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| 1 | Chemical screen identifies a geroprotective role of quercetin in premature aging显示文摘Aging increases the risk of various diseases. The main goal of aging research is to find therapies that attenuate aging and alleviate aging-related diseases. In this study, we screened a natural product library for geroprotective compounds using Werner syndrome (WS) human mesenchymal stem cells (hMSCs), a premature aging model that we recently established. Ten candidate compounds were identified and quercetin was investigated in detail due to its leading effects. Mechanistic studies revealed that quercetin alleviated senescence via the enhancement of cell proliferation and restoration of heterochromatin architecture in WS hMSCs. RNA-sequencing analysis revealed the transcriptional commonalities and differences in the geroprotective effects by quercetin and Vitamin C. Besides WS hMSCs, quercetin also attenuated cellular senescence in Hutchinson-Gilford progeria syndrome (HGPS) and physiological-aging hMSCs. Taken together, our study identifies quercetin as a geroprotective agent against accelerated and natural aging in hMSCs, providing a potential therapeutic intervention for treating age-associated disorders. | Lingling Geng Zunpeng Liu Weiqi Zhang Wei Li Zeming Wu Wei Wang Ruotong Ren Yao Su Peichang Wang Liang Sun Zhenyu Ju Piu Chan Moshi Song Jing Qu Guang-Hui Liu | 2019 | Protein & Cell2019，10，6： | 13 |
| 2 | Low-dose quercetin positively regulates mouse healthspan显示文摘Dear Editor,Aging is the leading risk factor for many chronic diseases,accounting for almost 60%of all deaths worldwide.How to achieve healthy aging,alleviate aging-related diseases,and extend healthspan has become a main topic of biomedical research(He et al.,2019).Geroprotective compounds,such as metformin and rapamycin,have been shown to improve both healthspan and lifespan in mice(Martin-Montalvo et al.,2013;Bitto et al.,2016),whereas nicotinamide partially improves healthspan in mice(Mitchell et al.,2018). | Lingling Geng Zunpeng Liu Si Wang Shuhui Sun Shuai Ma Xiaoqian Liu Piu Chan Liang Sun Moshi Song Weiqi Zhang Guang-Hui Liu Jing Qu | 2019 | Protein & Cell2019，10，10： | 12 |
| 3 | Modeling xeroderma pigmentosum associated neurological pathologies with patients-derived iPSCs显示文摘干皮病 pigmentosum (XP ) 是联系 XP 的基因的变化引起的一组基因混乱,导致 DNA 修理的缺陷。XP 病人经常展出神经病学的退化,而是内在的机制是未知的,部分地由于合适的疾病模型的缺乏。这里,我们产生了包括 XPA, XPB, XPC, XPG,和 XPV 在五不同 XP 基因怀有变化的病人特定的导致的 pluripotent 干细胞(iPSCs ) 。这些 iPSCs 进一步被区分到神经房间,并且他们到 DNA 损坏应力的危险性被调查。在神经干细胞(NSC ) 或神经原的 XPA 的变化导致了严重 DNA 损坏修理缺点,并且有变异的 XPA 的这些神经房间对 DNA 导致损坏的 apoptosis 过分敏感。因此, XP 变异的神经房间代表珍贵工具在 XP 病人澄清神经病学的畸形的分子的机制。 | Lina Fu Xiuling Xu Ruotong Ren Jun Wu Weiqi Zhang Jiping Yang Xiaoqing Ren Si Wang Yang Zhao Liang Sun Yang Yu Zhaoxia Wang Ze Yang Yun Yuan Jie Qiao Juan Carlos Izpisua Belmonte Jing Qu Guang-Hui Liu | 2016 | Protein & Cell2016，7，3： | 11 |
| 4 | Single-cell transcriptomic atlas of primate cardiopulmonary aging显示文摘Aging is a major risk factor for many diseases,especially in highly prevalent cardiopulmonary comorbidities and infectious diseases including Coronavirus Disease 2019(COVID-19).Resolving cellular and molecular mechanisms associated with aging in higher mammals is therefore urgently needed.Here,we created young and old non-human primate single-nucleus/cell transcriptomic atlases of lung,heart and artery,the top tissues targeted by SARS-CoV-2.Analysis of cell type-specific aging-associated transcriptional changes revealed increased systemic inflammation and compromised virus defense as a hallmark of cardiopulmonary aging.With age,expression of the SARS-CoV-2 receptor angiotensin-converting enzyme 2(ACE2)was increased in the pulmonary alveolar epithelial barrier,cardiomyocytes,and vascular endothelial cells.We found that interleukin 7(IL7)accumulated in aged cardiopulmonary tissues and induced ACE2 expression in human vascular endothelial cells in an NF-κB-dependent manner.Furthermore,treatment with vitamin C blocked IL7-induced ACE2 expression.Altogether,our findings depict the first transcriptomic atlas of the aged primate cardiopulmonary system and provide vital insights into age-linked susceptibility to SARS-CoV-2,suggesting that geroprotective strategies may reduce COVID-19 severity in the elderly. | Shuai Ma Shuhui Sun Jiaming Li Yanling Fan Jing Qu Liang Sun Si Wang Yiyuan Zhang Shanshan Yang Zunpeng Liu Zeming Wu Sheng Zhang Qiaoran Wang Aihua Zheng Shuguang Duo Yang Yu Juan Carlos Izpisua Belmonte Piu Chan Qi Zhou Moshi Song Weiqi Zhang Guang-Hui Liu | 2021 | Cell Research2021，31，4： | 10 |
| 5 | Vitamin C alleviates aging defects in a stem cell model for Werner syndrome显示文摘沃纳症候群(WS ) 是主要影响从中层导出的纸巾的早衰混乱。我们最近用 WRN 缺乏的人的间充质的干细胞(MSC ) 开发了一个新奇人的 WS 模型。这个模型概括 WS 的许多 phenotypic 特征。基于很多化学药品的一幅屏幕,这里,我们发现维生素 C 在出现在WRN缺乏的 MSC 的早衰为许多特征施加很有效的营救包括细胞生长拘捕,增加了反应的氧种层次, telomere 摩擦,煽动性的因素的过多的分泌物,象原子薄板和 heterochromatin 的组织的破坏一样。而且,维生素 C 在一个老鼠模型在 vivo 恢复 MSC 的生存能力。定序分析的 RNA 显示维生素 C 改变涉及染色质冷凝作用,房间周期规定, DNA 复制,和 DNA 损坏的一系列基因的表示在 WRN 缺乏的 MSC 的修理小径。我们的结果为 WS MSC 作为一个恢复因素识别维生素 C,它保持作为 WS 的处理的一种新奇类型被使用的潜力。 | Ying Li Weizhou Zhang Liang Chang Yan Han Liang Sun Xiaojun Gong Hong Tang Zunpeng Liu Huichao Deng Yanxia Ye Yu Wang Jian Li Jie Qiao Jing Qu Weiqi Zhang Guang-Hui Liu | 2016 | Protein & Cell2016，7，7： | 10 |
| 6 | Stabilization of heterochromatin by CLOCK promotes stem cell rejuvenation and cartilage regeneration显示文摘Accumulating evidence indicates an association between the circadian clock and the aging process.However,it remains elusive whether the deregulation of circadian clock proteins underlies stem cell aging and whether they are targetable for the alleviation of aging-associated syndromes.Here,we identified a transcription factor-independent role of CLOCK,a core component of the molecular circadian clock machinery,in counteracting human mesenchymal stem cell(hMSC)decay.CLOCK expression was decreased during hMSC aging.In addition,CLOCK deficiency accelerated hMSC senescence,whereas the overexpression of CLOCK,even as a transcriptionally inactive form,rejuvenated physiologically and pathologically aged hMSCs.Mechanistic studies revealed that CLOCK formed complexes with nuclear lamina proteins and KAP1,thus maintaining heterochromatin architecture and stabilizing repetitive genomic sequences.Finally,gene therapy with lentiviral vectors encoding CLOCK promoted cartilage regeneration and attenuated age-related articular degeneration in mice.These findings demonstrate a noncanonical role of CLOCK in stabilizing heterochromatin,promoting tissue regeneration,and mitigating aging-associated chronic diseases. | Chuqian Liang Zunpeng Liu Moshi Song Wei Li Zeming Wu Zehua Wang Qiaoran Wang Si Wang Kaowen Yan Liang Sun Tomoaki Hishida Yanning Cai Juan Carlos lzpisua Belmonte Pedro Guillen Piu Chan Qi Zhou Weiqi Zhang Jing Qu Guang-Hui Liu | 2021 | Cell Research2021，31，2： | 8 |
| 7 | CRISPR/Cas9-mediated gene knockout reveals a guardian role of NF-κB/RelA in maintaining the homeostasis of human vascular cells显示文摘 | Ping Wang Zunpeng Liu Xiaoqian Zhang Jingyi Li Liang Sun Zhenyu Ju Jian Li Piu Chan Guang-Hui Liu Weiqi Zhang Moshi Song Jing Qu | 2018 | Protein & Cell2018，9，11： | 8 |
| 8 | Modeling CADASIL vascular pathologies with patient-derived induced pluripotent stem cells显示文摘Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy(CADASIL)is a rare hereditary cerebrovascular disease caused by a NOTCH3 mutation.However,the underlying cellular and molecular mechanisms remain unidentified.Here,we generated non-integrative induced pluripotent stem cells(iPSCs)from fibroblasts of a CADASIL patient harboring a heterozygous NOTCH3 mutation(c.3226C>T,p.R1076C).Vascular smooth muscle cells(VSMCs)differentiated from CADASIL-specific iPSCs showed gene expression changes associated with disease phenotypes,including activation of the NOTCH and NF-kB signaling pathway,cytoskeleton disorganization,and excessive cell proliferation.In comparison,these abnormalities were not observed in vascular endothelial cells(VECs)derived from the patients iPSCs.Importantly,the abnormal upregulation of NF-kB target genes in CADASIL VSMCs was diminished by a NOTCH pathway inhibitor,providing a potential therapeutic strategy for CADASIL.Overall,using this iPSCbased disease model,our study identified clues for studying the pathogenic mechanisms of CADASIL and developing treatment strategies for this disease. | Chen Ling Zunpeng Liu Moshi Song Weiqi Zhang Si Wang Xiaoqian Liu Shuai Ma Shuhui Sun Lina Fu Qun Chu Juan Carlos Izpisua Belmonte Zhaoxia Wang Jing Qu Yun Yuan Guang-Hui Liu | 2019 | Protein & Cell2019，10，4： | 7 |
| 9 | Telomere-dependent and telomereindependent roles of RAP1 in regulating human stem cell homeostasis显示文摘RAP1 is a well-known telomere-binding protein, but its functions in human stem cells have remained unclea匚 Here we generated RAP1 -deficient human embryonic stem cells (hESCs) by using CRISPR/Cas9 technique and obtained RAP1-deficient human mesenchymal stem cells (hMSCs) and neural stem cells (hNSCs) via directed differentiation. In both hMSCs and hNSCs, RAP1 not only negatively regulated telomere length but also acted as a transcriptional regulator of RELN by tuning the methylation status of its gene promoter. RAP1 deficiency enhanced self-renewal and delayed senescence in hMSCs, but not in hNSCs, suggesting complicated lineage-specific effects of RAP1 in adult stem cells.Altogether, these results demonstrate for the first time that RAP1 plays both telomeric and nontelomeric roles in regulating human stem cell homeostasis. | Xing Zhang Zunpeng Liu Xiaoqian Liu Si Wang Yiyuan Zhang Xiaojuan He Shuhui Sun Shuai Ma Ng Shyh-Chang Feng Liu Qiang Wang Xiaoqun Wang Lin Liu Weiqi Zhang Moshi Song Guang-Hui Liu Jing Qu | 2019 | Protein & Cell2019，10，9： | 7 |
| 10 | Novel fabrication of copper nanowire/cuprous oxidebased semiconductor-liquid junction solar cells显示文摘Cu nanowire (NW )/cuprous 氧化物(Cu 2 O ) 有极大地提高的效率和减少的费用的基于的半导体液体连接太阳能电池被装配。Cu NW 象 Cu NWs/ Cu 2 O 同轴的结构,它显著地有益于费用分离。最好的太阳能电池在模仿的 AM1.5G 照明下面象 1.92% 一样高到达了变换效率,它基于做氟的符号的听氧化物和 Cu 2 O。 | Haitao Zhai Ranran Wang Weiqi Wang Xiao Wang Yin Cheng Liangjing Shi Yangqiao Liu Jing Sun | 2015 | Nano Research2015，8，10： | 6 |
| 11 | High-performance asymmetric electrodes photodiode based on Sb/WSe2 heterostructure显示文摘Two-dimensional (2D) van der Waals (vdWs) metal-semiconductor heterostructures with atomically sharp interface and matched work functions have recently attracted great attention due to their unique electronic and optoelectronic properties. Here we report the vapor phase epitaxial growth of large-scale vertical Sb/WSe2 metal-semiconductor vdWs heterostructures with uniform stacking orientation. Compared with the growth on S1O2/S1 substrate, the thick ness of Sb nan osheet on WSe2 can be reduced effectively to mono layer. We con struct Sb-WSe2-Au asymmetric electrodes photodiode based on the Sb/WSe2 heterostructures. Electrical transport measurements indicate that the photodiode show obvious rectifying effect. Optoelectronic characterizations show prominent photoresponse with a high photoresposivity of 364 mA/W, a fast response time of less than 8 ms, a large open-circuit voltage of 0.27 V and a maximum electrical power output of 0.11 nW. The direct growth of high-quality metal-semiconductor vdWs heterostructures may open up new realms in 2D functional electronics and optoelectronics. | Xiao Liu Guangzhuang Sun Peng Chen Junchi Liu Zhengwei Zhang Jia Li Huifang Ma Bei Zhao Ruixia Wu Weiqi Dang Xiangdong Yang Chen Dai Xuwan Tang Zhuojun Chen Lili Miao Xingqiang Liu Bo Li Yuan Liu Xidong Duan | 2019 | Nano Research2019，12，2： | 5 |
| 12 | Single-nucleus transcriptomic landscape of primate hippocampal aging显示文摘The hippocampus plays a crucial role in learning and memory,and its progressive deterioration with age is functionally linked to a variety of human neurodegenerative diseases.Yet a systematic profiling of the aging effects on various hippocampal cell types in primates is still missing.Here,we reported a variety of new aging-associated phenotypic changes of the primate hippocampus.These include,in particular,increased DNA damage and heterochromatin erosion with time,alongside loss of proteostasis and elevated inflammation.To understand their cellular and molecular causes,we established the first single-nucleus transcriptomic atlas of primate hippocampal aging.Among the 12 identified cell types,neural transiently amplifying progenitor cell(TAPC)and microglia were most affected by aging.In-depth dissection of gene-expression dynamics revealed impaired TAPC division and compromised neuronal function along the neurogenesis trajectory;additionally elevated pro-inflammatory responses in the aged microglia and oligodendrocyte,as well as dysregulated coagulation pathways in the aged endothelial cells may contribute to a hostile microenvironment for neurogenesis.This rich resource for understanding primate hippocampal aging may provide potential diagnostic biomarkers and therapeutic interventions against age-related neurodegenerative diseases. | Hui Zhang Jiaming Li Jie Ren Shuhui Sun Shuai Ma Weiqi Zhang Yang Yu Yusheng Cai Kaowen Yan Wei Li Baoyang Hu Piu Chan Guo-Guang Zhao Juan Carlos Izpisua Belmonte Qi Zhou Jing Qu Si Wang Guang-Hui Liu | 2021 | Protein & Cell2021，12，9： | 5 |
| 13 | Fermentation characteristics and probiotic activity of a purified fraction of polysaccharides from Fuzhuan brick tea显示文摘Polysaccharides from Fuzhuan brick tea(FBTPS),one of most important bioactive components in tea,showed various health-promoting functions.Our previous work demonstrated that the crude FBTPS(CFBTPS)could modulate the gut microbiota.However,which purified fraction in CFBTPS contributing to the modulation of gut microbiota remains unclear.Thus,the fermentation characteristics and probiotic activity of a purified fraction(FBTPS-2-1)of CFBTPS were evaluated in this work.The results showed that gut microbiota could utilize FBTPS-2-1 to produce short-chain fatty acids including acetic,propionic,n-butyric and n-valeric acids.FBTPS-2-1 could modulate the structure and metabolic pathways of gut microbiota.FBTPS-2-1 could increase the health-promoting gut microbiota such as Prevotellaceae and Bifidobacteriaceae,and decreased the harmful bacteria such as Enterobacteriaceae and Fusobacteriaceae.The results of metagenomics showed that Prevotella copri and Megamonas funiformis were the dominant bacteria after fermentation of FBTPS-2-1.Furthermore,FBTPS-2-1 could regulate the biosynthesis and metabolism pathways of gut microbiota.Thus,the enrichment of food with FBTPS-2-1 is expected as a potential strategy for promoting human health due to modulation of gut microbiota. | Guijie Chen Ziqi Zeng Minhao Xie Yujia Peng Wangting Zhou Weiqi Xu Yi Sun Xiaoxiong Zeng Zhonghua Liu | 2022 | Food Science and Human Wellness2022，11，3： | 4 |
| 14 | The landscape of aging显示文摘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. | Yusheng Cai Wei Song 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 | 2022 | Science China(Life Sciences)2022，65，12： | 4 |
| 15 | Visualization of aging-associated chromatin alterations with an engineered TALE system显示文摘在实时房间的特定的 genomic loci 的可视化在多样的生物过程期间是为在染色质建筑学的动态变化的调查的一个前提,例如细胞的老化。然而,当前的精确 genomic 成像方法被缺乏妨碍荧光灯有高特性和 signal-to-noise 的探针形成对照。我们发现那常规抄写像使活跃之物的受动器(故事) 趋于形成蛋白质总数,从而在成像应用程序损害他们的性能。通过屏蔽,我们发现有故事的那熔化 thioredoxin 阻止了总数形成,开基于故事的 genomic 成像的完整的力量。用熔化 thioredoxin 的故事(TTALE ) ,我们在各种各样的 genomic loci 完成了高质量的成像并且观察联系老化(epi ) 在在人和老鼠早衰模型的 telomeres 和着丝点的 genomic 改变。重要地,我们鉴别 ribosomal DNA 的摩擦为人的老化作为一个分子的标记重复。我们的学习为精确在 vitro 并且在 vivo 监视染色质动力学建立一个简单、柔韧的成像方法。 | Ruotong Ren Liping Deng Yanhong Xue Keiichiro Suzuki Weiqi Zhang Yang Yu Jun Wu Liang Sun Xiaojun Gong Huiqin Luan Fan Yang Zhenyu Ju Xiaoqing Ren Si Wang Hong Tang Lingling Geng Weizhou Zhang Jian Li Jie Qiao Tao Xu Jing Qu Guang-Hui Liu | 2017 | Cell Research2017，27，4： | 4 |
| 16 | Deciphering primate retinal aging at single-cell resolution显示文摘Dear Editor, The retina is a light-sensitive highly-organized tissue,which is vulnerable to aging and age-related retinal diseases.Specifically,progressive retinal degeneration leads to visual function deterioration and vision impairment in the elderly(Lin et al.,2016).In diseases such as age-related macular degeneration(AMD),retinitis pigmentosa(RP)and diabetic retinopathy(DR),pathological process lacking effective treatments profoundly and negatively impact on the quality of life in the elderly(Lin et al.,2016;Chen et al.,2019).Thus,an in-depth molecular assessment of the mechanisms driv-ing retinal aging is of urgent scientific and medical importance. | Si Wang Yuxuan Zheng Qingqing Li Xiaojuan He Ruotong Ren Weiqi Zhang Moshi Song Huifang Hu Feifei Liu Guoqiang Sun Shuhui Sun Zunpeng Liu Yang Yu Piu Chan Guo-Guang Zhao Qi Zhou Guang-Hui Liu Fuchou Tang Jing Qu | 2021 | Protein & Cell2021，12，11： | 4 |
| 17 | m6A RNA methylation-mediated HNF3γreduction renders hepatocellular carcinoma dedifferentiation and sorafenib resistance显示文摘Hepatocyte nuclear factor 3γ(HNF3γ)is a hepatocyte nuclear factor,but its role and clinical significance in hepatocellular carcinoma(HCC)remain unclear.Herein,we report that HNF3γexpression is downregulated in patient HCC and inversely correlated with HCC malignancy and patient survival.Moreover,our data suggested that the HNF3γreduction in HCC could be mediated by METTL14-dependent m6A methylation of HNF3γmRNA.HNF3γexpression was increased during hepatic differentiation and decreased in dedifferentiated HCC cells.Interestingly,HNF3γdelivery promoted differentiation of not only HCC cells but also liver CSCs,which led to suppression of HCC growth.Mechanistic analysis suggested an HNF3γ-centered regulatory network that includes essential liver differentiation-associated transcription factors and functional molecules,which could synergistically facilitate HCC cell differentiation.More importantly,enforced HNF3γexpression sensitized HCC cells to sorafenib-induced growth inhibition and cell apoptosis through transactivation of OATP1B1 and OATP1B3 expression,which are major membrane transporters for sorafenib uptake.Clinical investigation showed that patient-derived HCC xenografts with high HNF3γexpression exhibited a sorafenib response and patients with high HCC HNF3γlevels benefited from sorafenib therapy.Together,these results suggest that HNF3γplays an essential role in HCC differentiation and may serve as a therapeutic target and predictor of sorafenib benefit in patients. | Tengfei Zhou Shichao Li Daimin Xiang Junyu Liu Wen Sun Xiuliang Cui Beifang Ning Xiao Li Zhuo Cheng Weiqi Jiang Cheng Zhang Xijun Liang Liang Li Xin Cheng Liu Hui Hongyang Wang Jin Ding | 2020 | Signal Transduction and Targeted Therapy2020，5，1： | 4 |
| 18 | Aerosol-assisted submicronγ-Fe2O3/C spheres as a promising heterogeneous Fenton-like catalyst for soil and groundwater remediation:Transport,adsorption and catalytic ability显示文摘This research reports a novel heterogeneous Fenton-like catalyst which could freely move through the model sediments and easily seize the pollutants in addition to efficiently catalyze H2O2,well suitable for soil and groundwater remediation.Herein,submicron y-Fe2O3/C spheres were synthesized through a facile one-step aerosol-based process.In a series of column tests,these spheres exhibit better transport ability due to their optimal size,conforming to the prediction by the Tufenkji-Elimelech filtration theo ry.Meanwhile,y-Fe2O3/C spheres could act as a strong adsorbent for organic pollutants owing to the presence of carbon,thereby providing a driving force to gather contaminants into their vicinity and facilitating the reaction.In addition,immobilization of y-Fe2O3 nanoparticles into carbon spheres protects iron oxides from aggregation,and thus retains the number of active sites for catalytic decomposition of H2O2.Hence,the system containing the as-prepared y-Fe2O3/C spheres and H2O2 shows the high removal efficiency and degradation efficiency in the remediation of recalcitrant organic contaminants such as methylene blue and sulfamethoxazole. | Jingjing Zhan Mingfei Li Xiujuan Zhang Yu An Weiqi Sun Aixia Peng Hao Zhou | 2020 | Chinese Chemical Letters2020，31，3： | 3 |
| 19 | A single-cell transcriptomic atlas of primate pancreatic islet aging显示文摘Aging-related degeneration of pancreatic islet cells contributes to impaired glucose tolerance and diabetes.Endocrine cells age heterogeneously,complicating the efforts to unravel the molecular drivers underlying endocrine aging.To overcome these obstacles,we undertook single-cell RNA sequencing of pancreatic islet cells obtained from young and aged non-diabetic cynomolgus monkeys.Despite sex differences and increased transcriptional variations,agedβ-cells showed increased unfolded protein response(UPR)along with the accumulation of protein aggregates.We observed transcriptomic dysregulation of UPR components linked to canonical ATF6 and IRE1 signaling pathways,comprising adaptive UPR during pancreatic aging.Notably,we found aging-relatedβ-cell-specific upregulation of HSP90 B1,an endoplasmic reticulum-located chaperone,impeded high glucose-induced insulin secretion.Our work decodes aging-associated transcriptomic changes that underlie pancreatic islet functional decay at single-cell resolution and indicates that targeting UPR components may prevent loss of proteostasis,suggesting an avenue to delayingβ-cell aging and preventing aging-related diabetes. | Jingyi Li Yuxuan Zheng Pengze Yan Moshi Song Si Wang Liang Sun Zunpeng Liu Shuai Ma Juan Carlos Izpisua Belmonte Piu Chan Qi Zhou Weiqi Zhang Guang-Hui Liu Fuchou Tang Jing Qu | 2021 | National Science Review2021，8，2： | 3 |
| 20 | Crystal fractionation of granitic magma during its non-transport processes: A physics-based perspective显示文摘Granitic continental crust distinguishes the Earth from other planets in the Solar System. Consequently, for understanding terrestrial continent development, it is of great significance to investigate the formation and evolution of granite.Crystal fractionation is one of principal magma evolution mechanisms. Nevertheless, it is controversial whether crystal fractionation can effectively proceed in felsic magma systems because of the high viscosity and non-Newtonian behavior associated with granitic magmas. In this paper, we focus on the physical processes and evaluate the role of crystal fractionation in the evolution of granitic magmas during non-transport processes, i.e., in magma chambers and after emplacement. Based on physical calculations and analyses, we suggest that general mineral particles can settle only at tiny speed(~10^(-9)–10^(-7) m s^(-1))in a granitic magma body due to high viscosity of the magma; however, the cumulating can be interrupted with convection in magma chambers, and the components of magma chambers will tend to be homogeneous. Magma convection ceases once the magma chamber develops into a mush(crystallinity, F>~40–50%). The interstitial melts can be extracted by hindered settling and compaction, accumulating gradually and forming a highly silicic melt layer. The high silica melts can further evolve into high-silica granite or high-silica rhyolite. At various crystallinities, multiple rejuvenation of the mush and the following magma intrusion may generate a granite complex with various components. While one special type of granites, represented by the South China lithium-and fluoride-rich granite, has lower viscosity and solidus relative to general granitic magmas, and may form vertical zonation in mineral-assemblage and composition through crystal fractionation. Similar fabrics in general intrusions that show various components on small lengthscales are not the result of gravitational settling. Rather, the flowage differentiation may play a key role. In general, granitic magma can undergo effective crystal fractionation; high-silica granite and volcanics with highly fractionated characteristics may be the products of crystal fractionation of felsic magmas, and many granitoids may be cumulates. | CHEN Chen DING Xing LI Rui ZHANG WeiQi OUYANG DongJian YANG Lei SUN WeiDong | 2018 | Science China Earth Sciences2018，61，2： | 3 |
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