing events are significantly involved in metabolic processes, redox homeostasis, and RNA splicing and transport, underscoring their central role in BA pathogenesis. The expression of several RBPs (e.g., FUS, RBM15B) and coexpressed DEGs (e.g., AOX1, ADH6, UGDH) was markedly altered in BA. Similarly, validation of differentially spliced RBPs (e.g., CCNT2, YBX3, TRA2A) and their coexpressed targets (e.g., CFHR2, PRKACB) further corroborated the dysregulation of the RBP-splicing axis. In summary, our study links RBP dysregulation and aberrant splicing to biliary atresia, primarily through their association with disrupted redox and metabolic pathways. These findings point to the RBP-splicing axis as a potential contributor to BA pathogenesis and a candidate target for further investigation.

Aberrant O-glycosylation is a defining hallmark of epithelial cancers, where truncated mucin-type glycans such as Tn and sialyl-Tn (sTn) are prominently displayed. Despite their tumor specificity, these tumor-associated carbohydrate antigens (TACAs) elicit only weak immune responses, limiting their impact in vaccine-based immunotherapy. Growing evidence implicates two major factors in this poor immunogenicity: the intrinsic engagement of Tn/sTn with the immunosuppressive macrophage galactose-type lectin (MGL) on antigen-presenting cells and the "self" nature of Tn/sTn mucin carriers such as MUC1. Both processes critically depend on the N-acetyl functionalities of the Tn determinant. We previously developed a stable Tn mimetic, 2-deoxy-2-thio-&#x3b1;-O-galactoside (compound 1), which lacks the NHAc group and exhibits notable immunostimulatory properties in vivo. In this study, we provide new structural insights into the role of the NHAc moiety in the mimetic 1 presentation and its interaction with MGL, thereby advancing the design principles for next-generation Tn analogues with improved immunological behavior. An additional focus is on the pathogenic upregulation of sTn in tumors, primarily driven by overexpression of the sialyltransferase ST6GALNAC1. We demonstrate that mimetic 1 and its oxidized analogue 2 act as inhibitors of ST6GALNAC1&#xe5f8;representing, to the best of our knowledge, the first reported monosaccharide inhibitors of this enzyme. Although the inhibitory potency is modest, these compounds establish a valuable chemical starting point for targeting cancer-associated sialylation, an effort currently constrained by the lack of structural information for ST6GALNAC1.

(-)-Mitragynine, a natural alkaloid, is known for its analgesic effects and functions as a G protein-biased ligand of the &#x3bc;-opioid receptor (&#x3bc;OR). This study examined the structural alterations in the &#x3bc;OR upon binding with (-)-mitragynine, (+)-mitragynine, 7-OH-mitragynine, and morphine using molecular docking and 1 &#x3bc;s classical all-atom molecular dynamics simulations. The &#x3bc;OR showed relatively stable RMSD ranging from 1.6 to 3.2 &#xc5; for mitragynine derivatives and morphine during dynamics, though residues 260-280 exhibited notable fluctuations. (-)-Mitragynine formed an average of one hydrogen bond more consistently than the other ligands throughout the simulation period. MM/PBSA calculations suggested that Asp-147 (3.32), Tyr-148 (3.33), Met-151 (3.36), and Trp-293 (6.84) contributed to ligand binding. Asp-147 (3.32) plays a critical role in the formation of a salt bridge and contributes the most to binding all mitragynine derivatives and morphine. All four ligands preferentially interacted with Trp-293 (6.84) in helix-6, highlighting its role in receptor activation and postsignaling activities. A plot of the binding free energy versus the helix-6 tilt angle and the distance between Asp-147 (3.32) and the tertiary nitrogen of the ligand revealed a distinct conformational population at 6 to 10 &#xc5; and 90 to 140&#xb0; tilting of the receptor for morphine compared to mitragynine, which may explain helix-6's role and salt bridge distance in &#x3bc;OR activation and downstream signaling biases. Our study provides a structural foundation for designing novel &#x3bc;OR ligands as potential new analgesics.

The extensive use of single-use personal protective equipment (PPE) during the COVID-19 pandemic has substantially increased the generation of plastic-rich medical waste, raising concerns regarding its safe thermal treatment and bottom ash management. This study investigates the thermochemical behavior of commonly used PPE items, nitrile gloves, polypropylene gowns, and polypropylene face masks, analyzed individually and in blended mixtures representative of hospital practice. Thermal degradation under combustion and pyrolysis conditions was characterized using TGA/DTG and DSC, while bottom ash was analyzed via SEM-EDX and ICP-OES. The environmental assessment performed in this study is intentionally limited in scope and focuses only on bottom-ash elemental composition and slagging tendency without evaluating leaching, emissions, or long-term stability. The results show that nitrile gloves exhibit multistage degradation and higher ash yields, whereas polypropylene-based PPE undergoes single-stage decomposition with distinct melting behavior. Synergistic interactions observed in blended waste streams lowered peak and burnout temperatures, indicating an enhanced combustion reactivity. Ash analyses identified Ca, Ti, and Zn as dominant constituents, with heavy-metal concentrations remaining below reported thresholds for nonhazardous waste classification. Within the restricted scope of ash chemistry and slagging performance, the findings suggest that cocombustion of mixed PPE waste may influence operational behavior during incineration; however, broader environmental implications require dedicated assessment through leaching, emissions monitoring, and mechanical performance testing.

The global sugar industry generates substantial byproducts and waste, posing significant environmental challenges. In alignment with circular economy and zero-waste principles, this study explores the valorization of sugarcane residues through solvent-based extraction and advanced metabolomic profiling. Various organic solvents were employed to extract metabolites from different sugarcane parts, followed by N,O-bis-(trimethylsilyl)-trifluoroacetamide (BSTFA) derivatization and analysis using gas chromatography-mass spectrometry (GC-MS). Automated spectral deconvolution and molecular networking, conducted via open-source platforms (MSHub, GNPS, and Cytoscape), enabled structural dereplication and clustering of metabolite spectra. Integration of metabolomic data with sample metadata facilitated system-level comparisons of chemical diversity and metabolite abundance across extraction conditions. Machine learning techniques, particularly random forest and multivariate statistical analyses, were applied to the metabolomic data set. These approaches enabled the identification of chemotypic drivers responsible for differentiating biomass types and extraction solvent systems. Results revealed that specific solvent-biomass pairings significantly influenced both the yield and specificity of high-value compounds, including policosanols, phytosterols, triterpenoids, and phenolic acids. Notably, trash and filter cake emerged as promising matrices for lipid-based compound recovery. Methanol and ethanol provided the highest overall extraction efficiency, whereas nonpolar solvents such as tert-butyl methyl ether (TBME) and hexane enabled selective enrichment of sterols and long-chain alcohols. By integrating molecular data with statistical modeling and yield analysis, this study presents a data-driven framework for optimizing biorefinery processes. These findings offer critical insights into aligning solvent systems with specific biomass types to enhance the efficiency, economic value, and environmental sustainability of sugarcane residue valorization.

Bionic slippery liquid infused porous surface effectively tackles biofouling and corrosion issues in marine environments. However, there are challenges regarding lubricant loss, poor stability, and environmental threats posed by fluorine- and silicon-containing lubricants. Herein, a novel, highly stable, fluorine- and silicon-free solid-phase-change slippery surface (SPCSS) was proposed, which consists of a multilayer rough structure composed of flower-like ZnO-coated polydopamine and mesoporous silica loaded with antifouling agents, as well as a solid-phase-change lubricating layer comprised of polyethylene wax and tetradecane. SPCSS demonstrates an antifouling efficiency of up to 99.99% against proteins, bacteria, and algae. Electrochemical impedance spectroscopy reveals that SPCSS exhibits stable and outstanding corrosion resistance (|Z|0.01&#xa0;Hz = 5.48 &#xd7; 109 &#x3a9; cm2), significantly inhibiting microbial-induced corrosion. Furthermore, SPCSS undergoes rapid phase change and self-healing under near-infrared irradiation and maintains robustness after water erosion and high- or low-temperature exposure. This work presents a novel, stable, and efficient strategy for constructing slippery surfaces, offering broad application prospects in the fields of marine antifouling and anticorrosion.

Metal oxide nanomaterials, such as TiO2, are extensively utilized in photocatalysis for applications, including water purification, antibacterial disinfection, and energy harvesting. However, the wide bandgap (&#x223c;3.2 eV) of TiO2 constrains excitation to UV light, limiting its efficiency under solar irradiation. To extend photocatalytic activity into the visible spectrum, colloidal semiconductor quantum dots (QDs) can function either as independent photocatalysts or as sensitizers; in the latter case, facilitating charge transfer to TiO2 and enhancing reactive oxygen species (ROS) generation. Here, we demonstrate a photocatalytic platform, composed of QD supraparticles (SP), optionally coated with a titania shell. This hierarchical SP architecture bridges the electronic and photonic scales, significantly enhancing light-harvesting efficiency compared to conventional QDs or metal oxide nanocrystals. The photocatalytic performance of these QD-based SPs is systematically evaluated under both UV and white light illumination, using rhodamine B (RhB) degradation as a model reaction, and compared to QDs and TiO2 nanoparticles. We find that SPs facilitate both RhB degradation and N-deethylation, with titania-coated SPs (SP/TiO2) achieving full transformation to Rhodamine 110. We also show that for QDs and SPs with comparable overall surface area, SPs degrade RhB much faster under both UV and white light irradiation. In addition, the reusability of the QD-based SPs is dramatically improved compared to that of QDs. These findings demonstrate the strong potential of QD-based SPs as photocatalytic materials for environmental, energy, chemical, and biomedical applications.