Search Results (326)

Molten salt chlorination is a key industrial route for producing titanium tetrachloride (TiCl₄), yet the atomistic catalytic role of iron (Fe) in the carbothermic chlorination of titanium oxides remains unclear. Here, the chlorination behavior of the NaCl–C–Cl₂–FeTiO₃ system was investigated by combining thermodynamic calculations with Ab Initio Molecular Dynamics (AIMD) and Deep Potential Molecular Dynamics (DPMD) simulations. AIMD results show that carbon adjacent to Fe exhibits enhanced reactivity, and that Fe-C synergistic electron transfer promotes both titanium oxide reduction and subsequent titanium chlorination. DPMD results further reveal that Fe not only accelerates these transformations, but also improves interfacial contact among carbon, titanium oxides, and molten salt, thereby enhancing mass transfer and shortening the formation time of TiCl₄. Temperature-dependent analysis indicates that Fe-C and C-O coordination numbers remain high near 1073 K, where TiCl₄ formation is efficient and relatively stable. Although increasing temperature can further enhance diffusion, its effect on reaction acceleration is limited, while excessively high temperatures weaken Fe-C interactions and reduce catalytic efficiency. These findings clarify the catalytic mechanism of Fe in molten salt chlorination at the atomic scale and provide theoretical support for process optimization. Full article

Oxidative stress is intrinsically linked to mental disorders, involving an imbalance between reactive species and antioxidant defenses, where catalase is an essential, ubiquitous antioxidant enzyme. The pleiotropic effects of antipsychotic drugs, used for schizophrenia and mood disorders, are not fully elucidated at the molecular level. This study characterized the binding of a highly effective but potentially dangerous antipsychotic, clozapine (CLZ), to commercial bovine liver catalase (BLC). Using various spectroscopic methods under simulated physiological conditions, we found a moderate binding affinity of CLZ for BLC (K_a = 1.4 × 10⁻⁵ M⁻¹), subtly influencing the protein’s secondary and tertiary structures and slightly increasing its thermal stability. CLZ efficiently protected BLC against free-radical-induced oxidation and preserved its catalytic activity for decomposing toxic hydrogen peroxide. The effect of CLZ on BLC antioxidant activity was dual: no significant effect at lower, physiologically relevant concentrations, but significant inhibition at saturating, toxic drug concentrations. Molecular docking and molecular dynamics results indicated the presence of two specific binding sites within BLC monomers, one located near its active site. In conclusion, our in vitro results indicate that CLZ’s specific binding to BLC can be both beneficial and potentially harmful, and that this effect is dose-dependent. Full article

Development of green and efficient technologies for valorizing crayfish shell waste is crucial for enhancing industrial value. This study presents an integrated strategy for the extraction and structural engineering of chitin using a novel alkaline deep eutectic solvent (DES) system composed of lysine and monoethanolamine (LysMEA), which enables the simultaneous deproteinization and architectural modification of chitin. Following mild demineralization, the optimized process yielded chitin with 97.1% purity and a high molecular weight of 209.3 kDa. DES demonstrated considerable reusability and decolorization capability. Structural characterization revealed that the LysMEA system effectively engineered the chitin architecture, resulting in lower crystallinity and a larger surface area compared to conventional methods. This engineered structure rendered the chitin highly accessible to enzymes. Consequently, the chitin extracted by LysMEA exhibited superior reactivity, achieving a deacetylation degree of 63.7% when catalyzed by Bacillus aryabhattai chitin deacetylase, significantly outperforming chitin obtained via acid-alkali or acidic DES methods. Molecular dynamics simulations elucidated the mechanism, showing that lysine and monoethanolamine molecules penetrated the chitin fiber bundles at high temperatures, weakening interchain hydrogen bonds and partially separating the chains. This work provides a green route for producing enzymatically reactive chitin, demonstrating the potential of solvent-based structural engineering in biocatalytic valorization. Full article

The common metabolic disorder, lactose intolerance, is often treated with oral lactase enzyme supplements, which can frequently cause gastrointestinal instability. This work utilizes Malbranchea cinnamomea’s AA9 lytic polysaccharide monooxygenase (LPMO) to target β-lactose (β-lactose) in an investigation of a new enzymatic approach for lactose breakdown. Potential possibilities for lactose breakdown are AA9 LPMOs, copper-dependent enzymes that oxidatively cleave glycosidic bonds in polysaccharides. We employed a combined in silico method that incorporated molecular docking, density functional theory (DFT) calculations, and molecular dynamics (MD) simulations. Docking studies revealed that β-lactose formed hydrogen bonds with key residues SER100, ASN54, and ARG56, exhibiting a greater binding affinity (−5.4 kcal/mol) toward LPMO compared to the control citric acid (−4.9 kcal/mol). Upon DFT analysis, (LPMO) showed excellent stability and appropriate reactivity for enzyme interaction. The higher stability of the LPMO-β-lactose complex was highlighted by MD simulation over 100 ns, which showed lower root mean square deviation (RMSD) and root mean square fluctuation (RMSF) values, greater structural compactness, and reduced solvent accessibility when compared to the control. These collective findings suggest that β-lactose interacts efficiently with the AA9 LPMO active site, supporting its potential as a novel enzymatic target for lactose degradation. This computational study provides a theoretical foundation for developing alternative therapeutic strategies for lactose intolerance, though further in vitro and in vivo investigations are required to validate these findings. Full article

Alzheimer’s disease (AD) remains a significant global health challenge, highlighting the need for novel dual inhibitors targeting acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). This study investigated the trunk bark of Terminalia triptera Stapf. as a potential source of bioactive secondary metabolites for AD management. Bioassay-guided isolation led to the identification of two flavan-3-ol derivatives, epicatechin-(4β→8)-ent-catechin (1) and (−)-catechin (2), reported here for the first time from this species. In vitro assays demonstrated that the dimeric compound 1 exhibited stronger dual inhibitory activity against AChE and BChE, with IC₅₀ values of 4.41 × 10⁻⁴ and 4.75 × 10⁻⁴ mol/L, respectively, surpassing the reference compound berberine chloride. Molecular docking analysis revealed that compound 1 formed extensive interactions within both catalytic and peripheral anionic sites of the enzymes. Density Functional Theory (DFT) calculations indicated high kinetic stability, reflected by large HOMO–LUMO energy gaps (6.66–6.97 eV), while global reactivity descriptors suggested lower electrophilicity (ω = 2.19–2.34 eV), supporting a potentially favorable safety profile. Furthermore, 100 ns molecular dynamics simulations confirmed stable ligand–protein complexes stabilized by hydrogen-bond networks and deep binding within catalytic pockets. Overall, these findings highlight T. triptera and its dimeric proanthocyanidins as promising multi-target candidates for anti-Alzheimer drug development. Full article

The development of sustainable and environmentally benign N-methylation methodologies is essential for enhancing sustainable synthetic practice in pharmaceutical manufacturing. In this study, we demonstrate that microwave heating (MWH) markedly enhanced the efficiency of cobalt-catalyzed N-methylation using methanol or methanol-d₄ as green C1 sources. Compared with conventional heating (CH), MWH enabled highly efficient syntheses of key pharmaceutical intermediates—including 6-dimethylamino-1-hexanol, imipramine hydrochloride, and butenafine hydrochloride—under milder conditions and shorter reaction times and without generating hazardous halogen-containing waste. UV–vis spectroscopic analysis revealed that MWH accelerated the transformation of Co(acac)₂ into catalytically active Co species by approximately four-fold, providing a mechanistic basis for the enhanced reactivity. We hypothesized that this effect was caused by the selective microwave heating of the catalyst, which in turn promoted the rapid generation of catalytically active species. Notably, MWH also significantly improved the N-trideuteromethylation of amines using methanol-d₄, achieving a 95% yield for imipramine-d₃ hydrochloride versus 32% under CH. Molecular dynamics simulations indicated that methanol-d₄ exhibited slower dipole relaxation and enhanced cluster fragmentation under microwave fields, improving catalyst–substrate contact, while kinetic isotope effects stabilized reactive intermediates. These synergistic effects account for the pronounced microwave promotion observed in deuterated systems. Overall, the combination of MWH and cobalt catalysis offers an energy-efficient, waste-minimizing, and environmentally benign strategy for the scalable synthesis of both methylated and deuterated amines. Full article

The precursor infiltration and pyrolysis (PIP) route is widely adopted to fabricate carbon fiber-reinforced silicon carbide (C_f/SiC) composites; however, the atomic-scale restructuring of the pyrolytic carbon/silicon carbide (PyC/SiC) interface during ceramization—and its impact on mechanical integrity—remains elusive. Here, reactive molecular dynamics (ReaxFF MD) simulations elucidate the coupled thermochemical–mechanical evolution of polycarbosilane (PCS) precursors on PyC substrates with orientation angles (OAs) of 0°, 25°, 55°, and 85°. Dynamic pyrolysis triggers a pivotal transition from sp² to sp³ hybridization at the interface. High-OA substrates (55° and 85°) present a dense population of reactive edge sites, fostering extensive cross-interfacial covalent bonding. Subsequent shear loading reveals that these pyrolysis-induced chemical bridges govern failure modes, shifting from interlayer sliding dominated by weak non-bonded interactions (0°) to ductile fracture featuring uniform plasticity and crack deflection. The OA = 55° interface attains a theoretical peak shear strength of 15 GPa and exhibits the most favorable combination of high strength and ductile failure under tensile loading, owing to an optimal balance between reactive site availability and interlayer steric openness. In contrast, the OA = 85° interface, despite comparable peak stress, fails via brittle crack penetration into the SiC matrix. By correlating atomistic structure with macroscopic performance, this study provides a bottom-up framework for engineering C_f/SiC composites via interfacial texturing and optimized pyrolysis protocols. Full article

Background: Latent tuberculosis infection (LTBI) is the principal reservoir for active tuberculosis, with >85% of cases attributable to reactivation. Bacillus Calmette-Guérin fails to block this transition, leaving a critical gap in prevention. Methods: An immunoinformatics/reverse-vaccinology pipeline was applied to seven dormancy-related antigens retrieved from Mycobrowser. T-cell epitopes were predicted with NetMHCI/IIpan-4.1 and B-cell epitopes with ABCpred; antigenicity, allergenicity, and toxicity were evaluated with VaxiJen, AllerTOP, and ToxinPred. Secondary/tertiary structures were modeled with PSIPRED and AlphaFold-3; docking to Toll-like receptors (TLR) 2/4 and 100 ns molecular dynamics simulations assessed complex stability. Immune responses were simulated with C-ImmSim, and the mRNA sequence was human-codon-optimized using ExpOptimizer. Results: The resulting construct, RP14914P, encodes 14 cytotoxic T lymphocyte, 9 helper T lymphocyte, and 14 B-cell epitopes within an 866-aa, 90.4 kDa polypeptide. Antigenicity score = 0.7797, immunogenicity score = 8.58629. and no toxicity or allergenicity was predicted. Physicochemical analysis: instability index = 28.65, and solubility = 0.513. Estimated population coverage is 82.35% and 99.67% for Human Leukocyte Antigen (HLA)-I and HLA-II globally. Docking energies: −1477.8 kcal/mol (TLR2) and −1480.1 kcal/mol (TLR4). Molecular dynamics trajectories confirm stable binding. Immune simulation predicts potent activation of Natural Killer cells, macrophages, and dendritic cells, Th1 polarization, high interferon-γ/interleukin-2 secretion, and durable memory. Conclusions: In silico analyses predict that RP14914P exhibits favorable immunogenicity, safety, and broad population coverage, suggesting its potential as a promising mRNA vaccine candidate to prevent LTBI reactivation. However, these computational predictions require thorough experimental validation to confirm the vaccine’s immunogenicity and protective efficacy. Full article

Persimmon polyphenols (PP) are natural polyphenols with high reactivity and strong deodorization potential; however, their practical application in odor control is limited by their poor solubility. In this study, natural deep eutectic solvents (NADESs) were employed for the green extraction of PP, and the capabilities of extracts on the removal of ammonia (NH₃) and hydrogen sulfide (H₂S) were investigated. In addition, the underlying mechanisms were explored by integrating spectroscopic analysis, molecular dynamics simulations, and quantum chemical calculations. The results showed that chloride-citric acid (CC-CA) was the optimal system in both PP extraction and sustained NH₃ removal, while the betaine-urea (B-U) system was more effective for H₂S removal. NH₃ removal was governed by acid-base neutralization, with the resulting ammonium species being further stabilized within the PP-regulated NADES hydrogen-bond network. In contrast, H₂S interacted with the solvent network not only through acid-base neutralization but also via Van der Waals forces and hydrophobic contacts. Our data supported that NADESs enhanced the deodorization performance of PP through cooperative microenvironment regulation rather than irreversible chemical conversion. This work highlighted that NADESs could not only function as highly efficient extraction media for polyphenols, but also active platforms for enhancing selective gas-capture capability for polyphenols. Furthermore, it provided a new strategy for the rational design of green, persimmon-derived deodorants. Full article

Nanocrystalline CeO₂ exhibits size-dependent lattice distortions linked to defect chemistry and surface effects. However, the relationships between the oxidation state, surface interactions, and nanoparticle structure remain unclear in the existing literature, particularly when inferred from conventional nanoparticle diffraction techniques, including powder X-ray diffraction. As a result, the atomistic origin of lattice expansion or contraction with the crystallite size of ceria nanoparticles is still debated. Here, synchrotron X-ray powder diffraction data are analyzed using Rietveld refinement supported by advanced peak profile modeling based on whole powder pattern modeling (WPPM), including thermal diffuse scattering (TDS). The latter provides direct access to information on lattice dynamics. Indeed, we simultaneously determine the size distributions of crystalline domains and their atomic displacements, which are then compared and quantitatively validated with molecular dynamics (MD) simulations. Reactive MD simulations further reveal that vacancy-rich surfaces induce lattice contraction at small particle sizes under vacuum, whereas water adsorption causes surface hydroxylation and lattice expansion. These results explain lattice parameter variations in nanocrystalline ceria through the interplay of surface chemistry and environment. This insight is critical for the correct interpretation of diffraction-derived structural parameters in oxide nanocatalysts used in redox and oxygen storage applications. Full article

Dissolution of iron oxides in water plays a critical role in corrosion, mineral cycling, and surface reactivity; yet, the atomic-scale mechanisms governing Fe release remain poorly understood. Here, we employ ab initio molecular dynamics and well-tempered metadynamics simulations to investigate the stepwise dissolution of surface Fe atoms from the -Fe₂O₃(0001) surface in aqueous solution. The dissolution process initiates from a stable surface configuration in which Fe is coordinated to three lattice oxygen atoms and one water molecule. It proceeds through a series of metastable states involving additional water coordination, proton-assisted Fe-O bond weakening, and eventual detachment from the substrate. The first major transition, requiring 46.5 kJ/mol, involves breaking the hydrogen-bonding net and overcoming steric hindrance to allow adsorption of a second water molecule. Intermediate barriers (10.9–30.3 kJ/mol) are associated with further coordination and bond cleavage steps. In contrast, the final release of Fe into the solution, corresponding to a state coordinated with four water molecules and no lattice oxygen, exhibits a much higher free-energy barrier of ~93.0 kJ/mol. This barrier arises from the formation of a rigid hydrogen-bonded water cage and the loss of proton access to the remaining surface oxygen site, as confirmed by radial distribution function analysis. Our findings reveal why -Fe₂O₃(0001) is highly resistant to complete dissolution yet prone to surface roughening, defect formation, and adatom structures under aqueous conditions. Full article

Background/Objectives: Astragalus root is a classical qi-tonifying traditional Chinese medicine that has demonstrated potential therapeutic efficacy in type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). However, the precise mechanisms underlying its effects on the comorbidity of these two disorders remain unclear. This study investigated the molecular mechanisms by which Astragalus root ameliorated T2DM-NAFLD comorbidity. Methods: Network pharmacology, molecular docking, molecular dynamics simulation, and in vitro experiments were employed to elucidate the potential roles and mechanisms of Astragalus root in the management of T2DM-NAFLD comorbidity. Results: A total of 25 bioactive constituents and 152 corresponding targets associated with Astragalus root were identified. PPI network analysis revealed the top ten core candidate targets, among which six possessed suitable crystal structures for molecular docking, including interleukin-6 (IL-6), threonine-protein kinase 1(AKT1), transcription factor AP-1(JUN), tumor necrosis factor (TNF), cysteine-dependent aspartate-specific protease 3 (CASP3), and estrogen Receptor 1(ESR1). Kyoto encyclopedia of genes and genomes (KEGG) analysis further identified the phosphatidylinositol 3-kinase (PI3K)-AKT as the most significantly enriched pathway. Molecular docking validated the potential binding modes of formononetin to the six core targets, a finding that was further confirmed by molecular dynamics simulations, which proved the stability of the resulting complexes. In vitro experiments demonstrated that formononetin obviously decreased lipid droplet accumulation, downregulated total cholesterol (TC) and triglyceride (TG) levels, suppressed the expression of TNF-α, IL-6, and interleukin-1β (IL-1β), decreased reactive oxygen species (ROS) and malondialdehyde (MDA) levels, and enhanced glutathione (GSH) content and superoxide dismutase (SOD) activity. These therapeutic effects were achieved through inhibition of protein expression within the PI3K/AKT/mechanistic target of rapamycin (mTOR) signaling pathway. Conclusions: This study determined the potential therapeutic targets and underlying mechanisms of formononetin derived from Astragalus root in the T2DM-NAFLD management, thereby providing a scientific basis for its clinical application. Full article

A multiscale modeling approach is proposed to investigate the mechanical properties of carbon fiber/silicon carbide (C/SiC) composites fabricated by chemical vapor infiltration (CVI) process. First, reactive molecular dynamics simulations are conducted to estimate the mechanical properties of the SiC matrix fabricated via CVI. Subsequently, a two-level micromechanics-based homogenization is developed to account for the effects of various constituents (e.g., porosity and carbon fiber) on the mechanical properties of the C/SiC composites. A series of numerical parametric studies is performed to examine the influence of the model parameters on the mechanical properties of the C/SiC composites. In addition, experimental investigations, including tensile tests and scanning electron microscopy, are conducted to validate the proposed modeling approach. The results indicate that the proposed modeling approach provides predictions that are in good agreement with the experimental results, thereby demonstrating the effectiveness of the proposed modeling scheme. Full article

Peroxiredoxin 6 (Prdx6) is a bifunctional antioxidant enzyme with glutathione peroxidase and phospholipase A₂ activities that plays an essential role in cellular redox regulation. However, the modulation of Prdx6 activity by endogenous small metabolites remains poorly understood. In this study, we investigated the effect of β alanine on Prdx6 structure and function using biochemical, biophysical, computational, and cellular approaches. Enzymatic assays revealed that β alanine enhances the peroxidase activity of Prdx6 in a dose-dependent manner. Spectroscopic analyses demonstrated β alanine-induced conformational stabilization of Prdx6, which was further supported by increased thermal stability. Molecular docking and molecular dynamics simulations identified a stable interaction of β alanine at a distinct allosteric site on Prdx6, accompanied by reduced local flexibility. In a proof-of-concept cellular system, β alanine treatment resulted in a significant reduction in intracellular reactive oxygen species, consistent with enhanced Prdx6-associated antioxidant activity. Collectively, these findings identify β alanine as a biochemical modulator of Prdx6 activity. The study is limited to mechanistic and cellular redox regulation and does not address tissue- or disease-specific physiology. Full article

Lignin, an abundant and renewable biopolymer, holds significant potential for asphalt modification owing to its unique aromatic structure and reactive functional groups. This review summarizes the main lignin preparation routes and key physicochemical attributes and assesses its applicability for enhancing asphalt performance. The physical incorporation of lignin strengthens the asphalt matrix, improving its viscoelastic properties and resistance to oxidative degradation. These enhancements are mainly attributed to the cross-linking effect of lignin’s polymer chains and the antioxidant capacity of its phenolic hydroxyl groups, which act as free-radical scavengers. At the mixture level, lignin-modified asphalt (LMA) exhibits improved aggregate bonding, leading to enhanced dynamic stability, fatigue resistance, and moisture resilience. Nevertheless, excessive lignin content can have a negative impact on low-temperature ductility and fatigue resistance at intermediate temperatures. This necessitates careful dosage optimization or composite modification with softeners or flexible fibers. Mechanistically, lignin disperses within the asphalt, where its polar groups adsorb onto lighter components to boost high-temperature performance, while its strong interaction with asphaltenes alleviates water-induced damage. Furthermore, life cycle assessment (LCA) studies indicate that lignin integration can substantially reduce or even offset greenhouse gas emissions through bio-based carbon storage. However, the magnitude of the benefit is highly sensitive to lignin production routes, allocation rules, and recycling scenarios. Although the laboratory research results are encouraging, there is a lack of large-scale road tests on LMA. There is also a lack of systematic research on the specific mechanism of how it interacts with asphalt components and changes the asphalt structure at the molecular level. In the future, long-term service-road engineering tests can be designed and implemented to verify the comprehensive performance of LMA under different climates and traffic grades. By using molecular dynamics simulation technology, a complex molecular model containing the four major components of asphalt and lignin can be constructed to study their interaction mechanism at the microscopic level. Full article