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The complex effects of miR-146a in the pathogenesis of Alzheimer's disease

Neural Regeneration Research 2025年第5期20卷 1309-1323页

作者： Yunfan Long Jiajia Liu Yu wang Haidong Guo Guohong cui Department of Neurology Shanghai No.9 People’s HospitalShanghai Jiaotong University School of MedicineShanghaiChina Academy of Integrative Medicine Shanghai University of Traditional Chinese MedicineShanghaiChina school of Integrative Medicine Shanghai University of Traditional Chinese MedicineShanghaiChina Department of Neurology Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghaiChina

Alzheimer's disease is a neurodegenerative disorder characterized by cognitive dysfunction and behavioral *** plaques formed through the extracellular deposition of amyloid-βproteins,as well as neurofibrillary tangles formed by the intracellular deposition of hyperphosphorylated tau proteins,comprise two typical pathological features of Alzheimer's *** symptomatic treatment,there are no effective therapies for delaying Alzheimer's disease ***(miR)are small,non-coding RNAs that negatively regulate gene expression at the transcriptional and translational levels and play important roles in multiple physiological and pathological ***,miR-146a,a NF-κB-regulated gene,has been extensively implicated in the development of Alzheimer's disease through several *** has demonstrated substantial dysregulation of miR-146a both during the initial phases and throughout the progression of this *** R-146a is believed to reduce amyloid-βdeposition and tau protein hyperphosphorylation through the TLR/IRAK1/TRAF6 pathway;however,there is also evidence supporting that it can promote these processes through many other pathways,thus exacerbating the pathological manifestations of Alzheimer's *** has been widely reported that miR-146a mediates synaptic dysfunction,mitochondrial dysfunction,and neuronal death by targeting m RNAs encoding synapticrelated proteins,mitochondrial-related proteins,and membrane proteins,as well as other *** the impact on glial cells,miR-146a also exhibits differential *** one hand,it causes widespread and sustained inflammation through certain pathways,while on the other hand,it can reverse the polarization of astrocytes and microglia,alleviate neuroinflammation,and promote oligodendrocyte progenitor cell differentiation,thus maintaining the normal function of the myelin sheath and exerting a protective effect on *** this review,we provide a

关键词： Alzheimer's disease amyloid-β glial cells microRNAs miR-146a neuroinflammatory

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Comparative proteomic analysis of plasma exosomes reveals the functional contribution of N-acetyl-alpha-glucosaminidase to Parkinson’s disease

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Neural Regeneration Research 2025年第10期20卷 2998-3012页

作者： Yuan Zhao Yidan Zhang Xin Liu Jian Zhang Ya Gao shuyue Li cui Chang Xiang Liu Guofeng Yang Department of Geriatrics Second Hospital of Hebei Medical UniversityShijiazhuangHebei ProvinceChina Department of Neurosurgery The Second Hospital of Hebei Medical UniversityShijiazhuangHebei ProvinceChina

Parkinson’s disease is the second most common progressive neurodegenerative disorder,and few reliable biomarkers are available to track disease *** proteins,DNA,mRNA,and lipids carried by exosomes reflect intracellular changes,and thus can serve as biomarkers for a variety of *** this study,we investigated alterations in the protein content of plasma exosomes derived from patients with Parkinson’s disease and the potential therapeutic roles of these proteins in Parkinson’s *** a tandem mass tag-based quantitative proteomics approach,we characterized the proteomes of plasma exosomes derived from individual patients,identified exosomal protein signatures specific to patients with Parkinson’s disease,and identified N-acetyl-alpha-glucosaminidase as a differentially expressed protein.N-acetyl-alpha-glucosaminidase expression levels in exosomes from the plasma of patients and healthy controls were validated by enzyme-linked immunosorbent assay and western *** results demonstrated that the exosomal N-acetyl-alpha-glucosaminidase concentration was not only lower in Parkinson’s disease,but also decreased with increasing Hoehn-Yahr stage,suggesting that N-acetyl-alpha-glucosaminidase could be used to rapidly evaluate Parkinson’s disease ***,western blot and immunohistochemistry analysis showed that N-acetyl-alpha-glucosaminidase levels were markedly reduced both in cells treated with 1-methyl-4-phenylpyridinium and cells overexpressingα-synuclein compared with control ***,N-acetyl-alpha-glucosaminidase overexpression significantly increased cell viability and inhibitedα-synuclein expression in 1-methyl-4-phenylpyridinium-treated *** together,our findings demonstrate for the first time that exosomal N-acetyl-alpha-glucosaminidase may serve as a biomarker for Parkinson’s disease diagnosis,and that N-acetyl-alpha-glucosaminidase may reduceα-synuclein expression and 1-methyl-4-phenylpyridinium-induced n

关键词： biomarker diagnosis exosomes N-acetyl-alpha-glucosaminidase Parkinson’s disease proteomic α-synuclein

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Research status and prospects of the fractal analysis of metal material surfaces and interfaces

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International Journal of Minerals,Metallurgy and Materials 2025年第1期32卷 20-38页

作者： Qinjin Dai Xuefeng Liu Xin Ma shaojie Tian Qinghe cui Beijing Advanced Innovation Center for Materials Genome Engineering University of Science and Technology BeijingBeijing 100083China Beijing Laboratory of Metallic Materials and Processing for Modern Transportation University of Science and Technology BeijingBeijing 100083China Laboratory for Advanced Materials Processing of Ministry of Education University of Science and Technology BeijingBeijing 100083China school of Mechanical and Electrical Engineering Xinjiang Institute of EngineeringUrumqi 830023China

As a mathematical analysis method,fractal analysis can be used to quantitatively describe irregular shapes with self-similar or self-affine *** analysis has been used to characterize the shapes of metal materials at various scales and *** methods make it difficult to quantitatively describe the relationship between the regular characteristics and properties of metal material surfaces and ***,fractal analysis can be used to quantitatively describe the shape characteristics of metal materials and to establish the quantitative relationships between the shape characteristics and various properties of metal *** the perspective of two-dimensional planes and three-dimensional curved surfaces,this paper reviews the current research status of the fractal analysis of metal precipitate interfaces,metal grain boundary interfaces,metal-deposited film surfaces,metal fracture surfaces,metal machined surfaces,and metal wear *** relationship between the fractal dimensions and properties of metal material surfaces and interfaces is *** from three perspectives of fractal analysis,namely,research scope,image acquisition methods,and calculation methods,this paper identifies the direction of research on fractal analysis of metal material surfaces and interfaces that need to be *** is believed that revealing the deep influence mechanism between the fractal dimensions and properties of metal material surfaces and interfaces will be the key research direction of the fractal analysis of metal materials in the future.

关键词： metal material surfaces and interfaces fractal analysis fractal dimension homogeneity

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The cGAs-sTING-interferon regulatory factor 7 pathway regulates neuroinflammation in Parkinson's disease

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Neural Regeneration Research 2025年第8期20卷 2361-2372页

作者： shengyang Zhou Ting Li wei Zhang Jian wu Hui Hong wei Quan Xinyu Qiao Chun cui Chenmeng Qiao weijiang Zhao Yanqin shen Laboratory of Neurodegenerative and Neuroinjury Diseases Wuxi Medicine SchoolJiangnan UniversityWuxiJiangsu ProvinceChina

Interferon regulatory factor 7 plays a crucial role in the innate immune ***,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains *** we report that interferon regulatory factor 7 is markedly up-regulated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease and co-localizes with microglial *** the selective cyclic guanosine monophosphate adenosine monophosphate synthase inhibitor RU.521 and the stimulator of interferon genes inhibitor H151 effectively suppressed interferon regulatory factor 7 activation in BV2 microglia exposed to 1-methyl-4-phenylpyridinium and inhibited transformation of mouse BV2 microglia into the neurotoxic M1 *** addition,si RNA-mediated knockdown of interferon regulatory factor 7 expression in BV2 microglia reduced the expression of inducible nitric oxide synthase,tumor necrosis factorα,CD16,CD32,and CD86 and increased the expression of the anti-inflammatory markers ARG1 and *** together,our findings indicate that the cyclic guanosine monophosphate adenosine monophosphate synthase-stimulator of interferon genes-interferon regulatory factor 7 pathway plays a crucial role in the pathogenesis of Parkinson's disease.

关键词： cyclic guanosine monophosphate adenosine monophosphate synthase H151 interferon regulatory factor 7 M1 phenotype neurodegenerative disease neuroinflammation Parkinson’s disease RU521 sTING type I interferon

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Genistein:a possible solution for the treatment of Alzheimer’s disease

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Neural Regeneration Research 2025年第10期20卷 2903-2905页

作者： Karolina Pierzynowska Bartosz Karaszewski Grzegorz węgrzyn Department of Molecular Biology University of GdanskGdanskPoland Gdansk Polandand Department of Adult NeurologyFaculty of MedicineMedical University of GdanskGdanskPoland

Neurodegenerative diseases are defined as disorders resulting from the slow and progressive loss of function and eventual death of neural cells that result from the primary pathology of nervous *** can lead to severe nervous system dysfunction,eventually affecting multiple organs and *** hundred neurodegenerative diseases have been described,and owing to their prevalence,severity.

关键词： organs Alzheimer death

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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)

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Revisiting cerebral endothelial cells in Alzheimer’s disease

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Neural Regeneration Research 2025年第10期20卷 2911-2912页

作者： Amira s.Hanafy Department of Neurosurgery University Hospital BonnBonnGermany

Alzheimer’s disease(AD)is the most common neurodegenerative disorder characterized by slow and progressive decline of cognitive and memory *** only approximately 5%of the cases,AD is familial,as often predisposed by genetic mutations(Hoogmartens et al.,2021),while sporadic AD accounts for approximately 95%of the *** amyloid cascade hypothesis is one of the fundamental hypotheses put out to explain AD pathogenesis as dysregulated homeostasis of amyloid-β(Aβ)peptides that leads to the accumulation of Aβplaques in the parenchyma,an anatomical hallmark of AD.

关键词： Alzheimer Aβ cerebral

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Emerging structures and dynamic mechanisms ofγ-secretase for Alzheimer’s disease

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Neural Regeneration Research 2025年第1期20卷 174-180页

作者： Yinglong Miao Michael s.wolfe Computational Medicine Program and Department of Pharmacology University of North Carolina–Chapel HillChapel HillNCUSA Department of Medicinal Chemistry University of KansasLawrenceKSUSA

γ-secretase,called“the proteasome of the membrane,”is a membrane-embedded protease complex that cleaves 150+peptide substrates with central roles in biology and medicine,including amyloid precursor protein and the Notch family of cell-surface *** inγ-secretase and amyloid precursor protein lead to early-onset familial Alzheimer’s disease.γ-secretase has thus served as a critical drug target for treating familial Alzheimer’s disease and the more common late-onset Alzheimer’s disease as ***,critical gaps remain in understanding the mechanisms of processive proteolysis of substrates,the effects of familial Alzheimer’s disease mutations,and allosteric modulation of substrate cleavage byγ-*** this review,we focus on recent studies of structural dynamic mechanisms ofγ-*** mechanisms,including the“Fit-stay-Trim,”“sliding-Unwinding,”and“Tilting-Unwinding,”have been proposed for substrate proteolysis of amyloid precursor protein byγ-secretase based on all-atom molecular dynamics *** an incorrect registry of the Notch1 substrate was identified in the cryo-electron microscopy structure of Notch1-boundγ-secretase,molecular dynamics simulations on a resolved model of Notch1-boundγ-secretase that was reconstructed using the amyloid precursor protein-boundγ-secretase as a template successfully capturedγ-secretase activation for proper cleavages of both wildtype and mutant Notch,being consistent with biochemical experimental *** approach could be potentially applied to decipher the processing mechanisms of various substrates byγ-*** addition,controversy over the effects of familial Alzheimer’s disease mutations,particularly the issue of whether they stabilize or destabilizeγ-secretase-substrate complexes,is ***,an outlook is provided for future studies ofγ-secretase,including pathways of substrate binding and product release,effects of modulators on familial Alzheimer’s disease mutations

关键词： Alzheimer’s disease amyloid precursor protein cryo-EM structures drug design intramembrane proteolysis molecular dynamics Notch

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Complementary roles of glial cells in generating region-specific neuroinflammatory responses and phagocytosis in Parkinson’s disease

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Neural Regeneration Research 2025年第10期20卷 2917-2918页

作者： Leyre Ayerra Maria s.Aymerich Universidad de Navarra Facultad de CienciasDepartamento de Bioquímica y GenéticaPamplonaSpain CIMA-Universidad de Navarra PamplonaSpain IdisNA Instituto de Investigación Sanitaria de NavarraPamplonaSpain

Neuroinflammation is associated with Parkinson’s disease:Reactive gliosis and neuroinflammation are hallmarks of Parkinson’s disease(PD),a multisystem neurodegenerative disorder characterized by a progressive loss of dopaminergic *** has long been considered a mere consequence of neuronal loss,but whether it promotes PD or is a key player in disease progression remains to be *** leukocyte antigen.

关键词： inflammation leukocyte generating

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Geometrical reconstruction of fluorescence events observed by the LHAAsO experiment

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Chinese Physics C 2021年第4期45卷 416-425页

作者： F.Aharonian Q.An Axikegu L.X.Bai Y.X.Bai Y.w.Bao D.Bastieri X.J.Bi Y.J.Bi H.Cai J.T.Cai Z.Cao Z.Cao J.Chang J.F.Chang X.C.Chang B.M.Chen J.Chen L.Chen L.Chen L.Chen M.J.Chen M.L.Chen Q.H.Chen s.H.Chen s.Z.Chen T.L.Chen X.L.Chen Y.Chen N.Cheng Y.D.Cheng s.w.cui X.H.cui Y.D.cui B.Z.Dai H.L.Dai Z.G.Dai Danzengluobu D.della Volpe B.DEtorre Piazzoli X.J.Dong J.H.Fan Y.Z.Fan Z.X.Fan J.Fang J.Fang C.F.Feng L.Feng s.H.Feng Y.L.Feng B.Gao C.D.Gao Q.Gao w.Gao M.M.Ge L.s.Geng G.H.Gong Q.B.Gou M.H.Gu J.G.Guo X.L.Guo Y.Q.Guo Y.Y.Guo Y.A.Han H.H.He H.N.He J.C.He s.L.He X.B.He Y.He M.Heller Y.K.Hor C.Hou X.Hou H.B.Hu s.Hu s.C.Hu X.J.Hu D.H.Huang Q.L.Huang w.H.Huang X.T.Huang Z.C.Huang F.Ji X.L.Ji H.Y.Jia K.Jiang Z.J.Jiang C.Jin D.Kuleshov K.Levochkin B.B.Li C.Li C.Li F.Li H.B.Li H.C.Li H.Y.Li J.Li K.Li w.L.Li X.Li X.Li X.R.Li Y.Li Y.Z.Li Z.Li Z.Li E.w.Liang Y.F.Liang s.J.Lin B.Liu C.Liu D.Liu H.Liu H.D.Liu J.Liu J.L.Liu J.L.Liu J.s.Liu J.Y.Liu M.Y.Liu R.Y.Liu s.M.Liu w.Liu Y.N.Liu Z.X.Liu w.J.Long R.Lu H.K.Lv B.Q.Ma L.L.Ma X.H.Ma J.R.Mao A.Masood w.Mitthumsiri T.Montaruli Y.C.Nan B.Y..Pang P.Pattarakijwanich Z.Y.Pei M.Y.Qi D.Ruffolo V.Rulev A.saiz L.shao O.shchegolev X.D.sheng J.R.shi H.C.song Yu.V.stenkin V.stepanov Q.N.sun X.N.sun Z.B.sun P.H.T.Tam Z.B.Tang w.w.Tian B.D.wang C.wang H.wang H.G.wang J.C.wang J.s.wang L.P.wang L.Y.wang R.N.wang w.wang w.wang X.G.wang X.J.wang X.Y.wang Y.D.wang Y.J.wang Y.P.wang Z.wang Z.wang Z.H.wang Z.X.wang D.M.wei J.J.wei Y.J.wei T.wen C.Y.wu H.R.wu s.wu w.X.wu X.F.wu s.Q.Xi J.Xia J.J.Xia G.M.Xiang G.Xiao H.B.Xiao G.G.Xin Y.L.Xin Y.Xing D.L.Xu R.X.Xu L.Xue D.H.Yan C.w.Yang F.F.Yang J.Y.Yang L.L.Yang M.J.Yang R.Z.Yang s.B.Yang Y.H.Yao Z.G.Yao Y.M.Ye L.Q.Yin N.Yin X.H.You Z.Y.You Y.H.Yu Q.Yuan H.D.Zeng T.X.Zeng w.Zeng Z.K.Zeng M.Zha X.X.Zhai B.B.Zhang H.M.Zhang H.Y.Zhang J.L.Zhang J.w.Zhang L.Zhang L.Zhang L.X.Zhang P.F.Zhang P.F.Zhang R.Zhang s.R.Zhang s.s.Zhang X.Zhang X.P.Zhang Y.Zhang Y.Zhang Y.F.Zhang Y.L.Zhang B.Zhao J.Zhao L.Zhao L.Z.Zhao s.P.Zhao F.Zheng Y.Zheng B.Zhou H.Zhou J.N.Zhou P Key Laboratory of Particle Astrophyics&Experimental Physics Division&Computing Center Institute of High Energy PhysicsChinese Academy of SciencesBeijing 100049China University of Chinese Academy of sciences Beijing 100049China TIANFU Cosmic Ray Research Center ChengduSichuanChina state Key Laboratory of Paricle Detection and Electronics China University of science and Technology of China HefeiAnhui 230026China Department of Engineering Physics Tsinghua UniversityBeijing 100084China National Astronomical Observatories Chinese Academy of SciencesBeijing 100101China National space science Center Chinese Academy of SciencesBeijing 100190China school of Physics Peking UniversityBeijing 100871China Center for Astrophysics Guangzhou UniversityGuangzhouGuangdong 510006China school of Physics and Astronomy&school of Physics(Guangzhou) Sun Yat-sen UniversityZhuhaiGuangdong 519000China school of Physical science and Technology Guangxi UniversityNanningGuangxi 530004China Hebei Normal University ShijiazhuangHebei 050024China school of Physics and Microelectronics Zhengzhou UniversityZhengzhouHenan 450001China school of Astronomy and space science Nanjing UniversityNanjingJiangsu 210023China Key Laboratory of Dark Matter and space Astronomy Purple Mountain ObservatoryChinese Academy of SciencesNanjingJiangsu 210023China Institute of Frontier and Interdisciplinary science Shandong UniversityQingdaoShandong 266237China Key Laboratory for Research in Galaxies and Cosmology Shanghai Astronomical ObservatoryChinese Academy of SciencesShanghai 200030China Tsung-Dao Lee Institute&school of Physics and Astronomy Shanghai Jiao Tong UniversityShanghai 200240China school of Physical science and Technology Southwest Jiaotong UniversityChengduSichuan 610031China College of Physics Sichuan UniversityChengduSichuan 610065China Key Laboratory of Cosmic Rays(Tibet University) Ministry of EducationLhasaTibet 850000China school of physics and technology Wuhan UniversityWuhanHubei 430072Ch

The LHAAsO-wFCTA experiment,which aims to observe cosmic rays in the sub-EeV range using the fluorescence technique,uses a new generation of high-performance *** ensure that the experiment has ex-cellent detection capability associated with the measurement of the energy spectrum,the primary composition of cosmic rays,and so on,an accurate geometrical reconstruction of air-shower events is *** paper de-scribes the development and testing of geometrical reconstruction for stereo viewed events using the wFCTA(wide Field of view Cherenkov/Fluorescence Telescope Array)*** approaches,which take full advantage ofthe wFCTA *** *** is the stereo-angular method,which uses the pointing of triggered siPMs in the shower trajectory,and the other is the stereo-timing method,which uses the triggering time of the fired *** results show that both methods have good geometrical resolution:the resolution of the stereo-timing method is slightly better than the stereo-angular method because the resolution of the latter is slightly limited by the shower track length.

关键词： cosmic ray fluorescence telescope stereo observation geometrical reconstruction

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