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Mitochondrial transplantation confers protection against the effects of ischemic stroke by repressing microglial pyroptosis and promoting neurogenesis

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Neural Regeneration Research 2024年第6期19卷 1325-1335页

作者： li {1. zhaoyan zhao Jing Guo Yuan Qin Qian Yu xiaolong Shi Fei Guo Haiqin {3. Xude {1. Changjun Gao Qian Yang department of Experimental Surgery The Second Affiliated Hospital of Air Force Medical UniversityXi’anShaanxi ProvinceChina department of Anesthesiology The Second Affiliated Hospital of Air Force Medical UniversityXi’anShaanxi ProvinceChina

Transferring healthy and functional mitochondria to the lateral ventricles confers neuroprotection in a rat model of ischemia-reperfusion *** mitochondrial transplantation is also beneficial in pediatric patients with cardiac ischemia-reperfusion ***,transplantation of functional exogenous mitochondria may be a promising therapeutic approach for ischemic *** explore the neuroprotective effect of mitochondria transplantation and determine the underlying mechanism in ischemic stroke,in this study we established a photo-thrombosis-induced mouse model of focal ischemia and administered freshly isolated mitochondria via the tail vein or to the injury site(in situ).Animal behavior tests,immunofluorescence staining,2,{1.5-triphenyltetrazolium chloride(TTC)staining,mRNA-seq,and western blotting were used to assess mouse anxiety and memory,cortical infarct area,pyroptosis,and neurogenesis,*** bioinformatics analysis,western blotting,co-immunoprecipitation,and mass spectroscopy,we identified S1.0 calcium binding protein A9(S1.0A9)as a potential regulator of mitochondrial function and determined its possible interacting *** between exogenous and endogenous mitochondria,as well as the effect of exogenous mitochondria on recipient microglia,were assessed in *** data showed that:(1.mitochondrial transplantation markedly reduced mortality and improved emotional and cognitive function,as well as reducing infarct area,inhibiting pyroptosis,and promoting cortical neurogenesis;(2)microglial expression of S1.0A9 was markedly increased by ischemic injury and regulated mitochondrial function;({1.in vitro,exogenous mitochondria enhanced mitochondrial function,reduced redox stress,and regulated microglial polarization and pyroptosis by fusing with endogenous mitochondria;and(4.S1.0A9 promoted internalization of exogenous mitochondria by the microglia,thereby amplifying their pro-proliferation and anti-inflammatory ***

关键词： ischemic stroke microglia mitochondria transplantation neurogenesis pyroptosis

Tildrakizumab for moderate-to-severe plaque psoriasis in Chinese patients:A 1.-week randomized placebo-controlled phase III trial with long-term extension

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Chinese Medical Journal 2024年第10期137卷 1190-1198页

作者： Chen Yu Songmei Geng Bin Yang Yunhua Deng Fuqiu li {1.aojing Kang Mingye Bi Furen zhang Yi zhao Weili Pan Zhongwei Tian Jinhua Xu Zhenghua zhang Nan Yu {1.nsuo Duan Shuping Guo Qing {3. Weiquan li Juan Tao Zhijun liu Yuanyuan Yin Gang Wang department of Dermatology Xijing HospitalThe Fourth Military Medical UniversityXi’anShaanxi 710032China department of Dermatology The Second Affiliated Hospital of Xi’an Jiaotong UniversityXi’anShaanxi 710004China department of Dermatology Dermatology Hospital of Southern Medical UniversityGuangzhouGuangdong 510091China department of Dermatology Tongji HospitalHuazhong University of Science and TechnologyWuhanHubei 430030China department of Dermatology The Second Hospital of Jilin UniversityChangchunJilin 130041China department of Dermatology People’s Hospital of Xinjiang Uygur Autonomous RegionUrumqiXinjiang 830001China department of Dermatology Wuxi People’s Hospital of Wuxi CityWuxiJiangsu 214023China department of Dermatology Shandong Provincial Hospital for Skin Diseases&Shandong Provincial Institute of Dermatology and VenereologyShandong First Medical University&Shandong Academy of Medical SciencesJinanShandong 250022China department of Dermatology Beijing Tsinghua Changgung HospitalBeijing 102218China department of Dermatology Zhejiang Provincial People’s HospitalHangzhouZhejiang 310014China department of Dermatology The First Affiliated Hospital of Xinxiang Medical CollegeXinxiangHenan 453100China department of Dermatology Huashan Hospital Affiliated to Fudan UniversityShanghai 200040China department of Dermatology General Hospital of Ningxia Medical UniversityYinchuanNingxia 750000China department of Dermatology Affiliated Hospital of Chengde Medical UniversityChengdeHebei 067000China department of Dermatology The First Hospital of Shanxi Medical UniversityTaiyuanShanxi 030001China department of Dermatology Qilu Hospital of Shandong UniversityJinanShandong 250012China department of Dermatology Yuebei People’s HospitalShaoguanGuangdong 512026China department of Dermatology Union Hospital Tongji Medical Collage Huazhong University of Science and TechnologyWuhanHubei 430022China department of Dermatology and Venereal Diseases The First Affiliated Hospit

Background:There is a need for effective and safe therapies for psoriasis that provide sustained *** aim of this study was to assess the efficacy and safety of tildrakizumab,an anti-interleukin-23.19 monoclonal antibody,for treating moderate-to-severe plaque psoriasis in Chinese ***:In this multi-center,double-blind,phase III trial,patients with moderate-to-severe plaque psoriasis were enrolled and randomly assigned(1:1)to receive subcutaneous tildrakizumab 100 mg or placebo at weeks 0 and *** initially assigned to placebo were switched to receive tildrakizumab at weeks 12,16,and every 12 weeks *** in the tildrakizumab group continued with tildrakizumab at week 16,and every 12 weeks until week *** primary endpoint was the Psoriasis Area and Severity Index(PASI 75)response rate at week ***:At week 12,tildrakizumab demonstrated significantly higher PASI 75 response rates(66.4.[73.110]vs.12.7%[14.110];difference,51.4.[95%confidence interval(CI),4..72,62.13.;P4..1%[95%CI,3..64.59.62];Pximal efficacy after 28 weeks(86.8%[92/106]vs.82.4.[89/108])and maintained up to 52 weeks(91.3.[95/104.vs.87.4.[90/103.).Most treatment-emergent adverse events were mild and not related to ***:Tildrakizumab demonstrated durable efficacy through week 52 and was well tolerated in Chinese patients with moderate-to-severe plaque *** registration:***,NCT05108766.

关键词： Tildrakizumab Interleukin 23 Plaque psoriasis Chinese Randomized controlled trial

Long non-coding RNA high expressed in hepatocellular carcinoma(IncRNA-HEIH) facilitates tumor growth through enhancer of zeste homolog 2

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Long non-coding RNA high expressed in hepatocellular carcino...

Characterization and allergic role of IL-3.-induced neutrophil polarization

遗传学进步促进粮食安全与人口健康高峰论坛

作者： Fu Yang1,ling zhang1,xi-song Huo1,Ji-hang Yuan1,Dan Xu1,Sheng-xian Yuan2,Nan Zhu3.Wei-ping Zhou2,Guang-shun Yang3.Yu-zhao Wang1,Jing-li Shang1,Chun-fang Gao4.Feng-rui zhang5,Fang Wang1,Shu-han {3.1 department of Medical Genetics,Second Military Medical university,Shanghai,china 2 The Third department of Hepatic Surgery,Eastern Hepatobiliary Hospital,Second Military Medical university,Shanghai,china 3.The Second department of Hepatic Surgery,Eastern Hepatobiliary Hospital,Second Military Medical university, Shanghai,china 4.department of Laboratory Medicine,Eastern Hepatobiliary Hospital,Second Military Medical university,Shanghai,china 5 department of Hepatobiliary Surgery,Hebei Cancer Hospital,Hebei Medical university,Hebei,china.

Hepatocellular carcinoma(HCC) is one of the most common human cancers worldwide, particularly in Southeast Asia and *** than 70-80%of HCC cases occur in high hepatitis B virus(HBV) endemic regions,and 50%of HCC cases worldwide are attributable to chronic infection with ***,the 5-year survival rate of HBV-related HCC patients remains poor,and approximately 600,000 HCC patients die each year despite recent advances in surgical techniques and medical *** previous studies identified many aberrantly expressed protein-coding genes in HCC,novel molecular markers that can help in early diagnosis and risk assessment are still urgently *** is of paramount importance to understand the relationships between c{1.nical symptoms and molecular changes in HCC for developing new diagnosis and treatment strategies for HCC and improving the prognosis of diagnosed patients. The human transcriptome comprises not only large numbers of protein-coding messenger RNAs(mRNAs) but also a large set of non-protein coding transcripts that have structural,regulatory or unknown *** studies of small non-coding RNAs(1. to 200 nucleotides(nt)) have dominated the field of RNA biology in recent years,a surprisingly wide array of cellular functions has also been associated with long non-coding RNAs(IncRNAs).IncRNAs,tentatively defined as non-coding RNAs more than 200 nt in length,are characterized by the complexity and diversity of their sequences and mechanisms of action.A handful of studies have imp{1.cated IncRNAs in a variety of disease states,and altered IncRNA levels can result in aberrant expression of gene products that may contribute to cancer ***,there are only pre{1.minary studies on the role of IncRNAs in HCC,and the overall pathophysiological contributions of IncRNAs to HCC remain largely unknown. In this study,we have identified non-overlapping signatures of a small number of IncRNAs that are aberrantly expressed in human HBV

关键词： hepatocellular carcinoma noncoding RNAs PRC2 IncRNAs cell cycle

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Cellular & Molecular Immunology 2018年第8期15卷 782-793页

作者： Bo sun {1.nnan Zhu Ya{1.ng Tao Hai-xi sun Yang {1. Peng Wang Yuzhu Hou Yang zhao xiaodong {3. {1.anfeng {3. Ning Na Yong zhao State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China department of Urology Beijing Chaoyang HospitalCapital Medical UniversityBeijing 100101China Key Laboratory of Human Diseases Comparative Medicine Ministry of HealthInstitute of Laboratory Animal ScienceChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China department of Kidney Transplantation The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510630China

Neutrophils are involved in the pathogenesis of ***,the contribution of the different functionally polarized neutrophils in allergy needs to be *** sought to define the characteristics of interleukin(IL)-3.-induced neutrophils and the involvement of this subset of polarized neutrophils in allergic *** isolated neutrophils were treated with different cytokines and the cytokine expression levels were detected by realtime *** gene expression profile of IL-3.-induced neutrophils was determined by microarray *** transfer assay was used to investigate the function of IL-3.-induced neutrophils in an ovalbumin(OVA)-induced allergic asthma ***-3.-treated neutrophils selectively produced IL-4.IL-5,IL-9 and IL-13.referred as to N(IL-3.)cells)and displayed a distinctive gene expression profile in sharp contrast to resting and lipopolysaccharide(LPS)-treated ***-3.-induced neutrophils expressed high Levels of IL-1R2 on cell surface,whereas resting and LPS-treated neutrophils did not,indicating IL-1R2 might be used as a biomarker for N(IL-3.)***,N(IL-3.)neutrophils exist in the lungs of OVA-induced allergic asthma *** transfer of N(IL-3.)neutrophils significantly promotes the severity of the lung pathogenesis in this ***-3. induces neutrophil polarization through c-Jun N-terminal kinase-and nuclear factor-κB-dependent pathways.A previously unappreciated neutrophil polarization driven by IL-3. with unique cell surface markers and cytokine/chemokineproducing gene profile was *** newly identified N(IL-3.)subpopulation may have significant contribution to IL-3.-related pathogenesis.

关键词： allergy asthma IL-9 IL-3. inflammation neutrophils polarization

放射治疗通过调节肝癌细胞EZH2/CXCL1.通路增加自然杀伤细胞瘤内浸润的机制

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中华肝脏病杂志 2024年第9期32卷 835-844页

作者：赵晓芳王权孙静张爱民常小云李文刚段学章解放军医学院北京100039 西安大兴医院肿瘤内科西安710003 解放军总医院第五医学中心放射治疗科北京100039

目的探讨肝细胞癌(HCC)在接受放射治疗后自然杀伤(NK)细胞在肿瘤组织中的浸润作用及其相关机制。方法应用人肝癌细胞系SK-Hep-1.建HCC荷瘤小鼠模型,分为4.:对照组、放射治疗组、NK细胞清除组及NK清除联合放射治疗组,同时记录肿瘤生长... 详细信息

目的探讨肝细胞癌(HCC)在接受放射治疗后自然杀伤(NK)细胞在肿瘤组织中的浸润作用及其相关机制。方法应用人肝癌细胞系SK-Hep-1.建HCC荷瘤小鼠模型,分为4.:对照组、放射治疗组、NK细胞清除组及NK清除联合放射治疗组,同时记录肿瘤生长情况。应用流式细胞术及免疫组织化学检测小鼠外周血NK细胞比率及肿瘤组织内NK细胞浸润情况。应用慢病毒构建Zeste同源增强子2(EZH2)过表达的SK-Hep-1.胞,并检测放射治疗后EZH2过表达细胞的CXC趋化因子配体1.(CXCL1.)的表达量及对NK细胞的趋化作用。应用逆转录聚合酶链式反应(RT-PCR)、酶联免疫吸附试验(E{1.SA)、蛋白免疫印迹法(WB)及免疫组织化学检测评价SK-Hep-1.胞在体外、体内进行照射处理后EZH2、CXCL1. mRNA和蛋白的表达水平,通过趋化及阻断实验验证CXCL1.对NK细胞的趋化作用。组间的比较采用独立样本t检验。P1.胞及小鼠肿瘤组织相比,放射治疗组肝癌细胞系及肿瘤组织EZH2 mRNA和蛋白表达水平均下降(P值均1. mRNA和蛋白表达水平均升高(P值均1.后抑制了NK细胞趋化作用。EZH2过表达体内外实验证实,放射治疗可通过下调EZH2表达上调CXCL1. mRNA及蛋白表达水平(P值均2过表达对NK细胞趋化作用明显减弱。结论NK细胞作为免疫效应细胞直接参与放射治疗激活的抗HCC免疫过程。放射治疗通过抑制HCC中EZH2表达,上调CXCL1.表达量从而增强NK细胞瘤内浸润。

关键词：肝细胞癌放射治疗 EZH2 CXCL1. 自然杀伤细胞治疗

A Novel CA4. Polymeric Nanoparticle for Murine Hepatoma Therapy

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Chinese Journal of Polymer Science 2023年第8期41卷 1223-1229,I0007页

作者： Zhi-lin liu xi-Tong Ren Yue Huang Jia-li sun xiao-Shuang Wang Meng-Fei Zheng lin-Jie Cui Xue-Fei zhang zhao-Hui Tang Key Laboratory of Polymer Ecomaterials Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchun 130022China Jilin Biomedical Polymers Engineering Laboratory Changchun 130022China School of Applied {1. and Engineering University of Science and Technology of ChinaHefei 230026China No.1.department of Neurology China-Japan Union Hospital of Jilin UniversityChangchun 130033China Key Laboratory of Environmentally Friendly chemistry and App{1.cations of Ministry of Education and Key Laboratory of Polymeric Materials&App{1.cation Technology of Hunan Province College of ChemistryXiangtan UniversityXiangtan 411105China

Combretastatin A4.phosphate(CA4.)is a potent vascular disrupting agent with good water ***,it is only effective at high doses,which decreases clinical ***,we designed stable CA4. polymeric nanoparticles(CA4. NPs)consisting of various cholesterol derivatives,and with a drug loading efficacy of 93..The nanoparticles released CA4. in a sustained manner and achieved a 72%inhibition rate in the murine H22 liver tumor model,which was about 2.9-fold higher than that of free CA4.(24.6%).Furthermore,the carrier components of CA4. NPs were metabolized to arginine,cholesterol,ethanol and poly(ethylene glycol)in vivo;therefore,the CA4. NPs are safe and have significant potential for clinical translation.

关键词： CA4. polymeric nanoparticle Cholesterol derivatives Vascular disrupting agent Phosphate-guanidine coordination Drug controlled release

地高辛标记Ucp2基因RNA探针的制备和应用

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中国生物工程杂志 2018年第9期38卷 55-58页

作者：刘志贞加三三张凯丽孙雨晴赵虹郝宇卉牛勃李美宁山西医科大学生物化学与分子生物学教研室太原030001 第四军医大学口腔颌面外科国家重点实验室西安710032 忻州职业技术学院医学系忻州034000 首都儿科研究所生物技术室北京100020

目的：制备用于检测小鼠胚胎早期Ucp2基因表达的地高辛标记的特异性RNA探针。方法：提取小鼠胚胎脑组织总RNA,设计引物,通过RT-PCR方法获取Ucp2基因片段,将其克隆到pGEM-T载体。分别利用Sp6、T7和Ucp2特异性引物,PCR扩增获得转录模板,通... 详细信息

目的：制备用于检测小鼠胚胎早期Ucp2基因表达的地高辛标记的特异性RNA探针。方法：提取小鼠胚胎脑组织总RNA,设计引物,通过RT-PCR方法获取Ucp2基因片段,将其克隆到pGEM-T载体。分别利用Sp6、T7和Ucp2特异性引物,PCR扩增获得转录模板,通过Sp6及T7 RNA聚合酶,获得地高辛标记的正义、反义Ucp2 RNA原位杂交探针。检测标记探针的效价后,通过全胚胎原位杂交分析制备探针的特异性和杂交效果。结果：成功获得Ucp2基因正义、反义探针,反义探针能高效灵敏检测到Ucp2基因在小鼠胚胎Ed9.5、Ed1..5神经系统呈现高表达,而正义探针未能检测到表达信号。结论：成功制备了特异高效的地高辛标记Ucp2 RNA原位杂交探针,为进一步研究Ucp2基因在小鼠胚胎组织中的表达,尤其在神经组织的定位奠定基础。

关键词： Ucp2 RNA探针全胚胎原位杂交

Optimizing hydrogen ad/desorption of Mg-based hydrides for energy-storage applications

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Journal of Materials Science & Technology 2023年第10期141卷 221-235页

作者： Zeng-Yi li Yu-Jia {1. Chen-Chen zhang Sheng Wei li zhao Ju-Lan Zeng Zhong Cao Yong-Jin Zou Hai-liang Chu Fen Xu li-xian {1. Hong-Ge Pan Guangxi Key Laboratory of Information Materials and Guangxi Collaborative Innovation Center of Structure and Property for New Energy and Materials School of Material Science&EngineeringGuilin University of Electronic TechnologyGuilin 541004China department of Radiology Stanford UniversityStanfordCA 94305USA School of chemistry and Chemical Engineering Guangxi UniversityNanning 530004China beijing Advanced Innovation Center for Materials Genome Engineering Institute for Advanced Materials and TechnologyUniversity of Science and Technology BeijingBeijing 100083China School of chemistry and Chemical Engineering Changsha University Of Science&TechnologyChangsha 410114China Institute of Science and Technology for New Energy Xi’an Technological UniversityXi’an 710021China

Hydrogen energy is expected to be an“ideal fuel”in the era of *** discovery,de-velopment,and modification of high-performance hydrogen storage materials are the keys to the fu-ture development of solid-state hydrogen storage and hydrogen energy *** hydride(MgH_(2)),with its high hydrogen storage capacity,abundant natural reserves,and environmental friend-liness,has been extensively ***,we briefly summarize the typical structure and hy-drogenation/dehydrogenation reaction mechanism of MgH_(2)and provide a comprehensive overview of strategies to effectively tune the thermodynamics and kinetics of Mg-based materials,such as alloy-ing,nanosizing,the introduction of additives,and composite *** substantial efforts,great achievements have been achieved,such as lower absorption/desorption temperatures and better cy-cling ***,some pivotal issues remain to be addressed,such as unfavorable hydro-genation/dehydrogenation factors,harsh conditions,slow kinetics,incomplete dehydrogenation,low hy-drogen purity,expensive catalysts,and a lack of valid exploration of mechanisms in the hydrogena-tion/dehydrogenation ***,some future development prospects of MgH_(2)in energy-efficient conversion and storage have been presented,including advanced manufacturing ways,stabilization of nanostructures,the introduction of additives combined with structural modification,and utilization of advanced characterization techniques.

关键词： Mg-based hydrides Hydrogen storage A lloying Catalysts Mechanism

基于白光中子源的^(1.7)Au中子辐射俘获截面测量及共振参数分析

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物理学报 2024年第7期73卷 104-113页

作者：罗淏天张奇玮栾广源王晓宇邹翀任杰阮锡超贺国珠鲍杰孙琪黄翰雄王朝辉吴鸿毅顾旻皓余滔解立坤陈永浩安琪白怀勇鲍煜曹平陈昊磊陈琪萍陈裕凯陈朕崔增琪樊瑞睿封常青高可庆韩长材韩子杰何泳成洪杨黄蔚玲黄锡汝季筱璐吉旭阳蒋伟江浩雨姜智杰敬罕涛康玲康明涛李波李超李嘉雯李论李强李晓李样刘荣刘树彬刘星言穆奇丽宁常军齐斌斌任智洲宋英鹏宋朝晖孙虹孙康孙晓阳孙志嘉谭志新唐洪庆唐靖宇唐新懿田斌斌王丽娇王鹏程王琦王涛峰文杰温中伟吴青彪吴晓光吴煊羊奕伟易晗于莉于永积张国辉张林浩张显鹏张玉亮张志永赵豫斌周路平周祖英朱丹阳朱科军朱鹏朱兴华中国原子能科学研究院核数据重点实验室北京102413 中国科学院高能物理研究所北京100049 散裂中子源科学中心东莞523803 核探测与核电子学国家重点实验室北京100049 中国科学技术大学近代物理系核探测与核电子学国家重点实验室合肥230026 北京大学物理学院核物理与核技术国家重点实验室北京100871 中国工程物理研究院核物理与化学研究所绵阳621900 西北核技术研究院西安710024 中国科学院大学北京100049 中国科学技术大学工程与应用物理系合肥230026 北京航空航天大学物理学院北京100083 华能山东石岛湾核电有限公司荣成264312

中子辐射俘获反应在反应堆运行、核装置设计及核天体物理研究中起重要的作用.4.BaF_(2)探测装置有着高时间分辨能力、低中子灵敏度、高探测效率等优点,适合开展中子辐射俘获反应截面数据的测量.中国原子能科学研究院核数据重点实验室... 详细信息

中子辐射俘获反应在反应堆运行、核装置设计及核天体物理研究中起重要的作用.4.BaF_(2)探测装置有着高时间分辨能力、低中子灵敏度、高探测效率等优点,适合开展中子辐射俘获反应截面数据的测量.中国原子能科学研究院核数据重点实验室建立了伽马全吸收装置(Gamma total absorption faci{1.ty,GTAF),该装置用28块六棱BaF_(2)晶体和1.块五棱BaF_(2)晶体构成了外径25 cm,内径1. cm的球壳,覆盖了95.2%的立体角.利用GTAF在中国散裂中子源Back-n束线上,测量了1.7Au(n,γ)的反应截面数据.测量数据通过能量筛选、PSD方法、晶体多重性筛选进行了初步本底扣除,随后结合对^(nat)C及空样品的测量数据对本底进行了分析及扣除,获得了1.7Au俘获反应的产额,利用SAMMY程序拟合得到了^(1.7)Au在1.1.0 e V的共振能量、中子共振宽度和伽马共振宽度参数.实验测量结果与ENDF/B-VIII.0数据库符合良好,其共振参数存在一定差异,分析原因可能与GTAF能量分辨率、Back-n的中子能谱测量精度、以及实验本底扣除方法相关,这也是下一步工作的重点.

关键词：中子辐射俘获截面共振参数白光中子源伽马全吸收装置

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