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FSAP aggravated endothelial dysfunction and neurological deficits in acute ischemic stroke due to large vessel occlusion

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Signal Transduction and Targeted Therapy 2022年第2期7卷 466-478页

作者： dai-shi tian Chuan Qin Luo-Qi Zhou Sheng Yang Man Chen Jun Xiao Ke Shang Dale BBosco Long-Jun Wu Wei Wang Department of Neurology Tongji HospitalTongji Medical CollegeHuazhong University of Science and Technology430030 WuhanChina'2Department of NeurologyMayo ClinicRochesterMN 55905USA

Revascularization and angiogenesis,as substrates of sustained collateral circulation,play a crucial role in determining the severity and clinical outcome of acute ischemic stroke(AIS)due to large vessel occlusion(LVO).Developing an adjunct biomarker to help identify and monitor collateral status would aid stroke diagnosis and *** screen the potential biomarkers,proteomic analysis was performed in this study to identify those distinct plasma protein profiles in AIS due to LVO with different collateral ***,we found that levels of Plasma Factor VII Activating Protease(FSAP)significantly increased in those AIS patients with poor collaterals,and were correlated with worse neurological ***,both in vitro and in vivo models of ischemic stroke were used to explore pathological mechanisms of FSAP in endothelial *** demonstrated that the FSAP inhibitor,high-molecular-weight hyaluronan(HMW-HA),enhanced the pro-angiogenic vascular factors,improved the integrity of brain blood barrier,and promoted newly formed cerebral microvessels in the ischemic penumbra,consequently improving neurological *** elucidate the pathways that might contribute to revascularization during LVO,we applied transcriptomic analysis via unbiased RNA sequencing and showed that Wnt signaling was highly involved in FSAP mediated endothelial ***,inhibition of Wnt5a largely reversed the protective effects from HMW-HA treatment,implying that FSAP might aggravate endothelial dysfunction and neurological deficits by regulating Wnt5a ***,FSAP may represent a potential biomarker for collateral status after LVO and a promising therapeutic target to be explored in the treatment of stroke.

关键词： Wnt5a neurological protective

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Signaling pathways involved in ischemic stroke:molecular mechanisms and therapeutic interventions

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Signal Transduction and Targeted Therapy 2022年第8期7卷 2733-2761页

作者： Chuan Qin Sheng Yang Yun-Hui Chu Hang Zhang Xiao-Wei Pang Lian Chen Luo-Qi Zhou Man Chen dai-shi tian Wei Wang Department of Neurology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

Ischemic stroke is caused primarily by an interruption in cerebral blood flow,which induces severe neural injuries,and is one of the leading causes of death and disability ***,it is of great necessity to further detailly elucidate the mechanisms of ischemic stroke and find out new therapies against the *** recent years,efforts have been made to understand the pathophysiology of ischemic stroke,including cellular excitotoxicity,oxidative stress,cell death processes,and *** the meantime,a plethora of signaling pathways,either detrimental or neuroprotective,are also highly involved in the forementioned *** pathways are closely intertwined and form a complex signaling ***,these signaling pathways reveal therapeutic potential,as targeting these signaling pathways could possibly serve as therapeutic approaches against ischemic *** this review,we describe the signaling pathways involved in ischemic stroke and categorize them based on the pathophysiological processes they participate *** approaches targeting these signaling pathways,which are associated with the pathophysiology mentioned above,are also ***,clinical trials regarding ischemic stroke,which potentially target the pathophysiology and the signaling pathways involved,are summarized in ***,this review elucidated potential molecular mechanisms and related signaling pathways underlying ischemic stroke,and summarize the therapeutic approaches targeted various pathophysiology,with particular reference to clinical trials and future prospects for treating ischemic stroke.

关键词： therapeutic injuries protective

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Dual Functions of Microglia in Ischemic Stroke

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Neuroscience Bulletin 2019年第5期35卷 921-933页

作者： Chuan Qin Luo-Qi Zhou Xiao-Tong Ma Zi-Wei Hu Sheng Yang Man Chen Dale B. Bosco Long-Jun Wu dai-shi tian Department of Neurology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China Department of Neurology Mayo Clinic Rochester MN 55905 USA

Ischemic stroke is a leading cause of morbidity and mortality worldwide. Resident microglia are the principal immune cells of the brain, and the first to respond to the pathophysiological changes induced by ischemic stroke. Traditionally, it has been thought that microglial activation is deleterious in ischemic stroke, and therapies to suppress it have been intensively explored. However,increasing evidence suggests that microglial activation is also critical for neurogenesis, angiogenesis, and synaptic remodeling, thereby promoting functional recovery after cerebral ischemia. Here, we comprehensively review the dual role of microglia during the different phases of ischemic stroke, and the possible mechanisms controlling the post-ischemic activity of microglia. In addition, we discuss the dynamic interactions between microglia and other cells, such as neurons, astrocytes, oligodendrocytes,and endothelial cells within the brain parenchyma and the neurovascular unit.

关键词： Microglia Inflammation Ischemic stroke Signaling pathways

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Serum LDL Promotes Microglial Activation and Exacerbates Demyelinating Injury in Neuromyelitis Optica Spectrum Disorder

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Neuroscience Bulletin 2024年第8期40卷 1104-1114页

作者： Man Chen Yun‑Hui Chu Wen‑Xiang Yu Yun‑Fan You Yue Tang Xiao‑Wei Pang Hang Zhang Ke Shang Gang Deng Luo‑Qi Zhou Sheng Yang Wei Wang Jun Xiao dai‑shi tian Chuan Qin Department of Neurology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Hubei Key Laboratory of Neural Injury and Functional Reconstruction Huazhong University of Science and TechnologyWuhan 430030China Department of Neurology Hainan General HospitalHainan Affiliated Hospital of Hainan Medical UniversityHaikou 570311China

Neuromyelitis optica spectrum disorder(NMOSD)is an autoimmune inflammatory demyelinating disease of the central nervous system(CNS)accompanied by blood-brain barrier(BBB)*** in microglial lipid metabolism is believed to be closely associated with the neuropathology of ***,there is limited evidence on the functional relevance of circulating lipids in CNS demyelination,cellular metabolism,and microglial ***,we found that serum low-density lipoprotein(LDL)was positively correlated with markers of neurological damage in NMOSD *** addition,we demonstrated in a mouse model of NMOSD that LDL penetrates the CNS through the leaky BBB,directly activating *** activation leads to excessive phagocytosis of myelin debris,inhibition of lipid metabolism,and increased glycolysis,ultimately exacerbating myelin *** also found that therapeutic interventions aimed at reducing circulating LDL effectively reversed the lipid metabolic dysfunction in microglia and mitigated the demyelinating injury in *** findings shed light on the molecular and cellular mechanisms underlying the positive correlation between serum LDL and neurological damage,highlighting the potential therapeutic target for lowering circulating lipids to alleviate the acute demyelinating injury in NMOSD.

关键词： Neuromyelitis optica spectrum disorder Low-density lipoprotein Microglia

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Anti-BCMA CAR T-cell therapy CT103A in relapsed or refractory AQP4-IgG seropositive neuromyelitis optica spectrum disorders:phase 1 trial interim results

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Signal Transduction and Targeted Therapy 2023年第2期8卷 683-691页

作者： Chuan Qin dai-shi tian Luo-Qi Zhou Ke Shang Liang Huang Ming-Hao Dong Yun-Fan You Jun Xiao Ying Xiong Wen Wang Hao Pang Jing-Jing Guo Song-Bai Cai Di Wang Chun-Rui Li Min Zhang Bi-Tao Bu Wei Wang Department of Neurology Tongji HospitalTongji Medical CollegeHuazhong University of Science and Technology430030 WuhanChina Hubei Key Laboratory of Neural Injury and Functional Reconstruction Huazhong University of Science and Technology430030 WuhanChina Department of Hematology Tongji HospitalTongji Medical CollegeHuazhong University of Science and Technology430030 WuhanChina Department of Radiology Tongji HospitalTongji Medical CollegeHuazhong University of Science and Technology430030 WuhanChina Nanjing IASO Biotherapeutics Ltd NanjingChina

Chimeric antigen receptor(CAR)T-cell therapy that targets B-cell maturation antigen(BCMA)have great potentials in autoimmune diseases and could be novel therapeutics for relapsed/refractory neuromyelitis optica spectrum disorder(NMOSD).To evaluate the safety and efficacy of the CT103A,a self-developed BCMA-targeting CAR construct against BCMA,in patients with AQP4-IgG seropositive NMOSD,an ongoing,investigator-initiated,open-label,single-arm,phase 1 clinical trial is conducted at our *** total,12 patients were administered with a CAR-BCMA *** of the 12 patients dosed were women(83.3%),with a median age of 49.5 years(range,30-67).were The most common events of grade 3 or higher were hematologic toxic *** patients(58%)developed infections,but no grade 4 infections *** release syndrome was reported in all patients with only events of grade 1 or 2 *** the follow-up of a median 5.5 months,11 patients had no relapse;all patients generally reported improvement in disabilities and quality-of-life outcomes;11 patients’AQP-4 antibodies in serum showed a downward trend by the cutoff *** T-cell expansion was associated with responses,and persisted more than 6 months post-infusion in 17%of the *** summary,CAR T-cell therapy shows a manageable safety profile and therapeutic potentials for patients with relapsed/refractory AQP4-IgG seropositive *** expansion phase is currently underway to determine the safety and efficacy of CAR T-BCMA infusion in patients with other neuro-inflammatory diseases.

关键词： AQP4 BCMA infusion

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Prevalence and risk factors of stroke in China:a national serial cross-sectional study from 2003 to 2018

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Stroke & Vascular Neurology 2023年第3期8卷 238-248,I0086-I0095页

作者： dai-shi tian Chen-Chen Liu Chao-Long Wang Chuan Qin Ming-Huan Wang Wen-Hua Liu Jian Liu Han-Wen Zhang Rong-Guo Zhang Shao-Kang Wang Xiao-Xiang Zhang Liang Wang Deng-Ji Pan Jian-Ping Hu Xiang Luo Sha-Bei Xu Wei Wang Department of Neurology Tongji Hospital of Tongji Medical College of Huazhong University of Science and TechnologyWuhanHubeiChina Department of Epidemiology and Biostatistics Tongji Medical College of Huazhong University of Science and TechnologyWuhanHubeiChina Department of Scientific Research Management Tongji Hospital of Tongji Medical College of Huazhong University of Science and TechnologyWuhanHubeiChina Infervision Medical Technology Co. LtdBeijingChina Department of Computer Center Tongji Hospital of Tongji Medical College of Huazhong University of Science and TechnologyWuhanHubeiChina Centre for Health Statistics Information National Health Commission of the People's Republic of ChinaBeijingChina

Stroke imposes a substantial burden *** the rapid economic and lifestyle transition in China,trends of the prevalence of stroke across different geographic regions in China remain largely *** on the data in the National Health Services Surveys(NHSS),we assessed the prevalence and risk factors of stroke in China from 2003 to *** this study,data from 2003,2008,2013,and 2018 NHSS were *** cases were based on participants’self-report of a previous diagnosis by *** estimated the trends of stroke prevalence for the overall population and subgroups by age,sex,and socioeconomic factors,then compared across different geographic *** applied multivariable logistic regression to assess associations between stroke and risk *** number of participants aged 15 years or older were 154,077,146,231,230,067,and 212,318 in 2003,2008,2013,and 2018,respectively,among whom,1435,1996,3781,and 6069 were stroke *** age and sex standardized prevalence per 100,000 individuals was 879 in 2003,1100 in 2008,1098 in 2013,and 1613 in *** per 100,000 individuals in rural areas increased from 669 in 2003 to 1898 in 2018,while urban areas had a stable trend from 1261 in 2003 to 1365 in *** geographic regions,the central region consistently had the highest prevalence,but the western region has an alarmingly increasing trend from 623/100,000 in 2003 to 1898/100,000 in 2018(Ptrend<0.001),surpassing the eastern region in *** age,male sex,rural area,central region,hypertension,diabetes,depression,low education and income level,retirement or unemployment,excessive physical activity,and unimproved sanitation facilities were significantly associated with *** conclusion,the increasing prevalence of stroke in China was primarily driven by economically underdeveloped *** is important to develop targeted prevention programs in underdeveloped *** traditional risk factors,more attenti

关键词： prevention sectional income

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VALENCE ELECTRON STRUCTURE OF Cr IN Fe-C AUSTENITE AND BEHAVIOR OF Cr IN KINETICS OF PHASE TRANSFORMATION

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Chinese Science Bulletin 1989年第21期34卷 1830-1833页

作者：代天时刘志林张瑞林 Jilin University of Technology Changchun 130023 PRC Jilin University Changchun 130023 PRC

I. VALENCE ELECTRON STRUCTURES OF Fe-C AND Fe-C-Cr AUSTENITE The valence electron structures of Fe-C a ustenite containing 0. 15—2.00％ C are established on the basis of Refs. [1] and [2], as listed in Table 1. Accor... 详细信息

关键词： Cr.austenite phase transformation behavior

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Research status and prospects of the fractal analysis of metal material surfaces and interfaces

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International Journal of Minerals,Metallurgy and Materials 2025年第1期32卷 20-38页

作者： Qinjin dai Xuefeng Liu Xin Ma Shaojie tian Qinghe Cui Beijing Advanced Innovation Center for Materials Genome Engineering University of Science and Technology BeijingBeijing 100083China Beijing Laboratory of Metallic Materials and Processing for Modern Transportation University of Science and Technology BeijingBeijing 100083China Laboratory for Advanced Materials Processing of Ministry of Education University of Science and Technology BeijingBeijing 100083China School of Mechanical and Electrical Engineering Xinjiang Institute of EngineeringUrumqi 830023China

As a mathematical analysis method,fractal analysis can be used to quantitatively describe irregular shapes with self-similar or self-affine *** analysis has been used to characterize the shapes of metal materials at various scales and *** methods make it difficult to quantitatively describe the relationship between the regular characteristics and properties of metal material surfaces and ***,fractal analysis can be used to quantitatively describe the shape characteristics of metal materials and to establish the quantitative relationships between the shape characteristics and various properties of metal *** the perspective of two-dimensional planes and three-dimensional curved surfaces,this paper reviews the current research status of the fractal analysis of metal precipitate interfaces,metal grain boundary interfaces,metal-deposited film surfaces,metal fracture surfaces,metal machined surfaces,and metal wear *** relationship between the fractal dimensions and properties of metal material surfaces and interfaces is *** from three perspectives of fractal analysis,namely,research scope,image acquisition methods,and calculation methods,this paper identifies the direction of research on fractal analysis of metal material surfaces and interfaces that need to be *** is believed that revealing the deep influence mechanism between the fractal dimensions and properties of metal material surfaces and interfaces will be the key research direction of the fractal analysis of metal materials in the future.

关键词： metal material surfaces and interfaces fractal analysis fractal dimension homogeneity

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人工智能发展、干中学效应与技能溢价——基于内生技术进步模型的分析

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中国工业经济 2024年第2期 99-117页

作者：黄浩权戴天仕沈军暨南大学经济学院

人工智能技术正引领着新一轮科技革命和产业变革。在拥抱这些发展成果的同时,社会各界一直担忧人工智能发展会提升技能溢价,即扩大低技能劳动力与高技能劳动力之间的收入差距,并进一步扩大整个社会的收入差距。本文建立了一个内生技术... 详细信息

人工智能技术正引领着新一轮科技革命和产业变革。在拥抱这些发展成果的同时,社会各界一直担忧人工智能发展会提升技能溢价,即扩大低技能劳动力与高技能劳动力之间的收入差距,并进一步扩大整个社会的收入差距。本文建立了一个内生技术进步模型,通过引入劳动力的技能异质性,划分出新任务的创造和旧任务的自动化改造两种技术进步形式,并强调低技能劳动力的干中学效应,全面考察人工智能发展对技能溢价的影响。研究发现:考虑低技能劳动力的干中学效应后,新任务的创造在提升对高技能劳动力需求的同时会更大幅度地提升对低技能劳动力的需求,长期看会降低技能溢价;旧任务的自动化则会降低对低技能劳动力的需求,提升技能溢价。在此基础上,本文使用数值模拟方法,进一步量化分析了低技能劳动力的学习能力、新任务的创造效率以及高技能劳动力的供给等因素对技能溢价的影响。本文有助于理解人工智能发展对技能溢价的影响机制,为制定相关政策提供启示。

关键词：人工智能干中学效应技能溢价内生技术进步

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CALCULATION OF VALENCE ELECTRON STRUCTURE IN L_2~'-TYPE COMPLEX SOLID SOLUTIONS

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Science China Mathematics 1989年第11期32卷 1390-1397页

作者：刘志林戴天时杨双良张瑞林 Jilin University of Technology Changchun 130025 PRC Jilin University Changchun 130023 PRC

Based on the empirical electron theory of solids and molecules of S. H. Yu, this paper proposes (i) the calculating model of valence electron structures in L_2~'-type substitutional and interstitial complex solid solutions; (ii) the bond length difference analysis (BLD) method of unknown bond length structure solid solutions; (iii) the treatment of uncertainty of BLD analysis solution.

关键词： L_2~'-type solid solution valence electron structure (VES) calculation and strength.

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