Search Results (538)

Melatonin has evolved from its classical role as a pineal-derived circadian regulator to a molecule increasingly recognized for its mitochondrial and cytoprotective functions. This review examines the molecular mechanisms and translational implications of melatonin within a mitochondria-centered framework, with particular emphasis on reproductive medicine. Available evidence suggests that melatonin may influence mitochondrial quality control (MQC) through multiple interconnected processes, including ROS regulation, mitochondrial dynamics, mitophagy, biogenesis, and mitochondrial inflammatory signaling. In mitochondria, melatonin can attenuate electron transport chain-derived oxidative stress through direct radical-scavenging reactions, antioxidant metabolite formation, and indirect activation of endogenous antioxidant systems. Experimental studies further suggest that melatonin may modulate Drp1-mediated fission, OPA1- and Mfn1/2-associated fusion, PINK1/Parkin-mediated mitophagy, and SIRT1/PGC-1α-related mitochondrial biogenesis. In reproductive medicine, melatonin has been investigated as a potential adjunctive strategy in assisted reproductive technology, endometriosis, and polycystic ovary syndrome. However, clinical evidence remains heterogeneous, and most human studies have evaluated reproductive or biochemical outcomes rather than direct MQC-related biomarkers. Therefore, although melatonin represents a promising mitochondria-targeted adjunct, standardized dosing strategies, tissue-level pharmacodynamic assessment, and validated mitochondrial biomarkers are needed to determine whether these mechanisms translate into reproducible clinical benefit. Full article

Disordered Ag-nanowire localized surface plasmon resonance sensorgrams for glycated hemoglobin (HbA1c) detection exhibit reproducible multi-component temporal structures that cannot be fully explained within conventional equilibrium refractive-index models; in particular, the quantification of the molecular target escapes from the classical theory. The HbA1c-associated contribution emerges at earlier times while displaying slower relaxation dynamics compared with naïve hemoglobin-associated kinetics, revealing the coexistence of distinct activation and interfacial relaxation pathways. Analysis of temporal derivatives, phase-space trajectories, characteristic peak times, and relaxation times aims to suggest that the plasmonic response originates from multiple competing nonequilibrium processes evolving on different timescales. The description of the structured temporal response relies on a phenomenological framework incorporating activation and relaxation dynamics. Dynamical redistribution pathways associated with heterogeneous adsorption, hydration-shell relaxation, and plasmonic coupling within spatially non-uniform electromagnetic environments, along with resonance shift, support molecular fingerprint. The findings suggest that sensorgrams contain molecular information hidden beyond conventional equilibrium optical observables, motivating a transition toward dynamical and time-resolved approaches in plasmonic biosensing. Full article

Traditional macroscopic interfacial theory cannot fully explain the anomalous stability of nanobubbles, which limits their use in micro/nano interfacial engineering. In this study, molecular dynamics simulations were used to systematically investigate the evolution of oxygen nanobubbles with diameters of 3, 5, and 8 nm in water. The results show a clear size effect in bubble structural evolution: the 3 nm bubble had the largest motion radius, about 3.5 nm, which was 40% and 133% larger than those of the 5 and 8 nm bubbles, respectively. At the nanoscale, surface tension still provides a basic constraint, but its value is lower than the classical theoretical prediction, with a deviation of 35.7% for the 3 nm bubble, indicating that it is not the sole dominant stabilizing force. Water molecules at the gas–liquid interface experienced a net force of 371.92–421.56 pN, with 60–65% directed toward the bubble interior, forming an asymmetric force field that cooperates with surface tension to maintain bubble stability. This force field further drives directional polarization of water molecules and induces a dense hydrogen-bond network: stronger charge parameters correspond to denser hydrogen bonding, with the peak net charge of Charge4 being 37.5 times that of Charge1 and the hydrogen-bond number being 11.6 times that of Charge2. The dense hydrogen-bond network is quantitatively associated with restricted interfacial water mobility. The interfacial potential energy decreases, with an 8 nm bubble showing a reduction of 0.31 kcal/mol, and the U–T coupling energy exhibits a clear interfacial peak of 36–66 kcal/mol. Further analysis shows that the apparent diffusion coefficient decreases nearly exponentially with the maximum hydrogen-bond number, and the water MSD decreases markedly as hydrogen bonding increases, with the MSD of Charge1 being 1303 times that of Charge4. These results indicate that enhanced interfacial electrostatic force, densification of the hydrogen-bond network, and restricted interfacial water mobility jointly increase structural constraints at the gas–liquid interface and suggest a possible increase in gas-transfer resistance across the interface. This study clarifies, at the molecular scale, a physical picture in which surface tension, electrostatic force, hydrogen-bond densification, energy stabilization, and restricted mobility jointly maintain nanobubble stability. Full article

Multifunctional nano-contrast agent carriers are redefining molecular imaging by combining high-fidelity visualization with targeted delivery, controlled release, and, increasingly, therapeutic action. This review encompasses the development of nano-contrast platforms from conventional dendrimer, liposome, chitosan, and silica systems to modular nano-contrast platforms for multimodal, multi-parametric, and activatable imaging in clinically relevant environments. We dissect engineering strategies that govern surface chemistry, ligand organization, stimulus responsiveness, and microenvironmental sensing, and relate them to theranostic performance, immune system engagement, and quantitative image readouts. Biodistribution, pharmacokinetics, and safety are discussed from both classical and model-informed perspectives, with design principles that favor predictable behavior, manufacturability, and regulatory acceptance. Current clinical translation, regulatory pathway evolution, and market dynamics are critically reviewed to elucidate that a few nano-contrast agents have reached patients despite a widespread experimental landscape. Finally, we discuss emerging trends, including biomimetic and ultrasmall carriers, metal–organic and hybrid frameworks, AI-assisted design, digital twins, and precision medicine workflows, which are likely to shape the next-generation nano-contrast theranostics. By systematically relating material selection and carrier architecture to imaging function and translational limitations, this review suggests concrete research priorities for taking nano-contrast agents from sophisticated prototypes to robust, patient-tailored tools. Full article

Graphene oxide (GO) membranes present a compelling alternative to the permeability-selectivity trade-off inherent in conventional polymer membranes. However, the incomplete mechanistic understanding and the absence of scalable, defect-controlled fabrication processes continue to hinder their practical deployment. This review synthesizes and integrates transport mechanisms, computational modeling, fabrication, and translational constraints across graphene-based membrane architectures into a comprehensive design-oriented framework. Five key aspects of this synthesis are highlighted. Firstly, the available evidence supports a three-regime transport model, which unifies viscous near-frictionless flow, activated molecular hopping, and solution–diffusion. This reframes selectivity as a tunable function of the C/O ratio and interlayer chemistry. Secondly, a quantitative parity analysis of literature data reveals that classical molecular dynamics tends to overestimate GO laminate water permeance by a representative factor of approximately 3–8× across the matched comparisons examined. This discrepancy can be corrected using a tortuosity–porosity factor derived from wet-state XRD. Machine-learning force fields (GAP, MACE), while still in an early stage of development with limited reported applications, narrow the residual discrepancy to within 1.5–2× in the studies reviewed. Thirdly, a tiered computational roadmap identifies nuclear quantum effects as critical for proton-transport applications but unresolved for water permeance in GO laminate geometry. Fourthly, performance across water nanofiltration, gas separation, ion recovery, and osmotic energy harvesting is benchmarked against commercial references, with explicit caveats regarding the heterogeneity of testing conditions across cited studies, alongside a technology readiness assessment. Lastly, a standardized 500-h hydraulic stability protocol is proposed to facilitate cross-laboratory comparison. Collectively, this synthesis provides a structured, albeit not exhaustively validated, basis for the discussion of next-generation membrane design. Full article

Understanding how methane moves through nanoporous media is key to predicting performance in unconventional gas reservoirs. At these extremely small scales, pore sizes approach the molecular level, where classical flow assumptions begin to fail and multiple transport mechanisms can occur at the same time. In this work, a unified framework is developed to characterize methane flow regimes using a real-gas corrected Knudsen number. By combining pore size, pressure, and temperature within a single formulation, the approach captures how flow behavior evolves across realistic reservoir conditions. A unified flow regime map is used to characterize the gradual shift in transport behavior—from adsorption-dominated and diffusion-like mechanisms in ultra-tight pores, to transition and slip flow, and eventually to continuum (Darcy) flow in larger pores. The results show that pore size plays the dominant role in determining flow behavior, while pressure introduces a dynamic effect, particularly during reservoir depletion. Sensitivity analysis also highlights that flow regime classification depends not only on thermodynamic conditions but also on molecular-scale parameters such as methane diameter. Comparison with established models and experimental observations shows that the framework captures the expected increase in rarefaction effects at low pressures and small pore sizes. Overall, the results emphasize that gas transport in nanoporous systems is not governed by a single mechanism but evolves over time and across scales. The proposed framework offers a simple, physically grounded tool for identifying dominant transport mechanisms and supporting model selection, while also providing a foundation for more advanced descriptions of gas flow in unconventional reservoirs. Full article

Background/Aim: Motor skill acquisition is the foundation of athletic performance, from the novice learning a new technique to the elite athlete executing complex movements automatically under pressure. Although classical models have defined the neural substrates of motor control—the cerebellum for error correction, the basal ganglia for action selection, and the primary motor cortex (M1) for execution—emerging evidence suggests that motor learning is the result of the dynamic interaction of multiple parallel processes rather than a linear hierarchy. This narrative review integrates classical neuroanatomical knowledge with contemporary findings on multisite plasticity, with a particular focus on sport-specific adaptations. Methods: We examined three core learning mechanisms operating in parallel: error-based learning (cerebellar-dependent, driven by sensory prediction errors), reinforcement learning (striatal-dependent, driven by reward prediction errors and dopamine), and use-dependent learning (cortical-dependent, driven by mere repetition). We also summarize the biochemical pathways supporting these learning processes, including glutamatergic LTP-like cortical plasticity, cerebellar mGluR1–PKC–LTD signaling, dopaminergic corticostriatal plasticity, BDNF–TrkB-dependent neurotrophic mechanisms, growth-factor signaling, and exercise-induced muscle–brain communication. Results: We then propose a spatiotemporal model in which the relative contribution of each network shifts dynamically across the three stages of skill acquisition, from the early cognitive/strategic phase to the late automatic phase characteristic of elite performance. At the molecular level, these stage-dependent adaptations are supported by synaptic strengthening and weakening mechanisms, reward-dependent dopamine signaling, neurotrophic and growth-factor-mediated remodeling, and peripheral metabolic/myokine signals that modulate brain plasticity during training and recovery. Special attention is given to contextual and sport-specific adaptations, using the paradigmatic example of elite swimmers who demonstrate enhanced short-interval intracortical inhibition (SICI) selectively in the aquatic environment, reflecting long-term sport-induced neuroplasticity. Conclusions: Understanding these dynamic network mechanisms has direct implications for coaching, training periodization, and the development of targeted neuromodulatory interventions to accelerate skill acquisition and optimize athletic performance. Full article

The impact of force field models on the thermal and mechanical characteristics of polyimides was comprehensively examined for the first time. Polyimides (PI) are heterocyclic polymers with outstanding thermal and chemical stabilities and excellent dielectric properties. In this study, we used all-atom molecular dynamics (MD) simulations to examine how the flexibility of the dianhydride fragment affects the thermal and mechanical properties of three polyimides: PMDA-ODA, ODPA-ODA, and R-ODA. The considered polyimides have different dianhydride fragments based on pyromellitic acid (PMDA), tetracarboxylic acid diphenyl oxide (ODPA) and 1,3-bis(3′,4-dicarboxyphenoxy)benzene acid (R), with a constant diamine: 4,4′-oxydianiline (ODA). Models were built using five classical force fields (OPLS-AA, Amber/GAFF, Gromos, Charmm/CGenFF, and UFF). For each polyimide, eight models were generated using different force fields and charge schemes: (i) OPLS-AA with 1.14*CM1A charges, (ii) OPLS-AA with HF/6-31G* (RESP) charges, (iii) GAFF with AM1-BCC charges, (iv) GAFF with HF/6-31G* (RESP) charges, (v) CGenFF (version 4.6) with native charges, (vi) CGenFF (version 5.0) with native charges, (vii) Gromos54a7 with native charges, and (viii) UFF with QEq charges. The difference in the chemical structures of the polyimide repeating unit leads to differences in the thermodynamic and kinetic flexibilities that affect the thermal and mechanical properties. Simulations of glass transition temperatures (T_g) for three polyimides PMDA-ODA, ODPA-ODA, and R-ODA mostly replicate the experimental order T_g(PMDA-ODA) > T_g(ODPA-ODA) > T_g(R-ODA), except for the CGenFF (version 4.6) force field. The experimental density ratio ρ(PMDA-ODA) > ρ(ODPA-ODA) > ρ(R-ODA) is most accurately replicated by OPLS-AA (RESP) and CGenFF (version 5.0) polyimide models. The coefficients of thermal expansion (CTE) correspond with the experimental trend, exhibiting an increase in the following order: PMDA-ODA < ODPA-ODA < R-ODA. Gromos54a7 precisely delineates both the ratio and absolute values CTE for all polymers. OPLS-AA (RESP), OPLS-AA (CM1A), CGenFF (version 4.6), and UFF (QEq) models replicate PMDA-ODA’s CTE, while GAFF (RESP) and GAFF (AM1-BCC) models replicate ODPA-ODA and R-ODA CTE values. The ratio between the simulated values of Young’s modulus, yield strength, and strain-hardening modulus followed the sequence PMDA-ODA > ODPA-ODA > R-ODA for the OPLS-AA (RESP) and CGenFF (version 5.0) models. Full article

Background: Adipose tissue is increasingly recognized as a highly dynamic endocrine and immunometabolic organ with marked functional heterogeneity. It serves as a reservoir for the active form of vitamin D₃, 1α,25-dihydroxyvitamin D₃ or calcitriol (1α,25-D₃), since it expresses enzymes responsible for its activation and inactivation and contains the vitamin D receptor (VDR). Through both classical and non-classical mechanisms, calcitriol modulates adipocyte proliferation and differentiation, protein expression and energy metabolism. This review aims to explore the signal transduction mechanisms of calcitriol in adipocytes, detailing the classical pathways mediated by the nuclear VDR (VDRn), as well as non-classical pathways involving membrane-associated VDR (VDRm), microRNAs, AMP-activated protein kinase (AMPK), and sirtuin 1 (SIRT1). Methods: A literature search was conducted using PubMed, ScienceDirect, and MDPI-indexed journals, prioritizing studies published within the last 10 years to ensure the inclusion of up-to-date evidence. Results: This review summarizes current knowledge on both classical and non-classical signaling pathways that are activated by calcitriol and highlights key molecular targets with potential relevance for drug development and therapeutic intervention. Through VDRn, calcitriol regulates the expression of proteins involved in inflammation and energy metabolism. Additionally, it modulates cellular processes such as energy production and secretion via the AMPK/SIRT1 axis and microRNA-mediated pathways, contributing to mitochondrial function and metabolic homeostasis. Conclusions: Calcitriol plays a central role in adipocyte biology by integrating multiple signaling pathways that regulate metabolic and inflammatory responses. These mechanisms highlight its potential as a therapeutic target and biomarker in metabolic diseases. Moreover, microRNAs emerge as critical posttranscriptional regulators in these processes, reinforcing their relevance as both biomarkers and targets for future interventions. Full article

Background: Ferrocene-containing compounds have gained attention in medicinal chemistry due to their unique redox and structural properties. This study investigates ferrocene-based analogues of imatinib and nilotinib to define their binding determinants within the ABL1 kinase domain using an integrated in silico approach, in relation to their previously reported cytotoxic activity. Methods: Ligand geometries were optimized at the B3LYP/def2-TZVP level with D3(BJ) dispersion and SMD solvation. Molecular docking against ABL1 (PDB ID: 2HYY) was performed using Glide SP, validated by re-docking and enrichment screening. Docked poses were refined using MM-GBSA (Prime, VSGB 2.1/OPLS4). The most active compounds (9 and 15a), together with the inactive control 15e, were subjected to three independent 500 ns molecular dynamics simulations (Desmond, OPLS4), followed by trajectory analysis including RMSD, RMSF, radius of gyration, SASA, and polar surface area. Results: Compounds 9 and 15a maintained stable binding within the ATP-binding pocket despite lacking the canonical hinge interaction with Met318, indicating hinge-independent binding. Their binding was mainly driven by interactions with Asp381 (DFG motif) and cation–π contacts with Lys271. In contrast, the compound 15e showed unstable binding, increased conformational flexibility, reduced pocket burial, and loss of key stabilizing interactions. Active compounds also preserved stable P-loop dynamics, with Tyr253 engagement suggesting a role in loop stabilization. Compound 9 exhibited the most constrained and reproducible binding mode among all analogues. Conclusions: Ferrocene-based analogues can sustain stable ABL1 binding via non-classical interaction networks independent of hinge recognition. The clear distinction between active compounds and the inactive analogue 15e supports the robustness of the proposed binding mode and provides a structural basis for their reported cytotoxic activity. These findings support further experimental evaluation of ferrocene-containing scaffolds as potential BCR-ABL1 inhibitors. Full article

Background: The Taiwanese loach (Paramisgurnus dabryanus ssp. Taiwan, Dabry de Thiersant, 1872.) is an economically important aquaculture species in East Asia, and its body color directly affects its ornamental and market value. Our research group recently discovered a golden-red mutant, named “Gan Hong No. 1” (MR), within a wild-type (WT) population. During embryogenesis, MR individuals exhibit almost no melanophore deposition, and after hatching, xanthophores and erythrophores appear sequentially, suggesting that the body color variation likely originates from alterations in the gene regulatory network during early development. Objective: To systematically compare the transcriptomes of WT and MR-Taiwanese loach during early development, to identify the key regulatory pathways underlying red body color formation from a temporal perspective, to test whether the classical melanin synthesis pathway is impaired, and to provide a theoretical basis for selective breeding of body color traits. Methods: High-throughput transcriptome sequencing was performed on eight early developmental stages (0, 5, 10, 15, 20, 23, 28 and 43 h post-fertilization) of both loach types. Differential expression analysis, time-series trend analysis, and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment were used to systematically characterize gene expression dynamics. Transcriptomic data validation was performed using real-time PCR. Results: In MR, the core transcription factor mitfa was significantly downregulated, whereas the expression of melanin synthesis genes such as kita and dct showed no significant difference, indicating that the impairment of melanogenesis is caused by mitfa downregulation. Trend analysis and pathway enrichment revealed that in MR embryos, pathways related to oxidative stress, unsaturated fatty acid biosynthesis, C-type lectin receptor signaling, p53 signaling, and apoptosis were significantly activated, while the thyroid hormone synthesis pathway was markedly upregulated. In WT, these pathways showed the opposite trend. qRT-PCR results were consistent with the transcriptome data. Conclusions: This study demonstrates that downregulation of mitfa serves as the initial trigger for red body color variation in the Taiwanese loach. This mutation impedes melanin synthesis and concurrently activates a coordinated regulatory network involving oxidative stress, immune inflammation, and thyroid hormone signaling. Accumulation of unsaturated fatty acids alleviates oxidative damage and supports carotenoid deposition, while immune signals eliminate aberrant melanocytes and promote compensatory generation of red and yellow chromatophores. The upregulated thyroid hormone further fine-tunes pigment cell differentiation. For the first time in a cobitid species, this study elucidates the mitfa-mediated, multi-pathway synergistic molecular mechanism driving the transition from melanin-based to carotenoid/pteridine-based red coloration in fish, thereby providing a theoretical reference for molecular breeding of body color in aquaculture. Full article

Gas transport in rough nanochannels under rarefied conditions is of considerable interest in microscale and nanoscale flow applications. However, the influence of surface roughness on flow resistance in the transitional regime remains insufficiently understood. In this study, Event-Driven Molecular Dynamics (EDMD) simulations are used to investigate the effects of surface roughness height (k) and periodicity (Λ) on friction-factor behavior for Knudsen numbers between 0.25 and 0.35 and reported Reynolds numbers up to approximately 10². Here, Re is calculated from molecularly averaged density and mean velocity, the effective channel height, and the reduced MD-unit dynamic viscosity used in post-processing. Friction factors were evaluated from the equivalent pressure drop associated with the imposed periodic driving parameter after statistically steady conditions were reached. The results reveal variations in flow resistance with roughness geometry, enabling the development of empirical relations between the normalized friction factor and relative roughness. The resulting correlations describe the observed simulation trends within the parameter range investigated. In addition, velocity-profile and density-field analyses provide physical insight into the mechanisms governing the observed behavior. The findings suggest that classical continuum-based correlations may not fully capture roughness effects under the conditions investigated. The proposed formulation may serve as a practical tool for estimating friction-factor behavior within the investigated transitional rarefied-flow regime. Full article

Five modifications of polytetrafluoroethylene (PTFE) are considered as a modern alternative to PTFE as sliding layers of bridge bearing parts. Radiation-modified PTFE without additives and with nano-additives as well as composites based on PTFE with bronze inclusions and nanomodified carbon fiber fillers were investigated. Ultra-high-molecular-weight polyethylene (UHMWPE) and classic pure PTFE were considered as control samples. The thermomechanical properties of the materials were studied within the framework of dynamic mechanical analysis in the operating temperature range of bridge structures [−40; +80] °C. The exit zones from the linear theory of viscoelasticity were established for all the materials considered. Temperature dependencies of the storage modulus and the loss modulus were determined. Thermoviscoelastic models of material behavior were constructed using a numerical identification procedure, experimental data, and simulation models. The thermomechanics of materials during the deformation of the spherical support part of the bridge were analyzed. Temperature dependencies of the parameters of the contact stress-strain state were determined with an average coefficient of determination R² = 0.97 and an average error size RMSE = 0.092. Full article

Begomoviruses are among the most destructive plant viruses, causing substantial yield losses across diverse cropping systems. Their epidemiological success is driven by high genetic plasticity, broad host range, and efficient transmission by the whitefly vector Bemisia tabaci. Traditional epidemiological models based on the classical disease triangle (virus–host–vector) fail to fully capture the ecological and evolutionary complexity of begomovirus pathosystems. Increasing evidence highlights the critical role of non-cultivated plants, particularly weeds, as persistent reservoirs that maintain viral populations during off seasons, facilitate recombination, and act as primary inoculum sources for subsequent outbreaks. Here, we propose the Begomovirus Disease Tetrahedron, an integrative framework that expands the disease triangle by incorporating weeds as a fourth essential component. We synthesize current knowledge on begomovirus adaptive evolution, including genome plasticity, noncanonical protein functions, and virus–vector mutualism, alongside key ecological drivers such as seasonal dynamics, agricultural intensification, and landscape connectivity. By integrating molecular, ecological, and epidemiological perspectives, this framework provides a comprehensive understanding of begomovirus emergence and persistence, offering new insights for the development of sustainable and ecologically informed disease management strategies. Full article

This study aims to investigate the performance and mechanism of N′-[(E)-phenylmethylidene] furan-2-carbohydrazide (FNH), a hydrazone Schiff base, as a corrosion inhibitor for carbon steel in 1.0 M HCl. The research was conducted by coupling electrochemical testing (Tafel analysis and Impedance spectroscopy) with surface characterization (SEM and AFM) and advanced computational tools, including quantum-chemical modeling and classical molecular dynamics (MD) simulations. Tafel analysis revealed that FNH acts as a mixed-type inhibitor, concurrently slowing iron oxidation and hydrogen reduction. Impedance data showed that the Faradaic resistance grew monotonically with FNH dosage, reaching 95% protection at 1 × 10⁻⁴ M. Fitting the results to the Langmuir model indicated a joint physical–chemical anchoring pathway, further confirmed by SEM/AFM inspection which disclosed a uniform organic deposit. Quantum-chemical modeling revealed that protonated species broaden the molecule’s capacity for bidirectional electron exchange, while MD simulations on the Fe (110) slab confirmed a flat-lying geometry that maximizes heteroatom–metal contact. The consistency between laboratory observables and atomic-scale predictions provides a detailed, mechanism-oriented picture of how this organic protective layer curtails acid corrosion. Full article