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中国神经科学学会第十届全国学术会议

作者： qing-long miao Xiao-Hui ZHANG Laboratory of Neuronal Processing & Plasticity Institute of Neuroscience and State Key Laboratory of NeuroscienceShanghai Institutes for Biological SciencesChinese Academy of Sciences

Critical period is a well-defined early developmental time window in which the brain is extremely sensitive to experience *** studies suggest that maturation of cortical GABAergic inhibition mediated by parvalbumin(PV)-cells is necessary for opening the critical ***,it remains elusive what detailed developmental changes in this particular inhibitory PV-cell circuit endorse its key regulation on the occurrence of the critical period of visual *** the present study,by performing dual whole-cell recordings of cortical neurons in acute brain slices,we systematically investigated the functional maturation of the cortical PV-cell synaptic circuits in layer 4,the main thalamorecipient lamina,of mouse visual cortex aged from eye opening(14) to critical-period onset(20).Our results showed a dramatic reduction in the short-term depression(STD) of PC to PV synapses along with unchanged synaptic strength during P14-20,but little change in the STD of reciprocal PV to PC synapses and a two-fold increase in its transmission *** contrast,the recurrent excitatory synapse between PCs in layer 4decreased its strength by 50%with little change in its ***,there was no developmental change in the strength and STD at the GABAergic and electrical connections between the PV cells,or the STD of thalamocortical synapses onto both layer 4 PCs and PV-cells during the same *** experiments with mice dark reared from birth indicated that these above differential synaptic changes in layer 4 recurrent circuits could be blocked by the deprivation of early visual *** together,the differential modifications of synaptic function in the cortical PV-cell circuit and recurrent excitatory network by experience lead to a preferential promotion of the intra-cortical inhibition over the excitation in developing visual cortex at the time of critical period onset,which endorsing the role of cortical PV-cell circuit in regulating the criti

关键词： critical period onset excitation/inhibition short-term plasticity parvalbumin-positive intemeuron

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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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Experience-dependent maturation of parvalbumin-positive interneuron in mouse primary visual cortex across the critical Period

Experience-dependent maturation of parvalbumin-positive inte...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： qing-long miao,Xiao-Hui ZHANG~* Laboratory of Neuronal Processing & Plasticity,Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences,Shanghai 200031,China

＜正＞It is of long-standing interest about how early experiences sculpt the structure and function of cortical circuits during a brief postnatal development *** of classic paradigms for this critical-period plasticity is experience-induced ocular dominance plasticity of primary visual cortex（V1）,in which brief visual deprivation of one eye in a short period after the eye-opening often results in persistent changes of V1 ocular dominance in rodents and higher *** evidence has suggested that postnatal maturation of cortical inhibition, primarily mediated by a parvalbumin-positive（PV+） type of GABAergic interneurons,is important in regulating the critical period ***,it remains largely unclear how the PV+ cell maturation process endows an initiation of the critical period for ocular dominance *** the present study,we have systematically elucidated the functional maturation of the PV+ interneuron across the cortical period,by whole-cell recording of layer 4 PV+ cells in visual cortical slices of B13（PV-GFP） transgenic mice aged postnatal 15 to 30 *** found that the excitatory and inhibitory synaptic inputs onto the layer 4 PV+ interneuron underwent differential changes:an increase of the miniature excitatory synaptic event frequency but with scaled down amplitude,as well as only a frequency increase of inhibitory events,in mice from P15 to *** rearing of mice from their birth prevented all these synaptic changes, suggesting an experience-dependent *** pair recording of PV+ interneuron and pyramidal cell（PC） in layer 4 showed an attenuated short-term depression of PC→PV+ excitatory synapse from P15 to ***,we also observed that the intrinsic excitability of these PV+ interneurons was significantly elevated at P20 while that of neighboring pyramidal cells was significantly weakened,and such membrane property changes were not affected by the dark *** summary,our results suggest that synapses and in

关键词： critical period plasticity parvalbumin-positive interneuron synaptic transmission intrinsic excitability

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提速客车转向架动应力分布拟合的研究

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铁道学报 2001年第4期23卷 105-108页

作者：李强刘志明张桂青缪龙秀孙守光北方交通大学机电学院北京100044

结构应力分布状态的确定是结构进行疲劳强度评估和可靠性设计的重要依据。通过在全程实测提速客车转向架构架关键部位应力 -时间历程的基础上 ,对其进行雨流记数后 ,利用可靠性理论 ,通过合理的分组得到测点应力的直方图和失效率图 ,以... 详细信息

结构应力分布状态的确定是结构进行疲劳强度评估和可靠性设计的重要依据。通过在全程实测提速客车转向架构架关键部位应力 -时间历程的基础上 ,对其进行雨流记数后 ,利用可靠性理论 ,通过合理的分组得到测点应力的直方图和失效率图 ,以此为依据详细分析了提速客车转向架构架关键部位动应力分布特征 ,得出了我国提速机车车辆转向架构架在既有线路上运行时的应力特点是小载荷占绝对主导地位 ,并服从截尾正态分布。然后利用非线性单纯形最优化方法求得应力分布的分布参数 ,最后得到提速客车转向架应力分布规律。

关键词：提速客车转向架应力分布分布规律铁路

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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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Integrating lipidomics and gut microbiota to study the anti-hyperlipidemia effect of Sargentodoxae Caulis extract

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Traditional Medicine Research 2025年第1期10卷 1-11页

作者： Xiao-Xiao Zhang Li Jia Xiu-Jun Zhan Charity Ngina qing-Rui Zhang Xiao-Ge Li Qi-Bao Jiang Shi Bai miao-miao Jiang National Key Laboratory of Chinese Medicine Modernization Tianjin University of Traditional Chinese MedicineTianjin 301617China Haihe Laboratory of Modern Chinese Medicine Tianjin 301617China School of Medicine Taizhou UniversityTaizhou 318000China.

Background:Sargentodoxae Caulis(SC)is the vine stem of Sargentodoxa Cuneata(Oliv.)Rehd.&*** in ***,and it in traditional Chinese medicine has been known for promoting blood circulation and removing blood stasis as recorded in the ancient book“Illustrated Classics of Materia Medica”.It has been used effectively to treat blood stasis too in modern clinical ***,the anti-hyperlipidemia effect of SC is not fully *** paper aims at exploring the use of SC stems to improve the balance of blood lipids in the body,and its new role in treating ***:The effects of SC extract on hyperlipidemia were explored by combining lipidomics and gut ***,we explored the potential mechanism of SC in treating hyperlipidemia by pathway ***:The results showed that the stem extract of SC could restore the physiological and biochemical indices of hyperlipidemia in mice,as well as repair the morphological and structural damage to *** to the Model group,the SC extract significantly reduced the liver index,epididymal fat index,and Lee’s *** also significantly decreased serum levels of total cholesterol,triglycerides,low-density lipoprotein cholesterol,peroxisome proliferator-activated receptor gamma(PPAR-γ),D-lactate,and free fatty acids,while significantly increasing the relative content of peroxisome proliferator-activated receptor alpha(PPAR-α).These changes were statistically ***-targeted lipidomics,based on LC-MS,were utilized to investigate the lipid metabolism characteristics in serum,liver,and epididymal fat of the *** was observed that,compared to the blank group,the Model group exhibited significant changes primarily in glycerol lipids and *** treatment group also displayed alterations in these lipids.A total of 38,81,and 27 differential lipids were identified in serum,liver,and epididymal fat samples,*** these,14 common differenti

关键词： hyperlipidemia Sargentodoxae Caulis lipidomics intestinal flora

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Inspires effective alternatives to backpropagation:predictive coding helps understand and build learning

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Neural Regeneration Research 2025年第11期20卷 3215-3216页

作者： Zhenghua Xu miao Yu Yuhang Song School of Health Sciences and Biomedical Engineering Hebei University of TechnologyTianjinChina Department of Computer Science University of OxfordOxfordUK

Artificial neural networks are capable of machine learning by simulating the hiera rchical structure of the human *** enable learning by brain and machine,it is essential to accurately identify and correct the prediction errors,referred to as credit assignment(Lillicrap et al.,2020).It is critical to develop artificial intelligence by understanding how the brain deals with credit assignment in neuroscience.

关键词： assignment learning enable

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Infiltration by monocytes of the central nervous system and its role in multiple sclerosis: reflections on therapeutic strategies

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Neural Regeneration Research 2025年第3期20卷 779-793页

作者： Guangyong Zhang qing Yao Chubing long Pengcheng Yi Jiali Song Luojia Wu Wei Wan Xiuqin Rao Yue Lin Gen Wei Jun Ying Fuzhou Hua Department of Anesthesiology the Second Affiliated Hospital of Nanchang UniversityNanchangJiangxi ProvinceChina Key Laboratory of Anesthesiology of Jiangxi Province NanchangJiangxi ProvinceChina

Mononuclear macrophage infiltration in the central nervous system is a prominent feature of neuroinflammation. Recent studies on the pathogenesis and progression of multiple sclerosis have highlighted the multiple roles of mononuclear macrophages in the neuroinflammatory process. Monocytes play a significant role in neuroinflammation, and managing neuroinflammation by manipulating peripheral monocytes stands out as an effective strategy for the treatment of multiple sclerosis, leading to improved patient outcomes. This review outlines the steps involved in the entry of myeloid monocytes into the central nervous system that are targets for effective intervention: the activation of bone marrow hematopoiesis, migration of monocytes in the blood, and penetration of the blood–brain barrier by monocytes. Finally, we summarize the different monocyte subpopulations and their effects on the central nervous system based on phenotypic differences. As activated microglia resemble monocyte-derived macrophages, it is important to accurately identify the role of monocyte-derived macrophages in disease. Depending on the roles played by monocyte-derived macrophages at different stages of the disease, several of these processes can be interrupted to limit neuroinflammation and improve patient prognosis. Here, we discuss possible strategies to target monocytes in neurological diseases, focusing on three key aspects of monocyte infiltration into the central nervous system, to provide new ideas for the treatment of neurodegenerative diseases.

关键词： blood–brain barrier macrophages monocytes multiple sclerosis neuroinflammation review therapy

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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.

关键词： neuromorphic computing spintronics magnetic tunnel junction neural networks

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Correlation between the rock mass properties and maximum horizontal stress:A case study of overcoring stress measurements

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International Journal of Minerals,Metallurgy and Materials 2025年第1期32卷 39-48页

作者： Peng Li Meifeng Cai Shengjun miao Yuan Li Yu Wang Key Laboratory of Ministry of Education for Efficient Mining and Safety of Metal Mines University of Science and Technology BeijingBeijing 100083China State Key Laboratory of Coal Resources and Safe Mining China University of Mining and TechnologyXuzhou 221116China

Understanding the mechanical properties of the lithologies is crucial to accurately determine the horizontal stress *** investigate the correlation between the rock mass properties and maximum horizontal stress,the three-dimensional(3D)stress tensors at 89 measuring points determined using an improved overcoring technique in nine mines in China were adopted,a newly defined characteristic parameter C_(ERP)was proposed as an indicator for evaluating the structural properties of rock masses,and a fuzzy relation matrix was established using the information distribution *** results indicate that both the vertical stress and horizontal stress exhibit a good linear growth relationship with *** is no remarkable correlation between the elastic modulus,Poisson's ratio and depth,and the distribution of data points is scattered and ***,there is no obvious relationship between the rock quality designation(RQD)and *** maximum horizontal stress σ_(H) is a function of rock properties,showing a certain linear relationship with the C_(ERP)at the same *** addition,the overall change trend of σ_(H) determined by the established fuzzy identification method is to increase with the increase of C_(ERP).The fuzzy identification method also demonstrates a relatively detailed local relationship betweenσ_H and C_(ERP),and the predicted curve rises in a fluctuating way,which is in accord well with the measured stress data.

关键词： overcoring stress measurements elastic modulus Poisson's ratio rock quality designation maximum horizontal stress fuzzy identification

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