The migration mechanisms of ore-forming fluids have long been a focus in the field of ore deposit studies.Calcite is ubiquitously present in various types of rocks in the lithosphere,and the underlying mechanisms of i...The migration mechanisms of ore-forming fluids have long been a focus in the field of ore deposit studies.Calcite is ubiquitously present in various types of rocks in the lithosphere,and the underlying mechanisms of its influence on fluid migration are of crucial importance.While previous studies have revealed that salinity changes can modulate fluid migration,the underlying mechanisms remain poorly understood.We employ molecular dynamics simulations to elucidate how salinity variations in ore-forming fluids modulate the adsorption onto calcite nanopore walls,thereby revealing the microscopic mechanisms governing ore fluid transport through calcite nano-fractures.The results show that the adsorption energy Eint of the solution on the calcite surface increased from -14,948.84±182.48 kcal/mol to -12,144.08±118.2 kcal/mol as salinity increased,which is conducive to the long-range transport of the fluid in the calcite nanopore.展开更多
The equilibrium dynamics and nonlinear rheology of unentangled polymer blends remain inadequately understood,especially regarding the influence of short-chain matrix length N_(S) on the structure and rheological behav...The equilibrium dynamics and nonlinear rheology of unentangled polymer blends remain inadequately understood,especially regarding the influence of short-chain matrix length N_(S) on the structure and rheological behavior of dispersed long chains.Using molecular dynamics simulations based on the Kremer-Grest model,we systematically explore the N_(S)-dependence of static conformations,equilibrium dynamics,and nonlinear shear responses in unentangled long-chain/short-chain polymer blends.Our results demonstrate a decoupling between the static and dynamic sensitivity to N_(S):while the static chain size,R_g,follows Flory theory with slight swelling at small N_(S) due to incomplete excluded volume screening,the diffusion coefficient,D,and the relaxation time,τ_(0),exhibit a strong,non-monotonic N_(S)-dependence,transitioning from monomeric friction dominance at small N_(S) to collective segmental rearrangement at large N_(S).Additionally,we observe partial decoupling between the viscous and normal stress responses:while the zero-shear viscosity,η,is strongly N_(S)-dependent,the first and second normal stress coefficients,Ψ_(1) and Ψ_(2),collapse onto universal curves when scaled by the dimensionless shear rate,γτ_(0),suggesting a common mechanism of orientation and stretching.Under shear,long chains compress in the vorticity direction λ_(z)~Wi^(-0.2),which reduces collision frequency and contributes to shear thinning,while the scaling of weaker orientation resistance m_(G)~Wi^(0.35)reflects hydrodynamic screening by the short-chain matrix.These findings highlight the limitations of single-chain models and emphasize the necessity of considering N_(S)-dependent matrix dynamics and flow-induced structural changes in understanding the rheology of unentangled polymer blends.展开更多
In response to the increasing demand for hadron therapy facilities,significant efforts have been directed toward enhancing the performance of high-gradient and high-transmission injectors for light ion beams.For carbo...In response to the increasing demand for hadron therapy facilities,significant efforts have been directed toward enhancing the performance of high-gradient and high-transmission injectors for light ion beams.For carbon ion irradiations,which offer greater radiobiological efficiency in tumor treatment,recent research has focused on developing high-production sources of fully stripped C^(6+)ions and highly compact,high-frequency RFQ cavities.This study explores the design possibilities of a carbon ion acceleration section using 750 MHz Interdigital H-mode Drift Tube Linacs(IH-DTLs)as a high-efficiency solution for accelerating ions in the 5-10 MeV per nucleon energy range.A particle-tracking routine based on the TRAVEL code was developed to design the acceleration line through a tailored KONUS-type configuration.Three design solutions were proposed and compared,exploring different alternatives regarding the use of a MEBT to match the output beam phase space of the RFQ to the optics of the line,as well as varying considerations for magnetic systems to focus the beam.Additionally,the compatibility of the proposed solutions with the existing design of the carbon ion bent-linac for hadron therapy was assessed.展开更多
THE mechanical response and deformation mechanisms of pure nickel under nanoindentation were systematically investigated using molecular dynamics(MD)simulations,with a particular focus on the novel interplay between c...THE mechanical response and deformation mechanisms of pure nickel under nanoindentation were systematically investigated using molecular dynamics(MD)simulations,with a particular focus on the novel interplay between crystallographic orientation,grain boundary(GB)proximity,and pore characteristics(size/location).This study compares single-crystal nickel models along[100],[110],and[111]orientations with equiaxed polycrystalline models containing 0,1,and 2.5 nm pores in surface and subsurface configurations.Our results reveal that crystallographic anisotropy manifests as a 24.4%higher elastic modulus and 22.2%greater hardness in[111]-oriented single crystals compared to[100].Pore-GB synergistic effects are found to dominate the deformation behavior:2.5 nm subsurface pores reduce hardness by 25.2%through stress concentration and dislocation annihilation at GBs,whereas surface pores enable mechanical recovery via accelerated dislocation generation post-collapse.Additionally,size-dependent deformation regimes were identified,with 1 nm pores inducing negligible perturbation due to rapid atomic rearrangement,in contrast with persistent softening in 2.5 nm pores.These findings establish atomic-scale design principles for defect engineering in nickel-based aerospace components,demonstrating how crystallographic orientation,pore configuration,and GB interactions collectively govern nanoindentation behavior.展开更多
In this study,we perform particle-resolved simulations of settling spheroidal particles,considering oblate and prolate spheroids and spheres,and investigate the shape effect on the particle dynamics in suspensions wit...In this study,we perform particle-resolved simulations of settling spheroidal particles,considering oblate and prolate spheroids and spheres,and investigate the shape effect on the particle dynamics in suspensions with volume fraction 1%and 5%.We first examine the single-point statistics of the translational and rotational motion of the settling particles.The horizontal velocity has a symmetrical distribution with standard deviation dependent on the particle shape.The greater horizontal velocity fluctuations of the non-spherical particles,compared to that of spheres,are attributed to the horizontal drift of settling spheroids with oblique orientations induced by the fluid-particle and particle-particle interactions.The fluctuation of particle vertical velocity,instead,is skewed under the effect of wake-induced hydrodynamic interactions.Further,we explore the particle pair statistics,which demonstrate the formation of column-like particle micro-structures for the lowest volume fraction considered.This clustering is more pronounced for spheroidal particles than spheres,due to the stronger attractions among vertically-aligned settling spheroids.Moreover,the particle pair statistics are directly related to the collision rate among the dispersed particles.The local accumulation of oblate/prolate spheroids serves as the major mechanism to promote the particle-particle collisions in dilute suspensions.展开更多
Understanding the aerodynamic and dynamic characteristics of unloaded freight trains in crosswinds is pivotal for ensuring their operational safety and reliability.The dynamic performance of unloaded gondola cars unde...Understanding the aerodynamic and dynamic characteristics of unloaded freight trains in crosswinds is pivotal for ensuring their operational safety and reliability.The dynamic performance of unloaded gondola cars under varying windbreak heights is therefore investigated in this study,revealing distinct differences in lateral stability and safety indicators,and enabling the determination of an optimal windbreak height.A 3D unsteady aerodynamic model was developed using the improved delayed detached eddy simulation(IDDES)method and an overset numerical mesh.Also leveraging a multi-body dynamics(MBD)model of a three-wagon freight car configuration,we investigate time-averaged aerodynamic forces,transient flow field distributions,and nonlinear dynamic responses.Parametric analyses reveal a non-monotonic relationship between the height of the windbreak and the stability of the train.A windbreak with a critical height of 2 m(0.74 relative to the car body height)results in 76%,64%,and 81%lower values of the derailment coefficient CD,wheel unloading ratio R,and overturning coefficient C_(O),respectively.Notably,when the height of the windbreak exceeds 2 m,vortices within the gondola induce an adverse pressure coefficient distribution(C_(p)=−2.17)on the leeward internal wall,intensifying the lateral force and overturning moment.Furthermore,frequency-domain analysis reveals that the lateral sway and overturning vibration mode are associated with low-frequency(1.61 Hz)lateral vibrations under crosswind conditions.This study provides a theoretical foundation for the design and optimization of railway windbreaks.展开更多
Mitochondria are central regulators of cellular energy metabolism,redox balance,and survival,and their dysfunction contributes to neurodegenerative,cardiovascular,and metabolic diseases,as well as aging.Beyond its rol...Mitochondria are central regulators of cellular energy metabolism,redox balance,and survival,and their dysfunction contributes to neurodegenerative,cardiovascular,and metabolic diseases,as well as aging.Beyond its role as a circadian hormone,melatonin is now recognized as a key modulator of mitochondrial physiology.This review provides an overview of the mechanisms by which melatonin can preserve mitochondrial function through multifaceted mechanisms.Experimental evidence shows that melatonin enhances the activity of electron transport chain(ETC)complexes,stabilizes the mitochondrial membrane potential(Δψ),and prevents cardiolipin(CL)peroxidation,thereby limiting permeability transition pore(mPTP)opening and cytochrome c release.Through its direct radical scavenging capacity and the upregulation of mitochondrial antioxidant defenses,melatonin protects against oxidative stress(OS)and preserves mitochondrial DNA integrity.Melatonin also regulates mitochondrial dynamics by promoting fusion,restraining excessive fission,and supporting quality control mechanisms such as mitophagy,unfolded protein response(UPR),and proteostasis.Moreover,melatonin influences mitochondrial biogenesis and intercellular communication through tunneling nanotubes(TNTs)and mitokine signaling.Thus,melatonin may represent a promising multifaceted therapeutic strategy for preserving mitochondrial homeostasis in a range of pathological conditions,including neurodegeneration and cardiovascular and metabolic diseases.However,a significant translational gap still remains between the promising preclinical data and the established clinical practice.Therefore,the aim of this review is to provide a comprehensive synthesis of current knowledge on the mechanisms through which melatonin modulates mitochondrial function and to discuss its potential therapeutic implications in neurodegenerative,cardiovascular,and metabolic diseases.展开更多
Photo-assisted lithium–sulfur batteries(PALSBs)offer an eco-friendly solution to address the issue of sluggish reaction kinetics of conventional LSBs.However,designing an efficient photoelectrode for practical implem...Photo-assisted lithium–sulfur batteries(PALSBs)offer an eco-friendly solution to address the issue of sluggish reaction kinetics of conventional LSBs.However,designing an efficient photoelectrode for practical implementation remains a significant challenge.Herein,we construct a free-standing polymer–inorganic hybrid photoelectrode with a direct Z-scheme heterostructure to develop high-efficiency PALSBs.Specifically,polypyrrole(PPy)is in situ vapor-phase polymerized on the surface of N-doped TiO_(2) nanorods supported on carbon cloth(N-TiO_(2)/CC),thereby forming a well-defined p–n heterojunction.This architecture efficiently facilitates the carrier separation of photo-generated electron–hole pairs and significantly enhances carrier transport by creating a built-in electric field.Thus,the PPy@N-TiO_(2)/CC can simultaneously act as a photocatalyst and an electrocatalyst to accelerate the reduction and evolution of sulfur,enabling ultrafast sulfur redox dynamics,as convincingly validated by both theoretical simulations and experimental results.Consequently,the PPy@N-TiO_(2)/CC PALSB achieves a high discharge capacity of 1653 mAh g^(−1),reaching 98.7%of the theoretical value.Furthermore,5 h of photo-charging without external voltage enables the PALSB to deliver a discharge capacity of 333 mAh g^(−1),achieving dual-mode energy harvesting capabilities.This work successfully integrates solar energy conversion and storage within a rechargeable battery system,providing a promising strategy for sustainable energy storage technologies.展开更多
SalicS1 is a genetically encoded,ratiometric FRET biosensor that brings salicylic acid(SA)research to the same real-time imaging standard long available for ABA and GA.Built through a modular Golden Gate platform and ...SalicS1 is a genetically encoded,ratiometric FRET biosensor that brings salicylic acid(SA)research to the same real-time imaging standard long available for ABA and GA.Built through a modular Golden Gate platform and informed by NPR-NIMIN structural biology,SalicS1 achieves SA specificity,tunable affinity,reversibility,and non-perturbing expression in Arabidopsis.Using this sensor,pathogen infection,non-adapted fungal challenge,and aphid feeding are shown to elicit spatially propagating SA surges rather than purely local accumulation,revealing a tissue-level organization of immune signaling that bulk assays could not resolve.SalicS1 therefore provides a broadly deployable tool for dissecting the geometry,timing,and genotype dependence of SA-mediated plant defense.展开更多
The structural changes in the CaO-SiO_(2)-Al_(2)O_(3)-MgO slag system with varying CaO contents were investigated through molecular dynamics(MD)simulations,and its effect on the dissolution behavior of alumina inclusi...The structural changes in the CaO-SiO_(2)-Al_(2)O_(3)-MgO slag system with varying CaO contents were investigated through molecular dynamics(MD)simulations,and its effect on the dissolution behavior of alumina inclusions was characterized by the Kullback-Leibler(KL)divergence.The slag structure analysis revealed that the[AlO]tetrahedral structure was the primary network structure in the slag.With increasing the CaO content,the non-bridge oxygen(NBO)content in the slag structure increases,and the bridge oxygen(BO)content decreases,thereby reducing the complexity of the slag network structure.Raman spectroscopy detection verifies the results of the MD simulations.The results indicated that the dissolution rate of alumina inclusions accelerates with increasing the CaO content in the slag,owing to the reduced complexity of the slag network structure and the enhanced interatomic interactions.The simulation results for the dissolution of alumina inclusions were consistent with theoretical calculations based on the slag inclusion capacity and the dimensionless dissolution rate of inclusions.Radial distribution function analysis demonstrated that the interaction between atoms in the slag system and alumina inclusions strengthens,increasing the dissolution rate of alumina inclusions.The[AlO_(6)]octahedral structure of the alumina inclusions is disrupted,forming BO structures,which in turn enhances the complexity of the slag network structure,slowing the dissolution rate of alumina inclusions.In contrast,the slag system with a higher CaO content has a relatively simpler network structure,promoting faster alumina inclusion dissolution.展开更多
This study investigates the influence of hydrogen concentration at grain boundaries on the sensitivity of polycrystalline iron to hydrogen embrittlement using molecular dynamics simulations.These simulations reveal th...This study investigates the influence of hydrogen concentration at grain boundaries on the sensitivity of polycrystalline iron to hydrogen embrittlement using molecular dynamics simulations.These simulations reveal the diffusion behavior of hydrogen atoms at grain boundaries and their consequential impact on the hydrogen embrittlement sensitivity of iron alloys.The findings indicate that as the hydrogen concentration increases,both the yield strength and ultimate tensile strength of Fe-H alloys exhibit a declining trend.Moreover,the capture of hydrogen atoms at the grain boundaries significantly influences the fracture toughness of the material and promotes the formation and propagation of cracks.This study provides a novel theoretical basis for understanding and predicting the hydrogen embrittlement behavior of iron-based materials in hydrogen-rich environments,offering valuable insights for the design and development of Fe alloys with enhanced resistance to hydrogen embrittlement.展开更多
As China's high-speed railway technology advances,high-speed trains have emerged as a pivotal mode of transportation,instrumental in facilitating passenger and freight mobility while fostering robust regional eco-...As China's high-speed railway technology advances,high-speed trains have emerged as a pivotal mode of transportation,instrumental in facilitating passenger and freight mobility while fostering robust regional eco-nomic and trade interactions.Nonetheless,the safety of train operations remains a paramount concern,prompting extensive research into the dynamic behavior of critical components,which is essential to ensuring seamless and secure transportation services.This article commences by comprehensively reviewing the current landscape and evolutionary trajectory of dynamic model analysis for both traditional bearings and axle box bearings.Emphasis is placed on elucidating the profound influence of diverse bearing fault types on the system's kinematic state,alongside delving into the research methodologies employed in developing multi-physics field coupling models.Subsequently,it expounds on the content of investigations focusing on various wheel and track impairments,grounded in the dynamic modeling of the bearing vehicle coupling system.Concurrently,the intricate interplay between wheel-rail excitation and axle box bearing faults on the system's performance is elucidated.Concludingly,the article underscores the inadequacy of current multi-source fault diagnosis meth-odologies in tackling the intricacies of complex train operating environments,thereby highlighting its sig-nificance as a pressing and vital research agenda for the future.展开更多
The von Hippel-Lindau tumor suppressor(VHL)has been extensively used to develop degraders targeting numerous proteins of interest.However,studies on the rational design of VHL-proteolysis-targeting chimeras(PROTACs)re...The von Hippel-Lindau tumor suppressor(VHL)has been extensively used to develop degraders targeting numerous proteins of interest.However,studies on the rational design of VHL-proteolysis-targeting chimeras(PROTACs)remain scarce.This study aimed to develop strategies to investigate VHL-recruiting PROTACs connecting with varying attachment sites on VHL ligands,which could be utilized for KRAS^(G12C) degraders development and expanded to additional targets.We developed a molecular dynamics(MD)-based strategy to explore the stability of ternary complexes induced by KRAS^(G12C) PROTACs with four distinct attachment sites of VH032.We found a potent degrader namely YN14-H,linked to hydroxyl group on VH032 benzene ring,exhibited the most superior ability of inducing ternary complexes,reflected by the lowest dissociation constant(Kd)for ternary complex induction and the highest AlphaScreen(AS)-based interaction.YN14-H inhibited cell growth with low nanomolar half maximal inhibitory concentration(IC_(50))and half maximal degradation concentration(DC_(50))values as well as>98%of maximum degradation(D_(max))in NCI-H358 and MIA PaCa-2 cells harboring KRAS^(G12C)-mutation.Mechanistically,YN14-H significantly induced apoptosis and inhibited the migratory capacity.Notably,YN14-H demonstrated favorable pharmacokinetic properties and excellent antitumor activity in vivo.Furthermore,bromodomain-containing protein 7(BRD7)and Bruton tyrosine kinase(BTK)degraders attached to distinct sites on VH032 further verified the rationality and universality of our MD-based strategies.Our findings demonstrated that YN14-H could serve as a promising candidate for the treatment of tumors with KRAS^(G12C)-mutation and present a strategy for the rational design of VHL-recruiting PROTACs that target additional proteins at distinct attachment sites.展开更多
This study uses all-atom molecular dynamics simulations to investigate the dislocation propagation, stress transmission, and mechanical properties in poly(p-phenylene terephthalamide) fibers under uniaxial tension. Th...This study uses all-atom molecular dynamics simulations to investigate the dislocation propagation, stress transmission, and mechanical properties in poly(p-phenylene terephthalamide) fibers under uniaxial tension. The results indicate that the dislocation propagates and the stress transfers not only along the fiber axis but also between adjacent molecular chains through hydrogen bonds, demonstrating their influence on the yield behavior. As the degree of polymerization increases, breakage of covalent bonds and interchain slippage contribute to the yield of fibers together. This work provides theoretical guidance for the design and manufacturing of high-performance fibers.展开更多
Due to their chiral structure,carbon nanosprings possess unique properties that are promising for nanotechnology applications.The structural transformations of carbon nanosprings in the form of spiral macromolecules d...Due to their chiral structure,carbon nanosprings possess unique properties that are promising for nanotechnology applications.The structural transformations of carbon nanosprings in the form of spiral macromolecules derived from planar coronene and kekulene molecules(graphene helicoids and spiral nanoribbons)are analyzed using molecular dynamics simulations.The interatomic interactions are described by a force field including valence bonds,bond angles,torsional and dihedral angles,as well as van derWaals interactions.While the tension/compression of such nanosprings has been analyzed in the literature,this study investigates other modes of deformation,including bending and twisting.Depending on the geometric characteristics of the carbon nanosprings,the formation of structural and helix reversal topological defects is described.During these structural transformations of the nanosprings,only van der Waals bonds break and recover,but breaking or recovery of covalent bonds does not take place.It is found that nanosprings demonstrate a significantly higher coefficient of axial thermal expansion than many metals and alloys.Under axial compression,Euler instability leads to lateral bending with continuous deformation of the nanospring axis at relatively low compression,while at high compression,bending kinks form.Various types of topological defects form on the instantly released nanospring during its relaxation from a highly stretched configuration.These results are useful for the development of nanosensors operating over a wide temperature range.展开更多
In Chin.Phys.B 34114704(2025),Eq.(7)and the associated unit notation were incorrect.The correct ones are present here.Since Eq.(7)is an in-built expression in the simulation package,the correction is purely typographi...In Chin.Phys.B 34114704(2025),Eq.(7)and the associated unit notation were incorrect.The correct ones are present here.Since Eq.(7)is an in-built expression in the simulation package,the correction is purely typographical and does not affect the simulation procedure,numerical results,or the conclusions.展开更多
The airflow mechanics in adult nasal airways,whether healthy or abnormal,are extensively studied and investigated,but the flow mechanics in child nasal airways remain underexplored.This study investigates the airflow ...The airflow mechanics in adult nasal airways,whether healthy or abnormal,are extensively studied and investigated,but the flow mechanics in child nasal airways remain underexplored.This study investigates the airflow mechanics in the child’s nasal upper airway with adenoid hypertrophy,with an adenoid nasopharyngeal ratio(AN of 0.9),under cyclic inhalation and exhalation.An inlet respiratory cycle with three different flow rates(3.2 L/min calm breathing,8.6 L/min normal breathing,and 19.3 L/min intensive breathing)was simulated by using the computational fluid dynamics approach.To better capture the interaction between airflow and the flexible airway tissue,fluid-structure interaction analysis was performed at the normal breathing rate.Comparing the airflow dynamics during inhalation and exhalation,the pressure drops,nasal resistance,and wall shear stress show significant differences in the nasopharyngeal region for all different flow rates.This observation suggests that the inertial effect associated with the transient flow is important during exhalation and inhalation.Furthermore,the considerable temporal variation in flow rate distribution across a specific cross-section of the nasal airway highlights the critical role of transient data in virtual surgery planning and data for clinical decisions.展开更多
Compared to the well-studied two-dimensional(2D)ferroelectricity,the appearance of 2D antiferroelectricity is much rarer,where local dipoles from the nonequivalent sublattices within 2D monolayers are oppositely orien...Compared to the well-studied two-dimensional(2D)ferroelectricity,the appearance of 2D antiferroelectricity is much rarer,where local dipoles from the nonequivalent sublattices within 2D monolayers are oppositely oriented.Using NbOCl_(2) monolayer with competing ferroelectric(FE)and antiferroelectric(AFE)phases as a 2D material platform,we demonstrate the emergence of intrinsic antiferroelectricity in NbOCl_(2) monolayer under experimentally accessible shear strain,along with new functionality associated with electric field-induced AFE-to-FE phase transition.Specifically,the complex configuration space accommodating FE and AFE phases,polarization switching kinetics,and finite temperature thermodynamic properties of 2D NbOCl_(2) are all accurately predicted by large-scale molecular dynamics simulations based on deep learning interatomic potential model.Moreover,room temperature stable antiferroelectricity with low polarization switching barrier and one-dimensional collinear polarization arrangement is predicted in shear-deformed NbOCl_(2) monolayer.The transition from AFE to FE phase in 2D NbOCl_(2) can be triggered by a low critical electric field,leading to a double polarization–electric(P–E)loop with small hysteresis.A new type of optoelectronic device composed of AFE-NbOCl_(2) is proposed,enabling electric“writing”and nonlinear optical“reading”logical operation with fast operation speed and low power consumption.展开更多
Mitochondrial dysfunction has emerged as a critical factor in the etiology of various neurodevelopmental disorders, including autism spectrum disorders, attention-deficit/hyperactivity disorder, and Rett syndrome. Alt...Mitochondrial dysfunction has emerged as a critical factor in the etiology of various neurodevelopmental disorders, including autism spectrum disorders, attention-deficit/hyperactivity disorder, and Rett syndrome. Although these conditions differ in clinical presentation, they share fundamental pathological features that may stem from abnormal mitochondrial dynamics and impaired autophagic clearance, which contribute to redox imbalance and oxidative stress in neurons. This review aimed to elucidate the relationship between mitochondrial dynamics dysfunction and neurodevelopmental disorders. Mitochondria are highly dynamic organelles that undergo continuous fusion and fission to meet the substantial energy demands of neural cells. Dysregulation of these processes, as observed in certain neurodevelopmental disorders, causes accumulation of damaged mitochondria, exacerbating oxidative damage and impairing neuronal function. The phosphatase and tensin homolog-induced putative kinase 1/E3 ubiquitin-protein ligase pathway is crucial for mitophagy, the process of selectively removing malfunctioning mitochondria. Mutations in genes encoding mitochondrial fusion proteins have been identified in autism spectrum disorders, linking disruptions in the fusion-fission equilibrium to neurodevelopmental impairments. Additionally, animal models of Rett syndrome have shown pronounced defects in mitophagy, reinforcing the notion that mitochondrial quality control is indispensable for neuronal health. Clinical studies have highlighted the importance of mitochondrial disturbances in neurodevelopmental disorders. In autism spectrum disorders, elevated oxidative stress markers and mitochondrial DNA deletions indicate compromised mitochondrial function. Attention-deficit/hyperactivity disorder has also been associated with cognitive deficits linked to mitochondrial dysfunction and oxidative stress. Moreover, induced pluripotent stem cell models derived from patients with Rett syndrome have shown impaired mitochondrial dynamics and heightened vulnerability to oxidative injury, suggesting the role of defective mitochondrial homeostasis in these disorders. From a translational standpoint, multiple therapeutic approaches targeting mitochondrial pathways show promise. Interventions aimed at preserving normal fusion-fission cycles or enhancing mitophagy can reduce oxidative damage by limiting the accumulation of defective mitochondria. Pharmacological modulation of mitochondrial permeability and upregulation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha, an essential regulator of mitochondrial biogenesis, may also ameliorate cellular energy deficits. Identifying early biomarkers of mitochondrial impairment is crucial for precision medicine, since it can help clinicians tailor interventions to individual patient profiles and improve prognoses. Furthermore, integrating mitochondria-focused strategies with established therapies, such as antioxidants or behavioral interventions, may enhance treatment efficacy and yield better clinical outcomes. Leveraging these pathways could open avenues for regenerative strategies, given the influence of mitochondria on neuronal repair and plasticity. In conclusion, this review indicates mitochondrial homeostasis as a unifying therapeutic axis within neurodevelopmental pathophysiology. Disruptions in mitochondrial dynamics and autophagic clearance converge on oxidative stress, and researchers should prioritize validating these interventions in clinical settings to advance precision medicine and enhance outcomes for individuals affected by neurodevelopmental disorders.展开更多
MgO has been shown to facilitate the precipitation of MgO-rich crystalline phases within the MgO-CaO-Al_(2)O_(3)-SiO_(2)(MCAS)glassy inclusion system,which possesses a high liquidus temperature and a significant Young...MgO has been shown to facilitate the precipitation of MgO-rich crystalline phases within the MgO-CaO-Al_(2)O_(3)-SiO_(2)(MCAS)glassy inclusion system,which possesses a high liquidus temperature and a significant Young’s modulus.The underlying linkage between the structural evolution and the crystallization characteristics of the MCAS system was systematically investigated using molecular dynamics simulation and thermodynamic calculation.The results revealed that Mg^(2+) ions played a dual role,constructing networks through the formation of tricluster oxygens while consuming bridging oxygens(BOs)in a mechanism similar to Ca^(2+) ions.However,despite this dual role,the network connectivity was still decreased with the increase in MgO/(MgO+Al_(2)O_(3))(M/(M+A))and CaO/(CaO+SiO_(2))(C/(C+S))ratios,primarily due to the reduction in BOs.This microscopic structural evolution resulted in a reduction in viscosity and an enhancement of crystallization ability.Furthermore,the remarkable diffusion capability of Mg^(2+) ions,coupled with the increased proportion of 6-coordinated Mg^(2+)ions,unveiled the mechanism underlying the precipitation of MgSiO_(3) and Mg_(2)SiO_(4) crystals,which exhibited high Young’s moduli of 165.23 and 196.67 GPa,respectively.To prevent the precipitation of MgO-rich crystalline phases,it was crucial to maintain the M/(M+A)ratio below 0.42 and the C/(C+S)ratio below 0.16 within the MCAS system.展开更多
基金financed jointly by the National Major Science and Technology Special Project on Deep Earth Exploration(2024ZD1001701-5)the National Natural Science Foundation of China(42472127,42172086)+2 种基金the Yunnan Major Project of Basic Research(202401BN070001-002)Yunnan Mineral Resources Prediction and Evaluation Engineering Research Center(2011)Innovation Team Program of Kunming University of Science and Technology,Yunnan Province。
文摘The migration mechanisms of ore-forming fluids have long been a focus in the field of ore deposit studies.Calcite is ubiquitously present in various types of rocks in the lithosphere,and the underlying mechanisms of its influence on fluid migration are of crucial importance.While previous studies have revealed that salinity changes can modulate fluid migration,the underlying mechanisms remain poorly understood.We employ molecular dynamics simulations to elucidate how salinity variations in ore-forming fluids modulate the adsorption onto calcite nanopore walls,thereby revealing the microscopic mechanisms governing ore fluid transport through calcite nano-fractures.The results show that the adsorption energy Eint of the solution on the calcite surface increased from -14,948.84±182.48 kcal/mol to -12,144.08±118.2 kcal/mol as salinity increased,which is conducive to the long-range transport of the fluid in the calcite nanopore.
基金financially supported by the National Natural Science Foundation of China(Nos.22341304,22303100 and 12205270)the National Key R&D Program of China(Nos.2023YFA1008800 and 2020YFA0713601)the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDC0180303)。
文摘The equilibrium dynamics and nonlinear rheology of unentangled polymer blends remain inadequately understood,especially regarding the influence of short-chain matrix length N_(S) on the structure and rheological behavior of dispersed long chains.Using molecular dynamics simulations based on the Kremer-Grest model,we systematically explore the N_(S)-dependence of static conformations,equilibrium dynamics,and nonlinear shear responses in unentangled long-chain/short-chain polymer blends.Our results demonstrate a decoupling between the static and dynamic sensitivity to N_(S):while the static chain size,R_g,follows Flory theory with slight swelling at small N_(S) due to incomplete excluded volume screening,the diffusion coefficient,D,and the relaxation time,τ_(0),exhibit a strong,non-monotonic N_(S)-dependence,transitioning from monomeric friction dominance at small N_(S) to collective segmental rearrangement at large N_(S).Additionally,we observe partial decoupling between the viscous and normal stress responses:while the zero-shear viscosity,η,is strongly N_(S)-dependent,the first and second normal stress coefficients,Ψ_(1) and Ψ_(2),collapse onto universal curves when scaled by the dimensionless shear rate,γτ_(0),suggesting a common mechanism of orientation and stretching.Under shear,long chains compress in the vorticity direction λ_(z)~Wi^(-0.2),which reduces collision frequency and contributes to shear thinning,while the scaling of weaker orientation resistance m_(G)~Wi^(0.35)reflects hydrodynamic screening by the short-chain matrix.These findings highlight the limitations of single-chain models and emphasize the necessity of considering N_(S)-dependent matrix dynamics and flow-induced structural changes in understanding the rheology of unentangled polymer blends.
基金Project co-funded by European Union in the context of the precommercial public procurement of RD services managed by CDTI E.P.Eco-funded by the European Regional Development Fund(ERDF)as part of the project for the development of a Compact Linear Accelerator for Hadrontherapy,Exp.CPP 03/2023 AB(DCCPI/OCPI)。
文摘In response to the increasing demand for hadron therapy facilities,significant efforts have been directed toward enhancing the performance of high-gradient and high-transmission injectors for light ion beams.For carbon ion irradiations,which offer greater radiobiological efficiency in tumor treatment,recent research has focused on developing high-production sources of fully stripped C^(6+)ions and highly compact,high-frequency RFQ cavities.This study explores the design possibilities of a carbon ion acceleration section using 750 MHz Interdigital H-mode Drift Tube Linacs(IH-DTLs)as a high-efficiency solution for accelerating ions in the 5-10 MeV per nucleon energy range.A particle-tracking routine based on the TRAVEL code was developed to design the acceleration line through a tailored KONUS-type configuration.Three design solutions were proposed and compared,exploring different alternatives regarding the use of a MEBT to match the output beam phase space of the RFQ to the optics of the line,as well as varying considerations for magnetic systems to focus the beam.Additionally,the compatibility of the proposed solutions with the existing design of the carbon ion bent-linac for hadron therapy was assessed.
基金The National Natural Science Foundation of China(Grant No.12462006)Beijing Institute of Structure and Environment Engineering Joint Innovation Fund(No.BQJJ202414).
文摘THE mechanical response and deformation mechanisms of pure nickel under nanoindentation were systematically investigated using molecular dynamics(MD)simulations,with a particular focus on the novel interplay between crystallographic orientation,grain boundary(GB)proximity,and pore characteristics(size/location).This study compares single-crystal nickel models along[100],[110],and[111]orientations with equiaxed polycrystalline models containing 0,1,and 2.5 nm pores in surface and subsurface configurations.Our results reveal that crystallographic anisotropy manifests as a 24.4%higher elastic modulus and 22.2%greater hardness in[111]-oriented single crystals compared to[100].Pore-GB synergistic effects are found to dominate the deformation behavior:2.5 nm subsurface pores reduce hardness by 25.2%through stress concentration and dislocation annihilation at GBs,whereas surface pores enable mechanical recovery via accelerated dislocation generation post-collapse.Additionally,size-dependent deformation regimes were identified,with 1 nm pores inducing negligible perturbation due to rapid atomic rearrangement,in contrast with persistent softening in 2.5 nm pores.These findings establish atomic-scale design principles for defect engineering in nickel-based aerospace components,demonstrating how crystallographic orientation,pore configuration,and GB interactions collectively govern nanoindentation behavior.
基金supported by the National Natural Science Foundation of China(Grant Nos.92252104,12388101,and 12472224).
文摘In this study,we perform particle-resolved simulations of settling spheroidal particles,considering oblate and prolate spheroids and spheres,and investigate the shape effect on the particle dynamics in suspensions with volume fraction 1%and 5%.We first examine the single-point statistics of the translational and rotational motion of the settling particles.The horizontal velocity has a symmetrical distribution with standard deviation dependent on the particle shape.The greater horizontal velocity fluctuations of the non-spherical particles,compared to that of spheres,are attributed to the horizontal drift of settling spheroids with oblique orientations induced by the fluid-particle and particle-particle interactions.The fluctuation of particle vertical velocity,instead,is skewed under the effect of wake-induced hydrodynamic interactions.Further,we explore the particle pair statistics,which demonstrate the formation of column-like particle micro-structures for the lowest volume fraction considered.This clustering is more pronounced for spheroidal particles than spheres,due to the stronger attractions among vertically-aligned settling spheroids.Moreover,the particle pair statistics are directly related to the collision rate among the dispersed particles.The local accumulation of oblate/prolate spheroids serves as the major mechanism to promote the particle-particle collisions in dilute suspensions.
基金supported by the National Natural Science Foundation of China(No.52388102)the Science and Technology Research and Development Program of China State Railway Group Co.,Ltd.(No.N2024J039).
文摘Understanding the aerodynamic and dynamic characteristics of unloaded freight trains in crosswinds is pivotal for ensuring their operational safety and reliability.The dynamic performance of unloaded gondola cars under varying windbreak heights is therefore investigated in this study,revealing distinct differences in lateral stability and safety indicators,and enabling the determination of an optimal windbreak height.A 3D unsteady aerodynamic model was developed using the improved delayed detached eddy simulation(IDDES)method and an overset numerical mesh.Also leveraging a multi-body dynamics(MBD)model of a three-wagon freight car configuration,we investigate time-averaged aerodynamic forces,transient flow field distributions,and nonlinear dynamic responses.Parametric analyses reveal a non-monotonic relationship between the height of the windbreak and the stability of the train.A windbreak with a critical height of 2 m(0.74 relative to the car body height)results in 76%,64%,and 81%lower values of the derailment coefficient CD,wheel unloading ratio R,and overturning coefficient C_(O),respectively.Notably,when the height of the windbreak exceeds 2 m,vortices within the gondola induce an adverse pressure coefficient distribution(C_(p)=−2.17)on the leeward internal wall,intensifying the lateral force and overturning moment.Furthermore,frequency-domain analysis reveals that the lateral sway and overturning vibration mode are associated with low-frequency(1.61 Hz)lateral vibrations under crosswind conditions.This study provides a theoretical foundation for the design and optimization of railway windbreaks.
文摘Mitochondria are central regulators of cellular energy metabolism,redox balance,and survival,and their dysfunction contributes to neurodegenerative,cardiovascular,and metabolic diseases,as well as aging.Beyond its role as a circadian hormone,melatonin is now recognized as a key modulator of mitochondrial physiology.This review provides an overview of the mechanisms by which melatonin can preserve mitochondrial function through multifaceted mechanisms.Experimental evidence shows that melatonin enhances the activity of electron transport chain(ETC)complexes,stabilizes the mitochondrial membrane potential(Δψ),and prevents cardiolipin(CL)peroxidation,thereby limiting permeability transition pore(mPTP)opening and cytochrome c release.Through its direct radical scavenging capacity and the upregulation of mitochondrial antioxidant defenses,melatonin protects against oxidative stress(OS)and preserves mitochondrial DNA integrity.Melatonin also regulates mitochondrial dynamics by promoting fusion,restraining excessive fission,and supporting quality control mechanisms such as mitophagy,unfolded protein response(UPR),and proteostasis.Moreover,melatonin influences mitochondrial biogenesis and intercellular communication through tunneling nanotubes(TNTs)and mitokine signaling.Thus,melatonin may represent a promising multifaceted therapeutic strategy for preserving mitochondrial homeostasis in a range of pathological conditions,including neurodegeneration and cardiovascular and metabolic diseases.However,a significant translational gap still remains between the promising preclinical data and the established clinical practice.Therefore,the aim of this review is to provide a comprehensive synthesis of current knowledge on the mechanisms through which melatonin modulates mitochondrial function and to discuss its potential therapeutic implications in neurodegenerative,cardiovascular,and metabolic diseases.
基金the financial support from the National Natural Science Foundation of China (22109127)the Chinese Postdoctoral Science Foundation (2021M702666)+2 种基金the Research Fund of the State Key Laboratory of Solidification Processing (NPU),China (Grant No.2023-TS-02)The financial support from the Youth Project of"Shaanxi High-level Talents Introduction Plan"the Key Laboratory of Advanced Energy Materials Chemistry (Ministry of Education) are also sincerely appreciated
文摘Photo-assisted lithium–sulfur batteries(PALSBs)offer an eco-friendly solution to address the issue of sluggish reaction kinetics of conventional LSBs.However,designing an efficient photoelectrode for practical implementation remains a significant challenge.Herein,we construct a free-standing polymer–inorganic hybrid photoelectrode with a direct Z-scheme heterostructure to develop high-efficiency PALSBs.Specifically,polypyrrole(PPy)is in situ vapor-phase polymerized on the surface of N-doped TiO_(2) nanorods supported on carbon cloth(N-TiO_(2)/CC),thereby forming a well-defined p–n heterojunction.This architecture efficiently facilitates the carrier separation of photo-generated electron–hole pairs and significantly enhances carrier transport by creating a built-in electric field.Thus,the PPy@N-TiO_(2)/CC can simultaneously act as a photocatalyst and an electrocatalyst to accelerate the reduction and evolution of sulfur,enabling ultrafast sulfur redox dynamics,as convincingly validated by both theoretical simulations and experimental results.Consequently,the PPy@N-TiO_(2)/CC PALSB achieves a high discharge capacity of 1653 mAh g^(−1),reaching 98.7%of the theoretical value.Furthermore,5 h of photo-charging without external voltage enables the PALSB to deliver a discharge capacity of 333 mAh g^(−1),achieving dual-mode energy harvesting capabilities.This work successfully integrates solar energy conversion and storage within a rechargeable battery system,providing a promising strategy for sustainable energy storage technologies.
基金supported by the Anhui Province Tongxin Science and Technology Innovation Project(202523b11020014)the Anhui Province Higher Education Quality Engineering Program(2024fwxx003).
文摘SalicS1 is a genetically encoded,ratiometric FRET biosensor that brings salicylic acid(SA)research to the same real-time imaging standard long available for ABA and GA.Built through a modular Golden Gate platform and informed by NPR-NIMIN structural biology,SalicS1 achieves SA specificity,tunable affinity,reversibility,and non-perturbing expression in Arabidopsis.Using this sensor,pathogen infection,non-adapted fungal challenge,and aphid feeding are shown to elicit spatially propagating SA surges rather than purely local accumulation,revealing a tissue-level organization of immune signaling that bulk assays could not resolve.SalicS1 therefore provides a broadly deployable tool for dissecting the geometry,timing,and genotype dependence of SA-mediated plant defense.
基金supported by Special Funding Projects for Local Science and Technology Development guided by the Central Committee(No.YDZJSX2022C028)the Fundamental Research Program of Shanxi Province(Nos.20210302123218 and 202203021211187)+4 种基金Innovation and Entrepreneurship Training Program for College Students in Shanxi Province(202210109006)the National Natural Science Foundation(52474367)the Key Research and Development for University-Local Government Collaboration of Lvliang City(2024XDHZ01)the Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi(2025Q022)the Foundation of State Key Laboratory of Advanced Metallurgy,USTB(K22-10).
文摘The structural changes in the CaO-SiO_(2)-Al_(2)O_(3)-MgO slag system with varying CaO contents were investigated through molecular dynamics(MD)simulations,and its effect on the dissolution behavior of alumina inclusions was characterized by the Kullback-Leibler(KL)divergence.The slag structure analysis revealed that the[AlO]tetrahedral structure was the primary network structure in the slag.With increasing the CaO content,the non-bridge oxygen(NBO)content in the slag structure increases,and the bridge oxygen(BO)content decreases,thereby reducing the complexity of the slag network structure.Raman spectroscopy detection verifies the results of the MD simulations.The results indicated that the dissolution rate of alumina inclusions accelerates with increasing the CaO content in the slag,owing to the reduced complexity of the slag network structure and the enhanced interatomic interactions.The simulation results for the dissolution of alumina inclusions were consistent with theoretical calculations based on the slag inclusion capacity and the dimensionless dissolution rate of inclusions.Radial distribution function analysis demonstrated that the interaction between atoms in the slag system and alumina inclusions strengthens,increasing the dissolution rate of alumina inclusions.The[AlO_(6)]octahedral structure of the alumina inclusions is disrupted,forming BO structures,which in turn enhances the complexity of the slag network structure,slowing the dissolution rate of alumina inclusions.In contrast,the slag system with a higher CaO content has a relatively simpler network structure,promoting faster alumina inclusion dissolution.
基金supported by the National Science Fund for Distinguished Young Scholars(No.52425404).
文摘This study investigates the influence of hydrogen concentration at grain boundaries on the sensitivity of polycrystalline iron to hydrogen embrittlement using molecular dynamics simulations.These simulations reveal the diffusion behavior of hydrogen atoms at grain boundaries and their consequential impact on the hydrogen embrittlement sensitivity of iron alloys.The findings indicate that as the hydrogen concentration increases,both the yield strength and ultimate tensile strength of Fe-H alloys exhibit a declining trend.Moreover,the capture of hydrogen atoms at the grain boundaries significantly influences the fracture toughness of the material and promotes the formation and propagation of cracks.This study provides a novel theoretical basis for understanding and predicting the hydrogen embrittlement behavior of iron-based materials in hydrogen-rich environments,offering valuable insights for the design and development of Fe alloys with enhanced resistance to hydrogen embrittlement.
基金Supported by the National Natural Science Foundation of China(Grant Nos.12393783,12302067,12172235,52072249)Joint Funds of the National Natural Science Foundation of China(Grant No.U24A2003)+3 种基金College Education Scientific Research Project of Hebei Province(Grant No.JZX2024006)Central Guiding Local Scientific and Technological Development Funding Project(Grant No.246Z2206G)the Key Research Project of China State Railway Group Co.,Ltd.(Grant No.N2024T009)S&T Program of Hebei(Grant No.21567622H).
文摘As China's high-speed railway technology advances,high-speed trains have emerged as a pivotal mode of transportation,instrumental in facilitating passenger and freight mobility while fostering robust regional eco-nomic and trade interactions.Nonetheless,the safety of train operations remains a paramount concern,prompting extensive research into the dynamic behavior of critical components,which is essential to ensuring seamless and secure transportation services.This article commences by comprehensively reviewing the current landscape and evolutionary trajectory of dynamic model analysis for both traditional bearings and axle box bearings.Emphasis is placed on elucidating the profound influence of diverse bearing fault types on the system's kinematic state,alongside delving into the research methodologies employed in developing multi-physics field coupling models.Subsequently,it expounds on the content of investigations focusing on various wheel and track impairments,grounded in the dynamic modeling of the bearing vehicle coupling system.Concurrently,the intricate interplay between wheel-rail excitation and axle box bearing faults on the system's performance is elucidated.Concludingly,the article underscores the inadequacy of current multi-source fault diagnosis meth-odologies in tackling the intricacies of complex train operating environments,thereby highlighting its sig-nificance as a pressing and vital research agenda for the future.
基金supported by National Natural Science Foundation of China(No.82404417)State Key Laboratory of National Security Specially Needed Medicines Program(No.LTMC2022Zz006).
文摘The von Hippel-Lindau tumor suppressor(VHL)has been extensively used to develop degraders targeting numerous proteins of interest.However,studies on the rational design of VHL-proteolysis-targeting chimeras(PROTACs)remain scarce.This study aimed to develop strategies to investigate VHL-recruiting PROTACs connecting with varying attachment sites on VHL ligands,which could be utilized for KRAS^(G12C) degraders development and expanded to additional targets.We developed a molecular dynamics(MD)-based strategy to explore the stability of ternary complexes induced by KRAS^(G12C) PROTACs with four distinct attachment sites of VH032.We found a potent degrader namely YN14-H,linked to hydroxyl group on VH032 benzene ring,exhibited the most superior ability of inducing ternary complexes,reflected by the lowest dissociation constant(Kd)for ternary complex induction and the highest AlphaScreen(AS)-based interaction.YN14-H inhibited cell growth with low nanomolar half maximal inhibitory concentration(IC_(50))and half maximal degradation concentration(DC_(50))values as well as>98%of maximum degradation(D_(max))in NCI-H358 and MIA PaCa-2 cells harboring KRAS^(G12C)-mutation.Mechanistically,YN14-H significantly induced apoptosis and inhibited the migratory capacity.Notably,YN14-H demonstrated favorable pharmacokinetic properties and excellent antitumor activity in vivo.Furthermore,bromodomain-containing protein 7(BRD7)and Bruton tyrosine kinase(BTK)degraders attached to distinct sites on VH032 further verified the rationality and universality of our MD-based strategies.Our findings demonstrated that YN14-H could serve as a promising candidate for the treatment of tumors with KRAS^(G12C)-mutation and present a strategy for the rational design of VHL-recruiting PROTACs that target additional proteins at distinct attachment sites.
基金financially supported by the National Natural Science Foundation of China(Nos.22473105 and 22341302).
文摘This study uses all-atom molecular dynamics simulations to investigate the dislocation propagation, stress transmission, and mechanical properties in poly(p-phenylene terephthalamide) fibers under uniaxial tension. The results indicate that the dislocation propagates and the stress transfers not only along the fiber axis but also between adjacent molecular chains through hydrogen bonds, demonstrating their influence on the yield behavior. As the degree of polymerization increases, breakage of covalent bonds and interchain slippage contribute to the yield of fibers together. This work provides theoretical guidance for the design and manufacturing of high-performance fibers.
基金funded by the Russian Science Foundation(RSF),grant No.25-73-20038(conceptualization,methodology,manuscript writing).
文摘Due to their chiral structure,carbon nanosprings possess unique properties that are promising for nanotechnology applications.The structural transformations of carbon nanosprings in the form of spiral macromolecules derived from planar coronene and kekulene molecules(graphene helicoids and spiral nanoribbons)are analyzed using molecular dynamics simulations.The interatomic interactions are described by a force field including valence bonds,bond angles,torsional and dihedral angles,as well as van derWaals interactions.While the tension/compression of such nanosprings has been analyzed in the literature,this study investigates other modes of deformation,including bending and twisting.Depending on the geometric characteristics of the carbon nanosprings,the formation of structural and helix reversal topological defects is described.During these structural transformations of the nanosprings,only van der Waals bonds break and recover,but breaking or recovery of covalent bonds does not take place.It is found that nanosprings demonstrate a significantly higher coefficient of axial thermal expansion than many metals and alloys.Under axial compression,Euler instability leads to lateral bending with continuous deformation of the nanospring axis at relatively low compression,while at high compression,bending kinks form.Various types of topological defects form on the instantly released nanospring during its relaxation from a highly stretched configuration.These results are useful for the development of nanosensors operating over a wide temperature range.
文摘In Chin.Phys.B 34114704(2025),Eq.(7)and the associated unit notation were incorrect.The correct ones are present here.Since Eq.(7)is an in-built expression in the simulation package,the correction is purely typographical and does not affect the simulation procedure,numerical results,or the conclusions.
基金supported by the National Key Research and Development Program of China(Grant No.2022YFF0707601).
文摘The airflow mechanics in adult nasal airways,whether healthy or abnormal,are extensively studied and investigated,but the flow mechanics in child nasal airways remain underexplored.This study investigates the airflow mechanics in the child’s nasal upper airway with adenoid hypertrophy,with an adenoid nasopharyngeal ratio(AN of 0.9),under cyclic inhalation and exhalation.An inlet respiratory cycle with three different flow rates(3.2 L/min calm breathing,8.6 L/min normal breathing,and 19.3 L/min intensive breathing)was simulated by using the computational fluid dynamics approach.To better capture the interaction between airflow and the flexible airway tissue,fluid-structure interaction analysis was performed at the normal breathing rate.Comparing the airflow dynamics during inhalation and exhalation,the pressure drops,nasal resistance,and wall shear stress show significant differences in the nasopharyngeal region for all different flow rates.This observation suggests that the inertial effect associated with the transient flow is important during exhalation and inhalation.Furthermore,the considerable temporal variation in flow rate distribution across a specific cross-section of the nasal airway highlights the critical role of transient data in virtual surgery planning and data for clinical decisions.
基金supported by the National Natural Science Foundation of China (Grant No.11574244 for G.Y.G.)the XJTU Research Fund for AI Science (Grant No.2025YXYC011 for G.Y.G.)the Hong Kong Global STEM Professorship Scheme (for X.C.Z.)。
文摘Compared to the well-studied two-dimensional(2D)ferroelectricity,the appearance of 2D antiferroelectricity is much rarer,where local dipoles from the nonequivalent sublattices within 2D monolayers are oppositely oriented.Using NbOCl_(2) monolayer with competing ferroelectric(FE)and antiferroelectric(AFE)phases as a 2D material platform,we demonstrate the emergence of intrinsic antiferroelectricity in NbOCl_(2) monolayer under experimentally accessible shear strain,along with new functionality associated with electric field-induced AFE-to-FE phase transition.Specifically,the complex configuration space accommodating FE and AFE phases,polarization switching kinetics,and finite temperature thermodynamic properties of 2D NbOCl_(2) are all accurately predicted by large-scale molecular dynamics simulations based on deep learning interatomic potential model.Moreover,room temperature stable antiferroelectricity with low polarization switching barrier and one-dimensional collinear polarization arrangement is predicted in shear-deformed NbOCl_(2) monolayer.The transition from AFE to FE phase in 2D NbOCl_(2) can be triggered by a low critical electric field,leading to a double polarization–electric(P–E)loop with small hysteresis.A new type of optoelectronic device composed of AFE-NbOCl_(2) is proposed,enabling electric“writing”and nonlinear optical“reading”logical operation with fast operation speed and low power consumption.
文摘Mitochondrial dysfunction has emerged as a critical factor in the etiology of various neurodevelopmental disorders, including autism spectrum disorders, attention-deficit/hyperactivity disorder, and Rett syndrome. Although these conditions differ in clinical presentation, they share fundamental pathological features that may stem from abnormal mitochondrial dynamics and impaired autophagic clearance, which contribute to redox imbalance and oxidative stress in neurons. This review aimed to elucidate the relationship between mitochondrial dynamics dysfunction and neurodevelopmental disorders. Mitochondria are highly dynamic organelles that undergo continuous fusion and fission to meet the substantial energy demands of neural cells. Dysregulation of these processes, as observed in certain neurodevelopmental disorders, causes accumulation of damaged mitochondria, exacerbating oxidative damage and impairing neuronal function. The phosphatase and tensin homolog-induced putative kinase 1/E3 ubiquitin-protein ligase pathway is crucial for mitophagy, the process of selectively removing malfunctioning mitochondria. Mutations in genes encoding mitochondrial fusion proteins have been identified in autism spectrum disorders, linking disruptions in the fusion-fission equilibrium to neurodevelopmental impairments. Additionally, animal models of Rett syndrome have shown pronounced defects in mitophagy, reinforcing the notion that mitochondrial quality control is indispensable for neuronal health. Clinical studies have highlighted the importance of mitochondrial disturbances in neurodevelopmental disorders. In autism spectrum disorders, elevated oxidative stress markers and mitochondrial DNA deletions indicate compromised mitochondrial function. Attention-deficit/hyperactivity disorder has also been associated with cognitive deficits linked to mitochondrial dysfunction and oxidative stress. Moreover, induced pluripotent stem cell models derived from patients with Rett syndrome have shown impaired mitochondrial dynamics and heightened vulnerability to oxidative injury, suggesting the role of defective mitochondrial homeostasis in these disorders. From a translational standpoint, multiple therapeutic approaches targeting mitochondrial pathways show promise. Interventions aimed at preserving normal fusion-fission cycles or enhancing mitophagy can reduce oxidative damage by limiting the accumulation of defective mitochondria. Pharmacological modulation of mitochondrial permeability and upregulation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha, an essential regulator of mitochondrial biogenesis, may also ameliorate cellular energy deficits. Identifying early biomarkers of mitochondrial impairment is crucial for precision medicine, since it can help clinicians tailor interventions to individual patient profiles and improve prognoses. Furthermore, integrating mitochondria-focused strategies with established therapies, such as antioxidants or behavioral interventions, may enhance treatment efficacy and yield better clinical outcomes. Leveraging these pathways could open avenues for regenerative strategies, given the influence of mitochondria on neuronal repair and plasticity. In conclusion, this review indicates mitochondrial homeostasis as a unifying therapeutic axis within neurodevelopmental pathophysiology. Disruptions in mitochondrial dynamics and autophagic clearance converge on oxidative stress, and researchers should prioritize validating these interventions in clinical settings to advance precision medicine and enhance outcomes for individuals affected by neurodevelopmental disorders.
基金support from the National Key R&D Program of China(Grant Nos.2023YFB3709900 and 2023YFB3709903)the National Natural Science Foundation of China(Grant Nos.52174293 and U22A20171)+1 种基金the High Steel Center(HSC)at North China University of TechnologyUniversity of Science and Technology Beijing(USTB).
文摘MgO has been shown to facilitate the precipitation of MgO-rich crystalline phases within the MgO-CaO-Al_(2)O_(3)-SiO_(2)(MCAS)glassy inclusion system,which possesses a high liquidus temperature and a significant Young’s modulus.The underlying linkage between the structural evolution and the crystallization characteristics of the MCAS system was systematically investigated using molecular dynamics simulation and thermodynamic calculation.The results revealed that Mg^(2+) ions played a dual role,constructing networks through the formation of tricluster oxygens while consuming bridging oxygens(BOs)in a mechanism similar to Ca^(2+) ions.However,despite this dual role,the network connectivity was still decreased with the increase in MgO/(MgO+Al_(2)O_(3))(M/(M+A))and CaO/(CaO+SiO_(2))(C/(C+S))ratios,primarily due to the reduction in BOs.This microscopic structural evolution resulted in a reduction in viscosity and an enhancement of crystallization ability.Furthermore,the remarkable diffusion capability of Mg^(2+) ions,coupled with the increased proportion of 6-coordinated Mg^(2+)ions,unveiled the mechanism underlying the precipitation of MgSiO_(3) and Mg_(2)SiO_(4) crystals,which exhibited high Young’s moduli of 165.23 and 196.67 GPa,respectively.To prevent the precipitation of MgO-rich crystalline phases,it was crucial to maintain the M/(M+A)ratio below 0.42 and the C/(C+S)ratio below 0.16 within the MCAS system.
