Search Results (7,605)

Monocrystalline silicon is an excellent semiconductor material for integrated circuits. Its surface quality has an enormous effect on its service life. The surfaces are formed by ultra-precision machining using nano-grinding, one of the technologies that can achieve surface roughness at the nano- or sub-nano-scale. Therefore, subsurface damage of monocrystalline silicon in nano-grinding was studied by establishing a molecular dynamics simulation model, and the impact of machining parameters on the force–thermal behavior was analyzed. The results reveal that the mechanism of subsurface damage is mainly structural phase transformation and amorphization. In nano-grinding of monocrystalline silicon, the tangential grinding force has a relatively major role in material removal. With increasing grinding depth and grinding speed, the grinding heat rises, and a certain degree of high temperature strengthens the toughness of the material, improving the subsurface quality of monocrystalline silicon. Therefore, subsurface damage in monocrystalline silicon can be controlled by reducing the grinding depth and increasing the grinding speed. Full article

The hyaluronidase enzyme derived from Vespa tropica (VesT2a) venom contains two putative catalytic residues. Herein, a double mutation was introduced into VesT2a at its catalytic sites by substituting Asp107 and Glu109 with Asn and Gln, respectively, to assess their essential roles in enzymatic function. We used Pichia pastoris to produce the mutated version of the VesT2a (mVesT2a) protein, and the process was more efficient when employing the methanol-inducible promoter (P_AOX1) compared to the constitutive promoter (P_GAP). In bioreactor scale-up, P. pastoris harboring the pAOX1-αMF-mVesT2a plasmid secreted 34.03 ± 2.31 mg/L of mVesT2a, with an apparent molecular mass of 46.6 kDa, retaining only 2.9% of hyaluronidase activity, thus indicating successful mutation. The newly developed indirect ELISA-based method using mVesT2a demonstrated its potential as an alternative approach for measuring hyaluronic acid (HA) at low concentrations and was also used to confirm HA-binding capacity. In silico docking and molecular dynamics simulations further supported the stable interaction of the mVesT2a–HA complex while suggested other surrounded acidic amino acid residues, which may play a minor role in HA degradation, supporting the remaining activity observed in the in vitro experiments. Full article

Side-chain engineering is versatile for tuning the chain mobility of graft polymers and governs their thermal stability. However, it remains elusive to predict the graft effect on chain mobility, especially for competitive side-chain types. Here, relying on molecular dynamics simulation and energy landscape theory, we introduce a three-stage virtual pipeline to sequentially refine the screening of graft chain mobility while minimizing computation cost, by taking the example of grafting similar side-chain types (hydroxyethyl methacrylate (HEMA), methyl methacrylate (MMA), and vinyl acetate (VAC)) onto amorphous polypropylene (PP). Ascribed to their structural similarity, these graft systems exhibit a non-evident chain mobility distinction, with the atom displacement—governing the local “roughness” in potential energy landscape (PEL)—exhibiting only weak-to-modest correlation with their initial atomic energy, volume, and stress. This necessitates the subsequent-stage screening for broader PEL navigation, which confirms a stability and roughness rank of VAC ≥ MMA > HEMA > PP, with their chain activation energy revealing that these side chains enhance the PEL roughness through a counterbalance between possibly lowering the overall energy barrier but extensively wrinkling the landscape. Overall, the three-stage screening establishes a state-of-the-art efficient strategy to evaluate thermal stability of graft polymers in stepwise higher precision from local to ergodic roughness inspection. Full article

Background: Helcococcus kunzii, a facultative anaerobe and Gram-positive coccus, has been documented as a cunning pathogen, mainly in immunocompromised individuals, as evidenced by recent clinical and microbiological reports. It has been associated with a variety of polymicrobial infections, comprising diabetic foot ulcers, prosthetic joint infections, osteomyelitis, endocarditis, and bloodstream infections. Despite its emerging clinical relevance, no licensed vaccine or targeted immunotherapy currently exists for H. kunzii, and its rising resistance to conventional antibiotics presents a growing public health concern. Objectives: In this study, we employed an integrated subtractive proteomics and immunoinformatics pipeline to design a multi-epitope subunit vaccine (MEV) candidate against H. kunzii. Initially, pan-proteome analysis identified non-redundant, essential, non-homologous, and virulent proteins suitable for therapeutic targeting. Methods/Results: From these, two highly conserved and surface-accessible proteins, cell division protein FtsZ and peptidoglycan glycosyltransferase FtsW, were selected as promising vaccine targets. Comprehensive epitope prediction identified nine cytotoxic T-lymphocyte (CTL), five helper T-lymphocyte (HTL), and two linear B-cell (LBL) epitopes, which were rationally assembled into a 397-amino-acid-long chimeric construct. The construct was designed using appropriate linkers and adjuvanted with the cholera toxin B (CTB) subunit (NCBI accession: AND74811.1) to enhance immunogenicity. Molecular docking and dynamics simulations revealed persistent and high-affinity ties amongst the MEV and essential immune receptors, indicating a durable ability to elicit an immune reaction. In silico immune dynamic simulations predicted vigorous B- and T-cell-mediated immune responses. Codon optimization and computer-aided cloning into the E. coli K12 host employing the pET-28a(+) vector suggested high translational efficiency and suitability for bacterial expression. Conclusions: Overall, this computationally designed MEV demonstrates favorable immunological and physicochemical properties, and presents a durable candidate for subsequent in vitro and in vivo validation against H. kunzii-associated infections. Full article

Adoxophyes orana (Lepidoptera: Tortricidae) is a significant polyphagous leafroller that damages trees and shrubs in Rosaceae and other families. However, the molecular mechanisms by which this pest recognizes sex pheromones and host plant volatiles remain largely unknown. Tissue expression profiles indicated that two general odorant-binding proteins (AoraGOBP1 and AoraGOBP2) were more abundant in the antennae and wings of both sexes, with AoraGOBP1 being rich in the female head and abdomen. Temporal expression profiles showed that AoraGOBP1 was expressed at the highest level in 5 day-nmated adults, while AoraGOBP2 exhibited high expression in 5 day-unmated, 7 day-unmated, and mated female adults. Fluorescence competitive binding assays of heterologous expressed AoraGOBPs demonstrated that AoraGOBP2 strongly bound to the primary sex pheromone Z9-14:Ac, and two minor sex pheromones Z9-14:OH and Z11-14:OH, whereas AoraGOBP1 only showed a high binding affinity to Z9-14:Ac. What is more, AoraGOBP1 exhibited a broader binding spectrum for host plant volatiles than AoraGOBP2. Molecular dockings, molecular dynamic simulations, and per-residue binding free decompositions indicated that the van der Waals interaction was the predominant contributor to the binding free energy. Electrostatic interactions between aldehydes, or alcohols and AoraGOBPs stabilized the conformational structures. Phe12 from AoraGOBP1, and Phe13 from AoraGOBP2 were identified as the most important residues that contributed to bind free energy. Our findings provide a comprehensive insight into the molecular mechanisms of olfactory recognition in A. orana, facilitating the development of chemical ecology-based approaches for the control. Full article

Orthodontic tooth movement (OTM) is accompanied by sterile inflammation, a necessary biological process that facilitates tooth displacement but also contributes to adverse effects, including hyalinization and orthodontically induced external apical root resorption (OEARR). Despite advancements in orthodontic therapies, the inflammatory response—regulated by dynamic interactions between tissue-specific cells and their molecular mediators—remains a critical factor influencing treatment outcomes. This review summarizes the current understanding of the cellular and molecular mechanisms underlying OTM, with a focus on how these insights can support the development of targeted therapeutic strategies. These include cell- and molecule-based therapies, biomaterial-mediated delivery systems, and applications of artificial intelligence (AI). Notably, AI offers promising opportunities for modeling and simulating biological responses, enabling the optimization of individualized treatment planning. We further discuss current clinical practices and highlight emerging experimental findings, with an emphasis on unresolved research questions pivotal to improving therapeutic efficacy and reducing complications such as OEARR. This comprehensive overview aims to inform future directions in orthodontics by integrating mechanistic knowledge with technological innovation. Full article

Background: Trimetazidine is a clinically established cardioprotective agent with anti-ischemic and antioxidant properties, widely used in the management of coronary artery disease. Combining its metabolic and cytoprotective effects with the potent anti-inflammatory activity of profens presents a promising therapeutic strategy. Methods: Five novel trimetazidine–profen hybrid compounds were synthesized using N,N′-dicyclohexylcarbodiimide-mediated coupling and structurally characterized by NMR and high-resolution mass spectrometry. Their antioxidant activity was evaluated by hydroxyl radical scavenging assays (HRSA), and the anti-inflammatory potential was assessed via the inhibition of albumin denaturation (IAD). Lipophilicity was determined chromatographically. Molecular docking and 100 ns molecular dynamics simulations were performed to investigate the binding modes and stability in human serum albumin (HSA) binding sites. The acute toxicity of the hybrid molecules was predicted in silico using GUSAR software. Results: All synthesized hybrids demonstrated varying degrees of biological activity, with compound 3c exhibiting the most potent antioxidant (HRSA IC₅₀ = 71.13 µg/mL) and anti-inflammatory (IAD IC₅₀ = 108.58 µg/mL) effects. Lipophilicity assays indicated moderate membrane permeability, with compounds 3c and 3d showing favorable profiles. Docking studies revealed stronger binding affinities of S-enantiomers, particularly 3c and 3d, to Sudlow sites II and III in HSA. Molecular dynamics simulations confirmed stable ligand–protein complexes, highlighting compound 3c as maintaining consistent and robust interactions. The toxicity results indicate that most hybrids, particularly compounds 3b–3d, exhibit a favorable safety profile compared to the parent trimetazidine. Conclusion: The hybrid trimetazidine–profen compounds synthesized herein, especially compound 3c, demonstrate promising dual antioxidant and anti-inflammatory therapeutic potential. Their stable interaction with serum albumin and balanced physicochemical properties support further development as novel agents for managing ischemic heart disease and associated inflammatory conditions. Full article

Global climate change has intensified the frequency, intensity, and spatial heterogeneity of drought events, posing severe threats to the stability of terrestrial ecosystems. Plant drought resilience, which encompasses a plant’s capacity for drought resistance, post-stress recovery, and long-term adaptation and transformation to sustain ecosystem functionality, has emerged as a central focus in botanical and ecological research. This review synthesizes the conceptual evolution of plant drought resilience, from early emphasis on resistance and recovery to the current multi-dimensional framework integrating adaptation and transformation, and synthesizes advances in understanding multi-scale drought resilience in terrestrial plants—spanning molecular, physiological, individual, community, and ecosystem levels. Key mechanisms include molecular/physiological adaptations (osmotic adjustment, antioxidant defense, hydraulic regulation, carbon–water reallocation via gene networks and aquaporins), morpho-anatomical traits (root architectural plasticity, leaf structural modifications, and hydraulic vulnerability segmentation), community/ecosystem drivers (biodiversity effects, microbial symbioses, and soil–plant–feedback dynamics). We critically evaluate quantitative metrics and expose critical gaps, including neglect of stress legacy effects, oversimplified spatiotemporal heterogeneity, and limited integration of concurrent stressors. Future research should prioritize multi-scale and multi-dimensional integrated analysis, long-term multi-scenario simulations with field validation, and harnessing plant–microbe interactions to enhance drought resilience, providing a theoretical basis for ecosystem sustainability and agricultural production under climate change. Full article

Monoclonal antibodies (mAbs), as potent therapeutic agents, have been widely applied in the treatment of various major diseases, including infectious diseases, autoimmune disorders, cancers, and neurodegenerative diseases. However, early-generation mAbs were limited by high immunogenicity, short half-life, and insufficient affinity, which compromised their therapeutic efficacy. With technological advancements, novel approaches such as high-throughput screening and glycosyl modification have been introduced to improve the performance of mAbs. Furthermore, computer-aided design techniques—including molecular docking, molecular dynamics simulations, and artificial intelligence -based methods—are increasingly being employed to accelerate the optimization process. This review summarizes recent progress in the optimization of therapeutic mAbs, with a focus on technological breakthroughs and applications in affinity enhancement, development of broad-spectrum mAbs, specificity modulation, immunogenicity reduction, and stability improvement. Additionally, it discusses current challenges and future directions in antibody optimization. This review aims to provide insights and references for the development and optimization of next-generation antibody drugs, ultimately promoting the clinical application of safer and more effective mAb-based therapies. Full article

Cancer cells can adapt to their surrounding microenvironment by upregulating glucose-regulated protein 78 kDa (GRP78) and vacuolar-type ATPase (V-ATPase) proteins to increase their proliferation and resilience to anticancer therapy. Therefore, targeting these proteins can obstruct cancer progression. A comprehensive computational study was conducted to investigate the inhibitory potential of four proton pump inhibitors (PPIs), dexlasnoprazole (DEX), esomeprazole (ESO), pantoprazole (PAN), and rabeprazole (RAB), against GRP78 and V-ATPase. Molecular docking revealed high-affinity scores for PPIs against both proteins. Moreover, molecular dynamics showed favorable root mean square deviation values for GRP78 and V-ATPase complexes, whereas root mean square fluctuations were high at the substrate-binding subdomains of GRP78 complexes and the α-helices of V-ATPase. Meanwhile, the radius of gyration and the surface-accessible surface area of the complexes were not significantly affected by ligand binding. Trajectory projections of the first two principal components showed similar motions of GRP78 structures and the fluctuating nature of V-ATPase structures, while the free-energy landscape revealed the thermodynamically favored GRP78-RAB and V-ATPase-DEX conformations. Furthermore, the binding free energy was −16.59 and −18.97 kcal/mol for GRP78-RAB and V-ATPase-DEX, respectively, indicating their stability. According to our findings, RAB and DEX are promising candidates for GRP78 and V-ATPase inhibition experiments, respectively. Full article

Background: Pancreatic lipase (PL), the principal enzyme catalyzing the hydrolysis of dietary triacylglycerols in the intestinal lumen, is pivotal for efficient lipid absorption and plays a central role in metabolic homeostasis. Enhanced PL activity promotes excessive lipid assimilation and contributes to positive energy balance, key pathophysiological mechanisms underlying the escalating global prevalence of obesity—a complex, multifactorial condition strongly associated with metabolic disorders, including type 2 diabetes mellitus and cardiovascular disease. Inhibition of pancreatic lipase (PL) constitutes a well-established therapeutic approach for attenuating dietary lipid absorption and mitigating obesity. Methods: With the aim to identify putative PL inhibitors, a Structure-Based Virtual Screening (SBVS) of PhytoHub database naturally occurring derivatives was performed. A refined library of 10,404 phytochemicals was virtually screened against a crystal structure of pancreatic lipase. Candidates were filtered out based on binding affinity, Lipinski’s Rule of Five, and structural clustering, resulting in six lead compounds. Results: In vitro, enzymatic assays confirmed theoretical suggestions, highlighting Pinoresinol as the best PL inhibitor. Molecular dynamics simulations, performed to investigate the stability of protein–ligand complexes, revealed key interactions, such as persistent hydrogen bonding to catalytic residues. Conclusions: This integrative computational–experimental workflow highlighted new promising natural PL inhibitors, laying the foundation for future development of safe, plant-derived anti-obesity therapeutics. Full article

The BCR-ABL1 fusion protein is a critical therapeutic target in Chronic Myeloid Leukemia (CML). Current monotherapy approaches involve types of inhibitors that can be categorized into ATP competitive inhibitors and allosteric inhibitors. However, resistance mutations in the tyrosine kinase domain of BCR-ABL1 have limited the effectiveness of these drugs. Research indicates that dual inhibition of BCR-ABL1 by combining these two types of inhibitors effectively addresses the issue of drug resistance as there are no overlapping resistance mechanisms. However, the underlying reasons for the observed synergistic effects have not yet been thoroughly elucidated. In this study, we employed molecular dynamics simulation to observe the synergistic interactions of BCR-ABL1 by the allosteric inhibitor asciminib and ATP competitive inhibitors nilotinib and ponatinib. Our study reveals that when asciminib binds to BCR-ABL1, nilotinib and ponatinib exhibit more substantial binding stability compared to monotherapy. At the atomic level, we have elucidated the reasons for the enhanced binding affinity of nilotinib and ponatinib when using a co-inhibition therapy. Our study reveals the allosteric communication pathway between asciminib and ponatinib, providing more detailed insights into the effectiveness of combination therapy. These findings provide valuable insights into combination therapies, aiding in the rational use of medications and guiding the design of novel inhibitors. Full article

This study investigates the vibrational characteristics of multi-layered graphene sheets with variable thickness (VTGSs) by using molecular dynamics (MD) simulations. It is aimed to determine how the natural frequencies and vibration damping ratios of variable-thickness graphene change with respect to temperature. Atomistic models for six distinct geometries (1L, 3LT, 3LTB, 5LT, 5LTB, and 9LTB) were generated to analyze the influence of structural design and temperature on their natural frequencies. The simulations were performed using the Large-Scale Atomic/Molecular Massively Parallel Simulator (LAMMPS) with an AIREBO potential to represent interatomic carbon interactions. Natural frequencies of all atomistic models were extracted by applying the Fast Fourier Transform (FFT) method to the Velocity Autocorrelation Function (VACF) data obtained from the simulations. In addition, the analysis was conducted at three different temperatures: 250 K, 300 K, and 350 K. Key findings reveal that an increase in the number of graphene layers results in a decrease in the fundamental natural frequency due to the increased mass of the structure. Moreover, it was noted that natural frequencies decrease with increasing temperature. It is attributed to the reduction in structural rigidity at higher thermal energies. These results provide critical insights into how geometric and thermal variations affect the dynamic behavior of complex multi-layered graphene structures. Full article

The mismatch of the coefficient of thermal expansion (CTE) between the reinforcement and the matrix leads to thermal residual stresses and defects upon cooling from the processing temperature to room temperature. The residual stresses and defects have a significant impact on the mechanical properties of metal-matrix composites. To investigate the effect of cooling temperature on the residual stresses’ distribution and mechanical properties of SiC/Al, we investigated the cooling process of SiC/Al from different initial temperatures to room temperature. We found that residual stresses mainly distributed in the interface of SiC/Al composites after cooling, and the higher the initial temperature of cooling, the higher the value of residual stresses and the greater the degree of atomic displacement. During the cooling process, the Shockley partials and stair-rod dislocations were the two dominant dislocation structures. After cooling, the length of Shockley partials was about 80% and the length of stair-rod dislocations was about 18%. The mechanical properties of SiC/Al composites reduced after cooling. These results have filled the gap in understanding the mechanism of defect evolution in SiC/Al composites under cooling conditions, as well as the influence of cooling conditions on the mechanical properties of the material. Full article

The present study aims to investigate the orientation-dependent mechanical behaviors of ZnO single crystals under nanoindentation by molecular dynamics simulation. The load–indentation depth curves, atomic displacement, shear strain and dislocations for the c-plane, m-plane and a-plane ZnO single crystals were analyzed in detail. The simulation results showed that the elastic deformation stage of the loading curves for the three oriented ZnO single crystals can be described well by the Herz elastic contact model. The Young modulus values for the c-plane, m-plane and a-plane ZnO were calculated to be 122.5 GPa, 158.3 GPa and 170.5 GPa, respectively. The onset of plastic deformation occurred first in a-plane ZnO, then in m-plane ZnO, and lastly in c-planeZnO. The atomic displacement vectors in the three oriented ZnO single crystals were in good agreement with the primary activated slip systems predicted by the maximum Schmid factor. For the c-plane ZnO, the activated pyramidal {$11\overline{2}2$}<$11\overline{2}3$> slip system led to a complex dislocation pattern surrounding the indenter. A U-shaped prismatic half-loop was formed in the [$2\overline{11}0$] direction, confirming the activation of the prismatic {$10\overline{1}0$}<$11\overline{2}0$> slip system. For the m-plane ZnO, the activated prismatic {$10\overline{1}0$}<$11\overline{2}0$> slip system led to the preferential nucleation of dislocations along the $\left[\overline{11}20\right]$ and [$\overline{2}110$] directions. A prismatic loop was formed and emitted along the [$\overline{2}110$] direction, governed by a confined glide on {$10\overline{1}0$} planes. For the a-plane ZnO, the activated prismatic {$10\overline{1}0$}<$11\overline{2}0$> slip system led to dislocations concentrated in the [$\overline{1}\overline{1}20$] direction beneath the indentation pit, emitting a prismatic loop along this direction. Perfect dislocation (with a Burgers vector of 1/3 <$1\overline{2}10$>) is the dominant dislocation in the three oriented ZnO single crystals. The findings are expected to deepen insights into the anisotropic mechanical properties of ZnO single crystals, offering guidance for the development and applications of ZnO-based devices. Full article