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Toward understanding the role of genomic repeat elements in neurodegenerative diseases

Neural Regeneration Research 2025年第3期20卷 646-659页

作者： Zhengyu An Aidi Jiang Jingqi Chen Institute of Science and Technology for Brain-Inspired Intelligence Fudan UniversityShanghaiChina MOE Frontiers center for Brain Science Fudan UniversityShanghaiChina MOE Key Laboratory of computational Neuroscience and Brain-Inspired Intelligence Fudan UniversityShanghaiChina Zhangjiang Fudan International Innovation center ShanghaiChina

Neurodegenerative diseases cause great medical and economic burdens for both patients and society;however, the complex molecular mechanisms thereof are not yet well understood. With the development of high-coverage sequencing technology, researchers have started to notice that genomic repeat regions, previously neglected in search of disease culprits, are active contributors to multiple neurodegenerative diseases. In this review, we describe the association between repeat element variants and multiple degenerative diseases through genome-wide association studies and targeted sequencing. We discuss the identification of disease-relevant repeat element variants, further powered by the advancement of long-read sequencing technologies and their related tools, and summarize recent findings in the molecular mechanisms of repeat element variants in brain degeneration, such as those causing transcriptional silencing or RNA-mediated gain of toxic function. Furthermore, we describe how in silico predictions using innovative computational models, such as deep learning language models, could enhance and accelerate our understanding of the functional impact of repeat element variants. Finally, we discuss future directions to advance current findings for a better understanding of neurodegenerative diseases and the clinical applications of genomic repeat elements.

关键词： Alzheimer's disease ataxia deep learning long-read sequencing neurodegeneration neurodegenerative diseases Parkinson's disease repeat element structural variant

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A low redox potential and long life organic anode material for sodium-ion batteries

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Journal of Energy chemistry 2025年第1期100卷 557-564页

作者： Zhi Li Yang Wei Kang Zhou Xin Huang Xing Zhou Jie Xu Taoyi Kong Junwei Lucas Bao Xiaoli Dong Yonggang Wang Department of chemistry and shanghai Key Laboratory of Molecular Catalysis and Innovative Materials Institute of New Energy Collaborative Innovation Center of Chemistry for Energy Materials (iChEM) Fudan University Department of chemistry Boston College School of Materials Science and Engineering Anhui University of Technology

Sodium-ion batteries （SIBs） with organic electrodes are an emerging research direction due to the sustainability of organic materials based on elements like C,H,O,and sodium ***,organic electrode materials for SIBs are mainly used as cathodes because of their relatively high redox potentials（>1 V）.Organic electrodes with low redox potential that can be used as anode are ***,a novel organic anode material （tetrasodium 1,4,5,8-naphthalenetetracarboxylate,Na4TDC） has been developed with low redox potential （<0.7 V） and excellent cyclic *** three-sodium storage mechanism was demonstrated with various in-situ/ex-situ spectroscopy and theoretical calculations,showing a high capacity of 208 mAh/g and an average decay rate of merely 0.022%per ***,the Na4TDC-hard carbon composite can further acquire improved capacity and cycling stability for 1200 cycles even with a high mass loading of up to 20 mg *** pairing with a thick Na3V2（PO4）3cathode (20.6 mg cm-2),the as-fabricated full cell exhibited high operating voltage （2.8 V）,excellent rate performance and cycling stability with a high capacity retention of 88.7% after 200 cycles,well highlighting the Na4TDC anode material for SIBs.

关键词： Organic anode material Low redox potential Composite anode Sodium-ion batteries

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Reaction Mechanism and Product Branching Ratios of OH+C2H3F Reaction:A Theoretical Study

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Chinese Journal of Chemical Physics 2020年第2期33卷 203-209,I0003页

作者： Chih-Hao Chin Tong Zhu John Zeng-Hui Zhang School of chemistry and Molecular Engineering East China Normal UniversityShanghai 200062China nyu-ecnu center for computational chemistry at nyu shanghai Shanghai 200062China Department of chemistry New York UniversityNew York 10003United States of America

Ab initio CCSD(T)/CBS//B3LYP/6-311G(d,p)calculations of the potential energy surface for possible dissociation channels of HOC2H3F,as well as Rice-Ramsperger-Kassel-Marcus(RRKM)calculations of rate constants,were carried out,in order to predict statistical product branching ratios in dissociation of HOC2H3F at various internal *** most favorable reaction pathway leading to the major CH2CHO+HF products is as the following:OH+C2H3F→i2→TS14→i6→TS9→i3→TS3→CH2CHO+HF,where the rate-determining step is HF elimination from the CO bridging position via TS11,lying above the reactants by 3.8 kcal/*** CH2O+CH2F products can be formed by F atom migration from Cαto Cβposition via TS14,then H migration from O to Cαposition via TS16,and C-C breaking to form the products via TS5,which is 1.8 kcal/mol lower in energy than the reactants,and 4.0 kcal/mol lower than TS11.

关键词： Ab initio Potential energy surface Reaction mechanism Rice-Ramsperger-Kassel-Marcus Branching ratio

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Establishment of human cerebral organoid systems to model early neural development and assess the central neurotoxicity of environmental toxins

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Neural Regeneration Research 2025年第1期20卷 242-252页

作者： Daiyu Hu Yuanqing Cao Chenglin Cai Guangming Wang Min Zhou Luying Peng Yantao Fan Qiong Lai Zhengliang Gao Fundamental Research center Shanghai Yangzhi Rehabilitation Hospital(Shanghai Sunshine Rehabilitation Center)School of MedicineTongji UniversityShanghaiChina Institute of Geriatrics(shanghai University) Affiliated Nantong Hospital of Shanghai University(The Sixth People’s Hospital of Nantong)Shanghai University School of MedicineNantongJiangsu ProvinceChina shanghai Engineering Research center of Organ Repair Shanghai University School of MedicineShanghaiChina Key Laboratory of Arrhythmias Ministry of EducationShanghai East HospitalSchool of MedicineTongji UniversityShanghaiChina

Human brain development is a complex process,and animal models often have significant *** address this,researchers have developed pluripotent stem cell-derived three-dimensional structures,known as brain-like organoids,to more accurately model early human brain development and *** enable more consistent and intuitive reproduction of early brain development,in this study,we incorporated forebrain organoid culture technology into the traditional unguided method of brain organoid *** involved embedding organoids in matrigel for only 7 days during the rapid expansion phase of the neural epithelium and then removing them from the matrigel for further cultivation,resulting in a new type of human brain organoid *** cerebral organoid system replicated the temporospatial characteristics of early human brain development,including neuroepithelium derivation,neural progenitor cell production and maintenance,neuron differentiation and migration,and cortical layer patterning and formation,providing more consistent and reproducible organoids for developmental modeling and toxicology *** a proof of concept,we applied the heavy metal cadmium to this newly improved organoid system to test whether it could be used to evaluate the neurotoxicity of environmental *** organoids exposed to cadmium for 7 or 14 days manifested severe damage and abnormalities in their neurodevelopmental patterns,including bursts of cortical cell death and premature *** exposure caused progressive depletion of neural progenitor cells and loss of organoid integrity,accompanied by compensatory cell proliferation at ectopic *** convenience,flexibility,and controllability of this newly developed organoid platform make it a powerful and affordable alternative to animal models for use in neurodevelopmental,neurological,and neurotoxicological studies.

关键词： cadmium cell death cell proliferation cortical development environmental toxins neural progenitor cells neurogenesis neurotoxicology organoids stem cells

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Peripheral mitochondrial DNA as a neuroinflammatory biomarker for major depressive disorder

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Neural Regeneration Research 2025年第6期20卷 1541-1554页

作者： Jinmei Ye Cong Duan Jiaxin Han Jinrong Chen Ning Sun Yuan Li Tifei Yuan Daihui Peng Division of Mood Disorder Shanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghaiChina Department of Psychiatry First Hospital of Shanxi Medical UniversityTaiyuanShanxi ProvinceChina shanghai Key Laboratory of Psychotic Disorders Brain Health InstituteNational Center for Mental DisordersShanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghaiChina Co-Innovation center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina

In the pathogenesis of major depressive disorder, chronic stress-related neuroinflammation hinders favorable prognosis and antidepressant response. Mitochondrial DNA may be an inflammatory trigger, after its release from stress-induced dysfunctional central nervous system mitochondria into peripheral circulation. This evidence supports the potential use of peripheral mitochondrial DNA as a neuroinflammatory biomarker for the diagnosis and treatment of major depressive disorder. Herein, we critically review the neuroinflammation theory in major depressive disorder, providing compelling evidence that mitochondrial DNA release acts as a critical biological substrate, and that it constitutes the neuroinflammatory disease pathway. After its release, mitochondrial DNA can be carried in the exosomes and transported to extracellular spaces in the central nervous system and peripheral circulation. Detectable exosomes render encaged mitochondrial DNA relatively stable. This mitochondrial DNA in peripheral circulation can thus be directly detected in clinical practice. These characteristics illustrate the potential for mitochondrial DNA to serve as an innovative clinical biomarker and molecular treatment target for major depressive disorder. This review also highlights the future potential value of clinical applications combining mitochondrial DNA with a panel of other biomarkers, to improve diagnostic precision in major depressive disorder.

关键词： biomarker cytokine exosomes inflammasome major depressive disorder microglia mitochondrial DNA mitochondrial dysfunction neuroinflammation Toll-like receptor

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Recent progress in the applications of presynaptic dopaminergic positron emission tomography imaging in parkinsonism

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Neural Regeneration Research 2025年第1期20卷 93-106页

作者： Yujie Yang Xinyi Li Jiaying Lu Jingjie Ge Mingjia Chen Ruixin Yao Mei Tian Jian Wang Fengtao Liu Chuantao Zuo Key Laboratory of Arrhythmias Ministry of EducationDepartment of Medical GeneticsShanghai East HospitalSchool of MedicineTongji UniversityShanghaiChina Department of Neurology National Research Center for Aging and MedicineNational Center for Neurological Disordersand State Key Laboratory of Medical NeurobiologyHuashan HospitalFudan UniversityShanghaiChina Department of Nuclear Medicine&PET center National Center for Neurological Disordersand National Clinical Research Center for Aging and MedicineHuashan HospitalFudan UniversityShanghaiChina International Human Phenome Institutes(shanghai) ShanghaiChina Human Phenome Institute Fudan UniversityShanghaiChina

Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of *** review provides a comprehensive summary of the latest developments in the application of presynaptic dopaminergic positron emission tomography imaging in disorders that manifest *** conducted a thorough literature search using reputable databases such as PubMed and Web of *** criteria involved identifying peer-reviewed articles published within the last 5 years,with emphasis on their relevance to clinical *** findings from these studies highlight that presynaptic dopaminergic positron emission tomography has demonstrated potential not only in diagnosing and differentiating various Parkinsonian conditions but also in assessing disease severity and predicting ***,when employed in conjunction with other imaging modalities and advanced analytical methods,presynaptic dopaminergic positron emission tomography has been validated as a reliable in vivo *** validation extends to screening and exploring potential neuropathological mechanisms associated with dopaminergic *** summary,the insights gained from interpreting these studies are crucial for enhancing the effectiveness of preclinical investigations and clinical trials,ultimately advancing toward the goals of neuroregeneration in parkinsonian disorders.

关键词： aromatic amino acid decarboxylase brain imaging dopamine transporter Parkinson’s disease parkinsonism positron emission tomography presynaptic dopaminergic function vesicle monoamine transporter type 2

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Resting-state brain network remodeling after different nerve reconstruction surgeries:a functional magnetic resonance imaging study in brachial plexus injury rats

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Neural Regeneration Research 2025年第5期20卷 1495-1504页

作者： Yunting Xiang Xiangxin Xing Xuyun Hua Yuwen Zhang Xin Xue Jiajia Wu Mouxiong Zheng He Wang Jianguang Xu School of Rehabilitation Science Shanghai University of Traditional Chinese MedicineShanghaiChina Engineering Research center of Traditional Chinese Medicine Intelligent Rehabilitation Ministry of EducationShanghaiChina Department of Rehabilitation Medicine Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghaiChina Department of Traumatology and Orthopedics Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghaiChina Institute of Science and Technology for Brain-Inspired Intelligence Fudan UniversityShanghaiChina Key Laboratory of computational Neuroscience and Brain-Inspired Intelligence(Fudan University) Ministry of EducationShanghaiChina Human Phenome Institute Fudan UniversityShanghaiChina

Distinct brain remodeling has been found after different nerve reconstruction strategies,including motor representation of the affected ***,differences among reconstruction strategies at the brain network level have not been *** study aimed to explore intranetwork changes related to altered peripheral neural pathways after different nerve reconstruction surgeries,including nerve repair,endto-end nerve transfer,and end-to-side nerve ***–Dawley rats underwent complete left brachial plexus transection and were divided into four equal groups of eight:no nerve repair,grafted nerve repair,phrenic nerve end-to-end transfer,and end-to-side transfer with a graft sutured to the anterior upper ***-state brain functional magnetic resonance imaging was obtained 7 months after *** independent component analysis algorithm was utilized to identify group-level network components of interest and extract resting-state functional connectivity values of each voxel within the *** in intra-network resting-state functional connectivity were compared among the *** muscle reinnervation was assessed by behavioral observation(elbow flexion)and *** results showed that alterations in the sensorimotor and interoception networks were mostly related to changes in the peripheral neural *** repair was related to enhanced connectivity within the sensorimotor network,while end-to-side nerve transfer might be more beneficial for restoring control over the affected limb by the original motor *** thalamic-cortical pathway was enhanced within the interoception network after nerve repair and end-to-end nerve *** areas related to cognition and emotion were enhanced after end-to-side nerve *** study revealed important brain networks related to different nerve *** networks may be potential targets for enhancing motor recovery.

关键词： brain functional networks end-to-end nerve transfer end-to-side nerve transfer independent component analysis nerve repair peripheral plexus injury resting-state functional connectivity

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Subretinal fibrosis secondary to neovascular age-related macular degeneration:mechanisms and potential therapeutic targets

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Neural Regeneration Research 2025年第2期20卷 378-393页

作者： Jingxiang Zhang Xia Sheng Quanju Ding Yujun Wang Jiwei Zhao Jingfa Zhang Department of Ophthalmology People’s Hospital of Huangdao DistrictQingdaoShandong ProvinceChina Department of Urology People’s Hospital of Huangdao DistrictQingdaoShandong ProvinceChina Department of Ophthalmology Shanghai General Hospital(Shanghai First People’s Hospital)Shanghai Jiao Tong University School of MedicineShanghaiChina National Clinical Research center for Eye Diseases Shanghai Key Laboratory of Ocular Fundus DiseasesShanghai Engineering Center for Visual Science and PhotomedicineShanghai Engineering Center for Precise Diagnosis and Treatment of Eye DiseasesShanghaiChina

Subretinal fibrosis is the end-stage sequelae of neovascular age-related macular *** causes local damage to photoreceptors,retinal pigment epithelium,and choroidal vessels,which leads to permanent central vision loss of patients with neovascular age-related macular *** pathogenesis of subretinal fibrosis is complex,and the underlying mechanisms are largely ***,there are no effective treatment options.A thorough understanding of the pathogenesis of subretinal fibrosis and its related mechanisms is important to elucidate its complications and explore potential *** current article reviews several aspects of subretinal fibrosis,including the current understanding on the relationship between neovascular age-related macular degeneration and subretinal fibrosis;multimodal imaging techniques for subretinal fibrosis;animal models for studying subretinal fibrosis;cellular and non-cellular constituents of subretinal fibrosis;pathophysiological mechanisms involved in subretinal fibrosis,such as aging,infiltration of macrophages,different sources of mesenchymal transition to myofibroblast,and activation of complement system and immune cells;and several key molecules and signaling pathways participating in the pathogenesis of subretinal fibrosis,such as vascular endothelial growth factor,connective tissue growth factor,fibroblast growth factor 2,platelet-derived growth factor and platelet-derived growth factor receptor-β,transforming growth factor-βsignaling pathway,Wnt signaling pathway,and the axis of heat shock protein 70-Toll-like receptors 2/*** review will improve the understanding of the pathogenesis of subretinal fibrosis,allow the discovery of molecular targets,and explore potential treatments for the management of subretinal fibrosis.

关键词： choroidal neovascularization epithelial-mesenchymal transition mesenchymal transition myofibroblast neovascular age-related macular degeneration submacular fibrosis subretinal fibrosis therapeutic targets transforming growth factor-β vascular endothelial growth factor

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High Fe‑Loading Single‑Atom Catalyst Boosts ROS Production by Density Effect for Efficient Antibacterial Therapy

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Nano-Micro Letters 2025年第2期17卷 187-203页

作者： Si Chen Fang Huang Lijie Mao Zhimin Zhang Han Lin Qixin Yan Xiangyu Lu Jianlin Shi Department of Cardiology Shanghai Tenth People’s HospitalSchool of MedicineTongji UniversityShanghai 200092People’s Republic of China shanghai Institute of Ceramics Chinese Academy of SciencesShanghai 200050People’s Republic of China shanghai Frontiers Science center of Nanocatalytic Medicine School of MedicineTongji UniversityShanghai 200092People’s Republic of China

The current single-atom catalysts(SACs)for medicine still suffer from the limited active site ***,we develop a synthetic method capable of increasing both the metal loading and mass-specific activity of SACs by exchanging zinc with *** constructed iron SACs(h^(3)-FNC)with a high metal loading of 6.27 wt%and an optimized adjacent Fe distance of~4 A exhibit excellent oxidase-like catalytic performance without significant activity decay after being stored for six months and promising antibacterial ***,a“density effect”has been found at a high-enough metal doping amount,at which individual active sites become close enough to interact with each other and alter the electronic structure,resulting in significantly boosted intrinsic activity of single-atomic iron sites in h^(3)-FNCs by 2.3 times compared to low-and medium-loading ***,the overall catalytic activity of h^(3)-FNC is highly improved,with mass activity and metal mass-specific activity that are,respectively,66 and 315 times higher than those of commercial Pt/*** addition,h^(3)-FNCs demonstrate efficiently enhanced capability in catalyzing oxygen reduction into superoxide anion(O_(2)·^(−))and glutathione(GSH)*** in vitro and in vivo assays demonstrate the superior antibacterial efficacy of h^(3)-FNCs in promoting wound *** work presents an intriguing activity-enhancement effect in catalysts and exhibits impressive therapeutic efficacy in combating bacterial infections.

关键词： Nanocatalytic medicine Single-atom catalysts Reactive oxygen species(ROS) High metal loading Oxidase catalysis

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An efficient method for computing excess free energy of liquid

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Science China chemistry 2018年第1期61卷 135-140页

作者： Jianing Song Linqiong Qiu John Z.H. Zhang School of chemistry and Molecular Engineering East China Normal University Shanghai 200062 China nyu-ecnu center for computational chemistry at nyu ShanghaL shanghai 200062 China State Key Laboratory of Precision Spectroscopy East China Normal University Shanghai 200062 China Department of chemistry New York University NY NY 10003 USA

We present a new theoretical method for efficient calculation of free energy of liquid. This interaction entropy method allows one to compute entropy and free energy of liquid from standard single step MD(molecular dynamics) simulation directly in liquid state without the need to perform MD simulations at many intermediate states as required in thermodynamic integration or free energy perturbation methods. In this new approach, one only needs to evaluate the interaction energy of a single(fixed) liquid molecule with the rest of liquid molecules as a function of time from a standard MD simulation of liquid and the fluctuation of distribution of this interaction energy is then used to calculate the interaction entropy of the liquid. Explicit theoretical derivation of this interaction entropy approach is provided and numerical calculations for the benchmark liquid water system were carried out using three different water models. Numerical analysis of the result was performed and comparison of the computational result with experimental data and other theoretical results were provided. Excellent agreement of calculated free energies with the experimental data using TIP4 P model is obtained for liquid water.

关键词： excess free energy liquid MD simulation interaction entropy

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