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| 1 | Combined obeticholic acid and apoptosis inhibitor treatment alleviates liver fibrosis显示文摘Obeticholic acid(OCA), the first FXR-targeting drug, has been claimed effective in the therapy of liver fibrosis. However, recent clinical trials indicated that OCA might not be effective against liver fibrosis, possibly due to the lower dosage to reduce the incidence of the side-effect of pruritus. Here we propose a combinatory therapeutic strategy of OCA and apoptosis inhibitor for combating against liver fibrosis. CCl4-injured mice, D-galactosamine/LPS(GalN/LPS)-treated mice and cycloheximide/TNFα(CHX/TNFα)-treated HepG2 cells were employed to assess the effects of OCA, or together with IDN-6556, an apoptosis inhibitor. OCA treatment significantly inhibited hepatic stellate cell(HSC)activation/proliferation and prevented fibrosis. Elevated bile acid(BA) levels and hepatocyte apoptosis triggered the activation and proliferation of HSCs. OCA treatment reduced BA levels but could not inhibit hepatocellular apoptosis. An enhanced anti-fibrotic effect was observed when OCA was co-administrated with IDN-6556. Our study demonstrated that OCA inhibits HSCs activation/proliferation partially by regulating BA homeostasis and thereby inhibiting activation of HSCs. The findings in this study suggest that combined use of apoptosis inhibitor and OCA at lower dosage represents a novel therapeutic strategy for liver fibrosis. | Jiyu Zhou Ningning Huang Yitong Guo Shuang Cui Chaoliang Ge Qingxian He Xiaojie Pan Guangji Wang Hong Wang Haiping Hao | 2019 | Acta Pharmaceutica Sinica B2019，9，3： | 13 |
| 2 | The shallow meridional overturning circulation in the South China Sea and the related internal water movement显示文摘The structure of the annual-mean shallow meridional overturning circulation(SMOC) in the South China Sea(SCS) and the related water movement are investigated,using simple ocean data assimilation(SODA) outputs.The distinct clockwise SMOC is present above 400 m in the SCS on the climatologically annual-mean scale,which consists of downwelling in the northern SCS,a southward subsurface branch supplying upwelling at around 10°N and a northward surface flow,with a strength of about 1×10~6 m^3/s.The formation mechanisms of its branches are studied separately.The zonal component of the annual-mean wind stress is predominantly westward and causes northward Ekman transport above 50 m.The annual-mean Ekman transport across 18°N is about 1.2×10~6 m^3/s.An annual-mean subduction rate is calculated by estimating the net volume flux entering the thermocline from the mixed layer in a Lagrangian framework.An annual subduction rate of about 0.66×10~6m^3/s is obtained between 17° and 20°N,of which 87% is due to vertical pumping and 13% is due to lateral induction.The subduction rate implies that the subdution contributes significantly to the downwelling branch.The pathways of traced parcels released at the base of the February mixed layer show that after subduction water moves southward to as far as 11°N within the western boundary current before returning northward.The velocity field at the base of mixed layer and a meridional velocity section in winter also confirm that the southward flow in the subsurface layer is mainly by strong western boundary currents.Significant upwelling mainly occurs off the Vietnam coast in the southern SCS.An upper bound for the annual-mean net upwelling rate between 10° and 15°N is 0.7×10~6m^3/s,of which a large portion is contributed by summer upwelling,with both the alongshore component of the southwest wind and its offshore increase causing great upwelling. | ZHANG Ningning LAN Jian MA Jie CUI Fengjuan | 2016 | Acta Oceanologica Sinica2016，35，7： | 1 |
| 3 | A novel long-term intravenous combined with local treatment with human amnion-derived mesenchymal stem cells for a multidisciplinary rescued uremic calciphylaxis patient and the underlying mechanism显示文摘Calciphylaxis is a rare disease characterized histologically by microvessel calcification and microthrombosis,with high mortality and no proven therapy.Here,we reported a severe uremic calciphylaxis patient with progressive skin ischemia,large areas of painful malodorous ulcers,and mummified legs.Because of the worsening symptoms and signs refractory to conventional therapies,treatment with human amnion-derived mesenchymal stem cells(hAMSCs)was approved.Preclinical release inspections of hAMSCs,efficacy,and safety assessment,including cytokine secretory ability,immunocompetence,tumorigenicity,and genetics analysis in vitro,were introduced.We further performed acute and long-term hAMSC toxicity evaluations in C57BL/6 mice and rats,abnormal immune response tests in C57BL/6 mice,and tumorigenicity tests in neonatal Balbc-nu nude mice.After the preclinical research,the patient was treated with hAMSCs by intravenous and local intramuscular injection and external supernatant application to the ulcers.When followed up to 15 months,the blood-based markers of bone and mineral metabolism improved,with skin soft tissue regeneration and a more favorable profile of peripheral blood mononuclear cells.Skin biopsy after 1-month treatment showed vascular regeneration with mature noncalcified vessels within the dermis,and 20 months later,the re-epithelialization restored the integrity of the damaged site.No infusion or local treatment-related adverse events occurred.Thus,this novel long-term intravenous combined with local treatment with hAMSCs warrants further investigation as a potential regenerative treatment for uremic calciphylaxis due to effects of inhibiting vascular calcification,stimulating angiogenesis and myogenesis,anti-inflammatory and immune modulation,multidifferentiation,re-epithelialization,and restoration of integrity. | Lianju Qin Jing Zhang Yujie Xiao Kang Liu Yugui Cui Fangyan Xu Wenkai Ren Yanggang Yuan Chunyan Jiang Song Ning Xiaoxue Ye Ming Zeng Hanyang Qian Anning Bian Fan Li Guang Yang Shaowen Tang Zhihong Zhang Juncheng Dai Jing Guo Qiang Wang Bin Sun Yifei Ge Chun Ouyang Xueqiang Xu Jing Wang Yaoyu Huang Hongqing Cui Jing Zhou Meilian Wang Zhonglan Su Yan Lu Di Wu Jingping Shi Wei Liu Li Dong Yinbing Pan Baiqiao Zhao Ying Cui Xueyan Gao Zhanhui Gao Xiang Ma Aiqin Chen Jie Wang Meng Cao Qian Cui Li Chen Feng Chen Youjia Yu Qiang Ji Zhiwei Zhang Mufeng Gu Xiaojun Zhuang Xiaolin Lv Hui Wang Yanyan Pan Ling Wang Xianrong Xu Jing Zhao Xiuqin Wang Cuiping Liu Ningxia Liang Changying Xing Jiayin Liu Ningning Wang | 2022 | Journal of Molecular Cell Biology2022，14，2： | 1 |
| 4 | The most tenuous group query显示文摘Rtecently a lot of works have been investigating to find the tenuous groups,i.e.,groups with few social interactions and weak relationships among members,for reviewer selection and psycho-educational group formation.However,the metrics(e.g.,k-triangle,k-line,and k-tenuity)used to measure the tenuity,require a suitable k value to be specified which is difficult for users without background knowledge.Thus,in this paper we formulate the most tenuous group(MTG)query in terms of the group distance and average group distance of a group measuring the tenuity to eliminate the influence of parameter k on the tenuity of the group.To address the MTG problem,we first propose an exact algorithm,namely MTGVDIS,which takes priority to selecting those vertices whose vertex distance is large,to generate the result group,and also utilizes effective filtering and pruning strategies.Since MTGVDIS is not fast enough,we design an efficient exact algorithm,called MTG-VDGE,which exploits the degree metric to sort the vertexes and proposes a new combination order,namely degree and reverse based branch and bound(DRBB).MTG-VDGE gives priority to those vertices with small degree.For a large p,we further develop an approximation algorithm,namely MTG-VDLT,which discards candidate attendees with high degree to reduce the number of vertices to be considered.The experimental results on real datasets manifest that the proposed algorithms outperform existing approaches on both efficiency and group tenuity. | Na LI Huaijie ZHU Wenhao LU Ningning CUI Wei LIU Jian YIN Jianliang XU Wang-Chien LEE | 2023 | Frontiers of Computer Science2023，17，2： | 0 |
| 5 | Transcription factor ETV4 promotes the development of hepatocellular carcinoma by driving hepatic TNF-αsignaling显示文摘Background Hepatic inflammation is the major risk factor of hepatocellular carcinoma(HCC).However,the underlying mechanism by which hepatic inflammation progresses to HCC is poorly understood.This study was designed to investigate the role of ETS translocation variant 4(ETV4)in linking hepatic inflammation to HCC.Methods Quantitative real-time PCR and immunoblotting were used to detect the expression of ETV4 in HCC tissues and cell lines.RNA sequencing and luciferase reporter assays were performed to identify the target genes of ETV4.Hepatocyte-specific ETV4-knockout(ETV4fl/fl,alb-cre)and transgenic(ETV4Hep-TG)mice and diethylnitrosamine-carbon tetrachloride(DEN-CCL4)treatment experiments were applied to investigate the function of ETV4 in vivo.The Cancer Genome Atlas(TCGA)database mining and pathological analysis were carried out to determine the correlation of ETV4 with tumor necrosis factor-alpha(TNF-α)and mitogen-activated protein kinase 11(MAPK11).Results We revealed that ETV4 was highly expressed in HCC.High levels of ETV4 predicted a poor survival rate of HCC patients.Then we identified ETV4 as a transcription activator of TNF-αand MAPK11.ETV4 was positively correlated with TNF-αand MAPK11 in HCC patients.As expected,an increase in hepatic TNF-αsecretion and macrophage accumulation were observed in the livers of ETV4Hep-TG mice.The protein levels of TNF-α,MAPK11,and CD68 were significantly higher in the livers of ETV4Hep-TG mice compared with wild type mice but lower in ETV4fl/fl,alb-cre mice compared with ETV4fl/fl mice as treated with DEN-CCL4,indicating that ETV4 functioned as a driver of TNF-α/MAPK11 expression and macrophage accumulation during hepatic inflammation.Hepatocyte-specific knockout of ETV4 significantly prevented development of DEN-CCL4-induced HCC,while transgenic expression of ETV4 promoted growth of HCC.Conclusions ETV4 promoted hepatic inflammation and HCC by activating transcription of TNF-αand MAPK11.Both the ETV4/TNF-αand ETV4/MAPK11 axes represented two potential therapeutic targets for highly associated hepatic inflammation and HCC.ETV4+TNF-αwere potential prognostic markers for HCC patients. | Dandan Qi Min Lu Pengfei Xu Xinli Yao Yongchen Chen Lipeng Gan Yong Li Yahua Cui Xiaomei Tong Shuhong Liu Jingmin Zhao Ningning Liu Xin Ye | 2023 | Cancer Communications2023，43，12： | 0 |
| 6 | Residual Based A Posteriori Error Estimates for Convex Optimal Control Problems Governed by Stokes-Darcy Equations显示文摘In this paper,we derive a posteriori error estimates for finite element approximations of the optimal control problems governed by the Stokes-Darcy system.We obtain a posteriori error estimators for both the state and the control based on the residual of the finite element approximation.It is proved that the a posteriori error estimate provided in this paper is both reliable and efficient. | Ming Cui Ningning Yan | 2012 | Numerical Mathematics(Theory,Methods and Applications)2012，5，4： | 0 |
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