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

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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

Epigenetic regulation of the inflammatory response in stroke

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Neural Regeneration Research 2025年第11期20卷 3045-3062页

作者： Jingyi liang Fei Yang Zixiao li Qian li School of Basic Medical Sciences Capital Medical UniversityBeijingChina Department of Neurobiology School of Basic Medical SciencesCapital Medical UniversityBeijingChina Laboratory for Clinical Medicine Beijing Key Laboratory of Neural Regeneration and RepairCapital Medical UniversityBeijingChina Department of Neurology Beijing Tiantan HospitalCapital Medical UniversityBeijingChina China National Clinical Research Center for Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina National Center for Healthcare Quality Management in Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Chinese Institute for Brain Research BeijingChina Research Unit of Artificial Intelligence in Cerebrovascular Disease Chinese Academy of Medical SciencesBeijingChina Beijing Engineering Research Center of Digital Healthcare for Neurological Diseases BeijingChina Department of Biochemistry and Molecular Biology School of Basic Medical SciencesCapital Medical UniversityBeijingChina Beijing Key Laboratory of Cancer Invasion and Metastasis Research Capital Medical UniversityBeijingChina

Stroke is classified as ischemic or hemorrhagic,and there are few effective treatments for either *** mechanisms play a critical role in secondary brain injury following a stroke,which manifests as cytokine release,blood–brain barrier disruption,neuronal cell death,and ultimately behavioral *** the inflammatory response has been shown to mitigate this cascade of events in experimental stroke ***,in clinical trials of anti-inflammatory agents,longterm immunosuppression has not demonstrated significant clinical benefits for *** may be attributable to the dichotomous roles of inflammation in both tissue injury and repair,as well as the complex pathophysiologic inflammatory processes in *** acute harmful inflammatory responses or inducing a phenotypic shift from a pro-inflammatory to an anti-inflammatory state at specific time points after a stroke are alternative and promising therapeutic *** agents that can modulate inflammation requires a detailed understanding of the inflammatory processes of ***,epigenetic reprogramming plays a crucial role in modulating post-stroke inflammation and can potentially be exploited for stroke *** this review,we summarize current findings on the epigenetic regulation of the inflammatory response in stroke,focusing on key signaling pathways including nuclear factor-kappa B,Janus kinase/signal transducer and activator of transcription,and mitogen-activated protein kinase as well as inflammasome *** also discuss promising molecular targets for stroke *** evidence to date indicates that therapeutic targeting of the epigenetic regulation of inflammation can shift the balance from inflammation-induced tissue injury to repair following stroke,leading to improved post-stroke outcomes.

关键词： DNA methylation histone modification intracerebral hemorrhage ischemic stroke neuroinflammation neuroprotection non-coding RNA RNA methylation subarachnoid hemorrhage treatment

Multilevel analysis of the central-peripheral-target organ pathway:contributing to recovery after peripheral nerve injury

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Neural Regeneration Research 2025年第10期20卷 2807-2822页

作者： Xizi Song Ruixin li Xiaolei Chu Qi li Ruihua li Qingwen li Kai-Yu Tong Xiaosong Gu Dong Ming Academy of Medical Engineering and Translational Medicine Tianjin UniversityTianjinChina Haihe Laboratory of Brain-Machine Interface and Human-Machine Fusion TianjinChina Department of Rehabilitation Tianjin University Tianjin HospitalTianjinChina Department of Hand Microsurgery Tianjin University Tianjin HospitalTianjinChina School of Exercise and Health Tianjin University of SportTianjinChina Department of Biomedical Engineering the Chinese University of Hong KongHong Kong Special Administrative RegionChina

Peripheral nerve injury is a common neurological condition that often leads to severe functional limitations and *** on the pathogenesis of peripheral nerve injury has focused on pathological changes at individual injury sites,neglecting multilevel pathological analysis of the overall nervous system and target *** has led to restrictions on current therapeutic *** this paper,we first summarize the potential mechanisms of peripheral nerve injury from a holistic perspective,covering the central nervous system,peripheral nervous system,and target *** peripheral nerve injury,the cortical plasticity of the brain is altered due to damage to and regeneration of peripheral nerves;changes such as neuronal apoptosis and axonal demyelination occur in the spinal *** nerve will undergo axonal regeneration,activation of Schwann cells,inflammatory response,and vascular system regeneration at the injury *** damage to target organs can occur,including skeletal muscle atrophy and sensory receptor *** then provide a brief review of the research advances in therapeutic approaches to peripheral nerve *** main current treatments are conducted passively and include physical factor rehabilitation,pharmacological treatments,cell-based therapies,and physical ***,most treatments only partially address the problem and cannot complete the systematic recovery of the entire central nervous system-peripheral nervous system-target organ ***,we should further explore multilevel treatment options that produce effective,long-lasting results,perhaps requiring a combination of passive(traditional)and active(novel)treatment methods to stimulate rehabilitation at the central-peripheral-target organ levels to achieve better functional recovery.

关键词： central nervous system central peripheral target organ multilevel pathological analysis nerve regeneration peripheral nerve injury peripheral nervous system target organs therapeutic approach

Nanostructured ZnO/BiVO_(4)I-scheme heterojunctions for piezocatalytic degradation of organic dyes via harvesting ultrasonic vibration energy

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International Journal of Minerals,Metallurgy and Materials 2025年第2期32卷 488-497页

作者： Yiling li Xiaoyao Yu Yingjie Zhou Yao lin Ying Wu Key Laboratory of the Ministry of Education for Advanced Catalysis Materials College of Chemistry and Materials ScienceZhejiang Normal UniversityJinhua 321004China

BiVO_(4)porous spheres modified by ZnO were designed and synthesized using a facile two-step *** resulting ZnO/BiVO_(4)composite catalysts have shown remarkable efficiency as piezoelectric catalysts for degrading Rhodamine B(RhB)unde mechanical vibrations,they exhibit superior activity compared to pure *** 40wt%ZnO/BiVO_(4)heterojunction composite displayed the highest activity,along with good stability and *** enhanced piezoelectric catalytic activity can be attributed to the form ation of an I-scheme heterojunction structure,which can effectively inhibit the electron-hole ***,hole(h+)and superoxide radical(·O_(2)^(-))are proved to be the primary active ***,ZnO/BiVO_(4)stands as an efficient and stable piezoelectric catalyst with broad potential application in the field of environmental water pollution treatment.

关键词： piezoelectric catalytic heterojunction dye degradation ultrasonic vibration

Engineering atomic Rb-N configurations to tune radical pathways for highly selective photocatalytic H2O2 synthesis coupled with biomass valorization

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Journal of Energy Chemistry 2025年第1期100卷 215-225页

作者： Jiaye li Shuang Pan Yihuang Chen Qiong liu College of Chemistry and Materials Engineering Wenzhou University Guangdong Provincial Key Laboratory of Chemical Measurement and Emergency Test Technology (China) Institute of Analysis Guangdong Academy of Sciences (China National Analytical CenterGuangzhou)

Photocatalytic oxygen reduction for hydrogen peroxide （H2O2） synthesis presents a green and costeffective production ***,achieving highly selective H2O2synthesis remains challenging,necessitating precise control over free radical reaction pathways and minimizing undesirable oxidative ***,we report for the visible light-driven simultaneous co-photocatalytic reduction of O2to H2O2and oxidation of biomass using the atomic rubidium-nitride modified carbon nitride（CNRb）.The optimized CNRb catalyst demonstrates a record photoreduction rate of 8.01 mM h-1for H2O2generation and photooxidation rate of 3.75 mM h-1for furfuryl alcohol to furoic acid,achieving a remarkable solar-to-chemical conversion （SCC） efficiency of up to 2.27%.Experimental characterizations and DFT calculation disclosed that the introducing atomic Rb–N configurations allows for the high-selective generation of superoxide radicals while suppressing hydroxyl free radical *** is because the Rb–N serves as the new alternative site to perceive a stronger connection position for O2adsorption and reinforce the capability to extract protons,thereby triggering a high selective redox product *** study holds great potential in precisely regulating reactive radical processes at the atomic level,thereby paving the way for efficient synthesis of H2O2coupled with biomass valorization.

关键词： Atomic economy Radical pathway regulation Rubidium atom coordination Biomass valorization

Effect of lamellarization on the microstructure and mechanical properties of marine 10Ni5CrMoV steel

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International Journal of Minerals,Metallurgy and Materials 2025年第2期32卷 402-413页

作者： Tao Zou Yanwu Dong Zhouhua Jiang Shuyang Du Yushuo li School of Metallurgy Northeastern UniversityShenyang 110819China Key Laboratory of Rolling and Automation Northeastern UniversityShenyang 110819China Key Laboratory for Ecological Metallurgy of Multimetallic Ores(Ministry of Education) Northeastern UniversityShenyang 110819China

Multistage heat treatment involving quenching(Q),lamellarizing(L),and tempering(T)is applied to marine 10Ni5CrMoV *** microstructure and mechanical properties were studied by multiscale characterizations,and the kinetics of reverse austenite transformation,strain hardening behavior,and toughening mechanism were further *** lamellarized specimens possess low yield strength but high toughness,especially cryogenic *** leads to the development of film-like reversed austenite at the martensite block and lath boundaries,refining the martensite structure and lowering the equivalent grain *** analysis of austenite reversion based on the JMAK model shows that the isothermal transformation is dominated by the growth of reversed austenite,and the maximum transformation of reversed austenite is reached at the peak temperature(750℃).The strain hardening behavior based on the modified Crussard-Jaoul analysis indicates that the reversed austenite obtained from lamellarization reduces the proportion of martensite,significantly hindering crack propagation via martensitic transformation during the *** a consequence,the QLT specimens exhibit high machinability and low yield *** with the QT specimen,the ductile-brittle transition temperature of the QLT specimens decreases from-116 to-130℃due to the low equivalent grain size and reversed austenite,which increases the cleavage force required for crack propagation and absorbs the energy of external load,*** work provides an idea to improve the cryogenic toughness of marine 10Ni5CrMoV steel and lays a theoretical foundation for its industrial application and comprehensive performance improvement.

关键词： 10Ni5CrMoV steel lamellarizing reversed austenite cryogenic toughness ductile-brittle transition temperature

Photo‑Energized MoS_(2)/CNT Cathode for High‑Performance li–CO_(2)Batteries in a Wide‑Temperature Range

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Nano-Micro Letters 2025年第1期17卷 160-175页

作者： Tingsong Hu Wenyi lian Kang Hu Qiuju li Xueliang Cui Tengyu Yao Laifa Shen Jiangsu Key Laboratory of Materials and Technologies for Energy Storage College of Materials Science and TechnologyNanjing University of Aeronautics and AstronauticsNanjing 210016People’s Republic of China

li–CO_(2) batteries are considered promising energy storage systems in extreme environments such as Mars;however,severe performance degradation will occur at a subzero temperature owning to the sluggish reaction ***,a photo-energized strategy adopting sustainable solar energy in wide working temperature range li–CO_(2) battery was achieved with a binder-free MoS_(2)/carbon nanotube(CNT)photo-electrode as *** unique layered structure and excellent photoelectric properties of MoS_(2) facilitate the abundant generation and rapid transfer of photo-excited carriers,which accelerate the CO_(2) reduction and li_(2)CO_(3) decomposition upon *** illuminated battery at room temperature exhibited high discharge voltage of 2.95 V and mitigated charge voltage of 3.27 V,attaining superior energy efficiency of 90.2%and excellent cycling stability of over 120 *** at an extremely low temperature of−30℃,the battery with same electrolyte can still deliver a small polarization of 0.45 V by the photoelectric and photothermal synergistic mechanism of MoS_(2)/CNT *** work demonstrates the promising potential of the photo-energized wide working temperature range li–CO_(2) battery in addressing the obstacle of charge overpotential and energy efficiency.

关键词： li-CO_(2)batteries Photo-energized Wide operation-temperature Kinetics MoS_(2)

p21和REST基因与肥大细胞诱导前列腺癌细胞神经内分泌分化的相关性研究

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国际泌尿系统杂志 2021年第5期41卷 785-789页

作者：李鸿杰王兰孙李斌郐海洋杭天昆李通义马志方山西医科大学第一医院泌尿外科太原030000 山西医科大学太原030000

目的初步探讨p21和元件-1沉默转录因子(REST)基因在肥大细胞诱导前列腺癌细胞出现神经内分泌分化过程中的表达变化及两者的相关性。方法利用孔径为0.4μm的TnmSWell小室将人前列腺癌细胞(PC-3)与肥大细胞(P815)进行共培养,倒置显微镜观... 详细信息

目的初步探讨p21和元件-1沉默转录因子(REST)基因在肥大细胞诱导前列腺癌细胞出现神经内分泌分化过程中的表达变化及两者的相关性。方法利用孔径为0.4μm的TnmSWell小室将人前列腺癌细胞(PC-3)与肥大细胞(P815)进行共培养,倒置显微镜观察PC-3细胞的形态变化;CCK-8实验及平板克隆形成实验检测诱导前后PC-3的细胞活性及增殖能力变化;实时荧光定ft PCK法(KT-qPCK)检测诱导前后PC-3细胞中神经内分泌标志物[突触素(SYP)、嗜铬蛋白A(CHGA)和神经元特异性烯醇化酶(NSE)]、p21、REST的mRNA表达变化:结果与P815细胞共培养后,PC-3细胞形态从梭形变为较长的、带有树突状结构的不规则形,且细胞间隙变大。CCK-8实验结果显示,PC-3+P815组细胞0D值低于PC-3组细胞(P<0.05),但是随着共培养时间的延长,PC-3+P815组细胞0D值先下降后上升。平板克隆形成实验结果显示,P815浓度为10^(4)/孔、共培养4 d的PC-3+P815组细胞克隆形成率低于PC-3组细胞(P<0.05)。RT-qPCR实验结果显示,P815浓度为10^(4)/孔、共培养4 d的PC-3+P815组细胞相对PC-3组细胞来说,NSE、SYP、CHGA表达显著上调(P<0.05),p21表达上调(P<0.05),KEST表达下调(P<0.05)。结论肥大细胞可能诱导前列腺癌细胞出现了神经内分泌分化,并且P21和REST基因与这一过程存在一定的相关性。

关键词：前列腺肿瘤肥大细胞 p21 REST 神经内分泌分化

Glutamatergic CYLD deletion leads to aberrant excitatory activity in the basolateral amygdala:association with enhanced cued fear expression

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Neural Regeneration Research 2025年第11期20卷 3259-3272页

作者： Huidong li Faqin li Zhaoyi Chen Erwen Wu Xiaoxi Dai Danni li Haojie An Shiyi Zeng Chunyan Wang li Yang Cheng Long School of life Sciences South China Normal UniversityGuangzhouGuangdong ProvinceChina School of life Sciences Guangzhou UniversityGuangzhouGuangdong ProvinceChina Guangdong Provincial Key Laboratory of Major Obstetric Diseases The Third Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina South China Normal University-Panyu Central Hospital Joint Laboratory of Translational Medical Research Panyu Central HospitalGuangzhouGuangdong ProvinceChina

Neuronal activity,synaptic transmission,and molecular changes in the basolateral amygdala play critical roles in fear ***(CYLD)is a deubiquitinase that negatively regulates the nuclear factor kappa-B *** is well studied in non-neuronal cells,yet underinvestigated in the brain,where it is highly *** studies have shown involvement of CYLD in the remodeling of glutamatergic synapses,neuroinflammation,fear memory,and anxiety-and autism-like ***,the precise role of CYLD in glutamatergic neurons is largely ***,we first proposed involvement of CYLD in cued fear *** next constructed transgenic model mice with specific deletion of Cyld from glutamatergic *** results show that glutamatergic CYLD deficiency exaggerated the expression of cued fear in only male ***,loss of CYLD in glutamatergic neurons resulted in enhanced neuronal activation,impaired excitatory synaptic transmission,and altered levels of glutamate receptors accompanied by over-activation of microglia in the basolateral amygdala of male ***,our study suggests a critical role of glutamatergic CYLD in maintaining normal neuronal,synaptic,and microglial *** may contribute,at least in part,to cued fear expression.

关键词： basolateral amygdala cued fear expression cylindromatosis deubiquitinase glutamate receptor 1 glutamatergic neuron microglial activation N-methyl-D-aspartate receptor 1 neuronal activation synaptic transmission