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| 1 | Multiplexed activation of endogenous genes by CRISPR-on, an RNA-guided transcriptional activator system显示文摘允许的技术内长的基因的特定的规定为基因功能的学习是珍贵的并且在治疗学有大潜力。我们创造了在 CRISPR 上系统,由核酸酶死者 Cas9 (dCas9 ) 蛋白质组成的二部件的 transcriptional 使活跃之物与互补顺序与 transcriptional 激活域和单个指南 RNA (sgRNAs ) 熔化了到基因倡导者。我们证明在 CRISPR 上能高效地以一种悦耳的方式在人和老鼠房间激活外长的记者基因。另外,我们证明在 vivo 的柔韧的记者基因激活能被把系统部件注入老鼠接合子完成。而且,我们证明在 CRISPR 上能激活内长的 IL1RN, SOX2,和 OCT4 基因。最有效的基因激活被对近似倡导者有约束力的 3-4 sgRNAs 的簇完成,建议他们在基因正式就职的 synergistic 行动。显著地,当指向多重基因的 sgRNAs 同时被介绍进房间时,柔韧的多路的内长的基因激活被完成。染色体宽的表示介绍表明了系统的高特性。 | Albert W Cheng Haoyi Wang Hui Yang Linyu Shi Yarden Katz Thorold W Theunissen Sudharshan Rangarajan Chikdu S Shivalila Daniel B Dadon Rudolf Jaenisch | 2013 | Cell Research2013，23，10： | 65 |
| 2 | Homology-mediated end joining-based targeted integration using CRISPR/Cas9显示文摘 | Yao, Xuan Wang, Xing Hu, Xinde Liu, Zhen Liu, Junlai Zhou, Haibo Shen, Xiaowen Wei, Yu Huang, Zijian Ying, Wenqin Wang, Yan Nie, Yan-Hong Zhang, Chen-Chen Li, Sanlan Cheng, Leping Wang, Qifang Wu, Yan Huang, Pengyu Sun, Qiang Shi, Linyu Yang, Hui | 2017 | Cell Research2017，27，6： | 28 |
| 3 | Generation of haploid embryonic stem cells from Macaca fascicularis monkey parthenotes显示文摘在从经由单性生殖和男性单性生殖的老鼠的胚胎的干细胞(haESCs ) 启用了在修改基因的动物的哺乳动物的房间和代的基因屏蔽的 haploid 的推导的最近的成功。然而, haESCs 是否能从首领被导出,仍然保持未知。这里,我们从 Macaca fascicularis 猴子的单性生殖的胚囊报导 haESCs 的推导。这些房间,作为 PG-haESCs 称为,是 pluripotent 并且能在 vitro 或在 vivo 区分到三胚胎的细菌层的房间。有趣地,一根猴子 PG-haESC 线(MPH1 ) 的 haploidy 与另一个(MPH2 ) 的相比是更稳定的,作为没有排序的激活荧光的房间(FACS ) ,由 haploid 房间的存在出现超过 140 天 haploid 房间的丰富。重要地,转基因的猴子 PG-haESC 线能被 lentivirus- 和 piggyBac 产生调停 transposon 的基因转移。而且,基因屏蔽在猴子 PG-haESCs 是可行的。我们的结果证明 PG-haESCs 能从猴子被产生,提供为在首领的基因分析的一个理想的工具。 | Hui Yang Zhen Liu Yu Ma Cuiqing Zhong Qi Yin Chikai Zhou Linyu Shi Yijun Cai Hanzhi Zhao Hui Wang Fan Tang Yan Wang Chenchen Zhang Xin-yuan Liu Dongmei Lai Ying Jin Qiang Sun Jinsong Li | 2013 | Cell Research2013，23，10： | 22 |
| 4 | One-step generation of complete gene knockout mice and monkeys by CRISPR/Cas9-mediated gene editing with multiple sgRNAs显示文摘CRISPR/Cas9 系统是一个有效编辑基因的方法,但是编辑基因的动物的多数显示出 mosaicism,与编辑仅仅在房间的部分发生。这里,我们证明那单个基因或多重基因能被 Cas9 mRNA 和多重邻近的单个指南的 RNA 的 zygotic 注射完全在老鼠和猴子胚胎击倒(spaced 10-200 bp 分开) 指向仅仅一把单个钥匙每基因的 exon。个别地在 Y 染色体上跟随八基因的指向的删除的 F0 老鼠的 Phenotypic 分析在产生猛烈老鼠表明了这条途径的坚韧性。重要地,这条途径在高效率交付完全的基因大美人(Arntl 上的 100% 并且 91% 在 Prrt2 上) 在猴子胚胎。最后,我们能在一个单个步骤产生一只完全的 Prrt2 猛烈猴子,表明在很快建立编辑基因的猴子模型的这条途径的实用性。 | Erwei Zuo Yi-Jun Cai Kui Li Yu Wei Bang-An Wang Yidi Sun Zhen Liu Jiwei Liu Xinde Hu Wei Wei Xiaona Huo Linyu Shi Cheng Tang Dan Liang Yan Wang Yan-Hong Nie Chen-Chen Zhang Xuan Yao Xing Wang Changyang Zhou Wenqin Ying Qifang Wang Ren-Chao Chen Qi Shen Guo-Liang Xu Jinsong Li Qiang Sun Zhi-Qi Xiong Hui Yang | 2017 | Cell Research2017，27，7： | 21 |
| 5 | Haploid embryonic stem cells:an ideal tool for mammalian genetic analyses显示文摘Identification of the function of all genes in the mammalian genome is critical in understanding basic mechanisms of biology.However,the diploidy of mammalian somatic cells has greatly hindered efforts to elucidate the gene function in numerous biological processes by mutagenesis-based genetic approaches.Recently,mouse haploid embryonic stem(haES)cells have been successfully isolated from parthenogenetic and androgenetic embryos,providing an ideal tool for genetic analyses.In these studies,mouse haES cells have already shown that they could be used in cell-based forward or reverse genetic screenings and in generating gene-targeting via homologous recombination.In particular,haES cells from androgenetic embryos can be employed as novel,renewable form of fertilization agent for yielding live-born mice via injection into oocytes,thus showing the possibility that genetic analysis can be extended from cellular level to organism level. | Linyu Shi Hui Yang Jinsong Li | 2012 | Protein & Cell2012，3，11： | 14 |
| 6 | Hydrothermal synthesis of monodisperse α-Fe_2O_3 hexagonal platelets显示文摘Uniformly sized α-Fe2O3 hexagonal platelets were synthesized by a hydrothermal process using Fe(OH)3 suspension and large amount of NaOH.The reaction products were characterized by X-ray diffraction(XRD),scanning electron microscopy(SEM),transmission electron microscopy(TEM),selected area electron diffraction(SAED),and a vibrating sample magnetometer(VSM).The results show that the hexagonal platelets are fine,monodisperse and consisting of single-crystals.The magnetic hysteresis(M-H) curve of the samples measured at room temperature indicates that the α-Fe2O3 micro-platelets exhibit ferromagnetic behaviors with relatively low coercivity. | Dengfeng Peng Sadeh Beysen Qiang Li Yanfei Sun Linyu Yang | 2010 | Particuology2010，8，4： | 4 |
| 7 | Ecological compensation based on willingness to accept for conservation of drinking water sources显示文摘生态的赔偿是为在喝的水消息提供者被找到的区域的环境保护的一个强大的环境经济工具。我们基于回答者心甘情愿建立了一个生态的赔偿财务系统接受(WTA ) 。在这个系统,影响他们的股东偏爱和因素能用 logit 和 tobit 模型有效地被计量。我们为 Miyun 水库把这个财务系统用于生态的赔偿,中国北京。为 Miyun 水库居民的平均 WTA 价值比本地保护花费的每在 2012 的家庭是约 1186 CNY,它能被放作为一个合适的赔偿标准,自从它稍微高。因此,年度全部的生态的赔偿能是 5873 万 CNY。从到环境保护的水库,工作类型,和态度的距离是有 WTA 上的重要效果的变量。另外,为单个偏爱的趋势经由关键有影响的因素的分析被识别。结果为证实为喝的保存的生态的赔偿机制浇来源建议一些有用信息。建议包括在居民之中推广生态的赔偿的概念和意思,设置基于从水库的距离的不同赔偿层次,并且拿,就农民的要求而言各种各样在里面客气并且 out-of-kind 赔偿途径。 | Linyu XU Bing YU Yang LI | 2015 | Frontiers of Environmental Science & Engineering2015，9，1： | 3 |
| 8 | High-efficiency somatic reprogramming induced by intact MII oocytes显示文摘体的原子核能是进由原子转移,房间熔化和抄写因素的表示的一个 pluripotent 状态的 reprogrammed。然而,这些 reprogramming 过程是很低效的,它极大地妨碍了努力阐明内在的分子的机制。这里,我们报导把所有三 reprogramming 方法论的优点合为一个过程的新 reprogramming 策略。我们从积云房间把原子核注入了未经触动的 MII 卵母细胞。后面的激活,开发到胚胎的茎(ES ) 房间衬里的胚囊阶段,和 tetraploid (4N ) 的 80% 重建的胚胎每重建的卵母细胞以 30% 的率被产生。我们也产生了三倍性(3N ) 在进激活的卵母细胞的体的原子核的注射以后的 ES 房间。4N 和 3N ES 房间表示了 pluripotent 标记并且在 vivo 区分了进三胚胎的细菌层的房间类型。而且,所有 ES 房间产生了 histocompatible,在在免疫能力的 B6D2F1 老鼠被嫁接以后的区分的房间,显示出房间从这 reprogramming 策略导出的那 ES 可能为移植担任遗传上定制的纸巾的来源。因此,我们建立了为调查涉及体的 reprogramming 的分子的机制提供一个系统的一个简单、高度有效的 reprogramming 过程。 | Hui Yang Linyu Shi Shenghua Zhang Jiangwei Lin Jing Jiang Jinsong Li | 2010 | Cell Research2010，20，9： | 2 |
| 9 | Precise genome editing without exogenous donor DNA via retron editing system in human cells显示文摘Dear Editor,CRISPR-Cas9 mediated seamless genome editing can be achieved by incorporating donor DNA into the CRISPR-Cas9 target loci via homology-directed repair(HDR),albeit with relative low efficiency due to the inefficient delivery of exogenous DNA(Cox et al.,2015;Gao,2021).Retrons are bacterial phage-defense related operons composed of a specialized reverse transcriptase(RT)and a relevant non-coding RNA(ncRNA)which can be partially reverse tran-scribed by RT initiating at a conserved guanosine(G)residue to produce a multicopy single-stranded DNA(msDNA)(Yee et al.,1984;Millman et al.,2020).After being reverse transcribed,the msDNA is usually covalently teth-ered to the ncRNA through the 2',5'-phosphodiesterbond between the priming G in ncRNA and 5'end of msDNA(Dhundale et al.,1987).The reverse transcription process,of which the specialized RT recognizes the unique secondary structure of retron ncRNA,is highly specific(Hsu et al.,1989).Additionally,desired msDNA can be generated in vivo by replacing the dispensable region of retron ncRNA with desired sequences(Mirochnitchenko et al.,1994;Simon et al.,2019).Therefore,retrons are promising biological sources for in vivo generation of DNA donors for HDR-me-diated precise genome editing. | Xiangfeng Kong Zikang Wang Renxia Zhang Xing Wang Yingsi Zhou Linyu Shi Hui Yang | 2021 | Protein & Cell2021，12，11： | 2 |
| 10 | Mice generated after round spermatid injection into haploid two-cell blastomeres显示文摘 | Hui Yang Linyu Shi Charlie Degui Chen Jinsong Li | 2011 | Cell Research2011，21，5： | 2 |
| 11 | Porous fiber paper and 3D patterned electrodes composed high-sensitivity flexible piezoresistive sensor for physiological signal monitoring显示文摘The research on flexible pressure sensors has drawn widespread attention in recent years,especially in the fields of health care and intelligent robots.In practical applications,the sensitivity of sensors directly affects the precision and integrity of weak pressure signals.Here,a pressure sensor with high sensitivity and a wide measurement range composed of porous fiber paper and 3D patterned electrodes is proposed.Multi-walled carbon nanotubes with excellent conductivity were evenly sprayed on the fiber paper to form the natural spatial conducting networks,while the copper-deposited polydimethylsiloxane films with micropyramids array were used as electrodes and flexible substrates.Increased conducting paths between electrodes and fibers can be obtained when high-density micro-pyramids fall into the porous structures of the fiber paper under external pressure,thereby promoting the pressure sensor to show an ultra-high sensitivity of 17.65 kPa^(-1)in the pressure range of 0–2 kPa,16 times that of the device without patterned electrodes.Besides,the sensor retains a high sensitivity of 2.06 kPa^(-1)in an ultra-wide measurement range of 150 kPa.Moreover,the sensor can detect various physiological signals,including pulse and voice,while attached to the human skin.This work provides a novel strategy to significantly improve the sensitivity and measurement range of flexible pressure sensors,as well as demonstrates attractive applications in physiological signal monitoring. | HOU XiaoJuan ZHONG JiXin HE Jian YANG ChangJun YU JunBin MEI LinYu MU JiLiang GENG WenPing CHOU XiuJian | 2022 | Science China(Technological Sciences)2022，65，5： | 2 |
| 12 | CasRx-mediated RNA targeting prevents choroidal neovascularization in a mouse model of age-related macular degeneration显示文摘RNA-targeting CRISPR system Cas13 offers an efficient approach for manipulating RNA transcripts in vitro.In this perspective,we provide a proof-of-concept demonstration that Cas13-mediated Vegfa knockdown in vivo could prevent the development of laser-induced CNV in mouse model of Age-related macular degeneration. | Changyang Zhou Xinde Hu Cheng Tang Wenjia Liu Shaoran Wang Yingsi Zhou Qimeng Zhao Qiyu Bo Linyu Shi Xiaodong Sun Haibo Zhou Hui Yang | 2020 | National Science Review2020，7，5： | 2 |
| 13 | One-Step Generation of Mice Carrying Reporter and Conditional Alleles by CRISPR/Cas-Mediated Genome Engineering显示文摘 | Hui Yang Haoyi Wang Chikdu S. Shivalila Albert W. Cheng Linyu Shi Rudolf Jaenisch | 2013 | Cell2013，，6： | 1 |
| 14 | Reversal of Mdr1b-dependent Multidrug Resistance in a Rat Astrocyte Model by Adenoviral-delivered Short Hairpin RNA显示文摘 | Lei Chen Linyu Tian Tianhua Yang Xinwang Cheng Stefan Hermann Dong Zhou | 2008 | Cellular and Molecular Neurobiology2008，，8： | 1 |
| 15 | Modeling a policy making framework for urban sustainability: Incorporating system dynamics into the Ecological Footprint显示文摘 | Wei Jin Linyu Xu Zhifeng Yang | 2009 | Ecological Economics2009，，12： | 1 |
| 16 | Modeling a policy making framework for urban sustainability:Incorporating system dynamics into the Ecological Footprint显示文摘 | Wei Jin Linyu Xu Zhifeng Yang | | 0，，12： | 1 |
| 17 | A review of the application of machine learning in water quality evaluation显示文摘With the rapid increase in the volume of data on the aquatic environment,machine learning has become an important tool for data analysis,classification,and prediction.Unlike traditional models used in water-related research,data-driven models based on machine learning can efficiently solve more complex nonlinear problems.In water environment research,models and conclusions derived from machine learning have been applied to the construction,monitoring,simulation,evaluation,and optimization of various water treatment and management systems.Additionally,machine learning can provide solutions for water pollution control,water quality improvement,and watershed ecosystem security management.In this review,we describe the cases in which machine learning algorithms have been applied to evaluate the water quality in different water environments,such as surface water,groundwater,drinking water,sewage,and seawater.Furthermore,we propose possible future applications of machine learning approaches to water environments. | Mengyuan Zhu Jiawei Wang Xiao Yang Yu Zhang Linyu Zhang Hongqiang Ren Bing Wu Lin Ye | 2022 | Eco-Environment & Health2022，1，2： | 1 |
| 18 | Molecular dynamics and mesoscopic dynamics simulations for prediction of miscibility in polypropylene/polyamide-11 blends显示文摘 | Yizheng Fu Liqiong Liao Yanhua Lan Luxia Yang Linyu Mei Yaqing Liu Shuangqi Hu | 2011 | Journal of Molecular Structure2011，，： | 1 |
| 19 | Disruption of splicing-regulatory elements using CRISPR/Cas9 to rescue spinal muscular atrophy in human iPSCs and mice显示文摘We here report a genome-editing strategy to correct spinal muscular atrophy(SMA).Rather than directly targeting the pathogenic exonic mutations,our strategy employed Cas9 and guide-sg RNA for the targeted disruption of intronic splicing-regulatory elements.We disrupted intronic splicing silencers(ISSs,including ISS-N1 and ISS+100)of survival motor neuron(SMN)2,a key modifier gene of SMA,to enhance exon 7 inclusion and full-length SMN expression in SMA iPSCs.Survival of splicing-corrected iPSC-derived motor neurons was rescued with SMN restoration.Furthermore,co-injection of Cas9 mRNA from Streptococcus pyogenes(SpCas9)or Cas9 from Staphylococcus aureus(SaCas9)alongside their corresponding sgRNAs targeting ISS-N1 into zygotes rescued 56%and 100%of severe SMA transgenic mice(Smn-/-,SMN2tg/-).The median survival of the resulting mice was extended to>400 days.Collectively,our study provides proof-of-principle for a new strategy to therapeutically intervene in SMA and other RNA-splicing-related diseases. | Jin-Jing Li Xiang Lin Cheng Tang Ying-Qian Lu Xinde Hu Erwei Zuo He Li Wenqin Ying Yidi Sun Lu-Lu Lai Hai-Zhu Chen Xin-Xin Guo Qi-Jie Zhang Shuang Wu Changyang Zhou Xiaowen Shen Qifang Wang Min-Ting Lin Li-Xiang Ma Ning Wang Adrian R.Krainer Linyu Shi Hui Yang Wan-Jin Chen | 2020 | National Science Review2020，7，1： | 1 |
| 20 | Programmable deaminase-free base editors for G-to-Y conversion by engineered glycosylase显示文摘Current DNA base editors contain nuclease and DNA deaminase that enables deamination of cytosine(C)or adenine(A),but no method for guanine(G)or thymine(T)editing is available at present.Here we developed a deaminase-free glycosylase-based guanine base editor(gGBE)with G editing ability,by fusing Cas9 nickase with engineered N-methylpurine DNA glycosylase protein(MPG).By several rounds of MPG mutagenesis via unbiased and rational screening using an intron-split EGFP reporter,we demonstrated that gGBE with engineered MPG could increase G editing efficiency by more than 1500 fold.Furthermore,this gGBE exhibited high base editing efficiency(up to 81.2%)and high G-to-T or G-to-C(i.e.G-to-Y)conversion ratio(up to 0.95)in both cultured human cells and mouse embryos.Thus,we have provided a proof-of-concept of a new base editing approach by endowing the engineered DNA glycosylase the capability to selectively excise a new type of substrate. | Huawei Tong Nana Liu Yinghui Wei Yingsi Zhou Yun Li Danni Wu Ming Jin Shuna Cui Hengbin Li Guoling Li Jingxing Zhou Yuan Yuan Hainan Zhang Linyu Shi Xuan Yao Hui Yang | 2023 | National Science Review2023，10，8： | 1 |
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