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In patients who had a stroke or TIA, enlarged perivascular spaces in basal ganglia may cause future haemorrhagic strokes

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Stroke & Vascular Neurology 2024年第1期9卷 8-17,I0001-I0033页

作者： Yu Tian Mengxing Wang Yuesong Pan Xia Meng Xingquan Zhao Liping Liu Yongjun Wang Yilong Wang Department of Neurology Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Chinese Institute for brain Research BeijingChina National center for Neurological Diseases BeijingChina advanced innovation center for Human brain Protection Capital Medical UniversityBeijingChina China National Clinical Research center for Neurological Diseases BeijingChina

Introduction It remains unclear whether enlarged perivascular spaces(EPVS)predict poor clinical outcomes in patients with acute ischaemic stroke(AIS)or transient ischaemic attack(TIA).Method data were obtained from the Third China National Stroke Registry study.We estimated EPVS in basal ganglia(BG)and centrum semiovale(CSO)using a semiquantified scale(Grade from 0 to 4).Using Cox and logistic regression analyses,the associations of EPVS with 3-month and 1-year adverse outcomes(including recurrent stroke,ischaemic stroke,haemorrhagic stroke,combined vascular event,disability and mortality)were explored.Sensitivity analyses of any association of cerebral small vessel disease at baseline and development of a small arterial occlusion(SAO)were conducted.Result Among 12603 patients with AIS/TIA,median age was 61.7±11.6 years,and 68.2%were men.After adjusting for all potential confounders,frequent-to-severe BG-EPVS was associated with a decreased risk of recurrent ischaemic stroke(HR 0.71,95%CI 0.55 to 0.92,p=0.01)but an increased risk of haemorrhagic stroke(HR 1.99,95%CI 1.11 to 3.58,p=0.02)at 1 year after AIS/TIA,compared with none-to-mild BG-EPVS.Patients with frequent-to-severe CSO-EPVS had a decreased risk of disability(OR 0.76,95%CI 0.62 to 0.92,p=0.004)and all-cause death(HR 0.55,95%CI 0.31 to 0.98,p=0.04)within 3-month but not 1-year follow-ups,compared with those with none-to-mild BG-EPVS.Sensitivity analyses showed that both BG-EPVS(HR 0.43,95%CI 0.21 to 0.87,p=0.02)and CSO-EPVS(HR 0.58,95%CI 0.35 to 0.95,p=0.03)were associated with a decreased risk of subsequent ischaemic stroke in patients with SAO during 1-year follow-up.Conclusion BG-EPVS increased the risk of haemorrhagic stroke in patients already with AIS/TIA within 1 year.Therefore,caution is recommended when selecting antithrombotic agents for secondary stroke prevention in patients with AIS/TIA and more severe BG-EPVS.

关键词： patients haemorrhagic prevention

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Chitosan-based thermosensitive hydrogel with long-term release of murine nerve growth factor for neurotrophic keratopathy

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Neural Regeneration Research 2024年第3期19卷 680-686页

作者： Jie Wu Yulei Huang Hanrui Yu Kaixiu Li Shifeng Zhang Guoqing Qiao Xiao Liu Hongmei Duan Yifei Huang Kwok-Fai So Zhaoyang Yang Xiaoguang Li Liqiang Wang Department of Ophthalmology the Third Medical CenterChinese PLA General HospitalBeijingChina The PLA Medical College Department of NephrologyChinese PLA Institute of NephrologyState Key Laboratory of Kidney DiseasesNational Clinical Research Center for Kidney DiseasesBeijingChina Department of Ophthalmology Hainan Hospital of Chinese PLA General HospitalSanyaHainan ProvinceChina Medical School of Chinese PLA BeijingChina Department of Neurobiology School of Basic Medical SciencesCapital Medical 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 Administrative RegionChina center for brain Science and brain-Inspired Intelligence Guangdong-Hong Kong-Macao Greater Bay AreaGuangzhouGuangdong ProvinceChina Co-innovation center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina School of Engineering Medicine Beijing Key Laboratory for Biomaterials and Neural RegenerationBeihang UniversityBeijingChina beijing International Cooperation Bases for Science and Technology on Biomaterials and Neural Regeneration Beijing Advanced Innovation Center for Big Data-Based Precision MedicineBeihang UniversityBeijingChina

Neurotrophic keratopathy is a persistent defect of the corneal epithelium,with or without stromal ulceration,due to corneal nerve deficiency caused by a variety of etiologies.The treatment options for neurotrophic keratopathy are limited.In this study,an ophthalmic solution was constructed from a chitosan-based thermosensitive hydrogel with long-term release of murine nerve growth factor(CTH-mNGF).Its effectiveness was evaluated in corneal denervation(CD)mice and patients with neurotrophic keratopathy.In the preclinical setting,CTH-mNGF was assessed in a murine corneal denervation model.CTH-mNGF was transparent,thermosensitive,and ensured sustained release of mNGF for over 20 hours on the ocular surface,maintaining the local mNGF concentration around 1300 pg/mL in vivo.Corneal denervation mice treated with CTH-mNGF for 10 days showed a significant increase in corneal nerve area and total corneal nerve length compared with non-treated and CTH treated mice.A subsequent clinical trial of CTH-mNGF was conducted in patients with stage 2 or 3 neurotrophic keratopathy.Patients received topical CTH-mNGF twice daily for 8 weeks.Fluorescein sodium images,Schirmer’s test,intraocular pressure,Cochet-Bonnet corneal perception test,and best corrected visual acuity were evaluated.In total,six patients(total of seven eyes)diagnosed with neurotrophic keratopathy were enrolled.After 8 weeks of CTH-mNGF treatment,all participants showed a decreased area of corneal epithelial defect,as stained by fluorescence.Overall,six out of seven eyes had fluorescence staining scores<5.Moreover,best corrected visual acuity,intraocular pressure,Schirmer’s test and Cochet-Bonnet corneal perception test results showed no significant improvement.An increase in corneal nerve density was observed by in vivo confocal microscopy after 8 weeks of CTH-mNGF treatment in three out of seven eyes.This study demonstrates that CTH-mNGF is transparent,thermosensitive,and has sustained-release properties.Its effectiveness in healing corneal epithelial defects in

关键词： chitosan corneal reinnervation murine nerve growth factor neurotrophic keratopathy thermosensitive hydrogel

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Tuning the ferroelectricity of HfZrOwith alloy electrodes

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Science China(Information Sciences) 2024年

作者： Keqin LIU Bingjie DANG Zhiyu YANG Teng ZHANG Zhen YANG Jinxuan BAI Zelun PAN Ru HUANG Yuchao YANG beijing advanced innovation center for Integrated Circuits School of Integrated Circuits Peking University School of Electronic and Computer Engineering Peking University center for brain Inspired Chips Institute for Artificial Intelligence Peking University center for brain Inspired Intelligence Chinese Institute for Brain Research

Tuning ferroelectricity of Hf0.5Zr0.5O2 is crucial for facilitating its practical applications in various fields, including in-memory and neuromorphic computing. Previous studies have revealed that the electrodes have a significant influence on ferroelectricity, and changing electrode materials can realize different but discrete ferroelectric polarization values. Here, we introduce an alloy-electrode method, in order to achieve gradual and accurate modulation of ferroelectric polarization, especially useful for matching the polarization charges at the interface of ferroelectric insulators and ferroelectric semiconductors. Au and W electrodes are chosen as baselines for realizing weak and strong ferroelectric polarization, where the intermediate states can be achieved by adjusting the ratio of metals in the Au-W alloy. To demonstrate the generality of this approach, the Cu-W alloy electrode is also realized for tuning ferroelectric polarization. The effect of alloy electrodes on device leakage current, endurance, and retention is evaluated. In addition, the temperature stability of ferroelectric capacitors is tested, where limited changes in both remnant polarization and coercive voltages are observed, showing the great potential of the ferroelectric hafnium oxide. Such gradual modulation of ferroelectric polarization could facilitate the application of Hf0.5Zr0.5O2 in in-memory and neuromorphic computing.

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A Novel Retrograde AAV Variant for Functional Manipulation of Cortical Projection Neurons in Mice and Monkeys

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Neuroscience Bulletin 2024年第1期40卷 90-102页

作者： Yefei Chen Jingyi Wang Jing Liu Jianbang Lin Yunping Lin Jinyao Nie Qi Yue Chunshan Deng Xiaofei Qi Yuantao Li Ji Dai Zhonghua Lu Department of Anesthesiology Shenzhen Maternity and Child Healthcare HospitalThe First School of Clinical MedicineSouthern Medical UniversityShenzhen 518027China Shenzhen Technological Research center for Primate Translational Medicine Shenzhen Key Laboratory for Molecular Biology of Neural DevelopmentShenzhen-Hong Kong Institute of Brain ScienceShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China University of Chinese Academy of Sciences Beijing 100049China CAS Key Laboratory of brain Connectome and Manipulation the Brain Cognition and Brain Disease InstituteShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China Guangdong Provincial Key Laboratory of brain Connectome and Behavior the Brain Cognition and Brain Disease InstituteShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China Biomedical Research Institute Hubei University of MedicineShiyan 442000China Faculty of Life and Health Sciences Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China

Retrograde adeno-associated viruses(AAVs)are capable of infecting the axons of projection neurons and serve as a powerful tool for the anatomical and functional characterization of neural networks.However,few retro-grade AAV capsids have been shown to offer access to cor-tical projection neurons across different species and enable the manipulation of neural function in non-human primates(NHPs).Here,we report the development of a novel retro-grade AAV capsid,AAV-DJ8R,which efficiently labeled cortical projection neurons after local administration into the striatum of mice and macaques.In addition,intrastriatally injected AAV-DJ8R mediated opsin expression in the mouse motor cortex and induced robust behavioral alterations.Moreover,AAV-DJ8R markedly increased motor cortical neuron firing upon optogenetic light stimulation after viral delivery into the macaque putamen.These data demonstrate the usefulness of AAV-DJ8R as an efficient retrograde tracer for cortical projection neurons in rodents and NHPs and indicate its suitability for use in conducting functional interrogations.

关键词： Retrograde AAV Capsid variant Cortical projection neuron Optogenetics Monkey

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Identification of FOXO1 as a geroprotector in human synovium through single-nucleus transcriptomic profiling

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Protein & Cell 2024年第6期15卷 441-459页

作者： Feifei Liu Yi Lu Xuebao Wang Shuhui Sun Huize Pan Min Wang Zehua Wang Weiqi Zhang Shuai Ma Guoqiang Sun Qun Chu Si Wang Jing Qu Guang-Hui Liu State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Sports Medicine Department Beijing Jishuitan HospitalCapital Medical UniversityBeijing 100035China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China National Laboratory of Biomacromolecules Institute of BiophysicsChinese Academy of SciencesBeijing 100101China Division of Life Sciences and Medicine School of Life SciencesUniversity of Science and Technology of ChinaHefei 230001China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China The Fifth People’s Hospital of Chongqing Chongqing 400062China advanced innovation center for Human brain Protection and National Clinical Research center for Geriatric Disorders Xuanwu Hospital Capital Medical UniversityBeijing 100053China Aging Translational Medicine center International Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijing 100053China

The synovium,a thin layer of tissue that is adjacent to the joints and secretes synovial fluid,undergoes changes in aging that contribute to intense shoulder pain and other joint diseases.However,the mechanism underlying human synovial aging remains poorly characterized.Here,we generated a comprehensive transcriptomic profile of synovial cells present in the subacromial synovium from young and aged individuals.By delineating aging-related transcriptomic changes across different cell types and their associated regulatory networks,we identified two subsets of mesenchymal stromal cells(MSCs)in human synovium,which are lining and sublining MSCs,and found that angiogenesis and fibrosis-associated genes were upregulated whereas genes associated with cell adhesion and cartilage development were downregulated in aged MSCs.Moreover,the specific cell-cell communications in aged synovium mirrors that of aging-related inflammation and tissue remodeling,including vascular hyperplasia and tissue fibrosis.In particular,we identified forkhead box O1(FOXO1)as one of the major regulons for aging differentially expressed genes(DEGs)in synovial MSCs,and validated its downregulation in both lining and sublining MSC populations of the aged synovium.In human FOXO1-depleted MSCs derived from human embryonic stem cells,we recapitulated the senescent phenotype observed in the subacromial synovium of aged donors.These data indicate an important role of FOXO1 in the regulation of human synovial aging.Overall,our study improves our understanding of synovial aging during joint degeneration,thereby informing the development of novel intervention strategies aimed at rejuvenating the aged joint.

关键词： FOXO1 degeneration inflammation

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Multimodal Fusion of brain Imaging data: Methods and Applications

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Machine Intelligence Research 2024年第1期21卷 136-152页

作者： Na Luo Weiyang Shi Zhengyi Yang Ming Song Tianzi Jiang brainnetome center and National Laboratory of Pattern Recognition Institute of AutomationChinese Academy of SciencesBeijing 100190China School of Artificial Intelligence University of Chinese Academy of SciencesBeijing 100049China center for Excellence in brain Science and Intelligence Technology Institute of AutomationChinese Academy of SciencesBeijing 100190China Research center for Augmented Intelligence Zhejiang LaboratoryHangzhou 311100China

Neuroimaging data typically include multiple modalities,such as structural or functional magnetic resonance imaging,dif-fusion tensor imaging,and positron emission tomography,which provide multiple views for observing and analyzing the brain.To lever-age the complementary representations of different modalities,multimodal fusion is consequently needed to dig out both inter-modality and intra-modality information.With the exploited rich information,it is becoming popular to combine multiple modality data to ex-plore the structural and functional characteristics of the brain in both health and disease status.In this paper,we first review a wide spectrum of advanced machine learning methodologies for fusing multimodal brain imaging data,broadly categorized into unsupervised and supervised learning strategies.Followed by this,some representative applications are discussed,including how they help to under-stand the brain arealization,how they improve the prediction of behavioral phenotypes and brain aging,and how they accelerate the biomarker exploration of brain diseases.Finally,we discuss some exciting emerging trends and important future directions.Collectively,we intend to offer a comprehensive overview of brain imaging fusion methods and their successful applications,along with the chal-lenges imposed by multi-scale and big data,which arises an urgent demand on developing new models and platforms.

关键词： Multimodal fusion supervised learning unsupervised learning brain atlas cognition brain disorders

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Multimodal Omics Approaches to Aging and Age‑Related Diseases

Phenomics

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Phenomics 2024年第1期4卷 56-71页

作者： Qianzhao Ji Xiaoyu Jiang Minxian Wang Zijuan Xin Weiqi Zhang Jing Qu Guang‑Hui Liu State Key Laboratory of Membrane Biology Instituteof ZoologyChinese Academy of SciencesBeijing 100101China State Key Laboratory of Stem Cell and ReproductiveBiology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Key Laboratory of Organ Regeneration and Reconstruction Institute of ZoologyChinese Academy of SciencesBeijing 100101China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academyof Sciences and China National Center for BioinformationBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Institute for Stem Cell and Regeneration Chinese Academyof SciencesBeijing 100101China beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China School of Future Technology University of ChineseAcademy of SciencesBeijing 100190China advanced innovation center for Human brain Protection National Clinical Research Center for GeriatricDisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China Aging Translational Medicine center International Centerfor Aging and CancerXuanwu HospitalCapital MedicalUniversityBeijing 100053China

Aging is associated with a progressive decline in physiological capacities and an increased risk of aging-associated disorders.An increasing body of experimental evidence shows that aging is a complex biological process coordinately regulated by multiple factors at diferent molecular layers.Thus,it is difcult to delineate the overall systematic aging changes based on single-layer data.Instead,multimodal omics approaches,in which data are acquired and analyzed using complementary omics technologies,such as genomics,transcriptomics,and epigenomics,are needed for gaining insights into the precise molecular regulatory mechanisms that trigger aging.In recent years,multimodal omics sequencing technologies that can reveal complex regulatory networks and specifc phenotypic changes have been developed and widely applied to decode aging and age-related diseases.This review summarizes the classifcation and progress of multimodal omics approaches,as well as the rapidly growing number of articles reporting on their application in the feld of aging research,and outlines new developments in the clinical treatment of age-related diseases based on omics technologies.

关键词： Multimodal omics approaches Aging Genome Epigenome

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A Bitcoin Address Multi-Classification Mechanism Based on Bipartite Graph-Based Maximization Consensus

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Computer Modeling in Engineering & Sciences 2024年第4期139卷 783-800页

作者： Lejun Zhang Junjie Zhang Kentaroh Toyoda Yuan Liu Jing Qiu Zhihong Tian Ran Guo College of Information Engineering Yangzhou UniversityYangzhou225127China Cyberspace Institute advanced Technology Guangzhou UniversityGuangzhou510006China Research and Development center for E-Learning Ministry of EducationBeijing100039China Institute of High Performance computing(IHPC) Agency for ScienceTechnology and Research(A∗STAR)Singapore138632Singapore School of Physics and Materials Science Guangzhou UniversityGuangzhou510006China

Bitcoin is widely used as the most classic electronic currency for various electronic services such as exchanges,gambling,marketplaces,and also scams such as high-yield investment projects.Identifying the services operated by a Bitcoin address can help determine the risk level of that address and build an alert model accordingly.Feature engineering can also be used to flesh out labeled addresses and to analyze the current state of Bitcoin in a small way.In this paper,we address the problem of identifying multiple classes of Bitcoin services,and for the poor classification of individual addresses that do not have significant features,we propose a Bitcoin address identification scheme based on joint multi-model prediction using the mapping relationship between addresses and entities.The innovation of the method is to(1)Extract as many valuable features as possible when an address is given to facilitate the multi-class service identification task.(2)Unlike the general supervised model approach,this paper proposes a joint prediction scheme for multiple learners based on address-entity mapping relationships.Specifically,after obtaining the overall features,the address classification and entity clustering tasks are performed separately,and the results are subjected to graph-basedmaximization consensus.The final result ismade to baseline the individual address classification results while satisfying the constraint of having similarly behaving entities as far as possible.By testing and evaluating over 26,000 Bitcoin addresses,our feature extraction method captures more useful features.In addition,the combined multi-learner model obtained results that exceeded the baseline classifier reaching an accuracy of 77.4%.

关键词： Bitcoin multi-service classification graph maximization consensus data security

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Transcriptomic analysis of Andrias davidianus meat and experimental validation for exploring its bioactive components as functional foods

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Food Science and Human Wellness 2024年第1期13卷 166-172页

作者： Changge Guan Zhenglin Tan Shucheng Li Yi Wang Naoyuki Yamamoto Chong Zhang Songjun Wang Junjie Chen Xinhui Xing Key Laboratory for Industrial Biocatalysis Ministry of Education of ChinaDepartment of Chemical EngineeringTsinghua UniversityBeijing 100084China School of Life Science and Technology Tokyo Institute of TechnologyYokohama 226-0026Japan Sensing System Research center National Institute of Advanced Industrial Science and TechnologyTsukuba 305-8565Japan center for Synthetic and Systems Biology Tsinghua UniversityBeijing 100084China Henan Giant Salamander Protection and Development Association Luoyang 471000China Intelligent computing Research center Harbin Institute of TechnologyShenzhen 518071China Institute of Biopharmaceutical and Health Engineering Tsinghua Shenzhen International Graduate SchoolShenzhen 518055China Institute of Biomedical Health Technology and Engineering Shenzhen Bay LaboratoryShenzhen 518067China

Andrias davidianus(Chinese giant salamander,CGS)is the largest and oldest extant amphibian species in the world and is a source of prospective functional food in China.However,the progress of functional peptides mining was slow due to lack of reference genome and protein sequence data.In this study,we illustrated full-length transcriptome sequencing to interpret the proteome of CGS meat and obtain 10703 coding DNA sequences.By functional annotation and amino acid composition analysis,we have discovered various genes related to signal transduction,and 16 genes related to longevity.We have also found vast variety of functional peptides through protein coding sequence(CDS)analysis by comparing the data obtained with the functional peptide database.Val-Pro-Ile predicted by the CDS analysis was released from the CGS meat through enzymatic hydrolysis,suggesting that our approach is reliable.This study suggested that transcriptomic analysis can be used as a reference to guide polypeptide mining in CGS meat,thereby providing a powerful mining strategy for the bioresources with unknown genomic and proteomic sequences.

关键词： Chinese giant salamander Transcriptomic analysis Bioactive components Functional peptides mining

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Dear-DIA^(XMBD): Deep Autoencoder Enables Deconvolution of data-Independent Acquisition Proteomics

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Research 2024年第1期6卷 707-720页

作者： Qingzu He Chuan-Qi Zhong Xiang Li Huan Guo Yiming Li Mingxuan Gao Rongshan Yu Xianming Liu Fangfei Zhang Donghui Guo Fangfu Ye Tiannan Guo Jianwei Shuai Jiahuai Han Department of Physics and Fujian Provincial Key Laboratory for Soft Functional Materials ResearchXiamen UniversityXiamen 361005China Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)and Wenzhou InstituteUniversity of Chinese Academy of SciencesWenzhouZhejiang 325001China School of Life Sciences Xiamen UniversityXiamen 361102China State Key Laboratory of Cellular Stress Biology Innovation Center for Cell Signaling NetworkXiamen 361102China Department of Computer Science Xiamen UniversityXiamen 361005China National Institute for data Science in Health and Medicine School of MedicineXiamen UniversityXiamen 361102China Bruker(beijing)Scientific Technology Co.Ltd. BeijingChina Westlake Laboratory of Life Sciences and Biomedicine Key Laboratory of Structural Biology of Zhejiang ProvinceSchool of Life SciencesWestlake University18 Shilongshan RoadHangzhou 310024China Institute of Basic Medical Sciences Westlake Institute for Advanced Study18 Shilongshan RoadHangzhou 310024China Westlake Omics Ltd. Yunmeng Road 1HangzhouChina Department of Electronic Engineering Xiamen UniversityXiamen 361005China

data-independent acquisition(DIA)technology for protein identification from mass spectrometry and related algorithms is developing rapidly.The spectrum-centric analysis of DIA data without the use of spectra library from data-dependent acquisition data represents a promising direction.In this paper,we proposed an untargeted analysis method,Dear-DIA^(XMBD),for direct analysis of DIA data.Dear-DIA^(XMBD) first integrates the deep variational autoencoder and triplet loss to learn the representations of the extracted fragment ion chromatograms,then uses the k-means clustering algorithm to aggregate fragments with similar representations into the same classes,and finally establishes the inverted index tables to determine the precursors of fragment clusters between precursors and peptides and between fragments and peptides.We show that Dear-DIA^(XMBD) performs superiorly with the highly complicated DIA data of different species obtained by different instrument platforms.

关键词： Deep Auto Independent

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