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Adeno-associated virus as a delivery vector for gene therapy of human diseases

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1808-1840页

作者： jiang-Hui Wang Dominic j.Gessler Wei Zhan Thomas L.Gallagher Guangping Gao Horae Gene Therapy Center University of Massachusetts Chan Medical SchoolWorcesterMA01605USA Department of Microbiology and Physiological Systems University of Massachusetts Chan Medical SchoolWorcesterMA01605USA Centre for Eye Research Australia Royal Victorian Eye and Ear HospitalEast MelbourneVIC3002Australia Ophthalmology Department of SurgeryUniversity of MelbourneEast MelbourneVIC3002Australia Department of Neurological Surgery University of Massachusetts Chan Medical SchoolWorcesterMA01605USA Department of Neurosurgery University of MinnesotaMinneapolisMN55455USA Department of Medicine University of Massachusetts Chan Medical SchoolWorcesterMA01605USA Li Weibo Institute for Rare Diseases Research University of Massachusetts Chan Medical SchoolWorcesterMA01605USA

Adeno-associated virus(AAV)has emerged as a pivotal delivery tool in clinical gene therapy owing to its minimal pathogenicity and ability to establish long-term gene expression in different *** AAV(rAAV)has been engineered for enhanced specificity and developed as a tool for treating various ***,as rAAV is being more widely used as a therapy,the increased demand has created challenges for the existing manufacturing *** rAAV-based gene therapy products have received regulatory approval,but there continue to be concerns about safely using high-dose viral therapies in humans,including immune responses and adverse effects such as genotoxicity,hepatotoxicity,thrombotic microangiopathy,and *** this review,we explore AAV biology with an emphasis on current vector engineering strategies and manufacturing *** discuss how rAAVs are being employed in ongoing clinical trials for ocular,neurological,metabolic,hematological,neuromuscular,and cardiovascular diseases as well as *** outline immune responses triggered by rAAV,address associated side effects,and discuss strategies to mitigate these *** hope that discussing recent advancements and current challenges in the field will be a helpful guide for researchers and clinicians navigating the ever-evolving landscape of rAAV-based gene therapy.

关键词： diseases specificity approval

液相色谱-串联质谱法检测甲基化和乙酰化修饰的组蛋白H3及其在表观遗传药物评估中的应用

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分析化学 2024年第6期52卷 818-836页

作者：史钦鋆瞿敏敏李治马波陈佳徐斌徐华谢剑炜青岛大学药学院军事医学研究院国家安全特需药品全国重点实验室

基于液相色谱-串联质谱技术（Liquid chromatography tandem mass spectrometry, LC-MS/MS），采用三重四极杆质谱的多反应选择离子监测（Multiple reaction monitoring, MRM）模式，应用自下而上的蛋白分析策略，对细胞组蛋白H3 N端的... 详细信息

基于液相色谱-串联质谱技术（Liquid chromatography tandem mass spectrometry, LC-MS/MS），采用三重四极杆质谱的多反应选择离子监测（Multiple reaction monitoring, MRM）模式，应用自下而上的蛋白分析策略，对细胞组蛋白H3 N端的常见甲基化和乙酰化修饰位点及表达水平进行定量分析。将本方法应用于28种表观遗传药物引起的细胞组蛋白H3修饰变化的检测，结果表明，其中25种药物（包括去乙酰化酶抑制剂Abexinostat、Valproic acid和AGK7等）暴露HepG2细胞24 h后诱导的组蛋白H3修饰变化与其已报道的生物活性一致，同时也可检测到其它修饰变化；其余3种药物，包括去甲基化酶抑制剂IOX1、GSK-j1和乙酰化转移酶抑制剂L002，在暴露细胞后仅检测到与已报道活性不同的修饰变化；总体检测吻合率达到89.3%。本方法能通量化定量分析组蛋白H3修饰位点及其变化，具有特异性好和修饰信息丰富等优势，有望为表观遗传活性化合物的筛选评估及作用机制探讨提供新的技术工具。

关键词：表观遗传药物液相色谱-串联质谱组蛋白甲基化乙酰化

Corrigendum to“Active components of Dengzhan Shengmai ameliorate cognitive impairment by facilitating hippocampal long-term potentiation via the NMDA receptor-mediated Ca2+/CaMKII pathway”[***.14(2024)435–438]

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journal of Pharmaceutical Analysis 2024年第6期14卷 933-933页

作者： Congyu ma Ning Sheng jun Wu Lulu Wang jiandong jiang Haibo yu jinlan Zhang State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100050China Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100050China

The authors regret there was an unfortunate error in the reproduction of Fig.1I in the *** the original figure,the fluorescence picture of the positive control drug-ifenprodil was *** authors have corrected Fig.1I and provided the original fluorescence pictures of all groups(seven groups,n=5 for each group)to the editorial ***,the corrected Fig.1I is shown *** authors declare that this correction does not affect the description,interpretation,or the original conclusions of the article.

关键词： correction Active picture

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基于RBFNN的双星协同仅测角定轨方法

中国惯性技术学报 2024年第5期32卷 449-456页

作者：龚柏春刘一澎马艳红任默南京航空航天大学航天学院南京210016 北京控制工程研究所北京100094 航天系统部装备部北京100094

针对空间非合作目标空间态势感知任务中弱可观测无源定轨状态的快速捕获问题,提出了一种基于径向基函数神经网络(RBFNN)的双星协同稀疏无源测角定轨方法。首先,在限制性三体问题的假设下建立了考虑地球非球形j2项摄动的轨道动力学模型... 详细信息

针对空间非合作目标空间态势感知任务中弱可观测无源定轨状态的快速捕获问题,提出了一种基于径向基函数神经网络(RBFNN)的双星协同稀疏无源测角定轨方法。首先,在限制性三体问题的假设下建立了考虑地球非球形j2项摄动的轨道动力学模型和赤经赤纬测量模型。然后,构建了基于RBFNN的双星协同仅测角定轨框架,设计了训练数据集生成器、数据预处理方法和RBFNN结构。最后,利用地球静止轨道任务进行了数值仿真验证,并对测角频率等参数的定轨敏感性进行分析。仿真结果表明,在240 s内仅进行三次角度观测的条件下,该模型对初始相对距离估计的平均绝对百分比误差约为0.36%,目标轨道速度的估计误差在米/秒量级,可实现高精度的超短弧段稀疏无源测量定轨。

关键词：空间态势感知初始定轨仅测角径向基函数神经网络双星协同

250 km/h动车组气动载荷及动态气密特征的实车试验

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中南大学学报（自然科学版） 2024年第5期55卷 1889-1899页

作者：马瑶余以正夏春晶王雷梅元贵兰州交通大学甘肃省轨道交通力学应用工程实验室甘肃兰州730070 中车长春轨道客车股份有限公司国家轨道客车工程研究中心吉林长春130062

为了对长期运行的现役列车车体疲劳及静强度提供载荷边界输入条件,并加强对车体气动载荷特性和车内压力舒适性的长期运用评估,采用实车试验的方法得到CRH5A型动车组线路气动载荷和频率特征及不同隧道运行工况下车内外压力波动和车内压... 详细信息

为了对长期运行的现役列车车体疲劳及静强度提供载荷边界输入条件,并加强对车体气动载荷特性和车内压力舒适性的长期运用评估,采用实车试验的方法得到CRH5A型动车组线路气动载荷和频率特征及不同隧道运行工况下车内外压力波动和车内压力舒适性特征,结合实测数据和所提出的动态气密指数分析方法,计算整车动态气密指数。研究结果表明:在京沈客专沈阳—朝阳试验段,车体绝对气动压差变化范围为−2.53~0.71 kPa;车体外两侧压力无明显主频;间隔1 s和3 s的车内压力变化量最大值分别为294 Pa和383 Pa,尾车的车内压力波动最剧烈。列车通过黑山隧道、下窝堡隧道、扣莫明洞隧道、三棱山隧道4个典型长度隧道的整车动态气密性指数计算结果分别为10.46、12.13、11.06和14.40 s,对于同一列车而言,列车的动态气密指数未因所通过隧道长度的不同而有较明显的离散特征。

关键词： CRH5A型动车组隧道压力波车体气动载荷车内压力舒适性动态气密指数实车试验

铸牢中华民族共同体意识的社区实践研究——基于广州市j社区的调查

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广西民族研究 2024年第2期 86-93页

作者：马冬梅孟小鸽广东技术师范大学民族学院广东广州510665

随着城市化进程的不断推进和社会开放程度的日渐提高,我国人口大流动、大融居及各民族全方位互嵌态势日益凸显。社区已然成为各民族交往交流交融的重要场所和铸牢中华民族共同体意识的实践场域。这就需要从政治基础、社会基础、服务基... 详细信息

随着城市化进程的不断推进和社会开放程度的日渐提高,我国人口大流动、大融居及各民族全方位互嵌态势日益凸显。社区已然成为各民族交往交流交融的重要场所和铸牢中华民族共同体意识的实践场域。这就需要从政治基础、社会基础、服务基础及情感基础等方面入手,促进各族流动人口在空间、经济、文化、社会、心理等的全方位互嵌,推动社区铸牢中华民族共同体意识工作真正落到实处。

关键词：铸牢中华民族共同体意识社区实践

Formation of β' phase in LPSO structures in an Mg88Co5y7 alloy

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journal of magnesium and Alloys 2022年第1期10卷 175-182页

作者： Q.Q.jin X.H.Shao y.T.Zhou B.Zhang S.j.Zheng X.L.ma Shenyang National Laboratory for materials Science Institute of Metal ResearchChinese Academy of Sciences72 Wenhua Road110016 ShenyangChina materials Science and Engineering Research Center Guangxi University of Science and TechnologyLiuzhou 545006China School of materials Science and Engineering Research Institute for Energy Equipment MaterialsHebei University of TechnologyTianjin 300130China

Formation of β’ phase in long-period stacking ordered(LPSO) structures in an Mg;Co;y;(at.%) alloy after aging at 200 °C for 24 h or electron beam(EB) irradiation has been studied by high-angle annular dark-field scanning transmission electron microscopy(HAADFSTEM). β’ phase was precipitated only in the Mg matrix but not in LPSO structures after aging at 200 °C for 24 h. LPSO structure containing stacking defects transforms into the β’-long phase during EB irradiation, which plays a key role in accelerating solute atoms’ diffusion. New complex β’(LPSO) structures formed in the alloy after EB irradiation, such as β’(12 H) structure with an orthorhombic lattice(Mg;y, Cmcm,a = 2 _(a0)= 0.642 nm, b=4√3_(a0), c = 6 _(c0)= 3.12 nm).

关键词： magnesium alloys Long-period stacking ordered(LPSO)structure HAADF-STEM β’phase

A novel engineered IL-21 receptor arms T-cell receptor-engineered T cells(TCR-T cells)against hepatocellular carcinoma

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2215-2230页

作者： Wei Zhu Zhiming Zhang jinzhang Chen Xiaolan Chen Lei Huang Xiaoyong Zhang Xuan Huang Na ma Weikang Xu Xuan yi Xinyu Lu Xin Fu Siwei Li Guoheng Mo yiyue Wang Guosheng yuan Mengya Zang Qi Li Xiaotao jiang yajing He Sha Wu yukai He yongyin Li jinlin Hou State Key Laboratory of Organ Failure Research Guangdong Provincial Key Laboratory of Viral Hepatitis ResearchDepartment of Infectious DiseasesNanfang HospitalSouthern Medical UniversityGuangzhouChina Institute of Cellular Medicine Newcastle University Medical SchoolNewcastleUK Department of Pathology The First People’s Hospital of FoshanFoshanChina Dermatology Hospital Southern Medical UniversityGuangzhouChina Department of Immunology School of Basic Medical SciencesSouthern Medical UniversityGuangzhouChina Microbiome Medicine Center Department of Laboratory MedicineZhujiang HospitalSouthern Medical UniversityGuangzhouChina Key Laboratory of Proteomics of Guangdong Province Demonstration Center for Experimental Education of Basic Medical Sciences of ChinaGuangzhouChina Medical College of Georgia Augusta University112015th StreetAugustaGAUSA

Strategies to improve T cell therapy efficacy in solid tumors such as hepatocellular carcinoma(HCC)are urgently *** common cytokine receptorγchain(γc)family cytokines such as IL-2,IL-7,IL-15 and IL-21 play fundamental roles in T cell development,differentiation and effector *** study aims to determine the combination effects of IL-21 in T cell therapy against HCC and investigate optimized strategies to utilize the effect of IL-21 signal in T cell *** antitumor function of AFP-specific T cell receptor-engineered T cells(TCR-T)was augmented by exogenous IL-21 in vitro and in ***-21 enhanced proliferation capacity,promoted memory differentiation,downregulated PD-1 expression and alleviated apoptosis in TCR-T after activation.A novel engineered IL-21 receptor was established,and TCR-T armed with the novel engineered IL-21 receptors(IL-21R-TCR-T)showed upregulated phosphorylated STAT3 expression without exogenous IL-21 ***-21R-TCR-T showed better proliferation upon activation and superior antitumor function in vitro and in ***-21R-TCR-T exhibited a less differentiated,exhausted and apoptotic phenotype than conventional TCR-T upon repetitive tumor antigen *** novel IL-21 receptor in our study programs powerful TCR-T and can avoid side effects induced by IL-21 systemic *** novel IL-21 receptor creates new opportunities for next-generation TCR-T against HCC.

关键词： hepatocellular TCR utilize

440 MPa级高强钢焊条熔敷金属组织与低温冲击韧性研究

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焊接学报 2024年第3期45卷 120-128,I0010页

作者：曾道平郑韶先安同邦代海洋马成勇兰州交通大学兰州730070 钢铁研究总院焊接研究所北京100081

为满足440 MPa级高强钢对焊接材料的需求,研制了三种焊条,并进行了熔敷金属焊接试验,使用光学显微镜、扫描电镜和透射电镜等手段研究了熔敷金属组织与低温冲击韧性.结果表明,随着Mn,Ni,Cr和Cu含量的增大,熔敷金属的-40℃平均冲击吸收功... 详细信息

为满足440 MPa级高强钢对焊接材料的需求,研制了三种焊条,并进行了熔敷金属焊接试验,使用光学显微镜、扫描电镜和透射电镜等手段研究了熔敷金属组织与低温冲击韧性.结果表明,随着Mn,Ni,Cr和Cu含量的增大,熔敷金属的-40℃平均冲击吸收功从35.7 j逐渐增至96.3 j,低温冲击韧性逐渐提高;随着Mn,Ni,Cr和Cu含量的增大,虽然熔敷金属中M23C6型碳化物含量逐渐增大,但是熔敷金属的CCT曲线逐渐右移,相变温度逐渐降低,使得针状铁素体含量逐渐增加,铁素体板条尺寸逐渐减小和板条间交织状分布趋势逐渐增强,M-A组元含量及尺寸逐渐减小,是低温冲击韧性逐渐提高的主要原因;含Cu熔敷金属中夹杂物外层会形成CuS,针状铁素体形核更容易,有利于低温冲击韧性提高.

关键词： 440 MPa级高强钢熔敷金属针状铁素体 M-A组元低温冲击韧性