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Inflammation-induced inhibition of chaperone-mediated autophagy maintains the immunosuppressive function of murine mesenchymal stromal cells

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Cellular & Molecular Immunology 2021年第6期18卷 1476-1488页

作者： Jie Zhang Jiefang Huang Yuting Gu mingxing xue Fengtao Qian Bei Wang Wanlin Yang Hongshuang Yu Qiwei Wang Xin Guo Xinyuan Ding Jina Wang Min Jin Yanyun Zhang CAS Key Laboratory of Tissue Microenvironment and Tumor Shanghai Institute of Nutrition and HealthShanghai Institutes for Biological SciencesChinese Academy of SciencesShanghaiChina Pediatric Institute of Soochow University Institutes for Translational MedicineSoochow UniversitySuzhouChina Shanghai Institute of Immunology Shanghai Jiao Tong University School of MedicineShanghaiChina Department of Urology and Shanghai Key Laboratory of Organ Transplantation Zhongshan HospitalFudan UniversityShanghaiChina

Macroautophagy has been implicated in modulating the therapeutic function of mesenchymal stromal cells(MSCs).However,the biological function of chaperone-mediated autophagy(CMA)in MSCs remains ***,we found that CMA was inhibited in MSCs in response to the proinflammatory cytokines interferon-γ(IFN-γ)and tumor necrosis factor-α(TNF-α).In addition,suppression of CMA by knocking down the CMA-related lysosomal receptor lysosomal-associated membrane protein 2(LAMP-2A)in MSCs significantly enhanced the immunosuppressive effect of MSCs on T cell proliferation,and as expected,LAMP-2A overexpression in MSCs exerted the opposite effect on T cell *** effect of CMA on the immunosuppressive function of MSCs was attributed to its negative regulation of the expression of chemokine C-X-C motif ligand 10(CXCL10),which recruits inflammatory cells,especially T cells,to MSCs,and inducible nitric oxide synthase(iNOS),which leads to the subsequent inhibition of T cell proliferation via nitric oxide(NO).Mechanistically,CMA inhibition dramatically promoted IFN-γplus TNF-α-induced activation of NF-κB and STAT1,leading to the enhanced expression of CXCL10 and iNOS in ***,we found that IFN-γplus TNF-α-induced AKT activation contributed to CMA inhibition in *** interestingly,CMA-deficient MSCs exhibited improved therapeutic efficacy in inflammatory liver *** together,our findings established CMA inhibition as a critical contributor to the immunosuppressive function of MSCs induced by inflammatory cytokines nd highlighted a previously unknown function of CMA.

关键词： chaperone-mediated autophagy mesenchymal stromal cells immunosuppressive capacity inflammatory microenvironment

Modulation of metabolic functions through Cas13d-mediated gene knockdown in liver

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Protein & Cell 2020年第7期11卷 518-524页

作者： Bingbing He Wenbo Peng Jia Huang Hang Zhang Yingsi Zhou Xiali Yang Jing Liu Zhijle Li Chunlong Xu mingxing xue Hui Yang Pengyu Huang Instute of Neuroscience State Key Laboratory of NeuroscienceKey Laboratory of Primate NeurobiologyCAS Center for Excellence in Brain Science and Itelligence Technology.Shanghai Research Center for Brain Science and Brain-Inspired ItelligenceShanghai Institutes for Biological SciencesChinese Academy of SciencesShanghai 200031China School of Life Science and Technology.ShanghaiTech University Shanghai 201210China College of Life Sciences University of Chinese Academy of SciencesBeljing 100049China Center for Animal Genomics Agricultural Genome Institute at ShenzhenChinese Academy of Agricultural SciencesShenzhen 518124China CAS Center for Excellence in Molecular Cell Science Chinese Academy ot ScencesShanghal 200031China

Dear Editor,RNA knockdown in vivo carries significant potential for dis-ease modeling and *** the emerging approaches of CRISPR/Cas9-mediated permanent knock out of targeted genes,strategies targeting RNA for disruption are advantageous in the treatment of acquired metabolic disorders when permanent modification of genome DNA is not appropriate,and RNA virus infection diseases when pathogenic DNA is not available(such as SARS-Cov-2 and MERS infections).

关键词： CRISPR/Cas9 mediated diseases

Matrix-Mediated Color-Tunable Ultralong Organic Room Temperature Phosphorescence of 7H-Benzo[c]carbazole Derivatives

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CCS Chemistry 2024年第3期6卷 798-811页

作者： Chen Qian xue Zhang Zhimin Ma Xiaohua Fu Zewei Li Huiwen Jin mingxing Chen Hong Jiang Zhiyong Ma Beijing Advanced Innovation Center for Soft Matter Science and Engineering State Key Laboratory of Organic–Inorganic CompositesCollege of Chemical EngineeringBeijing University of Chemical TechnologyBeijing 100029 Beijing National Laboratory for Molecular Sciences College of Chemistry and Molecular EngineeringPeking UniversityBeijing 100871

Building on the recent systematic research on 1Hbenzo[f]indole(Bd),an important advancement in constructing ultralong organic room temperature(UORTP)materials with a universal strategy via a readily obtained unit(7H-Benzo[c]carbazole,BCz)is proposed in this *** powders of BCz and its derivatives merely exhibit blue fluorescence at ambient ***,when BCz and its derivatives are dispersed into polymer or powder matrixes,strong photo-activated green UORTP can be observed from their doped systems at room ***,the UORTP color can be tuned between green and yellow depending on the *** ultralong phosphorescence originates from the generation of charge-separated states via *** matrixes play a key role in both stabilizing charge-separated states and controlling UORTP *** interestingly,when using polymethyl methacrylate as matrix,the doped films achieve stronger photo-activated ultralong phosphorescence underwater than in air at room *** Bd,BCz achieves better performance not only in ultralong phosphorescence properties but also in practical *** work gains a deeper insight into the mechanism of UORTP and paves a new approach to applying organic phosphorescent materials to underwater coating and imaging.

关键词： 7H-Benzo[c]carbazole ultralong organic room temperature phosphorescence ion radical matrix-mediated color tunning underwater application

Conversion of Absolute Position Information and Relative Position Information of Satellite Positioning by Coordinate System Transformation

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Conversion of Absolute Position Information and Relative Pos...

Human 8-cell embryos enable efficient induction of disease-preventive mutations without off-target effect by cytosine base editor

新型导航技术及应用研讨会

作者： xue mingxing Feng Yuehua Sun Yandong Wu Qihong Gao Yang School of Electronic Information Northwestern Polytechnical University

With the development of space technology, the position system plays a crucial important role in both civil use and military use. The BeiDou Navigation Satellite System which designed by China has now reached the global layout stage and almost covered the whole region of China. To address the problem that The BeiDou Navigation Satellite System can only provide the absolute position information,latitude and longitude, this paper delivers a method which approximates the earth by a sphere in a small scope and uses the absolute position information,latitude and longitude in CGCS2000coordinate’s, to calculate the relative position *** result of the emulation experiment indicates that this method can be applied to obtain the high-precision relative position information in eighty kilometers of the practical use.

关键词： Space technology Position and Navigation the Relative Position CGCS2000 Coordinates

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Protein & Cell 2023年第6期14卷 416-432页

作者： Yinghui Wei Meiling Zhang Jing Hu Yingsi Zhou mingxing xue Jianhang Yin Yuanhua Liu Hu Feng Ling Zhou Zhifang Li Dongshuang Wang Zhiguo Zhang Yin Zhou Hongbin Liu Ning Yao Erwei Zuo Jiazhi Hu Yanzhi Du Wen Li Chunlong Xu Hui Yang Center for Reproductive Medicine International Peace Maternity and Child Health HospitalInnovative Research Team of High-level Local Universities in ShanghaiSchool of MedicineShanghai Jiao Tong UniversityShanghai 2000301.Center for Reproductive MedicineInternational Peace Maternity and Child Health HospitalInnovative Research Team of High-level Local Universities in ShanghaiSchool of MedicineShanghai Jiao Tong UniversityShanghai 200030China Institute of Neuroscience State Key Laboratory of NeuroscienceKey Laboratory of Primate NeurobiologyCAS Center for Excellence in Brain Science and Intelligence TechnologyShanghai Institutes for Biological SciencesChinese Academy of SciencesShanghai 200031China Lingang Laboratory Shanghai Research Center for Brain Science and Brain-Inspired Intelligence TechnologyShanghai 200031China Center for Reproductive Medicine Ren Ji HospitalSchool of MedicineShanghai Key Laboratory for Assisted Reproduction and Reproductive GeneticsShanghai Jiao Tong UniversityShanghai 200127China The MOE Key Laboratory of Cell Proliferation and Differentiation School of Life SciencesGenome Editing Research CenterPeking UniversityBeijing 100871China Center for Reproductive Medicine Shandong UniversityJinan 250012China Center for Reproductive Medicine Anhui Provincial Maternal and Child Health HospitalHefei 230001China Shenzhen Branch Guangdong Laboratory for Lingnan Modern AgricultureGenome Analysis Laboratory of the Ministry of AgricultureAgricultural Genomics Institute at ShenzhenChinese Academy of Agricultural SciencesShenzhen 518000China Reproductive Medicine Center Department of Obstetrics and Gynecologythe First Affiliated Hospital of Anhui Medical UniversityHefei 230022China

Approximately 140 million people worldwide are homozygous carriers of APOE4(ε4),a strong genetic risk factor for late onset familial and sporadic Alzheimer’s disease(AD),91%of whom will develop AD at earlier age than heterozygous carriers and *** to AD could be reduced by targeted editing of APOE4,but a technical basis for controlling the off-target effects of base editors is necessary to develop low-risk personalized gene ***,we first screened eight cytosine base editor variants at four injection stages(from 1-to 8-cell stage),and found that FNLS-YE1 variant in 8-cell embryos achieved the comparable base conversion rate(up to 100%)with the lowest bystander *** particular,80%of AD-susceptibleε4 allele copies were converted to the AD-neutralε3 allele in humanε4-carrying *** control measures combined with targeted deep sequencing,whole genome sequencing,and RNA sequencing showed no DNA or RNA off-target events in FNLS-YE1-treated human embryos or their derived stem ***,base editing with FNLS-YE1 showed no effects on embryo development to the blastocyst ***,we also demonstrated FNLS-YE1 could introduce known protective variants in human embryos to potentially reduce human susceptivity to systemic lupus erythematosus and familial *** study therefore suggests that base editing with FNLS-YE1 can efficiently and safely introduce known preventive variants in 8-cell human embryos,a potential approach for reducing human susceptibility to AD or other genetic diseases.

关键词： human embryo APOE4 disease-preventive mutations base editor

An engineered xCas12i with high activity,high specificity,and broad PAM range

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Protein & Cell 2023年第7期14卷 540-545页

作者： Hainan Zhang Xiangfeng Kong mingxing xue Jing Hu Zikang Wang Yinghui Wei Haoqiang Wang Jingxing Zhou Weihong Zhang Mengqiu Xu Xiaowen Shen Fengcai Yin Zhiyuan Ai Guangyan Huang Junhui Xia xueqiong Song Hengbin Li Yuan Yuan Jinhui Li Na Zhong Meiling Zhang Yingsi Zhou Hui Yang HuiEdit Therapeutics Co. Ltd.Shanghai 200120China HuiGene Therapeutics Co. Ltd.Shanghai 200120China Center for Reproductive Medicine International Peace Maternity and Child Health HospitalInnovative Research Team of High-level Local Universities in ShanghaiSchool of MedicineShanghai Jiao Tong UniversityShanghai 200030China

Dear Editor,The clustered regularly interspaced short palindromic repeats-Cas(CRISPR-Cas)systems,including type II Cas9 and type V Cas12 systems,which serve in the adaptive immunity of prokaryotes against viruses,have been developed into genome-editing tools(Anzalone et al.,2020;Doudna,2020).Compared with type II systems,the type V systems including V-A to V-K showed more functional diversity(Yan et al.,2019).Amongst them,Cas12i has a relatively smaller size(1,033-1,093 aa),compared to SpCas9 and Cas12a,and has a 5'-TTN protospacer adjacent motif(PAM)preference(Yan et al.,2019).

关键词： high specificity

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边缘检测技术在砂体连通研究中的应用

地球物理学进展 2022年第2期37卷 844-850页

作者：刘传奇宋俊亭薛明星中海石油(中国)有限公司天津分公司渤海石油研究院天津300459

边缘检测技术是基于计算机图形学算法提取数据或图像中的边缘信息,使得沉积体的边缘或储层之间的不连续性更加突出,为储层描述提供了新的手段和思路.目标油田为河流相沉积,砂体平面上叠置连片分布,主要发育水下分流河口坝沉积微相,砂体... 详细信息

边缘检测技术是基于计算机图形学算法提取数据或图像中的边缘信息,使得沉积体的边缘或储层之间的不连续性更加突出,为储层描述提供了新的手段和思路.目标油田为河流相沉积,砂体平面上叠置连片分布,主要发育水下分流河口坝沉积微相,砂体内部多期砂坝之间叠置明显,多期砂坝之间储层连通性较差,为了精细研究砂体内部的连通性,进而研究砂体的剩余油分布,首先提取砂体的振幅属性,然后应用Robert梯度算子对振幅属性求取振幅梯度,得到砂体基于振幅的边缘检测属性,该属性对砂坝叠置处有显著的增强作用,能够提高砂体内部多期砂坝间储层叠置的刻画精度.振幅属性能够刻画砂体平面厚度变化,基于振幅属性的边缘检测属性能够刻画砂体内部砂坝的叠置,融合这两种属性,再结合沉积模式、油田生产动态和数值模拟信息,开展精细剩余油分布研究,为油田后期调整挖潜、提高采收率提供支持.边缘检测技术在渤海Z油田的储层连通性研究中取得了很好的效果.在相似沉积背景下,综合运用地震地质手段,可以作为油田开发过程中解决储层内部连通性问题的有力工具,该技术具有广泛的应用前景.

关键词：边缘检测储层连通注采关系剩余油分布砂体叠置

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论中国平台经营者经营利益的保护

现代经济探讨 2024年第5期 108-120页

作者：薛婳钱明星北京大学法学院北京100871 北京大学国际知识产权研究中心

平台经营者的经营利益受到侵害所造成的损害属于纯粹经济损失。对于纯粹经济损失的赔偿,比较法上的做法看似迥异,实则并无本质差异,都注重考察侵权人的主观状态并均持谨慎认定的态度。通过考察中国平台经营者经营利益保护的实践可以发现... 详细信息

平台经营者的经营利益受到侵害所造成的损害属于纯粹经济损失。对于纯粹经济损失的赔偿,比较法上的做法看似迥异,实则并无本质差异,都注重考察侵权人的主观状态并均持谨慎认定的态度。通过考察中国平台经营者经营利益保护的实践可以发现,中国采取了一种较为宽松的司法政策,通过社会生活经验推断降低了纯粹经济损失的证明标准,扩张了经营利益的保护范围。平台经营者的经营利益宜作为民事利益受到《民法典》侵权责任编的保护,并应以行为的违法性来界定经营利益的保护范围。

关键词：平台经营者经营利益纯粹经济损失不正当竞争违法性

旋转式多比例分样方法对作物籽粒分样效果的研究

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中国农业大学学报 2022年第10期27卷 111-119页

作者：杨富淇谢美西薛鸣星高中斗谢光辉中国农业大学农学院北京100193 霍克光仪北京科技有限公司北京100012 国家能源非粮生物质原料研发中心北京100193

为验证旋转式多比例分样方法的可行性,探究旋转式多比例分样方法对作物籽粒的分样效果,以谷子、绿豆、大豆和玉米籽粒材料制备成混合样品,在不同转速(0~30.0r/min)处理和不同进样时间(60、90、120s)内比较旋转式多比例分样方法获得1/2、... 详细信息

为验证旋转式多比例分样方法的可行性,探究旋转式多比例分样方法对作物籽粒的分样效果,以谷子、绿豆、大豆和玉米籽粒材料制备成混合样品,在不同转速(0~30.0r/min)处理和不同进样时间(60、90、120s)内比较旋转式多比例分样方法获得1/2、1/4、1/8和1/16子样的代表性和缩分比误差。结果表明,在转速0~30.0r/min和进样时间60~120s的情况下,旋转式多比例分样方法获得子样的分样误差和均无显著差异,且均不高于四分法(CK)。但是,除不旋转(0r/min)处理的1/8四盒和1/16单盒及30r/min处理的1/16单盒子样的缩分比误差显著高于对照外,旋转处理(转速≥7.5r/min)的单盒、双盒或四盒子样的缩分比误差不高于四分法对照。因此,在进行样品前处理的分样工作中应用旋转式多比例分样方法是可行的,应设置转速≥7.5r/min,取相对2个扇盒或十字相对4个扇盒形成的子样。

关键词：分样分样误差缩分比误差旋转扇盒分样器