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Decreased levels of phosphorylated synuclein in plasma are correlated with poststroke cognitive impairment

Neural Regeneration Research 2025年第9期20卷 2598-2610页

作者： Yi Wang Yuning Li Yakun Gu Wei Ma Yuying Guan Mengyuan Guo Qianqian Shao Xunming Ji Jia Liu Department of Clinical Laboratory Beijing Bo’ai HospitalChina Rehabilitation Research CenterCapital Medical UniversityBeijingChina beijing institute of brain disorders Laboratory of Brain DisordersMinistry of Science and TechnologyCollaborative Innovation Center for Brain DisordersBeijing Advanced Innovation Center for Big Data-based Precision MedicineCapital Medical UniversityBeijingChina Department of Neurosurgery Xuanwu HospitalCapital Medical UniversityBeijingChina

Poststro ke cognitive impairment is a major secondary effect of ischemic stroke in many patients;however,few options are available for the early diagnosis and treatment of this *** aims of this study were to(1)determine the specific relationship between hypoxic andα-synuclein during the occur of poststroke cognitive impairment and(2)assess whether the serum phosphorylatedα-synuclein level can be used as a biomarker for poststro ke cognitive *** found that the phosphorylatedα-synuclein level was significantly increased and showed pathological aggregation around the cerebral infa rct area in a mouse model of ischemic *** addition,neuronalα-synuclein phosphorylation and aggregation were observed in the brain tissue of mice subjected to chronic hypoxia,suggesting that hypoxia is the underlying cause ofα-synuclein-mediated pathology in the brains of mice with ischemic *** phosphorylatedα-synuclein levels in patients with ischemic stroke were significantly lower than those in healt hy subjects,and were positively correlated with cognition levels in patients with ischemic ***,a decrease in serum high-density lipoprotein levels in stroke patie nts was significantly correlated with a decrease in phosphorylatedα-synuclein *** ischemic stroke mice did not show significant cognitive impairment or disrupted lipid metabolism 14 days after injury,some of them exhibited decreased cognitive function and reduced phosphorylatedα-synuclein *** together,our results suggest that serum phosphorylatedα-synuclein is a potential biomarker for poststroke cognitive impairment.

关键词： biomarker high-density lipoprotein ischemic stroke phosphorylatedα-synuclein poststroke cognitive impairment

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Timing of biomarker changes preceding Alzheimer's disease:for diagnosis,treatment or prevention?

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Science China(Life Sciences) 2025年第2期68卷 575-577页

作者： Meina Quan Innovation Center for Neurological disorders and Department of Neurology Xuanwu HospitalCapital Medical UniversityBeijing 100053China National Medical Center for Neurological Diseases and National Clinical Research Center for Geriatric Diseases Beijing 100053China Center of Alzheimer’s Disease Beijing Institute of Brain DisordersCollaborative Innovation Center for Brain DisordersBeijing 100053China

The pathophysiological and behavioural features of Alzheimer’s disease(AD)have been extensively investigated in transgenic mouse models,including the temporal sequence of each pathophysiological change and behavioural abnormality,a summary of which was recently presented by our team in this Journal(Li et al.,2023).Nevertheless,studying such features and timings directly in human patients before symptoms occur is challenging.

关键词： prevention Alzheimer diagnosis

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High-dose dexamethasone regulates microglial polarization via the GR/JAK1/STAT3 signaling pathway after traumatic brain injury

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Neural Regeneration Research 2025年第9期20卷 2611-2623页

作者： Mengshi Yang Miao Bai Yuan Zhuang Shenghua Lu Qianqian Ge Hao Li Yu Deng Hongbin Wu Xiaojian Xu Fei Niu Xinlong Dong Bin Zhang Baiyun Liu beijing Tiantan Hospital Capital Medical UniversityBeijingChina Department of Neurology The First Hospital of Tsinghua UniversityBeijingChina Department of Neurotrauma and beijing Key Laboratory of Central Nervous System Injury Beijing Neurosurgical InstituteCapital Medical UniversityBeijingChina Department of Critical Care Medicine Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Center for Nerve Injury and Repair Beijing Institute of Brain DisordersChina National Clinical Research Center for Neurological DiseasesBeijingChina

Although microglial polarization and neuroinflammation are crucial cellular responses after traumatic brain injury,the fundamental regulatory and functional mechanisms remain insufficiently *** potent anti-inflammato ry agents,the use of glucoco rticoids in traumatic brain injury is still controversial,and their regulatory effects on microglial polarization are not yet *** the present study,we sought to determine whether exacerbation of traumatic brain injury caused by high-dose dexamethasone is related to its regulatory effects on microglial polarization and its mechanisms of *** vitro cultured BV2 cells and primary microglia and a controlled cortical impact mouse model were used to investigate the effects of dexamethasone on microglial ***,dexamethasone,RU486(a glucocorticoid receptor antagonist),and ruxolitinib(a Janus kinase 1 antagonist)were ***-sequencing data obtained from a C57BL/6 mouse model of traumatic brain injury were used to identify potential targets of *** Morris water maze,quantitative reverse transcription-polymerase chain reaction,western blotting,immunofluorescence and confocal microscopy analysis,and TUNEL,Nissl,and Golgi staining were performed to investigate our ***-throughput sequencing results showed that arginase 1,a marker of M2 microglia,was significantly downregulated in the dexamethasone group compared with the traumatic brain injury group at3 days post-traumatic brain *** dexamethasone inhibited M1 and M2 microglia,with a more pronounced inhibitory effect on M2microglia in vitro and in *** receptor plays an indispensable role in microglial polarization after dexamethasone treatment following traumatic brain ***,glucocorticoid receptor activation increased the number of apoptotic cells and neuronal death,and also decreased the density of dendritic spines.A possible downstream receptor signaling mechanism is th

关键词： apoptosis BV2 microglia dexamethasone glucocorticoid receptor glucocorticoids innate immune system microglial polarization neuroinflammation primary microglia traumatic brain injury

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General Automatic Solution Generation for Social Problems

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Machine Intelligence Research 2025年第1期22卷 145-159页

作者： Tong Niu Haoyu Huang Yu Du Weihao Zhang Luping Shi Rong Zhao Center for brain-Inspired Computing Research(CBICR) Optical Memory National Engineering Research Centerand Department of Precision InstrumentTsinghua UniversityBeijing100084China IDG/McGovern institute for brain Research Tsinghua UniversityBeijing100084China THU-CET HIK Joint Research Center for brain-Inspired Computing Beijing100084China

Given the escalating intricacy and multifaceted nature of contemporary social systems,manually generating solutions to address pertinent social issues has become a formidable *** response to this challenge,the rapid development of artificial intelligence has spurred the exploration of computational methodologies aimed at automatically generating ***,current methods for the auto-generation of solutions mainly concentrate on local social regulations that pertain to specific ***,we report an automatic social operating system(ASOS)designed for general social solution generation built upon agent-based models that enables both global and local analyses and regulations of social problems across spatial and temporal *** adopts a hypergraph with extensible social semantics for a comprehensive and structured representation of social *** also incorporates a generalized protocol for standardized hypergraph operations and a symbolic hybrid framework that delivers interpretable solutions,yielding a balance between regulatory efficacy and functional *** demonstrate the effectiveness of the ASOS,we apply it to the domain of averting extreme events within international oil futures *** generating a new trading role supplemented by new mechanisms,ASOS can adeptly discern precarious market conditions and make front-running interventions for nonprofit *** study demonstrated that ASOS provides an efficient and systematic approach for generating solutions for enhancing our society.

关键词： General automatic generation global-local regulation hypergraph social representation symbolic hybrid scheme generalized operation protocol

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Increased excitatory amino acid transporter 2 levels in basolateral amygdala astrocytes mediate chronic stress–induced anxiety-like behavior

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Neural Regeneration Research 2025年第6期20卷 1721-1734页

作者： Xirong Xu Shoumin Xuan Shuai Chen Dan Liu Qian Xiao Jie Tu Shenzhen Key Laboratory of Neuroimmunomodulation for Neurological Diseases Shenzhen-Hong Kong Institute of Brain ScienceShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong ProvinceChina CAS Key Laboratory of brain Connectome and Manipulation Brain Cognition and Brain Disease Institute(BCBDI)Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong ProvinceChina Guangdong Provincial Key Laboratory of brain Connectome and Behavior the Brain Cognition and Brain Disease Institute(BCBDI)Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong ProvinceChina University of Chinese of Academy of Sciences BeijingChina Faculty of Life and Health Sciences Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong ProvinceChina

The conventional perception of astrocytes as mere supportive cells within the brain has recently been called into question by empirical evidence, which has revealed their active involvement in regulating brain function and encoding behaviors associated with ***, astrocytes in the basolateral amygdala have been found to play a role in the modulation of anxiety-like behaviors triggered by chronic stress. Nevertheless, the precise molecular mechanisms by which basolateral amygdala astrocytes regulate chronic stress–induced anxiety-like behaviors remain to be fully elucidated. In this study, we found that in a mouse model of anxiety triggered by unpredictable chronic mild stress, the expression of excitatory amino acid transporter 2 was upregulated in the basolateral amygdala. Interestingly, our findings indicate that the targeted knockdown of excitatory amino acid transporter 2 specifically within the basolateral amygdala astrocytes was able to rescue the anxiety-like behavior in mice subjected to stress. Furthermore, we found that the overexpression of excitatory amino acid transporter 2 in the basolateral amygdala, whether achieved through intracranial administration of excitatory amino acid transporter 2agonists or through injection of excitatory amino acid transporter 2-overexpressing viruses with GfaABC1D promoters, evoked anxiety-like behavior in mice. Our single-nucleus RNA sequencing analysis further confirmed that chronic stress induced an upregulation of excitatory amino acid transporter 2 specifically in astrocytes in the basolateral amygdala. Moreover, through in vivo calcium signal recordings, we found that the frequency of calcium activity in the basolateral amygdala of mice subjected to chronic stress was higher compared with normal *** knocking down the expression of excitatory amino acid transporter 2 in the basolateral amygdala, the frequency of calcium activity was not significantly increased, and anxiety-like behavior was ob

关键词： anxiety astrocytes basolateral amygdala behavior dihydrokainic acid excitatory amino acid transporter 2 fiber photometry glutamate LDN-212320 transporter

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Storage time affects the level and diagnostic efficacy of plasma biomarkers for neurodegenerative diseases

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Neural Regeneration Research 2025年第8期20卷 2373-2381页

作者： Lifang Zhao Mingkai Zhang Qimeng Li Xuemin Wang Jie Lu Ying Han Yanning Cai Department of Clinical Biobank Xuanwu HospitalCapital Medical UniversityBeijingChina beijing Geriatric Medical Research Center BeijingChina Department of Neurology Xuanwu HospitalCapital Medical UniversityBeijingChina Department of Radiology and Nuclear Medicine Xuanwu HospitalCapital Medical UniversityBeijingChina beijing Key Laboratory of Magnetic Resonance Imaging and brain Informatics BeijingChina Key Laboratory of Neurodegenerative diseases Ministry of EducationBeijingChina School of Biomedical Engineering Hainan UniversityHaikouHainan ProvinceChina Center of Alzheimer’s Disease Beijing Institute for Brain DisordersBeijingChina National Clinical Research Center for Geriatric Diseases BeijingChina institute of Biomedical Engineering Shenzhen Bay LaboratoryGaoke Innovation CenterShenzhenGuangdong ProvinceChina Department of Neurobiology Xuanwu HospitalCapital Medical UniversityBeijingChina

Several promising plasma biomarker proteins,such as amyloid-β(Aβ),tau,neurofilament light chain,and glial fibrillary acidic protein,are widely used for the diagnosis of neurodegenerative ***,little is known about the long-term stability of these biomarker proteins in plasma samples stored at-80°*** aimed to explore how storage time would affect the diagnostic accuracy of these biomarkers using a large *** samples from 229 cognitively unimpaired individuals,encompassing healthy controls and those experiencing subjective cognitive decline,as well as 99 patients with cognitive impairment,comprising those with mild cognitive impairment and dementia,were acquired from the Sino Longitudinal Study on Cognitive Decline *** samples were stored at-80°C for up to 6 years before being used in this *** results showed that plasma levels of Aβ42,Aβ40,neurofilament light chain,and glial fibrillary acidic protein were not significantly correlated with sample storage ***,the level of total tau showed a negative correlation with sample storage ***,in individuals without cognitive impairment,plasma levels of total protein and tau phosphorylated protein threonine 181(p-tau181)also showed a negative correlation with sample storage *** was not observed in individuals with cognitive ***,we speculate that the diagnostic accuracy of plasma p-tau181 and the p-tau181 to total tau ratio may be influenced by sample storage ***,caution is advised when using these plasma biomarkers for the identification of neurodegenerative diseases,such as Alzheimer's ***,in cohort studies,it is important to consider the impact of storage time on the overall results.

关键词： Alzheimer’s disease amyloid-β diagnostic ability glial fibrillary acidic protein neurodegeneration neurofilament light chain plasma biomarkers single molecule array storage time tau

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Critical biomarkers for responsive deep brain stimulation and responsive focal cortex stimulation in epilepsy field

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Fundamental Research 2025年第1期5卷 103-114页

作者： Zhikai Yu Binghao Yang Penghu Wei Hang Xu Yongzhi Shan Xiaotong Fan Huaqiang Zhang Changming Wang a d Jingjing Wang Shan Yu Guoguang Zhao Department of Neurosurgery Xuanwu HospitalCapital Medical UniversityBeijing 100053China Laboratory of brain Atlas and brain Inspired Intelligence Institute of AutomationChinese Academy of ScienceBeijing 100190China Clinical Research Center for Epilepsy Capital Medical UniversityBeijing 100053China Laboratory of brain Inspired Intelligence Capital Medical UniversityBeijing 100053China School of Future Technology University of Chinese Academy of ScienceBeijing 101408China

To derive critical signal features from intracranial electroencephalograms of epileptic patients in order to design instructions for feedback-type electrical stimulation *** Detrended Fluctuation Analysis(DFA)exponent is chosen as the classification exponent,and the disparities between indicators representing distinct seizure states and the classification efficacy of rudimentary machine learning models are *** DFA exponent exhibited a statistically significant variation among the pre-ictal,ictal period,and post-ictal *** Linear Discriminant Analysis model demonstrates the highest accuracy among the three basic machine learning models,whereas the Naive Bayesian model necessitates the least amount of computational and storage *** set of DFA exponents is employed as an intermediary variable in the machine learning *** resultant model possesses the capability to function as a feedback trigger program for electrical stimulation systems of the feedback variety,specifically within the domain of neural modulation in epilepsy.

关键词： Biomarker Critical state Feedback electrical stimulation Epilepsy brain computer interface

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Activation of adult endogenous neurogenesis by a hyaluronic acid collagen gel containing basic fibroblast growth factor promotes remodeling and functional recovery of the injured cerebral cortex

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Neural Regeneration Research 2025年第10期20卷 2923-2937页

作者： Yan Li Peng Hao Hongmei Duan Fei Hao Wen Zhao Yudan Gao Zhaoyang Yang Kwok-Fai So Xiaoguang Li Department of Neurobiology School of Basic Medical SciencesCapital Medical UniversityBeijingChina China Rehabilitation Science institute China Rehabilitation Research CenterBeijing Key Laboratory of Neural Injury and RehabilitationBeijingChina Center of Neural Injury and Repair Beijing Institute for Brain DisordersBeijingChina beijing Key Laboratory for Biomaterials and Neural Regeneration School of Engineering MedicineBeihang UniversityBeijingChina Guangdong-HongKong-Macao institute of CNS Regeneration Ministry of Education CNS Regeneration Collaborative Joint LaboratoryJinan UniversityGuangzhouGuangdong ProvinceChina Bioland Laboratory(Guangzhou Regenerative Medicine and Health Guangdong Laboratory) GuangzhouGuangdong ProvinceChina Department of Ophthalmology and State Key Laboratory of brain and Cognitive Sciences The University of Hong KongHong Kong Special Administration RegionChina Center for brain Science and brain-Inspired Intelligence Guangdong-HongKong-Macao Greater Bay AreaGuangzhouGuangdong ProvinceChina Co-innovation Center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina Department of Biomedical Engineering School of Biological Science and Medical EngineeringBeihang UniversityBeijingChina

The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after ***,whether it is possible to stimulate neurogenesis and reconstruct cortical layers II to VI in non-neurogenic regions,such as the cortex,remains *** this study,we implanted a hyaluronic acid collagen gel loaded with basic fibroblast growth factor into the motor cortex immediately following traumatic *** findings reveal that this gel effectively stimulated the proliferation and migration of endogenous neural stem/progenitor cells,as well as their differentiation into mature and functionally integrated ***,these new neurons reconstructed the architecture of cortical layers II to VI,integrated into the existing neural circuitry,and ultimately led to improved brain *** findings offer novel insight into potential clinical treatments for traumatic cerebral cortex injuries.

关键词： adult endogenous neurogenesis basic fibroblast growth factor-hyaluronic acid collagen gel cortical remodeling functional recovery migration motor cortex injury neural circuits neural stem cells newborn neurons proliferation

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Plasma circulating cell–free DNA integrity and relative telomere length as diagnostic biomarkers for Parkinson's disease and multiple system atrophy:a cross-sectional study

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Neural Regeneration Research 2025年第12期20卷 3553-3563页

作者： Chao Ying Chao Han Yuan Li Mingkai Zhang Shuying Xiao Lifang Zhao Hui Zhang Qian Yu Jing An Wei Mao Yanning Cai Department of Neurobiology Xuanwu HospitalCapital Medical UniversityBeijingChina beijing Municipal Geriatric Medical Research Center BeijingChina Key Laboratory for Neurodegenerative Diseases of the Ministry of Education Beijing Key Laboratory of Parkinson’s DiseaseParkinson’s Disease Center for Beijing Institute on Brain DisordersClinical and Research Center for Parkinson’s DiseaseCapital Medical UniversityBeijingChina National Clinical Research Center for Geriatric disorders Xuanwu HospitalCapital Medical UniversityBeijingChina Department of Neurology Xuanwu HospitalCapital Medical UniversityBeijingChina Department of Clinical Biobank and Central Laboratory Xuanwu HospitalCapital Medical UniversityBeijingChina School of Health Professions Stony Brook UniversityStony BrookNYUSA

In clinical specialties focusing on neurological disorders,there is a need for comprehensive and integrated non-invasive,sensitive,and specific testing *** Parkinson's disease and multiple system atrophy are classified asα-synucleinopathies,characterized by abnormal accumulation ofα-synuclein protein,which provides a shared pathological background for their comparative *** addition,both Parkinson's disease and multiple system atrophy involve neuronal death,a process that may release circulating cell–free DNA(cfDNA)into the bloodstream,leading to specific *** premise formed the basis for investigating cell–free DNA as a potential *** DNA has garnered attention for its potential pathological significance,yet its characteristics in the context of Parkinson's disease and multiple system atrophy are not fully *** study investigated the total concentration,nonapoptotic level,integrity,and cellfree DNA relative telomere length of cell-free DNA in the peripheral blood of 171 participants,comprising 76 normal controls,62 patients with Parkinson's disease,and 33 patients with multiple system *** our cohort,75.8%of patients with Parkinson's disease(stage 1–2 of Hoehn&Yahr)and 60.6%of patients with multiple system atrophy(disease duration less than 3 years)were in the early *** diagnostic potential of the cell-free DNA parameters was evaluated using receiver operating characteristic(ROC)analysis,and their association with disease prevalence was examined through logistic regression models,adjusting for confounders such as age,sex,body mass index,and education *** results showed that cell-free DNA integrity was significantly elevated in both Parkinson's disease and multiple system atrophy patients compared with normal controls(P<0.001 for both groups),whereas cell-free DNA relative telomere length was markedly shorter(P=0.003 for Parkinson's disease and P=0.010 for multiple system atrophy).Receiver operatin

关键词： biomarkers cell-free DNA diagnosis multiple system atrophy neurodegenerative diseases Parkinson’s disease risk factors

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Progress of research in the application of ultrasound technology for the treatment of Alzheimer’s disease

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Neural Regeneration Research 2025年第10期20卷 2823-2837页

作者： Qiuquan Cai Lianghui Meng Meina Quan Ling Wang Jing Ren Chenguang Zheng Jiajia Yang Dong Ming Academy of Medical Engineering and Translational Medicine Tianjin UniversityTianjinChina Innovation Center for Neurological disorders Xuanwu HospitalCapital Medical UniversityBeijingChina brain-Computer Interaction and Human-Machine Fusion Haihe Laboratory Tianjin UniversityTianjinChina Tianjin Key Laboratory of brain Science and Neural Engineering Tianjin UniversityTianjinChina

Alzheimer’s disease is a common neurodegenerative disorder defined by decreased reasoning abilities,memory loss,and cognitive *** presence of the blood-brain barrier presents a major obstacle to the development of effective drug therapies for Alzheimer’s *** use of ultrasound as a novel physical modulation approach has garnered widespread attention in recent *** a safe and feasible therapeutic and drug-delivery method,ultrasound has shown promise in improving cognitive *** article provides a summary of the application of ultrasound technology for treating Alzheimer’s disease over the past 5 years,including standalone ultrasound treatment,ultrasound combined with microbubbles or drug therapy,and magnetic resonance imaging-guided focused ultrasound *** is placed on the benefits of introducing these treatment methods and their potential *** found that several ultrasound methods can open the blood-brain barrier and effectively alleviate amyloid-βplaque *** believe that ultrasound is an effective therapy for Alzheimer’s disease,and this review provides a theoretical basis for future ultrasound treatment methods.

关键词： Alzheimer’s disease blood-brain barrier drugs magnetic resonance imaging-guided focused ultrasound microbubbles scanning ultrasound ultrasound ultrasound stimulation

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