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Nanomaterials-mediated lysosomal regulation:a robust protein-clearance approach for the treatment of Alzheimer’s disease

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Neural Regeneration Research 2025年第2期20卷 424-439页

作者： Mengqi Hao Jianjian Chu Tinglin Zhang Tong Yin Yuankai Gu Wendanqi Liang Wenbo Ji Jianhua Zhuang Yan Liu Jie Gao You Yin Department of Neurology Second Affiliated Hospital of Naval Medical University(Shanghai Changzheng Hospital)ShanghaiChina School of Health Science and Engineering University of Shanghai for Science and TechnologyShanghaiChina Changhai Clinical Research Unit Shanghai Changhai HospitalNaval Medical UniversityShanghaiChina Department of Clinical Pharmacy Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of Neurology Shanghai East HospitalSchool of MedicineTongji UniversityShanghaiChina

Alzheimer’s disease is a debilitating,progressive neurodegenerative disorder characterized by the progressive accumulation of abnormal proteins,including amyloid plaques and intracellular tau tangles,primarily within the ***,crucial intracellular organelles responsible for protein degradation,play a key role in maintaining cellular *** studies have suggested a link between the dysregulation of the lysosomal system and pathogenesis of neurodegenerative diseases,including Alzheimer’s *** the normal physiological function of lysosomes hold the potential to reduce the pathological burden and improve the symptoms of Alzheimer’s ***,the efficacy of drugs in treating Alzheimer’s disease is limited,with major challenges in drug delivery efficiency and ***,nanomaterials have gained widespread use in Alzheimer’s disease drug research owing to their favorable physical and chemical *** review aims to provide a comprehensive overview of recent advances in using nanomaterials(polymeric nanomaterials,nanoemulsions,and carbon-based nanomaterials)to enhance lysosomal function in treating Alzheimer’s *** review also explores new concepts and potential therapeutic strategies for Alzheimer’s disease through the integration of nanomaterials and modulation of lysosomal *** conclusion,this review emphasizes the potential of nanomaterials in modulating lysosomal function to improve the pathological features of Alzheimer’s *** application of nanotechnology to the development of Alzheimer’s disease drugs brings new ideas and approaches for future treatment of this disease.

关键词： Alzheimer’s disease autophagy dysfunction lysosomal acidification lysosomal system nanomaterials neurodegenerative diseases

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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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Toward understanding the role of genomic repeat elements in neurodegenerative diseases

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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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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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Potential role of tanycyte-derived neurogenesis in Alzheimer's disease

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Neural Regeneration Research 2025年第6期20卷 1599-1612页

作者： Guibo Qi Han Tang Jianian Hu Siying Kang Song Qin Department of Anatomy Histologyand EmbryologySchool of Basic Medical SciencesFudan UniversityShanghaiChina State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science Fudan UniversityShanghaiChina

Tanycytes, specialized ependymal cells located in the hypothalamus, play a crucial role in the generation of new neurons that contribute to the neural circuits responsible for regulating the systemic energy balance. The precise coordination of the gene networks controlling neurogenesis in naive and mature tanycytes is essential for maintaining homeostasis in adulthood. However, our understanding of the molecular mechanisms and signaling pathways that govern the proliferation and differentiation of tanycytes into neurons remains limited. This article aims to review the recent advancements in research into the mechanisms and functions of tanycyte-derived neurogenesis. studies employing lineage-tracing techniques have revealed that the neurogenesis specifically originating from tanycytes in the hypothalamus has a compensatory role in neuronal loss and helps maintain energy homeostasis during metabolic diseases. intriguingly,metabolic disorders are considered early biomarkers of Alzheimer's disease. Furthermore,the neurogenic potential of tanycytes and the state of newborn neurons derived from tanycytes heavily depend on the maintenance of mild microenvironments, which may be disrupted in Alzheimer's disease due to the impaired blood–brain barrier ***, the specific alterations and regulatory mechanisms governing tanycyte-derived neurogenesis in Alzheimer's disease remain unclear. Accumulating evidence suggests that tanycyte-derived neurogenesis might be impaired in Alzheimer's disease, exacerbating neurodegeneration. Confirming this hypothesis, however, poses a challenge because of the lack of long-term tracing and nucleus-specific analyses of newborn neurons in the hypothalamus of patients with Alzheimer's disease. Further research into the molecular mechanisms underlying tanycyte-derived neurogenesis holds promise for identifying small molecules capable of restoring tanycyte proliferation in neurodegenerative diseases. This line of investigation could pro

关键词： Alzheimer's disease blood–brain barrier ependymoglial cells hypothalamus metabolic diseases neural stem cells neurogenesis neuroinflammatory diseases neurons tanycyte

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Ultrafine particle emission characteristics of diesel engine by on-board and test bench measurement

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Journal of Environmental Sciences 2012年第11期24卷 1972-1978页

作者： Cheng Huang Diming Lou Zhiyuan Hu Piqiang Tai Di Yao Wei Hu Peng Li Jin Ren Changhong Chen School of Automobile studies Tongji UniversityShanghai 201804China shanghai Academy of Environmental Sciences Shanghai 200233China

This study investigated the emission characteristics of *** particles based on test bench and on-board measurements. The bench test results showed the ultrafine particle number concentration of the diesel engine to be in the range of （0.56-8.35）×10^8 cm^-3. The on-board measurement results illustrated that the ultra_fine particles were strongly correlated with changes in real-world driving cycles. The particle number concentration was down to 2.0 ×10^6 cm^-3 and 2.7 ×10^7 cm^-3 under decelerating and idling operations and as high as 5.0×10^8 cm^-3 under accelerating operation. It was also indicated that the particle number measured by the two methods increased with the growth of engine load at each engine speed in both cases. The particle number presented a ＂U＂ shaped distribution with changing speed at high engine load conditions, which implies that the particle number will reach its lowest level at medium engine speeds. The particle sizes of both measurements showed single mode distributions. The peak of particle size was located at about 50-80 nm in the accumulation mode particle range. Nucleation mode particles will significantly increase at low engine load operations like idling and decelerating caused by the high concentration of unburned organic compounds.

关键词： ultrafine particle emission emission factor diesel engine on-board emission measurement TSI EEPS

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Uncover the myths of voltage-gated sodium channels: cryo-EM structure of the EeNa_v1.4-β1 complex

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Science Bulletin 2017年第19期62卷 1291-1292页

作者： Yan Nie shanghai Institute for Advanced Immunochemical studies Shanghai Tech University

Ion channels are membrane-embedded macromolecular pores,which allow charged ions flow through the insulating lipid bilayer when channel pores are *** opening and closing(termed gating)of ion channels are modulated by various stimuli,such as changes of membrane potential and binding of ligands(neurotransmitters,toxins,etc.).Some ion channels are classified as‘‘voltage-gated ion channels',as they can be gated by altering

关键词：钠离子通道电压门控冷冻电镜结构神话带电离子神经递质膜电位

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2013年英国小说研究在中国

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外国文学研究 2014年第2期36卷 16-24页

作者：陈广兴 shanghai int studies univ Inst Literary Studies Shanghai 200083 Peoples R China

2013年我国在英国小说研究领域取得了极为丰硕的成果,虽然一些老问题依然存在,但进步不容忽视。虽然经典作家依然是我国英国小说研究的主体,但女性作家和少数族裔作家得到更多的关注;虽然重复研究和理论先行依然比较突出,但研究的社会... 详细信息

2013年我国在英国小说研究领域取得了极为丰硕的成果,虽然一些老问题依然存在,但进步不容忽视。虽然经典作家依然是我国英国小说研究的主体,但女性作家和少数族裔作家得到更多的关注;虽然重复研究和理论先行依然比较突出,但研究的社会意识有所加强,研究视角更加多元化。与外国2013年的英国小说研究相比,我们的研究应该扩大研究对象范围,采用更加灵活的研究视角,加强研究的系统性和国际化视野。

关键词： 2013 英国小说研究

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C -E interpreting of Political Neologisms in Contemporary Chinese Political Discourse

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学术界 2015年第1期 281-286页

作者： Ji Xiaowen Wan Hongyu Graduate School shanghai international studies university Shanghai 200083 School of English studies shanghai international studies university Shanghai 200083

Uniqueness of our political systems and tremendous changes brought about by reform and opening up are reflected in language use,so contem porary Chinese political discourse has its own distinctiveness,and is especially featured by increasing political neologisms,posing difficulties for interpreters and for China’s international *** of political neologisms interpreting has a direct bearing on whether or not success of interpreting the whole discourse can be *** authors believe that interpreting of contemporary Chinese political discourse,also for the purpose of com m unication can gain guidance from Bachman’s CLA *** the paper elaborates through exem plification on strategies for interpreting political neologisms in light of Bachm an’s Model,with a view to realizing discourse power of Chinese.

关键词：政治制度当代中国话语改革开放中国特色 CLA

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Output nonlocality and nonclassicality in a two-mode entanglement laser

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Chinese Optics Letters 2011年第9期9卷 70-73页

作者：平云霞张朝民吴建宝 College of Fundamental studies Shanghai University of Engineering Science

Output nonlocality and nonclassicality for the two modes are investigated in an entanglement laser system. Within the framework of a quantum theory of multiwave mixing, nonlocality and nonclassicality are discussed according to the violations of Bell inequality and Cauchy-Schwarz inequality. It is found that both nonlocality and nonclassicality can be fulfilled in the outside cavity fields under certain conditions. It is also shown that there are some nonclassical states that do not show nonlocality.

关键词： Optics Physics

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