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Enhanced autophagic clearance of amyloid-βvia histone deacetylase 6-mediated V-ATPase assembly and lysosomal acidification protects against Alzheimer's disease in vitro and in vivo

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Neural Regeneration Research 2025年第9期20卷 2633-2644页

作者： Zhimin Long Chuanhua Ge Yueyang zhao Yuanjie Liu Qinghua Zeng Qing Tang Zhifang Dong Guiqiong He Institute of Neuroscience School of Basic Medical SciencesChongqing Medical UniversityChongqingChina department of Anatomy Chongqing Medical UniversityChongqingChina department of Physiology Chongqing Medical UniversityChongqingChina Pediatric Research Institute Children’s Hospital of Chongqing Medical UniversityChongqingChina Ministry of Education Key Laboratory of Child development and Disorders Children’s Hospital of Chongqing Medical UniversityChongqingChina National Clinical Research Center for Child Health and Disorders Children’s Hospital of Chongqing Medical UniversityChongqingChina Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders Children’s Hospital of Chongqing Medical UniversityChongqingChina

Recent studies have suggested that abnormal acidification of lysosomes induces autophagic accumulation of amyloid-βin neurons,which is a key step in senile plaque ***,resto ring normal lysosomal function and rebalancing lysosomal acidification in neurons in the brain may be a new treatment strategy for Alzheimer's *** acetylation/deacetylation plays a central role in lysosomal ***,we show that inhibiting the classic microtubule deacetylase histone deacetylase 6 with an histone deacetylase 6 shRNA or thehistone deacetylase 6 inhibitor valproic acid promoted lysosomal reacidification by modulating V-ATPase assembly in Alzheimer's *** rthermore,we found that treatment with valproic acid markedly enhanced *** clearance of amyloid-βaggregates,and ameliorated cognitive deficits in a mouse model of Alzheimer's *** findings demonstrate a previously unknown neuroprotective mechanism in Alzheimer's disease,in which histone deacetylase 6 inhibition by valproic acid increases V-ATPase assembly and lysosomal acidification.

关键词： Alzheimer's disease amyloid-β APP/PS1 mice autophagy cognitive impairment histone deacetylase 6 lysosomal acidification microtubule acetylation valproic acid V-ATPase

Salsolinol as an RNA m~6A methylation inducer mediates dopaminergic neuronal death by regulating YAP1 and autophagy

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Neural Regeneration Research 2025年第3期20卷 887-899页

作者： Jianan Wang Yuanyuan Ran Zihan Li Tianyuan zhao Fangfang Zhang Juan Wang Zongjian Liu Xuechai Chen Beijing International Science and Technology Cooperation Base for Antiviral Drugs College of Chemistry and LifeBeijing University of TechnologyBeijingChina department of Rehabilitation Beijing Rehabilitation HospitalCapital Medical UniversityBeijingChina

Salsolinol(1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline,Sal)is a catechol isoquinoline that causes neurotoxicity and shares structural similarity with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine,an environmental toxin that causes Parkinson's ***,the mechanism by which Sal mediates dopaminergic neuronal death remains *** this study,we found that Sal significantly enhanced the global level of N~6-methyladenosine(m~6A)RNA methylation in PC12 cells,mainly by inducing the downregulation of the expression of m~6A demethylases fat mass and obesity-associated protein(FTO)and alk B homolog 5(ALKBH5).RNA sequencing analysis showed that Sal downregulated the Hippo signaling *** m~6A reader YTH domain-containing family protein 2(YTHDF2)promoted the degradation of m~6A-containing Yes-associated protein 1(YAP1)mRNA,which is a downstream key effector in the Hippo signaling ***,downregulation of YAP1 promoted autophagy,indicating that the mutual regulation between YAP1 and autophagy can lead to *** findings reveal the role of Sal on m~6A RNA methylation and suggest that Sal may act as an RNA methylation inducer mediating dopaminergic neuronal death through YAP1 and *** results provide greater insights into the neurotoxic effects of catechol isoquinolines compared with other studies and may be a reference for assessing the involvement of RNA methylation in the pathogenesis of Parkinson's disease.

关键词： ALKBH5 autophagy FTO Hippo pathway m~6A Parkinson's disease RNA methylation salsolinol YAP1 YTHDF2

MXene Hybridized Polymer with Enhanced Electromagnetic Energy Harvest for Sensitized Microwave Actuation and Self‑Powered Motion Sensing

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Nano-Micro Letters 2025年第3期17卷 265-279页

作者： Yu‑Ze Wang Yu‑Chang Wang Ting‑Ting Liu Quan‑Liang zhao Chen‑Sha Li Mao‑Sheng Cao School of Materials Science and Engineering Beijing Institute of TechnologyBeijing 100081People’s Republic of China School of Materials Science and Engineering Peking UniversityBeijing 100871People’s Republic of China School of Mechanical and Material Engineering North China University of TechnologyBeijing 100144People’s Republic of China Key Laboratory of Functional Inorganic Material Chemistry Ministry of Education of the People’s Republic of ChinaHeilongjiang UniversityHarbin 150080People’s Republic of China

Polymeric microwave actuators combining tissue-like softness with programmablemicrowave-responsive deformation hold great promise for mobile intelligentdevices and bionic soft robots. However, their application is challenged by restricted electromagneticsensitivity and intricate sensing coupling. In this study, a sensitized polymericmicrowave actuator is fabricated by hybridizing a liquid crystal polymer with Ti3C2Tx(MXene). Compared to the initial counterpart, the hybrid polymer exhibits unique spacechargepolarization and interfacial polarization, resulting in significant improvements of230% in the dielectric loss factor and 830% in the apparent efficiency of electromagneticenergy harvest. The sensitized microwave actuation demonstrates as the shortenedresponse time of nearly 10 s, which is merely 13% of that for the initial shape memory polymer. Moreover, the ultra-low content of MXene (upto 0.15 wt%) benefits for maintaining the actuation potential of the hybrid polymer. An innovative self-powered sensing prototype that combinesdriving and piezoelectric polymers is developed, which generates real-time electric potential feedback (open-circuit potential of ~ 3 mV) duringactuation. The polarization-dominant energy conversion mechanism observed in the MXene-polymer hybrid structure furnishes a new approachfor developing efficient electromagnetic dissipative structures and shows potential for advancing polymeric electromagnetic intelligent devices.

关键词： Microwave absorption Electromagnetic response Energy harvest Self-sensing Soft actuator

Multifunctional Nacre‑Like Nanocomposite Papers for Electromagnetic Interference Shielding via Heterocyclic Aramid/MXene Template‑Assisted In‑Situ Polypyrrole Assembly

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Nano-Micro Letters 2025年第3期17卷 37-54页

作者： Jinhua Xiong Xu zhao Zonglin Liu He Chen Qian Yan Huanxin Lian Yunxiang Chen Qingyu Peng Xiaodong He National Key Laboratory of Science and Technology On Advanced Composites in Special Environments Center for Composite Materials and StructuresHarbin Institute of TechnologyHarbin 150080People’s Republic of China

Robust, ultra-flexible, and multifunctional MXene-basedelectromagnetic interference (EMI) shielding nanocomposite filmsexhibit enormous potential for applications in artificial intelligence,wireless telecommunication, and portable/wearable electronic *** this work, a nacre-inspired multifunctional heterocyclic aramid(HA)/MXene@polypyrrole (PPy) (HMP) nanocomposite paper withlarge-scale, high strength, super toughness, and excellent tolerance tocomplex conditions is fabricated through the strategy of HA/MXenehydrogel template-assisted in-situ assembly of PPy. Benefiting from the"brick-and-mortar" layered structure and the strong hydrogen-bondinginteractions among MXene, HA, and PPy, the paper exhibits remarkable mechanical performances, including high tensile strength (309.7 MPa),outstanding toughness (57.6 MJ m−3), exceptional foldability, and structural stability against ultrasonication. By using the template effect ofHA/MXene to guide the assembly of conductive polymers, the synthesized paper obtains excellent electronic conductivity. More importantly,the highly continuous conductive path enables the nanocomposite paper to achieve a splendid EMI shielding effectiveness (EMI SE) of 54.1 dBat an ultra-thin thickness (25.4 μm) and a high specific EMI SE of 17,204.7 dB cm2g−1. In addition, the papers also have excellent applicationsin electromagnetic protection, electro-/photothermal de-icing, thermal therapy, and fire safety. These findings broaden the ideas for developinghigh-performance and multifunctional MXene-based films with enormous application potential in EMI shielding and thermal management.

关键词： MXene Remarkable mechanical properties Heterocyclic aramid Electromagnetic interference shielding Polypyrrole Multifunctionality

Wall-modeled large eddy simulation for the flows around an axisymmetric body of revolution

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Journal of Hydrodynamics 2023年第2期35卷 199-209页

作者： Song-tao Chen Lu-chun Yang Wei-wen zhao de-cheng Wan Computational Marine Hydrodynamics Lab(CMHL) School of Naval ArchitectureOcean and Civil EngineeringShanghai Jiao Tong UniversityShanghai200240China Wuhan Second Ship design and Research Institute Wuhan430205China

The flow around an axisymmetric body of revolution(DARPA SUBOFF bare model)at Re=1.2×10^(7)is numerically investigated using the wall-modeled large eddy simulation(WMLES).To evaluate the capabilities of WMLES in such wall-bounded turbulent flows,the effects of the wall stress model and sampling distance are systematically *** numerical results of the non-equilibrium wall stress model with an appropriate sampling distance are in good agreement with the experiments in terms of pressure coefficient,skin-friction coefficient,and drag *** this basis,the thickening of the turbulent boundary layer and the expansion of the wake can be clearly observed through flow visualization,especially using the Liutex vortex identification method.

关键词： Wall-modeled large eddy simulation(WMLES) axisymmetric body of revolution wall stress model sampling distance Liutex SUBOFF

Numerical simulation of liquid sloshing in a spherical tank by MPS method

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Journal of Hydrodynamics 2024年第2期36卷 232-240页

作者： Cong-yi Huang Ji-fei Wang Wei-wen zhao de-cheng Wan Computational Marine Hydrodynamic Lab(CMHL) School of Naval ArchitectureOcean and Civil EngineeringShanghai Jiao Tong UniversityShanghai200240China Shanghai Aerospace System Engineering Institute Shanghai201109China

This paper investigates the sloshing phenomena in a spherical liquid tank using the moving particle semi-implicit(MPS)method,a crucial study in fluid *** from previous research focused on rectangular or LNG tanks,this work explores the unique motion patterns inherent to spherical *** accuracy of our in-house MPS solver MLParticle-SJTU is validated against experimental data and finite volume method(FVM).And the MPS method reveals a closer alignment with experimental outcomes,which suggests that MPS method is particularly effective for modeling complex,non-linear fluid *** the fluid’s response to excitation at its natural frequency is simulated,showcasing vigorous sloshing and rotational *** analyses of the fluid motion are conducted by drawing streamline diagrams,velocity vector diagrams,and vorticity *** fluid’s motion response is explored using both time-domain and frequency-domain curves of the fluid centroid,as well as the sloshing force.

关键词： Moving particle semi-implicit(MPS)method spherical tank liquid sloshing model experiment

Numerical investigation of the coupled aero-hydrodynamic performances of a semi-submersible floating offshore wind turbine with inclined columns

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Journal of Hydrodynamics 2024年第2期36卷 316-330页

作者： Ying-jie Xue Xiao-long Yang Wei-wen zhao de-cheng Wan Computational Marine Hydrodynamics Lab(CMHL) School of Naval ArchitectureOcean and Civil EngineeringShanghai Jiao Tong UniversityShanghai200240China Offshore Oil Engineering Co.Ltd. Tianjin300461China

Numerical investigations of floating platforms with different outer column inclined angles under two operating conditions of regular wave and irregular wave are presented in this paper.A coupled aero-hydrodynamic computational fluid dynamics in-house solver FOWT-UALM-SJTU is applied for the ***,the validation for wave and wind generation are conducted to determine mesh distribution *** on these,the hydrodynamic motion response,aerodynamic performance and wake flow are analyzed to explore the impact of inclined *** spectral analysis on the motion response under wave action,discuss the aerodynamic attack angle and inflow wind velocity along the blade spanwise direction in detail,reveal different trends in wake development and *** results show that for the regular wave condition with the increase of inclined angles,the equilibrium position of surge motion is constantly rising,while pitch is *** maximum root mean square(rms)value occurs at angle=30°,compared with the original OC4 FOWT,the rms in power and thrust increase 0.35%,0.71%.And there are two low regions of attack angle and high regions of axial inflow velocity,corresponding to aerodynamic *** spectral analysis indicates that the natural frequency of pitch motion will increase with inclined ***,from the middle to far region of wake flow,the velocity recovery of FOWT with inclined angle will become faster,which is beneficial for downstream turbines to enhance more wind energy.

关键词： Floating offshore wind turbine numerical simulation aero-hydrodynamic coupled analysis floating platform with inclinedcolumns wake flow recovery

Assessment of subgrid-scale models in wall-modeled large-eddy simulations of turbulent channel flows

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Journal of Hydrodynamics 2023年第3期35卷 407-416页

作者： Wei-wen zhao Fu-chang Zhou Guo-qing Fan de-cheng Wan Computational Marine Hydrodynamics Lab(CMHL) School of Naval ArchitectureOcean and Civil EngineeringShanghai Jiao Tong UniversityShanghai 200240China Wuhan Second Ship design and Research Institute Wuhan 430205China

Considering the demanding of grid requirements for high-Reynolds-number wall-bounded flow,the wall-modeled large-eddy simulation(WMLES)is an attractive method to deal with near wall ***,the effect of subgrid-scale(SGS)models for wall-bounded turbulent flow in combination with wall stress models is still *** this paper,turbulent channel flow at Reτ=1000 are numerically simulated by WMLES in conjunction with four different SGS models,i.e.,the wall-adapting local eddy-viscosity model,the dynamic Smagorinsky model,the dynamic SGS kinetic energy model and the dynamic Lagrangian *** mean velocity profiles are compared with the law of the wall,and the velocity fluctuations are compared with direct numerical simulation *** energy spectrum of velocity and wall pressure fluctuations are presented and the role of SGS models on predicting turbulent channel flow with WMLES is discussed.

关键词： Wall-modeled large-eddy simulation(WMLES) subgrid-scale(SGS)model turbulent channel flow energy spectra

Liutex force field model applied to three-dimensional flows around a circular cylinder at Re=3900

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Journal of Hydrodynamics 2021年第3期33卷 479-487页

作者： Wei-wen zhao Chun-hui Ma de-cheng Wan Yi-qian Wang Computational Marine Hydrodynamics Lab(CMHL) School of Naval ArchitectureOcean and Civil EngineeringShanghai Jiao Tong UniversityShanghai200240China Ocean College Zhejiang UniversityZhoushan316021China School of Mathematical Science Soochow UniversitySuzhou215006China

Recently,the Liutex-based force field models are proposed and applied to some two-dimensional flows to explore the possibility of direct vortex control *** this paper,we applied the Liutex-based centripetal force model to three-dimensional flow around a circular cylinder at Re=*** turbulent flows around the three-dimensional cylinder are modeled by the delayed detached-eddy simulations based on the two-equation k-ω shear stress transport(SST)*** cylinder flow without adding the force field model is simulated in the first *** statistical flow quantities are compared with experimental data to validate the accuracy of the current numerical *** the force field model is applied to the momentum equation in a specific control region near the cylinder to study the change of flow field and hydrodynamic *** effect of different control region locations with the same force field strength is discussed to find out the most influenced locations on the drag and *** on the screened control region,the influence source term strength is further *** on the global statistical flow quantities,local instantaneous three-dimensional flow structures are analyzed and *** is concluded that the Liutex-based force field model can effectively change the hydrodynamic behavior of flow past a cylinder and may provide a new direction for performance improvement and optimization.

关键词： Vortex manipulate flow control vortex shedding Liutex vector