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| 1 | Efficient genome editing in plants using a CRISPR/Cas system显示文摘 | Zhengyan Feng Botao Zhang Wona Ding Xiaodong Liu Dong-Lei Yang Pengliang Wei Fengqiu Cao Shihua Zhu Feng Zhang Yanfei Mao Jian-Kang Zhu | 2013 | Cell Research2013，23，10： | 211 |
| 2 | One-step generation of p53 gene biallelic mutant Cynomolgus monkey via the CRISPR/Cas system显示文摘 | Haifeng Wan Chunjing Feng Fei Teng Shihua Yang Baoyang Hu Yuyu Niu Andy Peng Xiang Weizhen Fang Weizhi Ji Wei Li Xiaoyang Zhao Qi Zhou | 2015 | Cell Research2015，25，2： | 39 |
| 3 | TALEN-based generation of a cynomolgus monkey disease model for human microcephaly显示文摘基因在非人类的首领编辑可以为在人探索病原学和遗传上基于的神经病学的混乱的治疗学的策略导致珍贵模型。然而,仔细在人模仿病理学、行为的赤字的神经病学的混乱的一个猴子模型成功地还没被产生了。Microcephalin 1 (MCPH1 ) 在人的大脑,和智力迟钝伴随的 MCPH1 变化原因头小畸型的进化被含有。这里,我们产生了用抄写带 biallelic MCPH1 变化的一只 cynomolgus 猴子(Macaca fascicularis ) 像使活跃之物的受动器核酸酶。猴子概括了大多数在病人观察的重要临床的特征,包括在头圆周,早熟的染色体冷凝作用(PCC ) ,语料库 callosum 的发育不全和上面的手足 spasticity 的显著减小。而且,在变异的真皮的成纤维细胞的 MCPH1 的 overexpression 救了 PCC 症候群。这个猴子模型可以帮助我们阐明在人的头小畸型并且更好的致病的 MCPH1 的角色在首领大脑尺寸的进化理解这蛋白质的功能。 | Qiong Ke Weiqiang Li Xingqiang Lai Hong Chen Lihua Huang Zhuang Kang Kai Li Jie Ren Xiaofeng Lin Haiqing Zheng Weijun Huang Yunhan Ma Dongdong Xu Zheng Chen Xinming Song Xinyi Lin Min Zhuang Tao Wang Fengfeng Zhuang Jianzhong Xi Frank Fuxiang Mao Huimin Xia Bruce T Lahn Qi Zhou Shihua Yang Andy Peng Xiang | 2016 | Cell Research2016，26，9： | 13 |
| 4 | Species-dependent neuropathology in transgenic SOD' aigs显示文摘 | Huaqiang Yang Guohao Wang Haitao Sun Runzhe Shu Tao Liu Chuan-En Wang Zhaoming Liu Yu Zhao Bentian Zhao Zhen Ouyang Dongshan Yang Jiao Huang Yueling Zhou Shihua Li Xiaodan Jiang Zhicheng Xiao Xiao-Jiang Li Liangxue Lai | 2014 | Cell Research2014，24，4： | 13 |
| 5 | CRISPR/Cas9-mediated PINK1 deletion leads to neurodegeneration in rhesus monkeys显示文摘Dear Editor,PINK1 mutations cause autosomal recessive and early-onset Parkinson’s disease(PD)with selective neurodegeneration.Unfortunately,current PINK1 knockout(KO)mouse1,2 and pig models3,4 are unable to recapitulate the selective and overt neurodegeneration seen in PD patients.Furthermore,endogenous Pink1 in the mouse brain is expressed at very low levels and can only be detected via immunoprecipitation,5 meaning that PINK1’s function in the mammalian brain needs to be assessed using larger animals that are closer to humans.We previously used CRISPR/Cas9 to target the monkey gene in one-cell stage embryos.6 Using the same approach,we designed two gRNAs to target exon 2(T1)and exon 4(T2),which encode a kinase domain in the PINK1 gene of rhesus monkeys(Fig.1a).CRISPR/Cas9 and PINK1 gRNAs were injected into one-cell stage rhesus monkey embryos.A T7E1 assay and sequencing of PCR products from the injected embryos showed high efficiency(61.5%)in targeting PINK1(Fig.1b and Supplementary information,Fig.S1).Transfer of 87 embryos to 28 surrogate rhesus monkeys resulted in 11 pregnancies(39.2%)(Fig.1b).Eleven fetuses developed to term and were born naturally.Of these live monkeys,eight carried PINK1 mutations(M),and three were wild type(WT).However,three mutant monkeys(M1,M3 and M4)were newborn triplets that struggled to survive and died 3-4 days after birth.One WT newborn monkey also died after a difficult labor.Another mutant monkey(M2)died 7 days after birth without noticeable warning signs or symptoms.The other three mutant monkeys(M6,M7 and M8)have lived for three years;M5,however,reduced its food intake and showed weakness at the age of 1.5 years,and died 30 days after anesthesia for MRI examination. | Weili Yang Yunbo Liu Zhuchi Tu Chong Xiao Sen Yan Xishan Ma Xiangyu Guo Xiusheng Chen Peng Yin Zhengyi Yang Su Yang Tianzi Jiang Shihua Li Chuan Qin Xiao-Jiang Li | 2019 | Cell Research2019，29，4： | 12 |
| 6 | Characterization of polycyclic aromatic hydrocarbons in PM2.s and PMlo in Tanggu District, Tianjin Binhai New Area, China显示文摘 | Dan YANG Shihua QI Ningombam Linthoingambi DEVI Fang TIAN Ziping HUO Qingyuan ZHU Jing WANG | 2012 | Frontiers of Earth Science2012，6，3： | 9 |
| 7 | Dissecting the Genetic Basis of Grain Shape and Chalkiness Traits in Hybrid Rice Using Multiple Collaborative Populations显示文摘 | Junyi Gong Jiashun Miao Yan Zhao Qiang Zhao Qi Feng Qilin Zhan Benyi Cheng Junhui Xia Xuehui Huang Shihua Yang Bin Han | 2017 | Molecular Plant2017，10，10： | 8 |
| 8 | Soil concentrations and soil-air exchange of organochlorine pesticides along the Aba profile, east of the Tibetan Plateau, western China显示文摘MianzhuAba 侧面,西藏的高原的东方,被选择沿着一个高度的坡度学习 organochlorine 杀虫剂(OCP ) 的出现。在表面土壤的 Dichlorodiphenyltrichloroethanes (DDT ) , hexachlorocyclohexanes (HCH ) 和 Aldrin,狄氏剂和 Endrin (Drins ) 在冬季(三月) 和夏天(7 月) 被检测。 | Hongxia LIU Shihua QI Dan YANG Ying HU Feng LI Jia LIU Xinli XING | 2013 | Frontiers of Earth Science2013，7，4： | 6 |
| 9 | Mesenchymal stem cell treatment improves outcome of COVID-19 patients via multiple immunomodulatory mechanisms显示文摘The infusion of coronavirus disease 2019(COVID-19)patients with mesenchymal stem cells(MSCs)potentially improves clinical symptoms,but the underlying mechanism remains unclear.We conducted a randomized,single-blind,placebo-controlled(29 patients/group)phase II clinical trial to validate previous findings and explore the potential mechanisms.Patients treated with umbilical cord-derived MSCs exhibited a shorter hospital stay(P=0.0198)and less time required for symptoms remission(P=0.0194)than those who received placebo.Based on chest images,both severe and critical patients treated with MSCs showed improvement by day 7(P=0.0099)and day 21(P=0.0084).MSC-treated patients had fewer adverse events.MSC infusion reduced the levels of C-reactive protein,proinflammatory cytokines,and neutrophil extracellular traps(NETs)and promoted the maintenance of SARS-CoV-2-specific antibodies.To explore how MSCs modulate the immune system,we employed single-cell RNA sequencing analysis on peripheral blood.Our analysis identified a novel subpopulation of VNN2+hematopoietic stem/progenitorlike(HSPC-like)cells expressing CSF3R and PTPRE that were mobilized following MSC infusion.Genes encoding chemotaxis factors—CX3CR1 and L-selectin—were upregulated in various immune cells.MSC treatment also regulated B cell subsets and increased the expression of costimulatory CD28 in T cells in vivo and in vitro.In addition,an in vivo mouse study confirmed that MSCs suppressed NET release and reduced venous thrombosis by upregulating kindlin-3 signaling.Together,our results underscore the role of MSCs in improving COVID-19 patient outcomes via maintenance of immune homeostasis. | Rongjia Zhu Tingdong Yan Yingmei Feng Yan Liu Hongcui Cao Gongxin Peng Yanlei Yang Zhen Xu Jingqi Liu Wei Hou Xiaoyue Wang Zhe Li Luchan Deng Shihua Wang Jing Li Qin Han Hongling Li Guangliang Shan Yinghao Cao Xingyan An Jianshe Yan Zhonghui Zhang Huafei Li Xuebin Qu Jiaqi Zhu Shumin Zhou Jiao Wang Fengchun Zhang Jinming Gao Ronghua Jin Dayong Xu Yan-Qing Ma Tao Huang Shuang Peng Zhi Zheng Ilia Stambler Eric Gilson Lee Wei Lim Alexey Moskalev Antonio Cano Sasanka Chakrabarti Brun Ulfhake Huanxing Su Haoying Xu Sihuan Xu Feng Wei Holly MBrown-Borg Kyung-Jin Min Georgina Ellison-Hughes Calogero Caruso Kunlin Jin Robert Chunhua Zhao | 2021 | Cell Research2021，31，12： | 5 |
| 10 | HBB-deficient Macaca fascicularis monkey presents with human β-thalassemia显示文摘Dear Editor,β-Thalassemia is a common severe genetic disease caused by mutations in HBB and affects approximately 1.5% of the global population (Origa, 2017). In southern China, the carrier rate of β-thalassemia is as high as 6.43%, creating a high socio-economic burden (Xiong et al., 2010). In adult humans, there are three types of hemoglobin: HbA1 (~97%), HbA2 (~2%) and HbF (~1%). HbA1 (α2β2) is composed of two a-globin and two β-globi n sub units en coded by HBA and HBB, respectively;HbF (α2β2)is made up of two α-globin subunits and two β-globin sub units en coded by HBG. Mutations in the coding region or regulatory region of HBB are involved in β-thalassemia pathogenesis. Except for some rare dominant mutations, most HBB mutations are recessive (Origa, 2017). Depending on the mutation type, the β-globin level will either be reduced or completely depleted, resulting in α-globin accumulation and precipitation. These α-globin precipitates lead to red blood cell death, resulting in anemia and tissue damage, and even death in thalassemia major patients. Blood transfusions can help slow disease progression but lead to iron overload, ultimately resulting in iron toxicity. Bone marrow transfer is the only cure in the clinic and is available only to a small percentage of patients with human leukocyte antigervmatched donors. Recently, gene therapy and gene editing therapy have shown great promise in curing β-thalassemia (Glaser et al., 2015;Thompson et al., 2018). However, no appropriate animal models are available for evaluating the safety and efficacy of such advanced therapeutic strategies in vivo.β-thalassemia mice are the sole animal model available for research. However, substantial differences have been reported between the types and expressi on patter ns of human and mouse globins (McColl and Vadolas, 2016). Moreover, mice contain no fetal globin gene equivalent, and homozygous mutations of HBB in mouse for early models of β-thalassemia major or Cooley anemia are all embryonic lethal (Huo et al., 2009). Recently, significant phenotype and physiology differences have been reported between SIRT6- null mice and the non-human primate model (Zhang et al., 2018). Thus, an appropriate non-human primate model is needed for human β-thalassemia studies and treatments. | Yan Huang Chenhui Ding Puping Liang Duanduan Li Yu Tang Wei Meng Hongwei Sun Hongyu Lu Yu Chen Xueying Chen Qunshan Huang Jianpei Fang Canquan Zhou Shihua Yang Junjiu Huang | 2019 | Protein & Cell2019，10，7： | 4 |
| 11 | Comparative Analysis of the Endosperm Proteins Separated by 2-D Electrophoresis for Two Cultivars of Hybrid Rice (Oryza sativa L,)显示文摘Liangyoupeijiu 是 two-parental-line,并且 Shanyou63 是 three-parental-line 混血儿米饭(Oryza sativa L.) 。尽管两个属于 indica 亚种,他们关于形态学,生理学和谷物质量有明显的差别。在内乳蛋白质作文的变化被比较电气泳动(2-DE ) 为混合米饭的这二栽培变种印射的 2-D 学习。在飞行团 spectrometry (MALDI-TOF/MS ) 的帮助矩阵的激光解吸附作用 / 电离时间以后分析, 19-kDa 血球素的一位 21-kDa 先锋为两栽培变种作为主要存储蛋白质被识别。peroxiredoxin 和种子成熟蛋白质的某 isoforms 被发现仅仅在 Shanyou63 存在,而 aldose reductase 和淀粉小粒界限淀粉 synthase 仅仅在 Liangyoupeijiu 被检测。这些数据可能为混合米饭的这二栽培变种的进一步比较的研究提供一个基础。 | Pingfang Yang Shihua Shen Tingyun Kuang | 2006 | Journal of Integrative Plant Biology2006，48，9： | 3 |
| 12 | Theoretical and technological exploration of deep in situ fluidized coal mining显示文摘Mining industries worldwide have inevitably resorted to exploiting resources from the deep underground.However,traditional mining methods can cause various problems,e.g.,considerable mining difficulty,environmental degradations,and frequent disastrous accidents.To exploit deep resources in the future,the concept of mining must be reconsidered and innovative new theories,methods,and technologies must be applied.To effectively acquire coal resources deeper than 2000 m,new theoretical and technological concepts about deep in situ fluidized mining are required.The limits of mining depth need to be broken to acquire deep-coal resources in an environmentally friendly,safe,and efficient manner.This is characterized by‘There are no coal on the ground and no men in the coal mine’.First,this paper systematically explains deep in situ fluidized coal mining.Then,it presents a new theoretical concept,including the theories of mining-induced rock mechanics,three-field visualization,multi-physics coupling for in situ transformation,and in situ mining,transformation and transport.It also presents key technological concepts,including those of intelligent,unmanned,and fluidized mining.Finally,this paper presents a strategic roadmap for deep in situ fluidized coal mining.In summary,this paper develops new theoretical and technological systems for accomplishing groundbreaking innovations in mining technologies of coal resources in the deep underground. | Heping XIE Yang JU Shihua REN Feng GAO Jianzhong LIU Yan ZHU | 2019 | Frontiers in Energy2019，13，4： | 3 |
| 13 | PINK1 kinase dysfunction triggers neurodegeneration in the primate brain without impacting mitochondrial homeostasis显示文摘In vitro studies have established the prevalent theory that the mitochondrial kinase PINK1 protects neurodegeneration by removing damaged mitochondria in Parkinson's disease(PD).However,difficulty in detecting endogenous PINK1 protein in rodent brains and cell lines has prevented the rigorous investigation of the in vivo role of PINK1.Here we report that PINK1 kinase form is selectively expressed in the human and monkey brains.CRISPR/Cas9-mediated deficiency of PINK1 causes similar neurodegeneration in the brains of fetal and adult monkeys as well as cultured monkey neurons without affecting mitochondrial protein expression and morphology.Importantly,PINK1 mutations in the primate brain and human cells reduce protein phosphorylation that is important for neuronal function and survival.Our findings suggest that PINK1 kinase activity rather than its mitochondrial function is essential for the neuronal survival in the primate brains and that its kinase dysfunction could be involved in the pathogenesis of PD. | Weili Yang Xiangyu Guo Zhuchi Tu Xiusheng Chen Rui Han Yanting Liu Sen Yan Qi Wang Zhifu Wang Xianxian Zhao Yunpeng Zhang Xin Xiong Huiming Yang Peng Yin Huida Wan Xingxing Chen Jifeng Guo Xiao-Xin Yan Lujian Liao Shihua Li Xiao-Jiang Li | 2022 | Protein & Cell2022，13，1： | 3 |
| 14 | Investigation of Portevin–Le Chatelier Band Strain and Elastic Shrinkage in Al-Based Alloys Associated with Mg Contents显示文摘The Portevin–Le Chatelier(PLC) effect in Al–2.30wt%Mg, Al–4.57wt%Mg and Al–6.91wt%Mg alloys has been investigated at various applied strain rates at room temperature in this study. Three-dimensional digital image correlation(3D-DIC) technique was applied to obtaining the further insight into the spatiotemporal characteristics, in particular the influence of Mg content on deformation behaviors. Mg content has a pronounced effect on serration characteristics, including the serration type and amplitude; Mg content tends to weaken the spatial correlation of the propagative bands. Additionally, the serration amplitude linearly increases with the maximum PLC band strain; high Mg content generates a higher PLC band strain at a given serration amplitude compared with low Mg content. Mg content is found to be effective to enhance the serration amplitude, the maximum PLC band strain and also the amount of elastic shrinkage outside PLC bands. | Yulong Cai Suli Yang Shihua Fu Di Zhang Qingchuan Zhang | 2017 | Journal of Materials Science & Technology2017，33，6： | 3 |
| 15 | Development of a reverse transcription quantitative polymerase chain reaction-based assay for broad coverage detection of African and Asian Zika virus lineages显示文摘The Zika virus(ZIKV) is an arbovirus that has spread rapidly worldwide within recent times. There is accumulating evidence that associates ZIKV infections with Guillain-Barré Syndrome(GBS) and microcephaly in humans. The ZIKV is genetically diverse and can be separated into Asian and African lineages. A rapid, sensitive, and specific assay is needed for the detection of ZIKV across various pandemic regions. So far, the available primers and probes do not cover the genetic diversity and geographic distribution of all ZIKV strains. To this end, we have developed a one-step quantitative reverse transcription polymerase chain reaction(qRT-PCR) assay based on conserved sequences in the ZIKV envelope(E) gene. The detection limit of the assay was determined to be five RNA transcript copies and 2.94 × 10^(–3) 50% tissue culture infectious doses(TCID50) of live ZIKV per reaction. The assay was highly specific and able to detect five different ZIKV strains covering the Asian and African lineages without nonspecific amplification, when tested against other flaviviruses. The assay was also successful in testing for ZIKV in clinical samples. Our assay represents an improvement over the current methods available for the detection ZIKV and would be valuable as a diagnostic tool in various pandemic regions. | Yang Yang Gary Wong Baoguo Ye Shihua Li Shanqin Li Haixia Zheng Qiang Wang Mifang Liang George F Gao Lei Liu Yingxia Liu Yuhai Bi | 2017 | Virologica Sinica2017，32，3： | 3 |
| 16 | New pathogenic insights from large animal models of neurodegenerative diseases显示文摘Animal models are essential for investigating the pathogenesis and developing the treatment of human diseases.Identification of genetic mutations responsible for neurodegenerative diseases has enabled the creation of a large number of small animal models that mimic genetic defects found in the affected individuals.Of the current animal models,rodents with genetic modifications are the most commonly used animal models and provided important insights into pathogenesis.However,most of genetically modified rodent models lack overt neurodegeneration,imposing challenges and obstacles in utilizing them to rigorously test the therapeutic effects on neurodegeneration.Recent studies that used CRISPR/Cas9-targeted large animal(pigs and monkeys)have uncovered important pathological events that resemble neurodegeneration in the patient’s brain but could not be produced in small animal models.Here we highlight the unique nature of large animals to model neurodegenerative diseases as well as the limitations and challenges in establishing large animal models of neurodegenerative diseases,with focus on Huntington disease,Amyotrophic lateral sclerosis,and Parkinson diseases.We also discuss how to use the important pathogenic insights from large animal models to make rodent models more capable of recapitulating important pathological features of neurodegenerative diseases. | Peng Yin Shihua Li Xiao-Jiang Li Weili Yang | 2022 | Protein & Cell2022，13，10： | 2 |
| 17 | Measurements and Calculations of Solid-liquid Equilibria in Quaternary System Li2SO4-Na2SO4-K2SO4-H2O at 288 K显示文摘 | CUI Ruizhi YANG Lei WANG Wei SANG Shihua | 2017 | Chemical Research in Chinese Universities2017，33，3： | 2 |
| 18 | In situ observation of transmission and reflection of dislocations at twin boundary in CoCrNi alloys显示文摘The deformation mechanism of CoCrNi alloy with high density of annealing twins was studied by in situ transmission electron microscopy. Dislocation transmission and reflection at the twin boundary were observed during in situ loading. We characterized these reaction processes by combining TEM, dislocation theory and crystallography of twin. Twin boundary not only strengthens the material by impeding the motion of dislocation, but also acts as dislocation source to produce large of slip bands. These processes generate large of slip bands to accommodate the plastic deformation or strengthening material. | LIANG YanXiang YANG XiaoFang MING KaiSheng XIANG ShiHua LIU Qing | 2021 | Science China(Technological Sciences)2021，64，2： | 2 |
| 19 | MicroRNA-100 regulates osteogenic differentiation of human adipose-derived mesenchymal stem cells by targeting BMPR2显示文摘 | Yang Zeng Xuebin Qu Hongling Li Shan Huang Shihua Wang Qilin Xu Ruizhu Lin Qin Han Jing Li Robert Chunhua Zhao | 2012 | FEBS Letters2012，，16： | 2 |
| 20 | Factors Influencing Diurnal Variations of Cloud and Precipitation in the Yushu Area of the Tibetan Plateau显示文摘Using the cloud radar,ground observations,and ECMWF Reanalysis v5(ERA5)data,we investigate the factors influencing nighttime precipitation during summer in the Yushu area of the Tibetan Plateau(TP).The cloud top height(CTH),cloud base height(CBH),and liquid water content(LWC)are compared between non-precipitation and precipitation days.The results show that the average CTH on precipitation days in Yushu is below 10 km above ground level(AGL)in the daytime,whereas it exceeds 10 km AGL at night,with the maximum at 2300 BT(Beijing Time).The CBH is in-phase with the dewpoint spread.The precipitation intensity and CTH are in-phase with the LWC.The hourly averaged precipitation intensity and convective available potential energy in ERA5 reach their maximums at2100 BT,which is 3 h ahead of their observed counterparts.There is descending motion in the mid day on non-precipitation days,whereas there is ascending motion at night on precipitation days.In addition,the horizontal wind direction in the lower level(below 5000 m)shows clockwise rotation from morning to night.Wind shear occurs in the mid level of the atmosphere,accompanied by a subtropical westerly jet in the upper level.The difference in horizontal wind speed between 200 and 500 hPa is positively related to the LWC,thereby contributing to the formation of upper-level cloud. | Bangjun CAO Shihua LYU Yu ZHANG Xianyu YANG Boliang LI Liang YUAN Meilin LI | 2022 | Journal of Meteorological Research2022，36，2： | 2 |
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