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| 1 | The Tea Tree Genome Provides Insights into Tea Flavor and Independent Evolution of Caffeine Biosynthesis显示文摘茶是世界有巨大的经济、药用、文化的重要性的最旧、很流行的包含咖啡因的饮料。这里,我们在场第一个高质量的核苷酸序列充满重复(80.9%) ,栽培的茶树山茶 sinensis 的 3.02-Gb 染色体。我们证明茶树的一种非常地大的染色体尺寸从一些 LTR retrotransposon 家庭的慢、稳定、长期的扩大被结果。除了一个最近的整个染色体的复制事件,基因的系特定的扩大把新陈代谢的生合成与 flavonoid 联系了被发现,它提高 catechin 生产,萜烯酶激活,和应力公差,为茶风味和改编的重要特征。我们相对可可子和咖啡表明一个独立人士和茶咖啡因合成小径的快速的进化。在 25 山茶种类之中的比较研究表明那更高的表情大多数 flavonoid- 和咖啡因铺平 -- 然而并非 theanine 相关的基因贡献 catechins 和咖啡因的增加的生产并且因此提高处理茶的适用性和茶质量。这些新奇调查结果为进一步的 metabolomic 和典型生合成小径的功能的 genomic 精炼铺平道路并且将帮助开发将最后满足并且吸引世界范围的更多的茶喝酒者的茶风味的一个更多样化的集合。 | En-Hua Xia Hai-Bin Zhang Jun Sheng Kui Li Qun-Jie Zhang Changhoon Kim Yun Zhang Yuan Liu Ting Zhu Wei Li Hui Huang Yan Tong Hong Nan Cong Shi Chao Shi Jian-Jun Jiang Shu-Yan Mao Jun-Ying Jiao Dan Zhang Yuan Zhao You-Jie Zhao Li-Ping Zhang Yun-Long Liu Ben-Ying Liu Yue Yu Sheng-Fu Shao De-Jiang Ni Evan E. Eichler Li-Zhi Gao | 2017 | Molecular Plant2017，10，6： | 113 |
| 2 | Wnt/b-catenin signaling plays an ever-expanding role in stem cell self-renewal,tumorigenesis and cancer chemoresistance显示文摘Wnt signaling transduces evolutionarily conserved pathways which play important roles in initiating and regulating a diverse range of cellular activities,including cell proliferation,calcium homeostasis,and cell polarity.The role of Wnt signaling in controlling cell proliferation and stem cell self-renewal is primarily carried out through the canonical pathway,which is the best-characterized the multiple Wnt signaling branches.The past 10 years has seen a rapid expansion in our understanding of the complexity of this pathway,as many new components of Wnt signaling have been identified and linked to signaling regulation,stem cell functions,and adult tissue homeostasis.Additionally,a substantial body of evidence links Wnt signaling to tumorigenesis of cancer types and implicates it in the development of cancer drug resistance.Thus,a better understanding of the mechanisms by which dysregulation of Wnt signaling precedes the development and progression of human cancer may hasten the development of pathway inhibitors to augment current therapy.This review summarizes and synthesizes our current knowledge of the canonical Wnt pathway in development and disease.We begin with an overview of the components of the canonical Wnt signaling pathway and delve into the role this pathway has been shown to play in stemness,tumorigenesis,and cancer drug resistance.Ultimately,we hope to present an organized collection of evidence implicating Wnt signaling in tumorigenesis and chemoresistance to facilitate the pursuit of Wnt pathway modulators that may improve outcomes of cancers in which Wnt signaling contributes to aggressive disease and/or treatment resistance. | Maryam K.Mohammed Connie Shao Jing Wang Qiang Wei Xin Wang Zachary Collier Shengli Tang Hao Liu Fugui Zhang Jiayi Huang Dan Guo Minpeng Lu Feng Liu Jianxiang Liu Chao Ma Lewis L.Shi Aravind Athiviraham Tong-Chuan He Michael J.Lee | 2016 | Genes & Diseases2016，3，1： | 70 |
| 3 | Enhanced secondary pollution offset reduction of primary emissions during COVID-19 lockdown in China显示文摘To control the spread of the 2019 novel coronavirus(COVID-19),China imposed nationwide restrictions on the movement of its population(lockdown)after the Chinese New Year of 2020,leading to large reductions in economic activities and associated emissions.Despite such large decreases in primary pollution,there were nonetheless several periods of heavy haze pollution in eastern China,raising questions about the well-established relationship between human activities and air quality.Here,using comprehensive measurements and modeling,we show that the haze during the COVID lockdown was driven by enhancements of secondary pollution.In particular,large decreases in NOx emissions from transportation increased ozone and nighttime NO_(3)radical formation,and these increases in atmospheric oxidizing capacity in turn facilitated the formation of secondary particulate matter.Our results,afforded by the tragic natural experiment of the COVID-19 pandemic,indicate that haze mitigation depends upon a coordinated and balanced strategy for controlling multiple pollutants. | Xin Huang Aijun Ding Jian Gao Bo Zheng Derong Zhou Ximeng Qi Rong Tang Jiaping Wang Chuanhua Ren Wei Nie Xuguang Chi Zheng Xu Liangduo Chen Yuanyuan Li Fei Che Nini Pang Haikun Wang Dan Tong Wei Qin Wei Cheng Weijing Liu Qingyan Fu Baoxian Liu Fahe Chai Steven JDavis Qiang Zhang Kebin He | 2021 | National Science Review2021，8，2： | 47 |
| 4 | Improved survival of porcine acute liver failure by a bioartificial liver device implanted with induced human functional hepatocytes显示文摘 | Xiao-Lei Shi Yimeng Gao YupengYan HuchengMa Lulu Sun Pengyu Huang Xuan Ni Ludi Zhang Xin Zhao Haozhen Ren Dan Hu Yan Zhou Feng Tian Yuan Ji Xin Cheng Guoyu Pan Yi-Tao Ding LijianHui | 2016 | Cell Research2016，26，2： | 31 |
| 5 | Modulatory effects of acupuncture on brain networks in mild cognitive impairment patients显示文摘Functional magnetic resonance imaging has been widely used to investigate the effects of acupuncture on neural activity. However, most functional magnetic resonance imaging studies have focused on acute changes in brain activation induced by acupuncture. Thus, the time course of the therapeutic effects of acupuncture remains unclear. In this study, 32 patients with amnestic mild cognitive impairment were randomly divided into two groups, where they received either Tiaoshen Yizhi acupuncture or sham acupoint acupuncture. The needles were either twirled at Tiaoshen Yizhi acupoints, including Sishencong(EX-HN1), Yintang(EX-HN3), Neiguan(PC6), Taixi(KI3), Fenglong(ST40), and Taichong(LR3), or at related sham acupoints at a depth of approximately 15 mm, an angle of ± 60°, and a rate of approximately 120 times per minute. Acupuncture was conducted for 4 consecutive weeks, five times per week, on weekdays. Resting-state functional magnetic resonance imaging indicated that connections between cognition-related regions such as the insula, dorsolateral prefrontal cortex, hippocampus, thalamus, inferior parietal lobule, and anterior cingulate cortex increased after acupuncture at Tiaoshen Yizhi acupoints. The insula, dorsolateral prefrontal cortex, and hippocampus acted as central brain hubs. Patients in the Tiaoshen Yizhi group exhibited improved cognitive performance after acupuncture. In the sham acupoint acupuncture group, connections between brain regions were dispersed, and we found no differences in cognitive function following the treatment. These results indicate that acupuncture at Tiaoshen Yizhi acupoints can regulate brain networks by increasing connectivity between cognition-related regions, thereby improving cognitive function in patients with mild cognitive impairment. | Ting-ting Tan Dan Wang Ju-ke Huang Xiao-mei Zhou Xu Yuan Jiu-ping Liang Liang Yin Hong-liang Xie Xin-yan Jia Jiao Shi Fang Wang Hao-bo Yang Shang-jie Chen | 2017 | Neural Regeneration Research2017，12，2： | 32 |
| 6 | Effects of Traditional Chinese Medicine Shensong Yangxin Capsules on Heart Rhythm and Function in Congestive Heart Failure Patients with Frequent Ventricular Premature Complexes:A Randomized, Double-blind, Multicenter Clinical Trial显示文摘 | Xi Wang Dan HU Song Dang He Huang Cong-Xin Huang Ming-Jie Yuan Yan-Hong Tang Qing-Shan Zheng Fang Yin Shu Zhang Bo-Li Zhang Run-Lin Gao | 2017 | Chinese Medical Journal2017，，14： | 33 |
| 7 | Correction of β-thalassemia mutant by base editor in human embryos显示文摘 | Puping Liang Chenhui Ding Hongwei Sun Xiaowei Xie Yanwen Xu Xiya Zhang Ying Sun Yuanyan Xiong Wenbin Ma Yongxiang Liu Yali Wang Jianpei Fang Dan Liu Zhou Songyang Canquan Zhou Junjiu Huang | 2017 | Protein & Cell2017，8，11： | 34 |
| 8 | Effects of transmitters and interleukin-10 on rat hepatic fibrosis induced by CCl_4显示文摘AIM: To study the effects of transmitters ET, AgII, PGI2,CGRP and GG on experimental rat hepatic fibrosis and the antifibrogenic effects of IL-10.METHODS: One hundred SD rats were randomly divided into 3 groups: control group (N): intraperitoneal injection a week; IL-10 treated group (E): besides same dosage of the third week. In the fifth, the seventh and the ninth week,rats in three groups were selected randomly to collect plasma and liver tissues. The levels of ET, AgII, PGI2, CGRP and GG were assayed by radioimmunoassay (RIA). The liver fibrosis was observed with silver staining.RESULTS: The hepatic fibrosis was developed with the increase of the injection frequency of CCl4. The ET, AgII, PGI2, CGRP The histological examination showed that the degrees of the rats liver fibrosis in group E were lower than those in group C.CONCLUSION: The transmitters ET, AgII, PGI2, CGRP and GG play a significant role in the rat hepatic fibrosis induced by CCl4. IL-10 has the antagonistic action on these transmitters and can relieve the degree of the liver fibrosis. | Xiao-Zhong Wang Li-Juan Zhang Dan Li Yue-Hong Huang Zhi-Xin Chen BinLi Department of Gastroenterology, The Affiliated Union Hospital, Fujian Medical University, Fuzhou, 350001, Fujian Province, China | 2003 | World Journal of Gastroenterology2003，9，3： | 33 |
| 9 | Acupuncture-moxibustion in treating irritable bowel syndrome: How does it work?显示文摘Irritable bowel syndrome(IBS)is a functional intestinal disease characterized by abdominal pain or discomfort and altered bowel habits.It has drawn great attention because of its high prevalence,reoccurring symptoms,and severe influence on patients’lives.Many clinical studies have demonstrated the efficacy of acupuncturemoxibustion in treating IBS.Increasing attention has been paid to research regarding the action mechanisms of acupuncture-moxibustion for IBS,and the adoption of modern techniques has achieved some progress.This article reviews the latest advances among actionmechanism studies from the perspectives of gastrointestinal motility,visceral hypersensitivity,the braingut axis,the neuroendocrine system,and the immune system.It is shown that acupuncture-moxibustion can effectively regulate the above items,and thus,this treatment should have a high efficacy in the treatment of IBS.This article also identifies existing problems in current mechanism research and raises several ideas for future studies.Further revelations regarding these action mechanisms will promote the application of acupuncture-moxibustion in treating IBS. | Xiao-Peng Ma Jue Hong Cai-Ping An Dan Zhang Yan Huang Huan-Gan Wu Cui-Hong Zhang Sian Meeuwsen | 2014 | World Journal of Gastroenterology2014，20，20： | 30 |
| 10 | The Chromosome-Level Reference Genome of Tea Tree Unveils Recent Bursts of Nonautonomous LTR Retrotransposons in Driving Genome Size Evolution显示文摘Dear Editor,The tea tree Camellia sinensis,a member of the genus Camellia in the Theaceae family,includes two major cultivated varieties,C.sinensis var.assamica(CSA\Assam type)and C.sinensis var.sinensis(CSS;Chinese type)(Ming and Bartholomew,2007).Due to the high economic importance of the tea tree,considerable efforts have been made to explore genetic basis of the biosynthesis of natural metabolites that determine health benefits and diverse tea flavors(Shi et al.,2011;Li et al.,2011;Li et al.,2015;Xia et aL,2017;Liu et al.,2019). | Qun-Jie Zhang Wei L i Kui Li Hong Nan Cong Shi Yun Zhang Zhang-Yan Dai Yang-Lei Lin Xiao-Lan Yang Yan Tong Dan Zhang Cui Lu Li-Ying Feng Chen-Feng Wang Xiao-Xin Liu Jian-An Huang Wen-Kai Jiang Xing-Hua Wang Xing-Cai Zhang Evan E.Eichler Zhong-Hua Liu and Li-Zhi Gao | 2020 | Molecular Plant2020，13，7： | 27 |
| 11 | Expression of insulin-like growth factor 1 and insulin-like growth factor 1 receptor and its intervention by interleukin-10 in experimental hepatic fibrosis显示文摘AIM: To study the expression of IGF-1 and IGF-1R and its intervention by interleuldn-10 in the course of experimental hepatic fibrosis.METHODS: Hepatic fibrosis was induced in rats by carbon tetrachloride intoxication and liver specimens were taken from the rats administered CCl4 with or without IL-10 treatment and the animals of the control group.Immunoreactivities for insulin-like growth factor-1 (IGF-1)and IGF-1 receptor(IGF-1R) were demonstrated by immunohistochemistry, and their intensities were evaluated in different animal groups.RESULTS: The positive levels for IGF-1 and IGF-1R were increased with the development of hepatic fibrosis, with the positive signals localized in cytoplasm and/or at the plasmic membrane of hepatocytes. The positive signals of IGF-1 and IGF-1R were observed more frequently (P<0.01) in the CCl4-treated group (92.0 % and 90.0 %) compared to those in the control group. The positive signals decreased significantly (P<0.05) in IL-10-treated group. The responses in IGF-1 and IGF-1R expression correlated with the time of IL-10 treatment.CONCLUSION: The expression of IGF-1 and IGF-1R immunoreactivities in liver tissue seems to be up-regulated during development of hepatic fibrosis induced by CC14, and exogenic IL-10 inhibits the responses. | Xiao-Zhong Wang Zhi-Xin Chen Li-Juan Zhang Yun-Xin Chen Dan Li Feng-Lin Chen Yue-Hong Huang Department of Gastroenterology,Affiliated Union Hospital,Fujian Medical University,Fuzhou,350001,Fujian Province,China | 2003 | World Journal of Gastroenterology2003，9，6： | 27 |
| 12 | Single-cell RNA-seq highlights intra-tumoral heterogeneity and malignant progression in pancreatic ductal adenocarcinoma显示文摘Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer featured with high intra-tumoral heterogeneity and poor prognosis. To comprehensively delineate the PDAC intra-tumoral heterogeneity and the underlying mechanism for PDAC progression, we employed single-cell RNA-seq (scRNA-seq) to acquire the transcriptomic atlas of 57,530 individual pancreatic cells from primary PDAC tumors and control pancreases, and identified diverse malignant and stromal cell types, including two ductal subtypes with abnormal and malignant gene expression profiles respectively, in PDAC. We found that the heterogenous malignant subtype was composed of several subpopulations with differential proliferative and migratory potentials. Cell trajectory analysis revealed that components of multiple tumor-related pathways and transcription factors (TFs) were differentially expressed along PDAC progression. Furthermore, we found a subset of ductal cells with unique proliferative features were associated with an inactivation state in tumor-infiltrating T cells, providing novel markers for the prediction of antitumor immune response. Together, our findings provide a valuable resource for deciphering the intra-tumoral heterogeneity in PDAC and uncover a connection between tumor intrinsic transcriptional state and T cell activation, suggesting potential biomarkers for anticancer treatment such as targeted therapy and immunotherapy. | Junya Peng Bao-Fa Sun Chuan-Yuan Chen Jia-Yi Zhou Yu-Sheng Chen Hao Chen Lulu Liu Dan Huang Jialin Jiang Guan-Shen Cui Ying Yang Wenze Wang Dan Guo Menghua Dai Junchao Guo Taiping Zhang Quan Liao Yi Liu Yong-Liang Zhao Da-Li Han Yupei Zhao Yun-Gui Yang Wenming Wu | 2019 | Cell Research2019，29，9： | 24 |
| 13 | Crosstalk between tumor cells and microenvironment via Wnt pathway in colorectal cancer dissemination显示文摘Invasion and metastasis are the deadly face of malignant tumors. Considering the high rate of incidence and mortality of colorectal cancer, it is critical to determine the mechanisms of its dissemination. In the parallel investigation of the invasive front and tumor center area of colorectal cancer (CRC), observation of heterogeneous β-catenin distribution and epithelial-mesenchymal transition (EMT) at the invasive front suggested that there might be a crosstalk between tumor cells and the tumor microenvironment. Wnt signaling pathway is also involved in the cancer progression due to its key role in CRC tumorigenesis. Moreover, in recent years, there is increasing evidence that the regulators of microenvironment, including extracellular matrix, growth factors and inflammatory factors, are associated with the activation of Wnt pathway and the mobility of tumor cells. In this review, we will try to explain how these molecules trigger metastasis via the Wnt pathway. | Dan Huang, Xiang Du, Department of Pathology, Cancer Hospital of Fudan University Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China | 2008 | World Journal of Gastroenterology2008，14，12： | 22 |
| 14 | Ten cities cross-sectional questionnaire survey of children asthma and other allergies in China显示文摘Asthma,rhinitis and eczema(allergic or non-allergic)have increased throughout the world during the last decades,especially among children.Changes in the indoor environment are suspected to be important causes.China has experienced a dramatic change in indoor environmental exposures during the past two decades.However,such changes and their associations with children’s asthma and other health aspects have not been thoroughly studied.China,Children,Homes,Health(CCHH),Phase I,was a cross-sectional questionnaire survey of 48219 children 1–8 years old in 10 Chinese cities during 2010–2012.The questionnaire includes the International Study of Asthma and Allergies in Childhood(ISAAC)core health questions and additional questions regarding housing,life habits and outdoor environment.In health analyses,children aged 3–6 years old were included.The prevalences of doctor diagnosed asthma varied from 1.7%to 9.8%(mean 6.8%),a large increase from 0.91%in 1999 and 1.50%in2000.The prevalence of wheeze,rhinitis and atopic eczema(last 12 months)varied from 13.9%to 23.7%,24.0%to 50.8%and4.8%to 15.8%,respectively.Taiyuan had the lowest prevalences of all illnesses and Shanghai the highest,except for wheezewhere the highest value was for Urumqi.We found(1)no obvious association between disease prevalences and ambient PM10concentrations and(2)higher prevalences of disease in humid climates with hot summers and cold winters,but with no centrally heated buildings.Associations between the diseases and economic status as indexed by Gross Domestic Product(GDP)requires further study. | ZHANG YinPing LI BaiZhan HUANG Chen YANG Xu QIAN Hua DENG QiHong ZHAO ZhuoHui LI AnGui ZHAO JiaNing ZHANG Xin QU Fang HU Yu YANG Qin WANG Juan ZHANG Ming WANG Fang ZHENG XiaoHong LU Chan LIU ZhiJian SUN YueXia MO JinHan ZHAO YiLi LIU Wei WANG TingTing NORBCK Dan BORNEHAG Carl-Gustaf SUNDELL Jan | 2013 | Chinese Science Bulletin2013，58，34： | 22 |
| 15 | Total glucosides of paeony attenuates animal psoriasis induced inflammatory response through inhibiting STAT1 and STAT3 phosphorylation显示文摘OBJECTIVE Psoriasis is an immune system meditated disease,especially T cells.It disturbed many people around the world and hard to therapy.Paeonia lactiflora Pall has been used as a medicine in china for thousands of years.Recent studies has found that the main component of Paeonia lactiflora Pall can alleviates the immune response in many diseases.In this study,we researched the effects and possible mechanisms of total glucosides of paeony(TGP)on animal psoriasis in order to study the therapeutic effects and mechanisms of TGP in 5%propranolol creaminduced psoriasis in guinea pigs and Imiquimod(IMQ)cream-induced psoriasis in mice.METHODS The effect of TGP was evaluated using a psoriasis-like model of guinea pigs and mice.Ear thickness was accessed,and pathology injury was observed by HE staining.The levels of serum IL-1β,IL-6,IL-12,IL-17,IL-23,TNF-α,and IFN-γ,skin IL-17A,IL-22 and orphan nuclear receptor(RORγt)mRNA expression,proliferating cell nuclear antigen(PCNA),total or phosphorylated signal transducers and activators of transcription(STAT1 and STAT3)were determined by ELISA,real time PCR,immu⁃nohistochemical staining,and Western blotting,respectively.RESULTS Compared with model group,TGP treatment decreased the ear thickness,improved pathology of psoriasis,alleviated IMQ-induced keratinocyte proliferation,reduced the inflammatory cytokine,and downregulated IL-17A,IL-22,and RORγt mRNA in mice.Further study indicated that TGP inhibited STAT1 and STAT3 phosphorylation in lesion skins of psoriasis-like mice.CONCLUSION TGP alleviates the symptoms of psoriasis-like guinea pigs and mice,and the possible mechanism may relate to inhibit T helper 17(TH17)cell differentiation and keratinocytes proliferation by inhibiting STAT1 and STAT3 phosphorylation. | LI Bin-bin HE Shu-cheng LIU Rui HUANG Liang-liang LIU Ge WANG Rui-xuan YANG Zhuo-yue LIU Xin-yi LENG Ye LIU Dan YE Cheng-yu LI Yun-man CHEN Yong-jian IN Hong FANG Wei-rong | 2019 | 中国药理学与毒理学杂志2019，33，9： | 21 |
| 16 | From concept to reality-A review to the primary test stand and its preliminary application in high energy density physics显示文摘Pulsed power technology,whereas the electrical energy stored in a relative long period is released in much shorter timescale,is an efficient method to create high energy density physics(HEDP)conditions in laboratory.Around the beginning of this century,China Academy of Engineering Physics(CAEP)began to build some experimental facilities for HEDP investigations,among which the Primary Test Stand(PTS),a multi-module pulsed power facility with a nominal current of 10 MA and a current rising time~90 ns,is an important achievement on the roadmap of the electro-magnetically driven inertial confinement fusion(ICF)researches.PTS is the first pulsed power facility beyond 10 TW in China.Therefore,all the technologies have to be demonstrated,and all the engineering issues have to be overcome.In this article,the research outline,key technologies and the preliminary HEDP experiments are reviewed.Prospects on HEDP research on PTS and pulsed power development for the next step are also discussed. | Jianjun Deng Weiping Xie Shuping Feng Meng Wang Hongtao Li Shengyi Song Minghe Xia Ji Ce An He Qing Tian Yuanchao Gu Yongchao Guan Bin Wei Xianbin Huang Xiaodong Ren Jiakun Dan Jing Li Shaotong Zhou Hongchun Cai Siqun Zhang Kunlun Wang Qiang Xu Yujuan Wang Zhaohui Zhang Guilin Wang Shuai Guo Yi He Yiwei Zhou Zhanji Zhang Libing Yang Wenkang Zou | 2016 | Matter and Radiation at Extremes2016，1，1： | 19 |
| 17 | Organic anion transporting polypeptide-1B1 haplotypes in Chinese patients显示文摘瞄准:在搬运 polypeptide-1B1 的器官的阴离子检测 388G >A 和 521T >C 变体等位基因(OATP1B1,编码基因 SLCO1B1 ) 基因。方法:111 个健康志愿者在我们的学习为 OATP1B1 等位基因被屏蔽。PCR 限制碎片长度多型性被用来鉴别 388G >A 多型性和一个 1 步 tetra 教材方法为 521T >C 变化的决心被开发。结果:在中国人口的 388G >A 和 521T >C 变体等位基因的频率分别地是 73.4% 和 14.0% 。SLCO1B1 *1b 和 *15 haplotypes 的频率分别地是 59.9% 和 14.0% 。结论:SLCO1B1 *1b 和 SLCO1B1 *15 变体在中国人口是相对普通的。他们的频率类似于那在从那在白种人和黑人日本,却显著地不同。 | Lin-yong XU Yi-jing HE Wei ZHANG Sheng Deng Qing LI Wei-xia ZHANG Zhao-qian LIU Dan WANG Yuan-fei HUANG Hong-hao ZHOU Zhen-qiu SUN | 2007 | Acta Pharmacologica Sinica2007，28，10： | 18 |
| 18 | Expansion and differentiation of human hepatocyte-derived liver progenitor-like cells and their use for the study of hepatotropic pathogens显示文摘The study of pathophysiological mecha nisms in huma n liver disease has bee n constrained by the in ability to expa nd primary hepatocytes in vitro while maintaining proliferative capacity and metabolic function. We and others have previously shown that mouse mature hepatocytes can be con verted to liver progenitor-like cells in vitro with defined chemical factors. Here we describe a protocol achieving efficient conversion of human primary hepatocytes into liver progenitor-like cells (HepLPCs) through delivery of developmentally relevant cues, including NAD +-dependent deacetylase SIRT1 signaling. These HepLPCs could be expanded sign ifica ntly duri ng in vitro passage. The expa nded cells can readily be con verted back into metabolically functional hepatocytes in vitro and upon tran splantati on in vivo. Under three-dime nsional culture conditions, differentiated cells gen erated from HepLPCs regai ned the ability to support infect io n or reactivatio n of hepatitis B virus (HBV). Our work dem on strates the utility of the con versi on betwee n hepatocyte and liver proge nitor-like cells for studying HBV biology and an tiviral therapies. These fin dings will facilitate the study of liver diseases and regenerative medicine. | Gong-Bo Fu Wei-Jian Huang Min Zeng Xu Zhou Hong-Ping Wu Chang-Cheng Liu Han Wu Jun Weng Hong-Dan Zhang Yong-Chao Cai Charles Ashton Min Ding Dan Tang Bao-Hua Zhang Yi Gao Wei-Feng Yu Bo Zhai Zhi-Ying He Hong-Yang Wang He-Xin Yan | 2019 | Cell Research2019，29，1： | 18 |
| 19 | Effective gene editing by high-fidelity base editor 2 in mouse zygotes显示文摘通过相应再结合的指向的点 mutagenesis 广泛地在基因研究被使用了并且为在病人修理引起疾病的变化保持可观的诺言。然而,象 mosaicism 那样的问题和低 mutagenesis 效率继续提出挑战到如此的途径的临床的申请。最近,一个基础编辑器() 在 cytidine (C) 脱氨基酶上造的系统和 CRISPR/Cas9 技术在植物,酵母,和人的房间为指向的点 mutagenesis 作为一个其他的方法被开发。然而,基础编辑器高效地在 deamination 窗口中把 C 变换成 thymidine (T) 是否指向了在鼠标胚胎的基础编辑,仍然保持不清楚是可行的。在这份报告,我们产生了基础编辑的一个修改高保真版本 2 (HF2-BE2 ) ,并且调查了它在老鼠胚胎编辑功效的底。我们发现 HF2-BE2 能高效地把 C 变换成 T,与直到在老鼠胚胎的 100% biallelic 变化效率。不同于 BE3, HF2-BE2 能在目标和非目标海滨上把 C 变换成 T,扩展基础编辑器的编辑范围。令人惊讶地,我们发现 HF2-BE2 能也使脱去氨基对 gRNA 有约束力的区域近似的 C。一起拿,我们的工作表明由基础编辑,和下划线在鼠标产生点变化的可行性小心地优化编辑系统以便消除近似地点的 deamination 的底的需要。 | Puping Liang Hongwei Sun Ying Sun Xiya Zhang Xiaowei Xie Jinran Zhang zhen Zhang Yuxi Chen Chenhui Ding Yuanyan Xiong Wenbin Ma Dan Liu Junjiu Huang Zhou Songyang | 2017 | Protein & Cell2017，8，8： | 17 |
| 20 | Phase 1 clinical trial demonstrated that MUC1 positive metastatic seminal vesicle cancer can be effectively eradicated by modified Anti-MUC1 chimeric antigen receptor transduced T cells显示文摘Recent progress in chimeric antigen receptor-modified T-cell(CAR-T cell) technology in cancer therapy is extremely promising, especially in the treatment of patients with B-cell acute lymphoblastic leukemia. In contrast, due to the hostile immunosuppressive microenvironment of a solid tumor, CAR T-cell accessibility and survival continue to pose a considerable challenge, which leads to their limited therapeutic efficacy. In this study, we constructed two anti-MUC1 CAR-T cell lines. One set of CAR-T cells contained SM3 single chain variable fragment(sc Fv) sequence specifically targeting the MUC1 antigen and co-expressing interleukin(IL) 12(named SM3-CAR). The other CAR-T cell line carried the SM3 sc Fv sequence modified to improve its binding to MUC1 antigen(named p SM3-CAR) but did not co-express IL-12. When those two types of CAR-T cells were injected intratumorally into two independent metastatic lesions of the same MUC1+ seminal vesicle cancer patient as part of an interventional treatment strategy, the initial results indicated no side-effects of the MUC1 targeting CAR-T cell approach, and patient serum cytokines responses were positive. Further evaluation showed that p SM3-CAR effectively caused tumor necrosis, providing new options for improved CAR-T therapy in solid tumors. | Fengtao You Licui Jiang Bozhen Zhang Qiang Lu Qiao Zhou Xiaoyang Liao Hong Wu Kaiqi Du Youcai Zhu Huimin Meng Zhishu Gong Yunhui Zong Lei Huang Man Lu Jirong Tang Yafen Li Xiaochen Zhai Xiangling Wang Sisi Ye Dan Chen Lei Yuan Lin Qi Lin Yang | 2016 | Science China(Life Sciences)2016，59，4： | 16 |
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