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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 | Cryptotanshinone suppresses key onco-proliferative and drugresistant pathways of chronic myeloid leukemia by targeting STAT5 and STAT3 phosphorylation显示文摘C-Myc and signal transducer and activator of transcription(STAT) family proteins have been proposed to be important downstream genes of BCR-ABL, which characterizes most cases of chronic myeloid leukemia(CML). Here, we report a c-Myc pathway-targeted screening of seven natural anticancer compounds, in which we identified cryptotanshinone as a highly promising agent for CML therapy. Cryptotanshinone depletes c-Myc in CML by repressing the phosphorylation of STAT5.Decreased viability of K562 cells correlated with p-STAT5 suppression. Unexpectedly, imatinib activates rather than inhibits the phosphorylation of STAT3 in K562 cells. We demonstrated that cryptotanshinone, as a dual inhibitor of p-STAT5 and p-STAT3,can effectively block IL-6-mediated STAT3 activation and reverse BCR-ABL kinase-independent drug resistance. Moreover, we showed that the epigenetic rebalance between decreased BCR-ABL/STAT5/c-Myc and enhanced STAT3/multi-drug resistance(MDR) pathways is characteristic of the cancer stem cell-like property of K562/ADR. Simultaneously suppressing these two pathways using cryptotanshinone proves to be critical for the malignant network redress and MDR reversal of K562/ADR. These studies reveal the dual functions of cryptotanshinone that suppress key oncogenic proliferation and drug-resistant pathways in CML cells by targeting p-STAT5 and p-STAT3, providing a new strategy for CML therapy that takes advantage of natural products. | Bowen Dong Zirui Liang Zhirong Chen Bin Li Lingling Zheng Jianhua Yang Hui Zhou Lianghu Qu | 2018 | Science China(Life Sciences)2018，61，9： | 10 |
| 4 | Correlation analysis of Treg/Th17 cells and related cytokines in patients with psoriasis vulgaris显示文摘OBJECTIVE: To investigate potential differences in circulating levels of T regulatory (Treg)/T helper 17 (Th17) cells, related inflammatory cytokines and specific transcription factors in healthy individuals and patients with psoriasis conforming to one of three Traditional Chinese Medicine (TCM) syndromes: blood-heat syndrome (BHS), blood-stasis syndrome (BSS) and blood-dryness syndrome (BDS). METHODS: Sixty-seven patients with psoriasis were recruited and assigned to one of three corresponding TCM syndrome groups: BHS (n = 40), BSS (n = 14) and BDS (n = 13 patients). The control group comprised 21 healthy individuals. The circulating levels of Treg/Th17 cells in peripheral blood were assessed using flow cytometry;the levels of inflammatory cytokines interleukin (IL)-10 and tumor necrosis factor (TNF)-α by enzyme-linked immunosorbent assay;and the mRNA expression of T cell-specific transcription factors retinoic acid-related orphan receptor γt (RORγt) and forkhead box P3 (Foxp3) by quantitative real-time PCR. RESULTS: The ratio of Th17 cells and the levels of TNF-α and RORγt were all significantly higher in the BHS and BSS groups than the control group (P < 0.05), while the ratio of Treg cells and the levels of IL-10 and Foxp3 mRNA in the BHS group were significantly lower compared with the control group (P < 0.05). No significant differences were seen between the BSS group and the control group. The ratio of Th17 cells and the levels of TNF-α and RORγt in the BDS group were not significantly different from those of the control group;however, the ratio of Treg cells and the levels of IL-10 and Foxp3 were all lower than those in the healthy controls (P < 0.05). CONCLUSION: Compared with healthy individuals, the ratio of Th17 cells and the levels of related cytokines were higher, while the ratio of Treg cells and the levels of related cytokines were lower, in the peripheral blood of psoriasis/BHS patients;corresponding results for the BSS and BDS groups also showed differences. We propose that patterns of differentiation of immunological cells in psoriasis patients are reflected in corresponding TCM blood syndromes. | Qu Tiange Mei Chencheng Zeng Yajun Li Lingling Duan Xingwu | 2019 | Journal of Traditional Chinese Medicine2019，39，5： | 8 |
| 5 | Clinical study using mesenchymal stem cells for the treatment of patients with severe COVID-19显示文摘The coronavirus disease 2019(COVID-19)caused by SARS-CoV-2 was identified in December 2019.The symptoms include fever,cough,dyspnea,early symptom of sputum,and acute respiratory distress syndrome(ARDS).Mesenchymal stem cell(MSC)therapy is the immediate treatment used for patients with severe cases of COVID-19.Herein,we describe two confirmed cases of COVID-19 in Wuhan to explore the role of MSC in the treatment of COVID-19.MSC transplantation increases the immune indicators(including CD4 and lymphocytes)and decreases the inflammation indicators(interleukin-6 and C-reactive protein).High-flow nasal cannula can be used as an initial support strategy for patients with ARDS.With MSC transplantation,the fracrion of inspired O2(Fi02)of the two patients gradually decreased while the oxygen saturation(Sa02)and partial pressure of oxygen(P02)improved.Additionally,the patients9 chest computed tomography showed that bilateral lung exudate lesions were adsorbed after MSC infusion.Results indicated that MSC transplantation provides clinical data on the treatment of COVID-19 and may serve as an alternative method for treating COVID-19,particularly in patients with ARDS. | Lingling Tang Yingan Jiang Mengfei Zhu Lijun Chen Xiaoyang Zhou Chenliang Zhou Peng Ye Xiaobei Chen Baohong Wang Zhenyu Xu Qiang Zhang Xiaowei Xu Hainv Gao Xiaojun Wu Dong Li Wanli Jiang Jingjing Qu Charlie Xiang Lanjuan Li | 2020 | Frontiers of Medicine2020，14，5： | 8 |
| 6 | Rescue of premature aging defects in Cockayne syndrome stem cells by CRISPR/Cas9-mediated gene correction显示文摘Cockayne syndrome(CS)is a rare autosomal recessive inherited disorder characterized by a variety of clinical features,including increased sensitivity to sunlight,progressive neurological abnormalities,and the appearance of premature aging.However,the pathogenesis of CS remains unclear due to the limitations of current disease models.Here,we generate integration-free induced pluripotent stem cells(iPSCs)from fibroblasts from a CS patient bearing mutations in CSB/ERCC6 gene and further derive isogenic genecorrected CS-iPSCs(GC-iPSCs)using the CRISPR/Cas9 system.CS-associated phenotypic defects are recapitulated in CS-iPSC-derived mesenchymal stem cells(MSCs)and neural stem cells(NSCs),both of which display increased susceptibility to DNA damage stress.Premature aging defects in CS-MSCs are rescued by the targeted correction of mutant ERCC6.We next map the transcriptomic landscapes in CS-iPSCs and GC-iPSCs and their somatic stem cell derivatives(MSCs and NSCs)in the absence or presence of ultraviolet(UV)and replicative stresses,revealing that defects in DNA repair account for CS pathologies.Moreover,we generate autologous GC-MSCs free of pathogenic mutation under a cGMP(Current Good Manufacturing Practice)-compliant condition,which hold potential for use as improved biomaterials for future stem cell replacement therapy for CS.Collectively,our models demonstrate novel disease features and molecular mechanisms and lay a foundation for the development of novel therapeutic strategies to treat CS. | Si Wang Zheying Min Qianzhao Ji Lingling Geng Yao Su Zunpeng Liu Huifang Hu Lixia Wang Weiqi Zhang Keiichiro Suzuiki Yu Huang Puyao Zhang Tie-Shan Tang Jing Qu Yang Yu Guang-Hui Liu Jie Qiao | 2020 | Protein & Cell2020，11，1： | 7 |
| 7 | Computational RNomics:Structure identification and functional prediction of non-coding RNAs in silico显示文摘The eukaryotic genome contains varying numbers of non-coding RNA(ncRNA) genes.'Computational RNomics' takes a multidisciplinary approach,like information science,to resolve the structure and function of ncRNAs.Here,we review the main issues in 'Computational RNomics' of data storage and management,ncRNA gene identification and characterization,ncRNA target identification and functional prediction,and we summarize the main methods and current content of 'computational RNomics'. | ZHENG LingLing & QU LiangHu Key Laboratory of Gene Engineering of the Ministry of Education,State Key Laboratory for Biocontrol,Sun Yat-sen University,Guangzhou 510275,China | 2010 | Science China(Life Sciences)2010，53，5： | 7 |
| 8 | 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 |
| 9 | TiO2/EDTA-rich carbon composites: Synthesis, characterization and visible-light-driven photocatalytic reduction of Cr(Ⅵ)显示文摘Ti02/EDTA-rich carbon composites(TiO_2/EDTA-RC) have been successfully synthesized via a low temperature carbonization process. TiO_2/EDTA-RC exhibits marked absorption of visible light and excellent photoreduction of Cr(Ⅵ) activity under visible light irradiation(λ>420 nm). Due to the high carboxyl group content and strong coordination ability of EDTA, TiO_2-EDTA complex can be easily fabricated between EDTA incorporated in carbon sheet and titanol group on the surface of TiO_2. TiO_2-EDTA complexes on the surface of TiO_2/EDTA-RC, the LMCT complex, are responsible for the prominent photoreduction of Cr(Ⅵ) properties of Ti02/EDTA-RC under visible light irradiation. In addition, the unique structure ofTiO_2/EDTA-RC is also propitious to the visible-light photocatalytic reduction of Cr(Ⅵ).Carbon sheet of TiO_2/EDTA-RC acts as a supporter. TiO_2 nanoparticles and EDTA homogeneously disperse into the carbon sheet supporter and form the TiO_2-EDTA complexes, which can avoid the aggregation of TiO_2 nanoparticles in the aqueous solution and provide more photocatalytic reaction points for the reduction of Cr(Ⅵ). | Zhijun Luo Lingling Qu Jianzhong Ji Jing wang Suying Jiang Zhiren WU Xiangyang Wu | 2018 | Chinese Chemical Letters2018，29，3： | 3 |
| 10 | Review on observational studies of western tropical Pacific Ocean circulation and climate显示文摘The Western Tropical Pacific(WTP) Ocean holds the largest area of warm water(>28℃) in the world ocean referred to as the Western Pacific Warm Pool(WPWP),which modulates the regional and global climate through strong atmospheric convection and its variability.The WTP is unique in terms of its complex 3-D ocean circulation system and intensive multiscale variability,making it crucial in the water and energy cycle of the global ocean.Great advances have been made in understanding the complexity of the WTP ocean circulation and associated climate impact by the international scientific community since the 1960 s through field experiments.In this study,we review the evolving insight to the 3-D structure and multi-scale variability of the ocean circulation in the WTP and their climatic impacts based on in-situ ocean observations in the past decades,with emphasis on the achievements since 2000.The challenges and open que stions remaining are reviewed as well as future plan for international study of the WTP ocean circulation and climate. | HU Dunxin WANG Fan SPRINTALL Janet WU Lixin RISER Stephen CRAVATTE Sophie GORDON Arnold ZHANG Linlin CHEN Dake ZHOU Hui ANDO Kentaro WANG Jianing LEE Jae-Hak HU Shijian WANG Jing ZHANG Dongxiao FENG Junqiao LIU Lingling VILLANOY Cesar KALUWIN Chalapan QU Tangdong MA Yixin | 2020 | Journal of Oceanology and Limnology2020，38，4： | 3 |
| 11 | Dramatic reduction of liver cancer incidence in young adults: 28 year follow-up of etiological interventions in an endemic area of China显示文摘 | Zongtang Sun Taoyang Chen Snorri S. Thorgeirsson Qimin Zhan Jianguo Chen Ju-Hyun Park Peixin Lu Chu Chieh Hsia Nengjin Wang Libin Xu Lingling Lu Fei Huang Yuanrong Zhu Jianhua Lu Zhengping Ni Qinan Zhang Yuying Wu Guoting Liu Zhiyuan Wu Chunfeng Qu Mitche | 2013 | Carcinogenesis2013，，8： | 1 |
| 12 | Preparation of I- ren-Tungsten-Boron Ally Depositby Electroless Plating 显示文摘 | Yi Ge Wang Lingling Qu yang | 1996 | Metal Finishing1996，，11： | 1 |
| 13 | Structure formation on the surface of alloys irradiated by femtosecond laser pulses显示文摘 | Lingling Ran Shiliang Qu | 2010 | Appl Surface Sci2010，256，8： | 1 |
| 14 | Different cellular effects of four anti-inflammatory eye drops on human corneal epithelial cells:independent in active components显示文摘 | Mingli Qu Yao Wang Lingling Yang | 2011 | Molecular Vision2011，17，： | 1 |
| 15 | Self-organized periodic surface structures on ZnO induced by femtosecond laser 显示文摘 | Lingling Ran Zhongyi Guo Shiliang Qu | 2010 | Appl Phys A2010，100，2： | 1 |
| 16 | Near-infrared chemiluminescent carbon nanogels for oncology imaging and therapy显示文摘Carbon nanogels(CNGs)with dual ability of reactive oxygen species(ROS)imaging and photodynamic therapy have been designed with selfassembled chemiluminescent carbonized polymer dots(CPDs).With efficient deep-red/near-infrared chemiluminescence(CL)emission and distinctive photodynamic capacity,the H2O2-driven chemiluminescent CNGs are further designed by assembling the polymeric conjugate and CL donors,enabling an in vitro and in vivo ROS bioimaging capability in animal inflammation models and a high-performance therapy for xenograft tumors.Mechanistically,ROS generated in inflammatory sites or tumor microenvironment can trigger the chemically initiated electron exchange luminescence in the chemical reaction of peroxalate and H2O2,enabling in vivo CL imaging.Meanwhile,part of the excited-state electrons will transfer to the ambient H2O or dissolved oxygen and in turn lead to the type I and type II photochemical ROS production of hydroxyl radicals or singlet oxygen,endowing the apoptosis of tumor cells and thus enabling cancer therapy.These results open up a new avenue for the design of multifunctional nanomaterials for bioimaging and antienoplastic agents. | Chenglong Shen Tianci Jiang Qing Lou Wenbo Zhao Chaofan Lv Guangsong Zheng Hangrui Liu Pengfei Li Lingling Dai Kaikai Liu Jinhao Zang Feng Wang Lin Dong Songnan Qu Zhe Cheng Chongxin Shan | 2022 | SmartMat2022，3，2： | 1 |
| 17 | Efficient large fragment deletion in plants:double pairs of sgRNAs are better than dual sgRNAs显示文摘Dear Editor,Clustered Regularly Interspaced Short Palindromic Repeats(CRISPR)is a powerful and versatile gene editing system that has been extensively utilized in various animals and plants,which holds enormous potential and value for scientific research and breeding.However,single-targeted CRISPR can only induce a few base deletions,insertions,or substitution.Ideally,thesemutations result in premature termination of the protein encoded by the target gene,leading to a loss of function[1]. | Guoning Zhu Lingling Zhang Liqun Ma Qing Liu Kejian Wang Jinyan Li Guiqin Qu Benzhong Zhu Daqi Fu Yunbo Luo Hongliang Zhu | 2023 | Horticulture Research2023，10，10： | 1 |
| 18 | The functional analysis of transiently upregulated miR-101 suggests a “braking” regulatory mechanism during myogenesis显示文摘Skeletal muscle differentiation is a highly coordinated process that involves many cellular signaling pathways and microRNAs(miRNAs).A group of muscle-specific miRNAs has been reported to promote myogenesis by suppressing key signaling pathways for cell growth.However,the functional role and regulatory mechanism of most non-muscle-specific miRNAs with stage-specific changes during differentiation are largely unclear.Here,we describe the functional characterization of miR-101a/b,a pair of non-muscle-specific miRNAs that show the largest change among a group of transiently upregulated miRNAs during myogenesis in C2C12 cells.The overexpression of miR-101a/b inhibits myoblast differentiation by suppressing the p38/MAPK,Interferon Gamma,and Wnt pathways and enhancing the C/EBP pathway.Mef2a,a key protein in the p38/MAPK pathway,was identified as a direct target of miR-101a/b.Interestingly,we found that the long non-coding RNA(lncRNA)Malat1,which promotes muscle differentiation,interacts with miR-101a/b,and this interaction competes with Mef2a mRNA to relieve the inhibition of the p38/MAPK pathway during myogenesis.These results uncovered a“braking”role in differentiation of transiently upregulated miRNAs and provided new insights into the competing endogenous RNA(ceRNA)regulatory mechanism in myoblast differentiation and myogenesis. | Shurong Liu Shujuan Xie Huafeng Chen Bin Li Zhirong Chen Yeya Tan Jianhua Yang Lingling Zheng Zhendong Xiao Qi Zhang Lianghu Qu | 2021 | Science China(Life Sciences)2021，64，10： | 1 |
| 19 | Low-dose chloroquine treatment extends the lifespan of aged rats显示文摘Dear Editor,Chloroquine(CQ)has long been used as an anti-malarial agent(Wellems and Plowe,2001).Recently,CQ has also been applied to treat viral infection and related diseases(Wellems and Plowe,2001;Huang et al.,2020).However,the safety and efficacy of its applications are still under extensive debate(Solomon and Lee,2009).Here,we discovered that low-dose CQ has a geroprotective effect on physiologically aged rats.Low-dose CQ prolonged lifespan,repressed systemic inflammation,and inhibited fibrosis across multiple tissue types in aged rats.Furthermore,we constructed transcriptomic maps for 6 tissues(kidney,small intestine,liver,heart,lung,and aorta)upon CQ treatment,thus revealing the effects of CQ at a systemic level.CQ treatment mitigated age-related molecular changes and repressed genes linked to fibrosis and the inflammatory response.Altogether,our data provide a valuable resource for investigating the impact of CQ on multiple aged tissues,which may facilitate the development of clinical applications that mitigate age-related changes in the elderly. | Wei Li Zhiran Zou Yusheng Cai Kuan Yang Si Wang Zunpeng Liu Lingling Geng Qun Chu Zhejun Ji Piu Chan Guang-Hui Liu Moshi Song Jing Qu Weiqi Zhang | 2022 | Protein & Cell2022，13，6： | 1 |
| 20 | Physicochemical properties and antioxidant capacity of 3 polysaccharides from greentea,oolong tea,and black tea显示文摘 | CHEN Haixia QU Zhishuang FU Lingling | 2009 | Journal of Food Science2009，74，6： | 1 |
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