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The emerging role of nitric oxide in the synaptic dysfunction of vascular dementia

Neural Regeneration Research 2025年第2期20卷 402-415页

作者： Xiaorong Zhang Zhiying Chen Yinyi Xiong Qin Zhou Ling-Qiang Zhu Dan Liu Department of Pathology Affiliated Hospital of Jiujiang UniversityJiujiangJiangxi ProvinceChina Jiujiang Clinical Precision Medicine Research center JiujiangJiangxi ProvinceChina center for cognitive science and transdisciplinary studies Jiujiang UniversityJiangxi ProvinceChina Department of Neurology Affiliated Hospital of Jiujiang UniversityJiujiangJiangxi ProvinceChina Department of Rehabilitation Affiliated Hospital of Jiujiang UniversityJiujiangJiangxi ProvinceChina Department of Pathophysiology School of Basic MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina

With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic ***,few therapeutic options exist that can markedly improve the cognitive impairment and prognosis of vascular dementia *** in Alzheimer’s disease and other neurological disorders,synaptic dysfunction is recognized as the main reason for cognitive *** oxide is one of the ubiquitous gaseous cellular messengers involved in multiple physiological and pathological processes of the central nervous ***,nitric oxide has been implicated in regulating synaptic plasticity and plays an important role in the pathogenesis of vascular *** review introduces in detail the emerging role of nitric oxide in physiological and pathological states of vascular dementia and summarizes the diverse effects of nitric oxide on different aspects of synaptic dysfunction,neuroinflammation,oxidative stress,and blood-brain barrier dysfunction that underlie the progress of vascular ***,we propose that targeting the nitric oxide-sGC-cGMP pathway using certain specific approaches may provide a novel therapeutic strategy for vascular dementia.

关键词： endoplasmic reticulum stress endothelial nitric oxide synthase gene therapy nitric oxide NO-sGC-cGMP pathway synaptic dysfunction vascular dementia

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Potential role and therapeutic implications of glutathione peroxidase 4 in the treatment of Alzheimer's disease

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Neural Regeneration Research 2025年第3期20卷 613-631页

作者： Yanxin Shen Guimei Zhang Chunxiao Wei Panpan Zhao Yongchun Wang Mingxi Li Li Sun Department of Neurology and Neuroscience center The First Hospital of Jilin UniversityJilin UniversityChangchunJilin ProvinceChina cognitive Impairment center Department of NeurologyThe First Hospital of Jilin UniversityJilin UniversityChangchunJilin ProvinceChina

Alzheimer's disease is an age-related neurodegenerative disorder with a complex and incompletely understood pathogenesis. Despite extensive research, a cure for Alzheimer's disease has not yet been found. Oxidative stress mediates excessive oxidative responses, and its involvement in Alzheimer's disease pathogenesis as a primary or secondary pathological event is widely accepted. As a member of the selenium-containing antioxidant enzyme family, glutathione peroxidase 4 reduces esterified phospholipid hydroperoxides to maintain cellular redox homeostasis. With the discovery of ferroptosis, the central role of glutathione peroxidase 4 in anti-lipid peroxidation in several diseases, including Alzheimer's disease, has received widespread attention. Increasing evidence suggests that glutathione peroxidase 4 expression is inhibited in the Alzheimer's disease brain, resulting in oxidative stress, inflammation, ferroptosis, and apoptosis, which are closely associated with pathological damage in Alzheimer's disease. Several therapeutic approaches, such as small molecule drugs, natural plant products, and non-pharmacological treatments, ameliorate pathological damage and cognitive function in Alzheimer's disease by promoting glutathione peroxidase 4 expression and enhancing glutathione peroxidase 4 activity. Therefore, glutathione peroxidase 4 upregulation may be a promising strategy for the treatment of Alzheimer's disease. This review provides an overview of the gene structure, biological functions, and regulatory mechanisms of glutathione peroxidase 4, a discussion on the important role of glutathione peroxidase 4 in pathological events closely related to Alzheimer's disease, and a summary of the advances in small-molecule drugs, natural plant products, and non-pharmacological therapies targeting glutathione peroxidase 4 for the treatment of Alzheimer's disease. Most prior studies on this subject used animal models, and relevant clinical studies are lacking. Future clinica

关键词： apoptosis ferroptosis inflammation lipid peroxidation natural plant products neurodegenerative disorder neuroprotection oxidative stress small-molecule drugs

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Oxygen Metabolism-induced Stress Response Underlies Heartbrain Interaction Governing Human Consciousness-breaking and Attention

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Neuroscience Bulletin 2022年第2期38卷 166-180页

作者： Xiao-Juan Xue Rui Su Ze-Feng Li Xiao-Ou Bu Peng Dang Si-Fang Yu Zhi-Xin Wang Dong-Mei Chen Tong-Ao Zeng Ming Liu Hai-Lin Ma De-Long Zhang Key Laboratory of Brain Cognition and Education SciencesMinistry of EducationChinaSchool of PsychologyCenter for Studies of Psychological Applicationand Guangdong Key Laboratory of Mental Health and Cognitive ScienceSouth China Normal UniversityGuangzhou 510631China Plateau Brain science Research center South China Normal University/Tibet UniversityLhasa 850012China

Neuroscientists have emphasized visceral influences on consciousness and attention,but the potential neurophysiological pathways remain under ***,we found two neurophysiological pathways of heartbrain interaction based on the relationship between oxygen-transport by red blood cells(RBCs)and consciousness/*** this end,we collected a dataset based on the routine physical examination,the breaking continuous flash suppression(b-CFS)paradigm,and an attention network test(ANT)in 140 immigrants under the hypoxic Tibetan *** combined electroencephalography and multilevel mediation analysis to investigate the relationship between RBC properties and consciousness/*** results showed that RBC function,via two independent neurophysiological pathways,not only triggered interoceptive re-representations in the insula and awareness connected to orienting attention but also induced an immune response corresponding to consciousness and executive ***,consciousness played a fundamental role in executive function which might be associated with the level of perceived *** results indicated the important role of oxygen-transport in heart-brain interactions,in which the related stress response affected consciousness and executive *** findings provide new insights into the neurophysiological schema of heartbrain interactions.

关键词： Heart-brain interaction Breaking continuous flash suppression Executive attention Stress response

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Decision making module based on stochastic magnetic tunnel junctions

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science China(Physics,Mechanics & Astronomy) 2025年第1期Mechanics & Astronomy) .卷 202-209页

作者： Yifan Miao Li Zhao Yajun Zhang Zhe Yuan center for Advanced Quantum studies and Department of Physics Beijing Normal University Institute for Nanoelectric Devices and Quantum Computing Fudan University Interdisciplinary center for Theoretical Physics and Information sciences Fudan University

In biological neural systems, noise is ubiquitous but does not affect the correct decisions made in the complex cognitive ***-making in biological neural system is typically achieved by accumulating input information over a period of *** by recent developments in neurosciences, we design a decision-making module based on spintronic devices, utilizing superparamagnetic tunnel junctions as artificial neurons. The feasibility of this decision-making module is verified through circuit simulations. Taking a multi-layer perceptron as an example, the module significantly improves the accuracy of the perceptron in the handwritten digit recognition task. Furthermore, the spintronic decision-making module offers advantages over the conventional pooling methods, such as adaptive decision time, high performance and the absence of analog-to-digital conversion. The decision-making module is flexible to be integrated into artificial neural networks and provides a general yet effective solution to enhance performance against device noise.

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Aberrant auditory system and its developmental implications for autism

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science China(Life sciences) 2021年第6期64卷 861-878页

作者： Luodi Yu Suiping Wang Key Laboratory of Brain Cognition and Education SciencesMinistry of EducationChina School of Psychology Center for Studies of Psychological Applicationand Guangdong Key Laboratory of Mental Health and Cognitive ScienceSouth China Normal UniversityGuangzhou 510631China Autism Research center South China Normal UniversityGuangzhou 510631China

Most infants who are later diagnosed with autism show delayed speech and language and/or atypical language *** is a large body of research on abnormal speech and language in children with ***,auditory development has been relatively under-investigated in autism research,despite its inextricable relationship with language development and despite researchers'ability to detect abnormalities in brain development and behavior in early *** this review,we synthesize research on auditory processing in the prenatal period through infancy and childhood in typically developing children,children at high risk for autism,and children diagnosed with *** conclude that there are clear neurobiological and behavioral links between abnormal auditory development and the deficits in social communication seen in *** then offer perspectives on the need for a systematic characterization of early auditory development in autism,and identified questions to be addressed in future research on the development of autism.

关键词： autism auditory development auditory system early brain development language development infant learning speech processing

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The brain network hub degeneration in Alzheimer's disease

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Biophysics Reports 2024年第4期10卷 213-229页

作者： Suhui Jin Jinhui Wang Yong He Institute for Brain Research and Rehabilitation Guangdong Key Laboratory of Mental Health and cognitive science center for studies of Psychological Application South China Normal University IDG/McGovern Institute for Brain Research National Key Laboratory of cognitive Neuroscience and Learning Beijing Key Laboratory of Brain Imaging and Connectomics Beijing Normal University

Alzheimer's disease(AD) has been conceptualized as a syndrome of brain network dysfunction. Recent imaging connectomics studies have provided unprecedented opportunities to map structural and functional brain networks in AD. By reviewing molecular, imaging, and computational modeling studies, we have shown that highly connected brain hubs are primarily distributed in the medial and lateral prefrontal, parietal, and temporal regions in healthy individuals and that the hubs are selectively and severely affected in AD as manifested by increased amyloid-beta deposition and regional atrophy,hypo-metabolism, and connectivity dysfunction. Furthermore, AD-related hub degeneration depends on the imaging modality with the most notable degeneration in the medial temporal hubs for morphological covariance networks, the prefrontal hubs for structural white matter networks, and in the medial parietal hubs for functional networks. Finally, the AD-related hub degeneration shows metabolic,molecular, and genetic correlates. Collectively, we conclude that the brain-network-hub-degeneration framework is promising to elucidate the biological mechanisms of network dysfunction in AD, which provides valuable information on potential diagnostic biomarkers and promising therapeutic targets for the disease.

关键词： Connectomics Centrality Modularity Graph theory MRI Dementia

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Repetitive transcranial magnetic stimulation in Alzheimer’s disease:effects on neural and synaptic rehabilitation

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Neural Regeneration Research 2025年第2期20卷 326-342页

作者： Yi Ji Chaoyi Yang Xuerui Pang Yibing Yan Yue Wu Zhi Geng Wenjie Hu Panpan Hu Xingqi Wu Kai Wang Department of Neurology The First Affiliated Hospital of Anhui Medical UniversityHefeiAnhui ProvinceChina Anhui Province Key Laboratory of Cognition and Neuropsychiatric Disorders HefeiAnhui ProvinceChina Collaborative Innovation center of Neuropsychiatric Disorders and Mental Health HefeiAnhui ProvinceChina Institute of Artificial Intelligence Hefei Comprehensive National Science CenterHefeiAnhui ProvinceChina Department of Psychology and Sleep Medicine The Second Affiliated Hospital of Anhui Medical UniversityHefeiAnhui ProvinceChina

Alzheimer’s disease is a neurodegenerative disease resulting from deficits in synaptic transmission and *** Alzheimer’s disease brain tends to be hyperexcitable and hypersynchronized,thereby causing neurodegeneration and ultimately disrupting the operational abilities in daily life,leaving patients *** transcranial magnetic stimulation is a cost-effective,neuro-modulatory technique used for multiple neurological *** the past two decades,it has been widely used to predict cognitive decline;identify pathophysiological markers;promote neuroplasticity;and assess brain excitability,plasticity,and *** has also been applied to patients with dementia,because it can yield facilitatory effects on cognition and promote brain recovery after a neurological ***,its therapeutic effectiveness at the molecular and synaptic levels has not been elucidated because of a limited number of *** study aimed to characterize the neurobiological changes following repetitive transcranial magnetic stimulation treatment,evaluate its effects on synaptic plasticity,and identify the associated *** review essentially focuses on changes in the pathology,amyloidogenesis,and clearance pathways,given that amyloid deposition is a major hypothesis in the pathogenesis of Alzheimer’s *** mechanisms associated with repetitive transcranial magnetic stimulation procedures and different pathways mediating gene transcription,which are closely related to the neural regeneration process,are also ***,we discuss the outcomes of animal studies in which neuroplasticity is modulated and assessed at the structural and functional levels by using repetitive transcranial magnetic stimulation,with the aim to highlight future directions for better clinical translations.

关键词： Alzheimer’s disease amyloid deposition apoptotic mechanisms biomarker neural regeneration neurodegeneration repetitive transcranial magnetic stimulation synaptic plasticity

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Behavioral Switch of Food Preference upon Sugar Deficiency Is Regulated by GPCRs in Drosophila

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Journal of Genetics and Genomics 2015年第7期42卷 409-412页

作者： Chang Liu Xiaobing Bai Jinghan Sun Xiaofan Zhang Yan Li State Key Laboratory of Brain and cognitive science Institute of BiophysicsChinese Academy of Sciences University of Chinese Academy of sciences Sino-Danish center for Education and Research

Sugar and protein are the major macronutrients＇ sources, and their balanced intake is important for animal＇s health. It has been observed that animals are able to change food preference in an imbalanced nutritional condition to selectively consume nutrients that are deficient in the body （Dethier, 1976）. Early studies in both Drosophila and mouse have demonstrated that animals exhibit food rejection to imbalanced diets lacking essential amino acids （Hao et al., 2005; Bjordal et al., 2014）. Furthermore, the food preference change upon protein depri- vation has been characterized using a two choice assay in Drosophila （Ribeiro and Dickson, 2010; Vargas et al., 2010）. Different from protein food, sugar is the main energy source, and sugar deficiency severely affects animal survival （Lee et al., 2008）. However, whether animals adopt a strategy of fast food preference switch upon sugar deprivation had not been investigated, and the neural mechanisms underlying this behavior regulation remain poorly understood.

关键词： GPCRs Behavioral Switch of Food Preference upon Sugar Deficiency Is Regulated by GPCRs in Drosophila

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Metal‐organic frameworks‐derived novel nanostructured electrocatalysts for oxygen evolution reaction

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Carbon Energy 2021年第1期3卷 66-100页

作者： Xinyu Qin Dongwon Kim Yuanzhe Piao Department of transdisciplinary studies Graduate School of Convergence Science and TechnologySeoul National UniversitySuwon‐siGyeonggi‐doRepublic of Korea Advanced Institutes of Convergence Technology Seoul National UniversitySuwon‐siGyeonggi‐doRepublic of Korea

Engineering cost‐effective catalysts with exceptional performance for theelectrochemical oxygen evolution reaction (OER) remains crucial for theaccelerated development of renewable energy techniques, and especially so,given the pivotal role of OER in water electrolysis. On the basis of the metalnodes (clusters) and organic linkers, metal‐organic frameworks (MOFs) andtheir derivatives are rapidly gaining ground in the fabrication of electrocatalysts,with promising catalytic activity and sound durability in OER, thanksto their controllable pore structures, abundant unsaturated active sites of metalion, extensive specific surface area, as well as easily functionalized/modifiedsurfaces. This review presents an in‐depth understanding of the establishedprogress of MOFs‐derived materials for OER electrocatalysis. The materialdesigning strategies of the pristine, monometallic, and multimetallic MOFsbasedcatalysts are summarized to indicate the infinite possibilities of themorphology and the composition of MOF‐derived materials. While emphasisis laid on the essential features of MOF‐derived materials for the electrocatalysisof the corresponding reactions, insights about the applications in OERare discussed. Finally, this paper is concluded by presenting challengesand perspectives for MOF‐derived materials’ future applications in OERelectrocatalysis.

关键词： electrocatalyst high‐performance metal‐organic frameworks oxygen evolution reaction

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Enhanced autophagic clearance of amyloid-βvia histone deacetylase 6-mediated V-ATPase assembly and lysosomal acidification protects against Alzheimer's disease in vitro and in vivo

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Neural Regeneration Research 2025年第9期20卷 2633-2644页

作者： Zhimin Long Chuanhua Ge Yueyang Zhao Yuanjie Liu Qinghua Zeng Qing Tang Zhifang Dong Guiqiong He Institute of Neuroscience School of Basic Medical SciencesChongqing Medical UniversityChongqingChina Department of Anatomy Chongqing Medical UniversityChongqingChina Department of Physiology Chongqing Medical UniversityChongqingChina Pediatric Research Institute Children’s Hospital of Chongqing Medical UniversityChongqingChina Ministry of Education Key Laboratory of Child Development and Disorders Children’s Hospital of Chongqing Medical UniversityChongqingChina National Clinical Research center for Child Health and Disorders Children’s Hospital of Chongqing Medical UniversityChongqingChina Chongqing Key Laboratory of Child Neurodevelopment and cognitive Disorders Children’s Hospital of Chongqing Medical UniversityChongqingChina

Recent studies have suggested that abnormal acidification of lysosomes induces autophagic accumulation of amyloid-βin neurons,which is a key step in senile plaque ***,resto ring normal lysosomal function and rebalancing lysosomal acidification in neurons in the brain may be a new treatment strategy for Alzheimer's *** acetylation/deacetylation plays a central role in lysosomal ***,we show that inhibiting the classic microtubule deacetylase histone deacetylase 6 with an histone deacetylase 6 shRNA or thehistone deacetylase 6 inhibitor valproic acid promoted lysosomal reacidification by modulating V-ATPase assembly in Alzheimer's *** rthermore,we found that treatment with valproic acid markedly enhanced *** clearance of amyloid-βaggregates,and ameliorated cognitive deficits in a mouse model of Alzheimer's *** findings demonstrate a previously unknown neuroprotective mechanism in Alzheimer's disease,in which histone deacetylase 6 inhibition by valproic acid increases V-ATPase assembly and lysosomal acidification.

关键词： Alzheimer's disease amyloid-β APP/PS1 mice autophagy cognitive impairment histone deacetylase 6 lysosomal acidification microtubule acetylation valproic acid V-ATPase

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