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Targeting epigenetic mechanisms in amyloid-β-mediated Alzheimer’s pathophysiology:unveiling therapeutic potential

Neural Regeneration Research 2025年第1期20卷 54-66页

作者： jennie z.li Nagendran Ramalingam Shaomin li Ann Romney Center for Neurologic Diseases Brigham and Women’s Hospital and Harvard Medical SchoolBostonMAUSA

Alzheimer’s disease is a prominent chronic neurodegenerative condition characterized by a gradual decline in memory leading to *** evidence suggests that Alzheimer’s disease is associated with accumulating various amyloid-βoligomers in the brain,influenced by complex genetic and environmental *** memory and cognitive deficits observed during the prodromal and mild cognitive impairment phases of Alzheimer’s disease are believed to primarily result from synaptic *** life,environmental factors can lead to enduring changes in gene expression and the emergence of brain *** changes,known as epigenetic modifications,also play a crucial role in regulating the formation of synapses and their adaptability in response to neuronal *** this context,we highlight recent advances in understanding the roles played by key components of the epigenetic machinery,specifically DNA methylation,histone modification,and microRNAs,in the development of Alzheimer’s disease,synaptic function,and activity-dependent synaptic ***,we explore various strategies,including enriched environments,exposure to non-invasive brain stimulation,and the use of pharmacological agents,aimed at improving synaptic function and enhancing long-term potentiation,a process integral to epigenetic ***,we deliberate on the development of effective epigenetic agents and safe therapeutic approaches for managing Alzheimer’s *** suggest that addressing Alzheimer’s disease may require distinct tailored epigenetic drugs targeting different disease stages or pathways rather than relying on a single drug.

关键词： Alzheimer’s disease DNA methylation enriched environments histone modification microRNAs non-invasive brain stimulation synaptic plasticity

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Anisotropic time-dependent behaviors of shale under direct shearing and associated empirical creep models

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Journal of Rock Mechanics and Geotechnical Engineering 2024年第4期16卷 1262-1279页

作者： Yachen Xie Michael z.Hou Hejuan liu Cunbao li Shenzhen Key Laboratory of Deep Engineering Sciences and Green Energy Shenzhen UniversityShenzhen518060China Institute of Subsurface Energy Systems Clausthal University of TechnologyClausthal-Zellerfeld38678Germany State Key Laboratory of Geomechanics and Geotechnical Engineering Institute of Rock and Soil MechanicsChinese Academy of SciencesWuhan430071China

Understanding the anisotropic creep behaviors of shale under direct shearing is a challenging *** this context,we conducted shear-creep and steady-creep tests on shale with five bedding orientations (i.e.0°,30°,45°,60°,and 90°),under multiple levels of direct shearing for the first *** results show that the anisotropic creep of shale exhibits a significant stress-dependent *** a low shear stress,the creep compliance of shale increases linearly with the logarithm of time at all bedding orientations,and the increase depends on the bedding orientation and creep *** high shear stress conditions,the creep compliance of shale is minimal when the bedding orientation is 0°,and the steady-creep rate of shale increases significantly with increasing bedding orientations of 30°,45°,60°,and 90°.The stress-strain values corresponding to the inception of the accelerated creep stage show an increasing and then decreasing trend with the bedding orientation.A semilogarithmic model that could reflect the stress dependence of the steady-creep rate while considering the hardening and damage process is *** model minimizes the deviation of the calculated steady-state creep rate from the observed value and reveals the behavior of the bedding orientation's influence on the steady-creep *** applicability of the five classical empirical creep models is quantitatively *** shows that the logarithmic model can well explain the experimental creep strain and creep rate,and it can accurately predict long-term shear creep *** on an improved logarithmic model,the variations in creep parameters with shear stress and bedding orientations are *** abovementioned findings,a mathematical method for constructing an anisotropic shear creep model of shale is proposed,which can characterize the nonlinear dependence of the anisotropic shear creep behavior of shale on the bedding orientation.

关键词： Rock anisotropy Direct shear creep Creep compliance Steady-creep rate Empirical model Creep constitutive model

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Stability Investigation and Improvement for DC Cascade Systems with Simplified Impedance-based Stability Criterion

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CSEE Journal of Power and Energy Systems 2024年第3期10卷 1044-1052页

作者： Junbin Fang zhikang Shuai Yang li zhibing Wang Xiangyang Wu Xia Shen z.John Shen College of Electrical and Information Engineering Hunan UniversityChangsha 410082China Renewable Energy Department of China Electric Power Research Institute Beijing 100192China Department of Electrical and Computer Engineering Illinois Institute of TechnologyChicagoIL 60616USA IEEE

In DC distributed power systems(DPSs),the complex impedance interactions possibly lead to DC bus voltage oscillation or *** previous research,the stability analysis of DPSs is implemented based on mathematical analysis in control *** specific mechanisms of the instability of the cascade system have not been intuitively *** this paper,the stability analysis of DPSs based on the traditional Nyquist criterion is simplified to the resonance analysis of the seriesconnected port impedance(z=R+jX)of source and load *** reveals that the essential reason for impedance instability of a DC cascade system is that the negative damping characteristic(Rlifies the internal resonance source at reactance zero-crossing *** simplified stability criterion for DC cascade systems can be concluded as:in the negative damping frequency ranges(Rzero-crossing point of the reactance component(i.e.,X=0).According to the proposed stability criterion,the oscillation modes of cascade systems are classified.A typical one is the internal impedance instability excited by the negative damping,and the other one is that the external disturbance amplified by negativity in a low stability ***,the impedance reshaping method for stability improvement of the system can be further *** validity of the simplified criterion is verified theoretically and experimentally by a positive damping reshaping method.

关键词： DC cascaded system,impedance model impedance reconstruction stability criterion

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Greatly enhanced corrosion/wear resistances of epoxy coating for Mg alloy through a synergistic effect between functionalized graphene and insulated blocking layer

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Journal of Magnesium and Alloys 2024年第1期12卷 332-344页

作者： z.Y.Xue X.J.li J.H.Chu M.M.li D.N.zou L.B.Tong School of Metallurgical Engineering Xi’an University of Architecture and TechnologyXi’an 710055China State Key Laboratory of Advanced Design and Manufacturing for Vehicle Body Hunan UniversityChangsha 410082China

The poor corrosion and wear resistances of Mg alloys seriously limit their potential applications in various *** conventional epoxy coating easily forms many intrinsic defects during the solidification process,which cannot provide sufficient *** the current study,we design a double-layer epoxy composite coating on Mg alloy with enhanced anti-corrosion/wear properties,via the spin-assisted assembly *** outer layer is functionalized graphene(FG)in waterborne epoxy resin(WEP)and the inner layer is Ce-based conversion(Ce)*** FG sheets can be homogeneously dispersed within the epoxy matrix to fill the intrinsic defects and improve the barrier *** Ce film connects the outer layer with the substrate,showing the transition *** corrosion rate of Ce/WEP/FG composite coating is 2131 times lower than that of bare Mg alloy,and the wear rate is decreased by~90%.The improved corrosion resistance is attributed to the labyrinth effect(hindering the penetration of corrosive medium)and the obstruction of galvanic coupling *** synergistic effect derived from the FG sheet and blocking layer exhibits great potential in realizing the improvement of multi-functional integration,which will open up a new avenue for the development of novel composite protection coatings of Mg alloys.

关键词： Mg alloy Functionalized graphene Epoxy coating Corrosion/wear resistance Blocking layer

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Microstructure evolution and shape memory behaviors of Ni_(47)Ti_(44)Nb_(9)alloy subjected to multistep thermomechanical loading with different prestrain levels

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Journal of Materials Science & Technology 2024年第4期171卷 80-93页

作者： Y.H.zhang H.li z.W.Yang X.liu Q.F.Gu State Key Laboratory of Solidification Processing School of Materials Science and EngineeringNorthwestern Polytechnical UniversityXi’an 710072China Shaanxi Key Laboratory of High-Performance Precision Forming Technology and Equipment Northwestern Polytechnical UniversityXi’an 710072China

Ni_(47)Ti_(44)Nb_(9)shape memory alloy(SMA)is a promising material in the aerospace field due to its wide transformation *** application of shape memory effect depends on multistep thermomechan-ical loading,viz.,low-temperature deformation and subsequent heating to ***-temperature deformation prestrain plays a pivotal role in shape memory properties tailoring of SMA ***,microstructure evolution and deformation mechanisms of Ni_(47)Ti_(44)Nb_(9)SMA subjected to vari-ous prestrain levels are still *** this end,microstructure evolution and shape memory behaviors of Ni_(47)Ti_(44)Nb_(9)alloy subjected to multistep thermomechanical loading with prestrain levels of 8%-16%at-28℃(M_(s)+30℃)were *** results demonstrate that the stress-strain curve of the specimen exhibits four distinct stages at a maximal prestrain of 16%.Whereas stageⅡand stageⅢend at prestrains of∼8%and∼12%,*** stageⅡ,the stress-induced martensitic transformation is accompanied by the dislocation slip of the NiTi matrix andβ-Nb *** stageⅢ,in addition to the higher density of dislocations and further growth of stress-induced martensite variants(SIMVs),(001)compound twins are introduced as a result of the(001)deformation twinning in stress-induced ***{20-1}martensite twins are gradually introduced in stageⅣ.Correspondingly,after subsequent unloading and heating,a higher density of{114}austenite twins form in the specimen with a larger prestrain of 16%.With increasing prestrain from 8%to 16%,the recoverable strainε_(re)^(T)upon heating increases first and then ***ε_(re)^(T)obtains a maximum of 7.03%at 10%prestrain and de-creases to 6.17%at 16%*** increase ofε_(re)^(T)can be attributed to the formation of new SIMVs,the further growth of existing SIMVs,and the recoverable(001)compound *** the decrease ofε_(re)^(T)is mainly associated with the irrecoverable strain by{20−1}martensite *** effe

关键词： Ni_(47)Ti_(44)Nb_(9)shape memory alloy Wide transformation hysteresis Thermomechanical loading Microstructure evolution Shape memory behaviors Stress-induced martensitic transformation Deformation twinning

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Electromagnetic Performance Analysis of Variable Flux Memory Machines with Series-magnetic-circuit and Different Rotor Topologies

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CES Transactions on Electrical Machines and Systems 2024年第1期8卷 3-11页

作者： Qiang Wei z.Q.zhu Yan Jia Jianghua Feng Shuying Guo Yifeng li Shouzhi Feng Department of Electronic and Electrical Engineering The University of SheffieldSheffield S13JDU.K. IEEE the CRRC zhuzhou Institute Company Ltd. Zhuzhou 412001China

In this paper,the electromagnetic performance of variable flux memory(VFM)machines with series-magnetic-circuit is investigated and compared for different rotor *** on a V-type VFM machine,five topologies with different interior permanent magnet(IPM)arrangements are evolved and optimized under same *** on two-dimensional(2-D)finite element(FE)method,their electromagnetic performance at magnetization and demagnetization states is *** reveals that the iron bridge and rotor lamination region between constant PM(CPM)and variable PM(VPM)play an important role in torque density and flux regulation(FR)***,the global efficiency can be improved in VFM machines by adjusting magnetization state(MS)under different operating conditions.

关键词： Memory machine Permanent magnet Rotor topologies Series magnetic circuit Variable flux

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RNA modifications in the progression of liver diseases: from fatty liver to cancer

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Science China life Sciences 2024年

作者： Simiao li Wajahat z Mehal Xinshou Ouyang Yale University School of Medicine Section of Digestive Diseases Department of Internal Medicine

Non-alcoholic fatty liver disease (NAFLD) has emerged as a prominent global health concern associated with high risk of metabolic syndrome, and has impacted a substantial segment of the population. The disease spectrum ranges from simple fatty liver to non-alcoholic steatohepatitis (NASH), which can progress to cirrhosis and hepatocellular carcinoma (HCC) and is increasingly becoming a prevalent indication for liver transplantation. The existing therapeutic options for NAFLD, NASH, and HCC are limited, underscoring the urgent need for innovative treatment strategies. Insights into gene expression, particularly RNA modifications such as N6methyladenosine (m6A), hold promising avenues for interventions. These modifications play integral roles in RNA metabolism and cellular functions, encompassing the entire NAFLD-NASH-HCC progression. This review will encompass recent insights on diverse RNA modifications, including m6A, pseudouridine (Ψ), N1-methyladenosine (m1A), and 5-methylcytidine (m5C) across various RNA species. It will uncover their significance in crucial aspects such as steatosis, inflammation, fibrosis, and tumorigenesis. Furthermore, prospective research directions and therapeutic implications will be explored, advancing our comprehensive understanding of the intricate interconnected nature of these pathological conditions.

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Fast efficient photon deceleration in plasmas by using two laser pulses at different frequencies

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Matter and Radiation at Extremes 2024年第3期9卷 11-18页

作者： Y.X.Wang X.L.zhu S.M.Weng P.li X.F.li H.Ai H.R.Pan z.M.Sheng Key Laboratory for Laser Plasmas(moe) School of Physics and AstronomyShanghai Jiao Tong UniversityShanghai 200240China Collaborative Innovation Center of IFSA Shanghai Jiao Tong UniversityShanghai 200240China Research Center of Laser Fusion of China Academy of Engineering Physics MianyangSichuan 621900China State key Laboratory of High Field Laser Physics Shanghai Institute of Optics and Fine MechanicsChinese Academy of SciencesShanghai 201800China Tsung-dao Lee Institute Shanghai Jiao Tong UniversityShanghai 200240China

The generation of ultrashort high-power light sources in the mid-infrared(mid-IR)to terahertz(THz)range is of interest for applications in a number of fields,from fundamental research to biology and *** conventional laser technology,photon deceleration in plasma wakes provides an alternative approach to the generation of ultrashort mid-IR or THz ***,we present a photon deceleration scheme for the efficient generation of ultrashort mid-IR or THz pulses by using an intense driver laser pulse with a relatively short wavelength and a signal laser pulse with a relatively long *** signal pulse trails the driver pulse with an appropriate time delay such that it sits at the front of the second wake bubble that is driven by the driver *** to its relatively long wavelength,the signal pulse will be subjected to a large gradient of the refractive index in the plasma wake ***,the photon deceleration in the plasma wake becomes faster and more efficient for signal pulses with longer *** greatly enhances the capacity and efficiency of photon deceleration in the generation of ultrashort high-power light sources in the long-wavelength IR and THz spectral ranges.

关键词： laser ultrashort photon

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Effects of friction stir processing and nano-hydroxyapatite on the microstructure,hardness,degradation rate and in-vitro bioactivity of WE43 alloy for biomedical applications

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Journal of Magnesium and Alloys 2024年第1期12卷 209-224页

作者： Bo Wu Farazila Yusof Fuguo li Huan Miao A.R.Bushroa Mohd Ridha Bin Muhamad Irfan Anjum Badruddin Mahmoud z.Ibrahim Department of Mechanical Engineering Faculty of EngineeringUniversiti MalayaKuala Lumpur 50603Malaysia Centre of Advanced Manufacturing and Material Processing(AMMP Centre) Universiti MalayaKuala Lumpur 50603Malaysia Center of Foundation studies in Science Universiti MalayaKuala Lumpur 50603Malaysia State Key Laboratory of Solidification Processing School of Materials Science and EngineeringNorthwestern Polytechnical UniversityXi’an 710072China Mechanical Engineering Department College of EngineeringKing Khalid UniversityAbha 61421Saudi Arabia Design and Production Engineering Faculty of EngineeringAin Shams UniversityCairo 11517Egypt

Nowadays,magnesium alloys are emerging in biomedical implants for their similar properties to natural ***,the rapid degradation of magnesium alloys in biological media hinders successful *** of microstructure,as well as reinforcement particles can significantly improve the degradation *** this work,multi-pass friction stir processing(FSP)was proposed to synthesize WE43/nano-hydroxyapatite(n HA)surface composite,the microstructure,reinforced particle distribution,micro-hardness,corrosion behavior and in-vitro bioactivity were *** subsequent FSP passes of WE43 alloy and WE43/n HA composite refined the grain size which was reduced by 94.29%and 95.92%(2.63 and 1.88μm,respectively)compared to base metal after three *** resulted in increasing the microhardness by 120%(90.86 HV0.1)and 135%(105.59 HV0.1)for the WE43 and WE43-n HA,*** is found that increasing FSP passes improved the uniform distribution of n HA particles within the composite matrix which led to improved corrosion resistance and less degradation *** corrosion rate of the FSPed WE43/n HA composite after three passes was reduced by 38.2%(4.13 mm/year)and the degradation rate was reduced by 69.7%(2.87 mm/y).This is attributed to secondary phase(Mg24Y5and Mg41Nd5)particle fragmentation and redistribution,as well as a homogeneous distribution of n ***,the growing Ca-P and Mg(OH)2layer formed on the surface represented a protective layer that reduced the degradation *** wettability test revealed a relatively hydrophilic surface with water contact angle of 49.1±2.2°compared to 71.2±2.1°for base ***,biomineralization test showed that apatite layer grew after immersion 7d in simulated body fluid with atomic ratio of Ca/P 1.60 approaching the stoichiometric ratio(1.67)indicating superior bioactivity of FSPed WE43/n HA composite after three *** results raise that the grain refinement by FSP and introduction of n HA partic

关键词： Friction stir processing Magnesium-based composite Nano-hydroxyapatite Corrosion behavior In-vitro bioactivity

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Optical redox imaging of ANT1-de-cient muscles

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Journal of Innovative Optical Health Sciences 2024年第1期17卷 135-140页

作者： He N.Xu Ryan M.Morrow Min Feng Huaqing zhao Douglas Wallace lin z.li Britton Chance Laboratory of Redox Imaging Department of Radiology Perelman School of Medicine University of Pennsylvania PhiladelphiaPA 19104USA Center for Mitochondrial and Epigenomic Medicine Children's Hospital of Philadelphia Research Institute Philadelphia PA 19104USA Center for Biostatistics and Epidemiology Lewis Katz School of Medicine at Temple University Philadelphia PA 19140USA

Adenine nucleotide translocator(ANT)is a mitochondrial protein involved in the exchange of ADP and ATP across the mitochondrial inner *** plays a crucial role in cellular energy metabolism by facilitating the transport of ATP synthesized within the mitochondria to the *** isoform ANT1 predominately expresses in cardiac and skeletal *** or dysregulation in ANT1 have been implicated in various mitochondrial disorders and neuromuscular *** aimed to examine whether ANT1 deletion may affect mitochondrial redox state in our established ANT1-de-cient *** and quadriceps resected from age-matched wild type(WT)and ANT1-de-cient mice were snap-frozen in liquid *** Chance redox scanner was utilized to perform 3D optical redox *** sample underwent scanning across 3–5 *** averaging analysis showed no signi-cant differences in the redox indices(NADH,flavin adenine dinucleotide containing-flavoproteins Fp,and the redox ratio Fp/(NADH+Fp)between WT and ANT1-de-cient ***,quadriceps had higher Fp than hearts in both groups(p¼0:0004 and 0.01,respectively).Furthermore,the quadriceps were also more oxidized(a higher redox ratio)than hearts in WT group(p¼0:004).NADH levels were similar in all *** data suggest that under non-stressful physical condition,the ANT1-de-cient muscle cells were in the same mitochondrial state as WT ones and that the signi-cant difference in the mitochondrial redox state between quadriceps and hearts found in WT might be diminished in ANT1-de-cient *** imaging of muscles under physical stress can be conducted in future.

关键词： ANT1 redox ratio flavoproteins

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