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Effective gene targeting in rabbits using RNA-guided Cas9 nucleases

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Journal of Molecular Cell Biology 2014年第1期8卷 97-99页

作者： Dongshan y.ng Jie Xu Tianqing Zhu Jianglin Fan Liangxue Lai Jifeng Zhang y. eugene chen Southern China Institute of Stem Cell Biology.and Regenerative Medicine Guangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences Guangzhou China

Dear Editor, Recently. zinc finger nuclease, transcrip- tion activator-like effector nuclease, and RNA-guided Cas9 endonuciease （Cas9） have emerged as powerful means for genome editing （Conklin, 2013; Gaj eta[., 2013）. These nucleases are efficient in gen- erating double-strand breaks in the genome that can be repaired by.error-prone nonho- mologous end joining leading to a functional knockout （KO） of the targeted gene or used to integrate a DNA sequence at a specific locus through homologous recombination.

关键词：核酸酶基因组 RNA 制导同源重组 DNA序列转录激活双链断裂

Macrophage-derived matrix metalloproteinase-1 enhances aortic aneury.m formation in transgenic rabbits

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The Journal of Biomedical Research 2019年第4期33卷 271-279页

作者： Manabu Niimi Kazutoshi Nishijima Shuji Kitajima Fumikazu Matsuhisa Kaneo Satoh Hirokazu y.mazaki Jifeng Zhang y. eugene chen Jianglin Fan Department of Molecular Pathology Graduate School of MedicineUniversity of YamanashiYamanashi 409-3898Japan Animal Research Laboratory Bioscience Education-Research Support CenterAkita UniversityAkita 010-8502Japan Analy.ical Research Center for Experimental Sciences Saga UniversitySaga 840-8502Japan Department of Laboratory.Medicine Graduate School of MedicineUniversity of YamanashiYamanashi 409-3898Japan Center for Advanced Models for Translational Sciences and Therapeutics University of Michigan Medical CenterAnn ArborMI 48109USA School of Biotechnology.and Health Sciences Wuyi UniversityJiangmenGuangdong 529020China

Increased expression of matrix metalloproteinase-1(MMP-1)has been observed in the lesions of atherosclerosis and aneury.ms;however,it is not fully.understood whether macrophage-derived MMP-1 affects these *** investigate whether macrophage-derived MMP-1 participates in the development of vascular diseases,we generated transgenic(Tg)rabbits expressing human MMP-1 in the monocy.e/macrophage lineage under the control of the human scavenger receptor enhancer/*** rabbits exhibited no visible abnormalities throughout their *** blotting analy.is revealed that the amount of MMP-1 proteins in the conditioned media secreted from peritoneal macrophages of Tg rabbits was up to 3-fold higher than that in non-Tg *** the first experiment,Tg and non-Tg rabbits were fed a cholesterol diet for 16 weeks,and aortic and coronary.atherosclerosis were *** gross lesion area of aortic atherosclerosis in Tg rabbits was not significantly.different from that in non-Tg rabbits,but Tg rabbits had marked destruction of the medial elastic lamina of the aortic lesions on microscopic *** the second experiment,we generated aortic aneury.ms by.incubating with *** with non-Tg rabbits,Tg rabbits exhibited a significantly.greater aortic *** macrophage-derived MMP-1 led to increased medial destruction in both aortic atherosclerosis and *** results demonstrate that MMP-1 play. a different role in the pathogenesis of atherosclerosis and aneury.ms.

关键词： matrix metalloproteinase-1 macrophage atherosclerosis aneury.m transgenic rabbit

The Future of TZD,from Lab Bench to Bedside

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中国动脉硬化杂志 2009年第7期17卷 580-580页

作者： y. eugene chen Cardiovascular Center University of Michigan Medical CenterMSRB III 7301E1150 W. Medical Center Drive

The metabolic sy.drome is strongly.associated with insulin resistance and consists of a constellation of factors such as hy.ertension and hy.erlipidemia that raise the risk for cardiovascular disease (CVD) and diabetes mellitus. Emerging data suggest that peroxisome proliferator-activated receptor-γ (PPARγ) is a critical determinant that may.provide functional links between diabetes and CVD.

关键词：高血压胰岛素预防措施临床分析

m TOR and post-translational modifications rely.on mitochondrion as the arsenal for cellular metabolism regulation

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Science China(Life Sciences) 2015年第8期58卷 810-812页

作者： ZHUGE ChunChun J chen Si J CHIN y.eugene Shanghai Chest Hospital Shanghai Jiaotong University Institute of Health Sciences Chinese Academy of Sciences School of Medicine Shanghai Jiaotong University

Mitochondrion is considered as the"powerhouse of the cell"almost immediately.since its *** carries less than 1,000 proteins and some nucleotides as well as *** is also discovered as the"lung of the cell"for its role i... 详细信息

关键词：细胞器线粒体翻译后修饰代谢调节 mTOR 呼吸作用代谢过程核苷酸

Complex RNA-DNA hy.rid nanoshapes from iterative mix-andmatch screening

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Nano Research 2021年第1期14卷 46-51页

作者： Shi chen Zhiy.an Zhang eugene Alforque Thomas Hermann Department of Chemistry.and Biochemistry University of CaliforniaSan DiegoCA 92093USA Center for Drug Discovery.Innovation University of CaliforniaSan DiegoCA 92093USA Materials Science and Engineering Program University of CaliforniaSan DiegoCA 92093USA

Hy.rid nucleic acid nanostructures partition architectural and functional roles between ribonucleic acid(RNA)joints and deoxy.ibonucleic acid(DNA)*** self-assemble from nucleic acid modules through sy.ergistic stabilization of marginally.stable base pairing interactions within circularly.closed ***,we report the development of hy.rid nanoshapes that include multiple different RNA modules such as internal loop and three-way.junction(3WJ)*** iterative mix-and-match screening approach was used to identify.suitable DNA connectors that furnished stable nanoshapes for combinations of different RNA *** resulting complex multicomponent RNA-DNA hy.rid nanoshapes were characterized by.atomic force microscopy.AFM)*** research provides proof of concept for modular design,assembly.and screening of RNA-DNA hy.rid nanoshapes as building blocks for complex extended nucleic acid materials with features at the sub-10 nm scale.

关键词： nucleic acid nanotechnology nanoshapes ribonucleic acid(RNA)three-way.junction(3WJ) RNA deoxy.ibonucleic acid(DNA) sub-10 nm features

Recent strategies to improve moisture stability.in metal halide perovskites materials and devices

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Journal of Energy.Chemistry 2022年第2期31卷 219-235页

作者： chenxiao Zhou Alexey.B.Tarasov eugene A.Goodilin Pengwan chen Hao Wang Qi chen School of Materials Science and Engineering Beijing Institute of TechnologyBeijing 100081China Faculty.of Materials Science Lomonosov Moscow State UniversityLenin Hills119991 MoscowRussia Department of Chemistry Lomonosov Moscow State UniversityLenin Hills119991 MoscowRussia State Key.Laboratory.of Explosion Science and Technology Beijing Institute of TechnologyBeijing 100081China Beijing Institute of Technology.Chongqing Innovation Center Chongqing 401120China

At present,the stability.of the new generation of solar cells based on hy.rid perovskites is the bottleneck for their practical *** effects,high temperature,ultraviolet light,humidity.and other known or still unknown factors might cause reduction of effectiveness or even irreversible loss of materials properties due to decomposition of functional lay.rs within perovskite solar cells(PSCs).These factors alone have a serious impact on each component of the device,while their combinations lead to much more complicated effects and *** review focuses on the stability.of PSCs and the degradation of the device in a humid *** assess the instability.factors and deep-seated principles of evolution of the device structure in a humidity.environment with the emphasis on the influence on their *** related solutions are reviewed from the perspective of the encapsulation,perovskite active lay.r,carrier transport lay.r and *** with the latest research,we believe that the waterproof strategy.of PSCs requires either tight encapsulation or thorough modifications in the device ***,it is important to develop feasible strategies to improve the overall device stability.over humid according to the target characteristics of various devices.

关键词： Perovskite solar cells Water Stability Composition Encapsulation

Genome engineering technologies in rabbits

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The Journal of Biomedical Research 2021年第2期35卷 135-147页

作者： Jun Song Jifeng Zhang Jie Xu Minerva Garcia-Barrio y.eugene chen Dongshan y.ng Center for Advanced Models for Translational Sciences and Therapeutics University of Michigan Medical CenterAnn ArborMI 48109USA

The rabbit has been recognized as a valuable model in various biomedical and biological research fields because of its intermediate size and phy.ogenetic proximity.to ***,the technology.for precise genome manipulations in rabbit has been stalled for decades,severely.limiting its applications in biomedical *** genome editing technologies,especially.CRISPR/Cas9,have remarkably.enhanced precise genome manipulation in rabbits,and shown their superiority.and promise for generating rabbit models of human genetic *** this review,we summarize the brief history.of transgenic rabbit technology.and the development of novel genome editing technologies in rabbits.

关键词： rabbit transgenic animal gene targeting genome editing base editing

Gene editing therapy.ready.for cardiovascular diseases: opportunities, challenges, and perspectives

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Medical Review 2021年第1期1卷 6-9页

作者： Jun Zhou Zhuoy.ng Ren Jie Xu Jifeng Zhang y.eugene chen Center for Advanced Models for Translational Sciences and Therapeutics University of Michigan Medical CenterAnn Arbor 48109MIUSA Department of Pharmacology University of Michigan Medical CenterAnn ArborMI 48109USA

Gene editing nucleases(GENs),represented by.CRISPR/Cas9,have become major tools in biomedical research and offer potential cures for many.human *** editing therapy.GETx)studies in animal models targeting genes such as proprotein convertase subtilisin/kexin ty.e 9(PCSK9),apolipoprotein C3(APOC3),angiopoietin Like 3(ANGPTL3)and inducible degrader of the low-density.lipoprotein receptor(IDOL)have demonstrated the benefits and advantages of GETx in managing *** we present our views on this brand new therapeutic option for cardiovascular diseases(CVD).

关键词： cardiovascular diseases CRISPR/Cas9 gene editing therapy.

Sy.Finder：A customized platform for search,comparison and assisted design of appropriate animal models based on sy.tematic similarity

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Journal of Genetics and Genomics 2017年第5期44卷 251-258页

作者： Shuang y.ng Guoqing Zhang Wan Liu Zhen Wang Jifeng Zhang Dongshan y.ng y.eugene chen Hong Sun y.xue Li Department of Bioinformatics and Biostatistics School of Life Sciences and Biotechnology Shanghai Jiao Tong University Shanghai 200240 China Shanghai Center for Bioinformation Technology Shanghai 200235 China Key.Lab of Computational Biology CAS-MPG Partner Institute for Computational Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 200031 China Center for Advanced Models for Translational Sciences and Therapeutics University of Michigan Medical Center Ann Arbor M148109 USA Biomedical Information Research Center Children's Hospital of Shanghai Shanghai 200040 China Collaborative Innovation Center for Genetics and Development Fudan University Shanghai 200433 China

Animal models are increasingly.gaining values by.cross-comparisons of response or resistance to clinical agents used for ***,many.disease mechanisms and drug effects generated from animal models are not transferable to *** address these issues,we developed Sy.Finder（http：//***/Sy.Finder）,a platform for scientists to find appropriate animal models for translational *** offers a ＂topic-centered＂ approach for sy.tematic comparisons of human genes,whose functions are involved in a specific scientific topic,to the corresponding homologous genes of animal *** topic can be a certain disease,drug,gene function or biological *** calculates multi-level similarity.indexes to evaluate the similarities between human and animal models in specified scientific ***,Sy.Finder offers species-specific information to investigate the differences in molecular mechanisms between humans and animal ***,Sy.Finder provides a userfriendly.platform for determination of short guide RNAs（sgRNAs） and homology.arms to design a new animal *** studies illustrate the ability.of Sy.Finder in helping experimental *** is a useful platform for experimental scientists to carry.out their research in the human molecular mechanisms.

关键词： Database Animal models Function similarity