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Characterization of acute-on-chronic liver diseases: A multicenter prospective cohort study
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作者 Yuan-Yao Zhang Sen Luo +38 位作者 Hai Li Shu-Ning Sun Xian-Bo Wang Xin Zheng Yan Huang Bei-Ling Li Yan-Hang Gao Zhi-Ping Qian Feng liu Xiao-Bo Lu jun-ping liu Hao-Tang Ren Yu-Bao Zheng Hua-Dong Yan Guo-Hong Deng Liang Qiao Yan Zhang Wen-Yi Gu Xiao-Mei Xiang Yi Zhou Yi-Xin Hou Qun Zhang Yan Xiong Cong-Cong Zou Jun Chen Ze-Bing Huang Xiu-Hua Jiang Ting-Ting Qi Yuan-Yuan Chen Na Gao Chun-Yan liu Wei Yuan Xue Mei Jing Li Tao Li Rong-Jiong Zheng Xin-Yi Zhou Jun Zhao Zhong-Ji Meng 《World Journal of Hepatology》 2024年第5期809-821,共13页
BACKGROUND Acute-on-chronic liver disease(AoCLD)accounts for the majority of patients hospitalized in the Department of Hepatology or Infectious Diseases.AIM To explore the characterization of AoCLD to provide theoret... BACKGROUND Acute-on-chronic liver disease(AoCLD)accounts for the majority of patients hospitalized in the Department of Hepatology or Infectious Diseases.AIM To explore the characterization of AoCLD to provide theoretical guidance for the accurate diagnosis and prognosis of AoCLD.METHODS Patients with AoCLD from the Chinese Acute-on-Chronic Liver Failure(ACLF)study cohort were included in this study.The clinical characteristics and outcomes,and the 90-d survival rate associated with each clinical type of AoCLD were analyzed,using the Kaplan-Meier method and the log-rank test.RESULTS A total of 3375 patients with AoCLD were enrolled,including 1679(49.7%)patients with liver cirrhosis acute decompensation(LC-AD),850(25.2%)patients with ACLF,577(17.1%)patients with chronic hepatitis acute exacer-bation(CHAE),and 269(8.0%)patients with liver cirrhosis active phase(LC-A).The most common cause of chronic liver disease(CLD)was HBV infection(71.4%).The most common precipitants of AoCLD was bacterial infection(22.8%).The 90-d mortality rates of each clinical subtype of AoCLD were 43.4%(232/535)for type-C ACLF,36.0%(36/100)for type-B ACLF,27.0%(58/215)for type-A ACLF,9.0%(151/1679)for LC-AD,3.0%(8/269)for LC-A,and 1.2%(7/577)for CHAE.CONCLUSION HBV infection is the main cause of CLD,and bacterial infection is the main precipitant of AoCLD.The most common clinical type of AoCLD is LC-AD.Early diagnosis and timely intervention are needed to reduce the mortality of patients with LC-AD or ACLF. 展开更多
关键词 Acute-on-chronic liver disease Acute-on-chronic liver failure Liver cirrhosis Clinical features PROGNOSIS
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Response to the Lomagundi-Jatuli Event in the southwestern margin of the Yangtze Plate:Evidence from the carbon and oxygen isotopes of the Paleoproterozoic Yongjingshao Formation 被引量:10
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作者 jun-ping liu Wei Yin +5 位作者 Shi-pan Yang Jiang-tai Zhao Wen-tao Zeng Feng Tang Shi-jun He Wei-ke Li 《China Geology》 CAS CSCD 2023年第1期50-60,共11页
The Lomagundi-Jatuli Event(LJE)refers to the significant positive carbon isotope excursion in seawater constituents that occurred immediately after the increase in atmospheric oxygen content during the Paleoproterozoi... The Lomagundi-Jatuli Event(LJE)refers to the significant positive carbon isotope excursion in seawater constituents that occurred immediately after the increase in atmospheric oxygen content during the Paleoproterozoic(2.22-2.06 Ga).Theδ^(13)C values of 46 dolostone samples collected from the Paleoproterozoic Yongjingshao Formation varied in the range of 0.05‰-4.95‰(V-PDB;maximum:4.95‰)in this study,which may be related to the multicellular eukaryotes in the Liangshan Formation in the Yimen Group.They are much higher than theδ^(13)C values of marine carbonates(-1.16‰on average).Theδ^(13)C values of other formations in the Paleoproterozoic Yimen Group are negative.The notable positive carbon isotope anomalies of the Yongjingshao Formation indicate the response to the LJE at the southwestern margin of the Yangtze Block,which is reported for the first time.Furthermore,they are comparable to theδ^(13)C values of carbonates in the Dashiling Formation of the Hutuo Group in the Wutaishan area in the North China Craton,the Wuzhiling Formation of the Songshan Group in the Xiong'er area,Henan Province,and the Dashiqiao Formation of the Liaohe Group in the Guanmenshan area,Liaoning Province.Therefore,it can be further concluded that the LJE is a global event.This study reveals that LJE occurred in Central Yunnan at 2.15-2.10 Ga,lasting for about 50 Ma.The macro-columnar,bean-shaped,and microfilament fossils and reticular ultramicrofossils of multicellular eukaryotes in this period were discovered in the Liangshan Formation of the Yimen Group.They are the direct cause for the LJE and are also the oldest paleontological fossils ever found.The major events successively occurring in the early stage of the Earth include the Great Oxygenation Event(first occurrence),the global Superiortype banded iron formations(BIFs),the Huronian glaciation,the Great Oxygenation Event(second occurrence),the explosion of multicellular eukaryotes,the positive carbon isotope excursion,and the global anoxic and selenium-rich sedimentary event.The authors think that the North China Craton and the Yangtze Craton were possibly in different tectonic locations of the same continental block during the Proterozoic. 展开更多
关键词 Lomagundi-Jatuli Event Eucaryon PALEOPROTEROZOIC Bean-shaped fossil Micro-filament fossil Micro-columnar fossil Carbon and oxygen isotopes Yangtze Plate Geological survey engineering China
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Estrogen deficiency leads to telomerase inhibition, telomere shortening and reduced cell proliferation in the adrenal gland of mice 被引量:7
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作者 Sharyn Bayne Margaret EE Jones +3 位作者 He Li Alex R Pinto Evan R Simpson jun-ping liu 《Cell Research》 SCIE CAS CSCD 2008年第11期1141-1150,共10页
Estrogen deficiency mediates aging, but the underlying mechanism remains to be fully determined. We report here that estrogen deficiency caused by targeted disruption of aromatase in mice results in significant inhibi... Estrogen deficiency mediates aging, but the underlying mechanism remains to be fully determined. We report here that estrogen deficiency caused by targeted disruption of aromatase in mice results in significant inhibition of telomerase activity in the adrenal gland in vivo. Gene expression analysis showed that, in the absence of estrogen, telomerase reverse transcriptase (TERT) gene expression is reduced in association with compromised cell proliferation in the adrenal gland cortex and adrenal atrophy. Stem cells positive in c-kit are identified to populate in the parenchyma of adrenal cortex. Analysis of telomeres revealed that estrogen deficiency results in significantly shorter teiomeres in the adrenal cortex than that in wild-type (WT) control mice. To further establish the causal effects of estrogen, we conducted an estrogen replacement therapy in these estrogen-deficient animals. Administration of estrogen for 3 weeks restores TERT gene expression, telomerase activity and cell proliferation in estrogen-deficient mice. Thus, our data show for the first time that estrogen deficiency causes inhibitions of TERT gene expression, telomerase activity, telomere maintenance, and cell proliferation in the adrenal gland of mice in vivo, suggesting that telomerase inhibition and telomere shortening may mediate cell proliferation arrest in the adrenal gland, thus contributing to estrogen deficiency-induced aging under physiological conditions. 展开更多
关键词 ESTROGEN TELOMERASE TELOMERES cell proliferation aromatase knockout mice
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Discovery of rhyolitic tuffaceous slate in the southwestern margin of Yangtze Craton:Zircon U-Pb ages(2491 Ma)and tectonic-thermal events 被引量:7
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作者 jun-ping liu Su-mei Tian +7 位作者 Xun-zao Zhu Jin-hua Ma Jing Li Shao-bin Hu Sai-ying Yu Hu Zhang Zhong-ming She Xu-gui Li 《China Geology》 2021年第4期616-629,共14页
The Mesoproterozoic Dongchuan Group that is widely exposed in Yimen area,central Yunnan Province is a series of sedimentary sort of low-grade metamorphic rocks interbedded with volcanic rocks,which are closely related... The Mesoproterozoic Dongchuan Group that is widely exposed in Yimen area,central Yunnan Province is a series of sedimentary sort of low-grade metamorphic rocks interbedded with volcanic rocks,which are closely related to the early tectonic evolution of the Earth.However,its formation era,sedimentary filling sequence,and geotectonic characteristics have always been in dispute.In this study,several rhyolitic tuffaceous slate interlayers with a centimeter-level thickness were found in the previously determined Heishan Formation of the Dongchuan Group located to the western part of Yimen-Luoci fault zone.This paper focuses on the study of the rhyolitic tuffaceous slate in Qifulangqing Village,Tongchang Township,Yimen County.LA-ICP-MS zircon dating was conducted,achieving the crystallization age of magma of 2491±15 Ma and the metamorphic ages of about 2.3 Ga,2.0 Ga,and 1.8 Ga for the first time.Meanwhile,according to in-situ Hf isotope analysis,the zirconεHf(t)values were determined to range from−3.0 to 7.6,with an average of 2.7.Furthermore,the first-stage Hf model age(TDM1)was determined to be 2513−2916 Ma,indicating that the provenance of the rhyolitic tuffaceous slate is the depleted mantle or juvenile crust between the Middle Mesoarchean and the Late Neoarchean.Therefore,it is believed that the strata of the slate were deposited in the Late Neoarchean,instead of the Mesoproterozoic as determined by previous researchers.Accordingly,it is not appropriate to group the strata into the Mesoproterozoic Dongchuan Group.Instead,they should be classified as the Maolu Formation of the Neoarchean Puduhe Group given the lithologic association and regional information.Furthermore,the magma ages of 2491±15 Ma are highly consistent with the eras of the large-scale Late Neoarchean orogenic magmatic activities on the northern margin of the Yangtze Craton,and thus reflect the orogenic process consisting of subduction and collision from Late Neoarchean to Early Paleoproterozoic.The magmatic activities during this period were possibly caused by the convergence of the supercontinent Kenorland.Meanwhile,the metamorphic ages of 2.3 Ga,2.0 Ga,and 1.8 Ga are highly consistent with three metamorphic ages of 2.36 Ga,1.95 Ga,and 1.85 Ga of the northern margin of the Yangtze Craton,indicating that the strata experienced Paleoproterozoic tectonic-thermal events.The study area is located on the eastern margin of Qinghai-Tibet Plateau,and thus was possibly re-transformed by magmatism subjected to the subduction of the Meso-Tethys Ocean during the Early Cretaceous.The discoveries made in this study will provide strong petrological and chronological evidence for analyzing the early crustal evolution of the Yangtze block. 展开更多
关键词 Maolu Formation Puduhe Group Late Neoarchean Zircon U-Pb age Tectonic-thermal event Geological survey engineering Eastern margin of Qinghai-Tibet Plateau Yangtze Craton
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Protoconodont fossils for refining the Cambrian bottom and the contribution to shale gas formation along the southwest margin of Yangtze Block 被引量:8
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作者 jun-ping liu Si-cun Song +8 位作者 Wei Wang Feng Tang Jing Li Xiang-dong Duan Xiao-hu Wang Bai-dong Sun Sai-ying Yu Shao-bin Hu Wen-ting Duan 《China Geology》 2020年第4期558-566,共9页
It has been an intense debate on the exact boundary between Ediacaran and Cambrian in the southwest Yangtze Block.The calibration of this critical boundary has a remarkable influence on the further investigation of th... It has been an intense debate on the exact boundary between Ediacaran and Cambrian in the southwest Yangtze Block.The calibration of this critical boundary has a remarkable influence on the further investigation of the break-up of the Rodinia Supercontinent,the early life evolution,and the mechanism of the phosphorite deposit.Ediacaran and Cambrian strata and fossils are widely distributed in Anning,Yunnan Province in China.In recent years,the Xiaowaitoushan Member from the Lower Yuhucun Formation has been studied.Through this interval with continuous collections,the first appearance datums(FADs)of the protoconodont(Fomitchella cf.inchoate Yang et He,Protohertzina cf.anabarica Missarzhevsky)and globular embryos fossil(Olivooides sp.)earlier than these in the Lower Cambrian strata of the Meishucun Formation were discovered.This discovery indicates that the Xiaowaitoushan Member has included more FADs than the previously discovered single FAD of Anabarites primitivus Qian et Jiang,and the Ediacaran–Cambrian boundary in southwest China should be replaced below the Point“A”of the Meishucun Formation in Yunnan Province.The Point“B”of the Meishucun Formation is younger than the suggested age 541 Ma of the Ediacaran–Cambrian boundary and can no longer reference the Global Boundary Stratotype Section and Point(GSSP)correlation in southwest China.It can be suggested based on the previous stratigraphy and palaeontology studies from northern Sichuan and southern Shaanxi and the FAD of the globular embryos fossils that the Ediacaran‒Cambrian boundary in the southwest Yangtze Block should be placed at the base of the Xiaowaitoushan Member;other phosphorite strata refer to Xiaowaitoushan Member.The discovery of the FADs of the shelly fossils in the Xiaowaitoushan Member provides new evidence for the global correlation of the Ediacaran–Cambrian boundary in the southwest Yangtze Block.The conodont discoloration index(CAI)of the specimens in Anning is between 2 and 3,which indicates that the organic matter in Xiaowaitoushan Member is matured and has high potential to form a shale gas reservoir. 展开更多
关键词 Shale gas Ediacaran-Cambrian boundary Protoconodont Embryos fossil Xiaowaitoushan Member Southwest Yangtze Block Geological survey engineering Yunnan Province China
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Enigmatic ribbon-like fossil from Early Cambrian of Yunnan, China 被引量:3
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作者 Feng Tang Si-cun Song +2 位作者 Guang-xu Zhang Ai-lin Chen jun-ping liu 《China Geology》 2021年第2期205-214,共10页
During the Late Neoproterozoic and Early Cambrian,a series of paleogeographic and paleoecological events occurred associated with deglaciations and the evolution of life.The appearance of fossils representing diverse ... During the Late Neoproterozoic and Early Cambrian,a series of paleogeographic and paleoecological events occurred associated with deglaciations and the evolution of life.The appearance of fossils representing diverse phyla,novel body plans and complex ecologies in Ediacaran and Cambrian sedimentary successions has sparked diverse hypotheses about potential drivers for the radiation of early animals during this interval.Recently,new macroscopic fossils of carbonaceous compressions with unique features have been found in Anning,Yunnan,China.The fossils’bodies are ribbon-shaped and bilaterally symmetric,with dense longitudinal features and transversal features.The fossils occur 0.68 m below a bentonite interlayer which has been dated 535.2±1.7 Ma by Ri-xiang Zhu and his team in 2009.The relatively simply morphology of these fossils,coupled with a lack of preserved internal structures challenge efforts taxonomically identify the precursor organism and definitively ally it to a living group.However,the symmetry and unusual features of the body are analogous to members of Platyzoa.The presence of ribbon-shaped fossils in the Zhongyicun Member in Anning indicates that these organisms were at least a locally significant component of Cambrian seafloor ecosystems,and may hold important implications for our understanding of the early evolution of Bilateria. 展开更多
关键词 Early Cambrian Platyhelminthe BILATERIA MACROFOSSIL Eastern Yunnan Geological survey engineering
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Geochemical characteristics and genetic type of a lithium ore (mineralized) body in the central Yunnan Province, China 被引量:2
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作者 Bai-dong Sun jun-ping liu +6 位作者 Xiao-hu Wang Yan Dao Gui-xiang Xu Xiao-zhuang Xue-qing Guan Wei Wang Dong-hu Song 《China Geology》 2019年第3期287-300,共14页
Lithium ore (mineralized) bodies in the area A of central Yunnan Province belong to a sedimentary-type, which are controlled by stratum. The studied ore (mineralized) body mainly occurs in the Middle Permian Liangshan... Lithium ore (mineralized) bodies in the area A of central Yunnan Province belong to a sedimentary-type, which are controlled by stratum. The studied ore (mineralized) body mainly occurs in the Middle Permian Liangshan Formation. This work described the morphology, structures, main ore types and geochemical characteristics of this ore body in detail, and discussed the ore-forming material source, occurrence state of lithium and the formation mechanism of lithium ores to clarify the prospecting marks. In the further exploration, comprehensive evaluation of the lithium resources of known bauxite ore bodies in central Yunnan Province should be strengthened, and the exploration of hidden lithium ore bodies should be intensified in order to discover more large and super-large lithium orebodies, which will fill the gap of the national demand for lithium resources, and promote the national defense construction and new energy industry development. 展开更多
关键词 Sedimentary-type lithium DEPOSIT Stratified DEPOSIT GEOCHEMICAL characteristics METALLOGENIC mechanism Mineral resources exploration engineering Yunnan PROVINCE China
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From molecules and cells to diseases: West meets East for medical research in Tianjin
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作者 jun-ping liu 《Cell Research》 SCIE CAS CSCD 2009年第8期924-928,共5页
The second Australia-China Biomedical Research Conference was held at Nankai University in China's north from 24-27 April, 2009. Students from a number of China's famous universities turned out to welcome almost 100... The second Australia-China Biomedical Research Conference was held at Nankai University in China's north from 24-27 April, 2009. Students from a number of China's famous universities turned out to welcome almost 100 Australians and more than 200 Chinese scientists, researchers, university leaders and policy makers. The research findings presented at the conference, which included 16 plenary lectures and 8 symposia, covered basic to clinical investigations in the areas of stem cell biology, mechanisms of cancer, immunity and viral infection, membrane trafficking and neuroscience, cardiovascular and metabolic disorders, protein structures and microRNAs, intracellular signalling, biotechnology and drug development. 展开更多
关键词 干细胞生物学 生物医学 疾病 南开大学 天津 分子 澳大利亚 专题讨论会
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The landscape of aging 被引量:24
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作者 Yusheng Cai Wei Song +50 位作者 Jiaming Li Ying Jing Chuqian Liang Liyuan Zhang Xia Zhang Wenhui Zhang Beibei liu Yongpan An Jingyi Li Baixue Tang Siyu Pei Xueying Wu Yuxuan liu Cheng-Le Zhuang Yilin Ying Xuefeng Dou Yu Chen Fu-Hui Xiao Dingfeng Li Ruici Yang Ya Zhao Yang Wang Lihui Wang Yujing Li Shuai Ma Si Wang Xiaoyuan Song Jie Ren Liang Zhang Jun Wang Weiqi Zhang Zhengwei Xie Jing Qu Jianwei Wang Yichuan Xiao Ye Tian Gelin Wang Ping Hu Jing Ye Yu Sun Zhiyong Mao Qing-Peng Kong Qiang liu Weiguo Zou Xiao-Li Tian Zhi-Xiong Xiao Yong liu jun-ping liu Moshi Song Jing-Dong J.Han Guang-Hui liu 《Science China(Life Sciences)》 SCIE CAS CSCD 2022年第12期2354-2454,共101页
Aging is characterized by a progressive deterioration of physiological integrity,leading to impaired functional ability and ultimately increased susceptibility to death.It is a major risk factor for chronic human dise... Aging is characterized by a progressive deterioration of physiological integrity,leading to impaired functional ability and ultimately increased susceptibility to death.It is a major risk factor for chronic human diseases,including cardiovascular disease,diabetes,neurological degeneration,and cancer.Therefore,the growing emphasis on “healthy aging” raises a series of important questions in life and social sciences.In recent years,there has been unprecedented progress in aging research,particularly the discovery that the rate of aging is at least partly controlled by evolutionarily conserved genetic pathways and biological processes.In an attempt to bring full-fledged understanding to both the aging process and age-associated diseases,we review the descriptive,conceptual,and interventive aspects of the landscape of aging composed of a number of layers at the cellular,tissue,organ,organ system,and organismal levels. 展开更多
关键词 AGING MECHANISM INTERVENTION
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Estrogen deficiency reversibly induces telomere shortening in mouse granulosa cells and ovarian aging in vivo 被引量:11
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作者 Sharyn Bayne He Li +5 位作者 Margaret E.E.Jones Alex R.Pinto Michelle van Sinderen Ann Drummond Evan R.Simpson jun-ping liu 《Protein & Cell》 SCIE CSCD 2011年第4期333-346,共14页
Estrogen is implicated as playing an important role in aging and tumorigenesis of estrogen responsive tissues;however the mechanisms underlying the mitogenic actions of estrogen are not fully understood.Here we report... Estrogen is implicated as playing an important role in aging and tumorigenesis of estrogen responsive tissues;however the mechanisms underlying the mitogenic actions of estrogen are not fully understood.Here we report that estrogen deficiency in mice caused by targeted disruption of the aromatase gene results in a signi-ficant inhibition of telomerase maintenance of telomeres in mouse ovaries in a tissue-specific manner.The inhibition entails a significant shortening of telomeres and compromised proliferation in the follicular granulosa cell compartment of ovary.Gene expression analysis showed decreased levels of proto-oncogene c-Myc and the telomerase catalytic subunit,telomerase reverse transcriptase(TERT),in response to estrogen deficiency.Estrogen replacement therapy led to increases in TERT gene expression,telomerase activity,telomere length and ovarian tissue growth,thereby reinstating ovary development to normal in four weeks.Our data demonstrate for the first time that telomere maintenance is the primary mechanism mediating the mitogenic effect of estrogen on ovarian granulosa cell proliferation by upregulating the genes of c-Myc and TERT in vivo.Estrogen deficiency or over-activity may cause ovarian tissue aging or tumorigenesis,respectively,through estrogen regulation of telomere remodeling. 展开更多
关键词 ESTROGEN telomerase reverse transcriptase(TERT) TELOMERES OVARY mice
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Current aging research in China 被引量:12
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作者 Ruijuan Sun Heqi Cao +2 位作者 Xudong Zhu jun-ping liu Erdan Dong 《Protein & Cell》 SCIE CAS CSCD 2015年第5期314-321,共8页
The mini-review stemmed from a recent meeting on national aging research strategies in China discusses the components and challenges of aging research in China. Highlighted are the major efforts of a number of researc... The mini-review stemmed from a recent meeting on national aging research strategies in China discusses the components and challenges of aging research in China. Highlighted are the major efforts of a number of research teams, funding situations and outstanding examples of recent major research achievements. Finally, authors discuss potential targets and strategies of aging research in China. 展开更多
关键词 aging research FUNDING objectives and strategies
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Molecular regulation of telomerase activity in aging 被引量:2
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作者 Craig Nicholls He Li +1 位作者 Jian-Qiu Wang jun-ping liu 《Protein & Cell》 SCIE CSCD 2011年第9期726-738,共13页
The process of aging is mitigated by the maintenance and repair of chromosome ends(telomeres),resulting in extended lifespan.This review examines the molecular mechanisms underlying the actions and regulation of the e... The process of aging is mitigated by the maintenance and repair of chromosome ends(telomeres),resulting in extended lifespan.This review examines the molecular mechanisms underlying the actions and regulation of the enzyme telomerase reverse transcriptase(TERT),which functions as the primary mechanism of telomere maintenance and regulates cellular life expectancy.Underpinning increased cell proliferation,telomerase is also a key factor in facilitating cancer cell immortalization.The review focuses on aspects of hormonal regulations of telomerase,and the intracellular pathways that converge to regulate telomerase activity with an emphasis on molecular interactions at protein and gene levels.In addition,the basic structure and function of two key telomerase enzyme components—the catalytic subunit TERTand the template RNA(TERC)are discussed briefly. 展开更多
关键词 TELOMERASE AGING telomerase reverse transcriptase(TERT)
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TGF-beta receptor mediated telomerase inhibition, telomere shortening and breast cancer cell senescence 被引量:1
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作者 Lucy Cassar Craig Nicholls +4 位作者 Alex R. Pinto Ruping Chen Lihui Wang He Li jun-ping liu 《Protein & Cell》 SCIE CAS CSCD 2017年第1期39-54,共16页
Human telomerase reverse transcriptase (hTERT) plays a central role in telomere lengthening for continuous cell proliferation, but it remains unclear how extracellular cues regulate telomerase lengthening of telomer... Human telomerase reverse transcriptase (hTERT) plays a central role in telomere lengthening for continuous cell proliferation, but it remains unclear how extracellular cues regulate telomerase lengthening of telomeres. Here we report that the cytokine bone morphogenetic protein-7 (BMP7) induces the hTERT gene repression in a BMPRII receptor- and Smad3-dependent manner in human breast cancer cells. Chonic exposure of human breast cancer cells to BMP7 results in short telomeres, cell senescence and apoptosis. Mutation of the BMPRII receptor, but not TGFbRII, ACTRIIA or ACTRIIB receptor, inhibits BMP7-induced repression of the hTERT gene promoter activity, leading to increased telomerase activity, lengthened telomeres and continued cell proliferation. Expression of hTERT prevents BMP7-induced breast cancer cell senescence and apoptosis. Thus, our data suggest that BMP7 induces breast cancer cell aging by a mechanism involving BMPRII receptor- and Smad3-mediated repression of the hTERT gene. 展开更多
关键词 BMPRII TGFBETA HTERT telomerase telomeres SENESCENCE breast cancer cells
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Molecular dynamics and principal components of potassium binding with human telomeric intra-molecular G-quadruplex
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作者 Zhiguo Wang Ruping Chen +2 位作者 Ling Hou Jianfeng Li jun-ping liu 《Protein & Cell》 SCIE CAS CSCD 2015年第6期423-433,共11页
Telomere assumes intra-molecular G-quadruplex that is a significant drug target for inhibiting telomerase main- tenance of telomeres in cancer. Metal cations have been recognized as playing important roles in stabiliz... Telomere assumes intra-molecular G-quadruplex that is a significant drug target for inhibiting telomerase main- tenance of telomeres in cancer. Metal cations have been recognized as playing important roles in stabilizing G-quadruplex, but their binding processes to human telomeric G-quadruplex remain uncharacterized. To in- vestigate the detailed binding procedures, molecular dynamics simulations were conducted on the hybrid [3 + 1] form-one human telomeric intra-molecular G-quadruplex. We show here that the binding of a potas- sium ion to a G-tetrad core is mediated by two alternative pathways. Principal component analysis illustrated the dominant concerted motions of G-quadruplex occurred at the loop domains. MM-PBSA calculations revealed that binding was energetically favorable and driven by the electrostatic interactions. The lower binding site was found more constructive favorable for binding. Our data provide useful information on a potassium-mediated stable structure of human telomeric intra-molecular G-quadruplex, implicating in ion disorder associated conformationa| changes and targeted drug design. 展开更多
关键词 G-QUADRUPLEX potassium ion MOLECULARDYNAMICS principal component analysis MM-PBSA
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