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| 1 | Correction of a genetic disease by CRISPR-Cas9-mediated gene editing in mouse spermatogonial stem cells显示文摘Spermatogonial 干细胞(SSC ) 能在移植以后生产众多的男配偶子进接受者睾丸,介绍为基因治疗和修改基因的动物的连续生产的一条珍贵途径。然而, SSC 的成功的基因操作被限制了,部分由于复杂性和当前可得到的基因编辑技术的低效率。这里,我们证明有效基因修正能用 CRISPR-Cas9 系统被介绍进 SSC。我们使用了 CRISPR-Cas9 系统变异在 SCC 的 EGFP transgene 或内长的 Crygc 基因。变异的 SSC 在移植以后经历了精子发生进不肥沃的老鼠睾丸的生精的小管。圆 spermatids 被产生并且在进成熟卵母细胞的注射以后,支持了显示相应变异的显型的异质接合的后代的生产。而且,在 Crygc 的一个引起疾病的变化(在 SSC 先存在的 Crygc −/−) 能乐意地到加入的 CRISPR-Cas9-induced nonhomologous 结束(NHEJ ) 或指导相同的修理(HDR ) 被修理,导致没有是的离开目标修正的证据带改正的基因的 SSC 线由整个染色体的定序出现。用从这些线产生的圆 spermatids 的授精在 100% 的效率与改正的显型产生了后代。我们的结果表明有效基因由 CRISPR-Cas9 系统在老鼠 SSC 编辑,并且提供在 SSC 经由基因修正治好基因疾病的原则的证明。 | Yuxuan Wu Hai Zhou Xiaoying Fan Ying Zhang Man Zhang Yinghua Wang Zhenfei Xie Meizhu Bai Qi Yin Dan Liang Wei Tang Jiaoyang Liao Chikai Zhou Wujuan Liu Ping Zhu Hongshan Guo Hong Pan Chunlian Wu Huijuan Shi Ligang Wu Fuchou Tang Jinsong Li | 2015 | Cell Research2015，25，1： | 37 |
| 2 | Mechanical properties and corrosion behavior of selective laser melted 316L stainless steel after different heat treatment processes显示文摘Irregular grains, high interfacial stresses and anisotropic properties widely exist in 3D-printed metallic materials, and this paper investigated the effects of heat treatment on the microstructural, mechanical and corrosion properties of 316 L stainless steel fabricated by selective laser melting. Sub-grains and low-angle boundaries exist in the as-received selective laser melted(SLMed) 316 L stainless steel. After heat treatment at 1050℃, the sub-grains and low-angle boundaries changed slightly, and the stress state and strength decreased to some extent due to the decrease of dislocation density. After heat treatment at 1200℃, the grains became uniform, and the dislocation cells vanished, which led to a sharp decline in the hardness and strength. However, the ductility was improved after recrystallization heat treatment.The passive film thickness and corrosion potential of the SLMed 316 L stainless steel decreased after heat treatment, and the pitting potential also decreased due to the accelerated transition from metastable to steady-state pitting;this accelerated transition was caused by the presence of weak passive films at the enlarged pores after heat treatment, especially for an adequate solid solution treatment. | Decheng Kong Chaofang Dong Xiaoqing Ni Liang Zhang Jizheng Yao Cheng Man Xuequn Cheng Kui Xiao Xiaogang Li | 2019 | Journal of Materials Science & Technology2019，35，7： | 23 |
| 3 | Special Section:SARS-CoV-2 Preliminary evidence from a multicenter prospective observational study of the safety and efficacy of chloroquine for the treatment of COVID-19显示文摘Effective therapies are urgently needed for the SARS-CoV-2 pandemic.Chloroquine has been proved to have antiviral effect against coronavirus in vitro.In this study,we aimed to assess the efficacy and safety of chloroquine with different doses in COVID-19.In this multicenter prospective observational study,we enrolled patients older than 18 years old with confirmed SARS-CoV-2 infection excluding critical cases from 12 hospitals in Guangdong and Hubei Provinces.Eligible patients received chloroquinephosphate s00 mg,orally,once(half dose)or twice(full dose)daily.Patients treated with non-chloroquine therapy were included as historical controls.The primary endpoint is the time to undetectable viral RNA.Secondary outcomes include the proportion of patients with undetectable viral RNA by day 10 and 14,hospitalization time,duration of fever,and adverse events.A total of 197 patients completed chloroquine treatment,and 176patients were included as historical controls.The median time to achieve an undetectable viral RNA was shorter in chloroquine than in non-chloroquine(absolute difference in medians-6.0 days;95%CI-6.0 to—4.0).The duration of fever is shorter in chloroquine(geometric mean ratio 0.6;95%CIO.5 to 0.8).No serious adverse events were observed in the chloroquine group.Patients treated with half dose experienced lower rate of adverse events than with full dose.Although randomized trials are needed for further evaluation,this study provides evidence for safety and efficacy of chloroquine in COVID-19 and suggests that chloroquine can be a cost-effective therapy for combating the COVID-19 pandemic. | Mingxing Huang Man Li Fei Xiao Pengfei Pang Jiabi Liang Tiantian Tang Shaoxuan Liu Binghui Chen Jingxian Shu Yingying You Yang Li Meiwen Tang Jianhui Zhou Guanmin Jiang Jingfen Xiang Wenxin Hong Songmei He Zhaoqin Wang Jianhua Feng Changqing Lin Yinong Ye Zhilong Wu Yaocai Li Bei Zhong Ruilin Sun Zhongsi Hong Jing Liu Huili Chen Xiaohua Wang Zhonghe Li Duanqing Pei Lin Tian Jinyu Xia Shanping Jiang Nanshan Zhong Hong Shan | 2020 | National Science Review2020，7，9： | 20 |
| 4 | High levels of serum interleukin-6 increase mortality of hepatitis B virus-associated acute-on-chronic liver failure显示文摘BACKGROUND Patients with hepatitis B virus-associated acute-on-chronic liver failure(HBVACLF)present a complex and poor prognosis.Systemic inflammation plays an important role in its pathogenesis,and interleukin-6(IL-6)as a pro-inflammatory cytokine is related with severe liver impairment and also plays a role in promoting liver regeneration.Whether serum IL-6 influences HBV-ACLF prognosis has not been studied.AIM To determine the impact of serum IL-6 on outcome of patients with HBV-ACLF.METHODS We performed a retrospective study of 412 HBV-ACLF patients.The findings were analyzed with regard to mortality and the serum IL-6 level at baseline,as well as dynamic changes of serum IL-6 within 4 wk.RESULTS The serum IL-6 level was associated with mortality.Within 4 wk,deceased patients had significantly higher levels of IL-6 at baseline than surviving patients[17.9(7.3-57.6)vs 10.4(4.7-22.3),P=0.011].Patients with high IL-6 levels(>11.8 pg/mL)had a higher mortality within 4 wk than those with low IL-6 levels(≤11.8 pg/mL)(24.2%vs 13.2%,P=0.004).The odds ratios calculated using univariate and multivariate logistic regression were 2.10(95%confidence interval[CI]:1.26-3.51,P=0.005)and 2.11(95%CI:1.15-3.90,P=0.017),respectively.The mortality between weeks 5 and 8 in patients with high IL-6 levels at 4 wk was 15.0%,which was significantly higher than the 6.6%mortality rate in patients with low IL-6 levels at 4 wk(hazard ratio=2.39,95%CI:1.05-5.41,P=0.037).The mortality was 5.0%in patients with high IL-6 levels at baseline and low IL-6 levels at 4 wk,7.5%in patients with low IL-6 levels both at baseline and at 4 wk,11.5%in patients with low IL-6 levels at baseline and high IL-6 levels at 4 wk,and 16.7%in patients with high IL-6 levels both at baseline and at 4 wk.The increasing trend of the mortality rate with the dynamic changes of IL-6 was significant(P for trend=0.023).CONCLUSION A high level of serum IL-6 is an independent risk factor for mortality in patients with HBV-ACLF.Furthermore,a sustained high level or dynamic elevated level of serum IL-6 indicates a higher mortality. | Chao Zhou Ning Zhang Ting-Ting He Yao Wang Li-Fu Wang Yong-Qiang Sun Jing Jing Jing-Jing Zhang Shuang-Nan Fu Xuan Wang Xiao-Xiao Liang Xin Li Man Gong Jun Li | 2020 | World Journal of Gastroenterology2020，26，30： | 15 |
| 5 | Environment-Stable CoxNiy Encapsulation in Stacked Porous Carbon Nanosheets for Enhanced Microwave Absorption显示文摘Magnetic/dielectric@porous carbon composites,derived from metal–organic frameworks(MOFs)with adjustable composition ratio,have attracted wide attention due to their unique magnetoelectric properties.In addition,MOFs-derived porous carbon-based materials can meet the needs of lightweight feature.This paper reports a simple process for synthesizing stacked CoxNiy@C nanosheets derived from CoxNiy-MOFs nanosheets with multiple interfaces,which is good to the microwave response.The CoxNiy@C with controllable composition can be obtained by adjusting the ratio of Co^2+ and Ni^2+.It is supposed that the increased Co content is benefit to the dielectric and magnetic loss.Additionally,the bandwidth of CoNi@C nanosheets can take up almost the whole Ku band.Moreover,this composite has better environmental stability in air,which characteristic provides a sustainable potential for the practical application. | Xiaohui Liang Zengming Man Bin Quan Jing Zheng Weihua Gu Zhu Zhang Guangbin Ji | 2020 | Nano-Micro Letters2020，12，8： | 11 |
| 6 | Tom70 serves as a molecular switch to determine pathological cardiac hypertrophy显示文摘病理学的心脏的肥大是心失败的不可避免的 forerunner。不管心脏的肥大的病原学, cardiomyocyte mitochondrial 改变总是在这上下文被观察。mitochondrial 先锋蛋白质的进口调节在 pathophysiological 下面维持 mitochondrial 功能的外部膜(汤姆) 建筑群管理的 mitochondrial 的 translocases;然而,它在病理学的心脏的肥大的发展的角色仍然保持不清楚。这里,我们证明 Tom70 是在从人和试验性的动物的病理学的 hypertrophic 心的 downregulated。在 Tom70 表示的减小在 vivo 并且在 vitro 生产了不同病理学的 cardiomyocyte 肥大。指向 Tom70 的眼的 atrophy-1 的有缺点的 mitochondrial 进口触发了细胞内部的氧化应力,它导致了病理学的细胞的回答。重要地,如果有到多样的 pro-hypertrophic 的完整的抵抗的 cardiomyocytes 侮辱,增加了 Tom70 层次。一起,这些结果表明 Tom70 充当安排 hypertrophic 压力和 mitochondrial 回答决定病理学的心脏的肥大的一个分子的开关。 | Jun Li Man Qi Changming Li Dan Shi Dasheng Zhang Duanyang Xie Tianyou Yuan Jing Feng Yi Liu Dandan Liang Xinran Xu Jinjin Chen Liang Xu Hong Zhang Jiangchuan Ye Fei LV Jian Huang Luying Peng Yi-Han Chen | 2014 | Cell Research2014，24，8： | 9 |
| 7 | Characterizing the optimal operation of photocatalytic degradation of BDE-209 by nano-sized TiO_2显示文摘Brominated flame retardants have been widely used in industry.There is a rapid growing public concern for their availabilities in the environment.Advanced oxidation process(AOP) is a promising and efficient technology which may be used to remove emerging chemicals such as brominated flame retardants.This study aims at investigating optimal operational conditions for the removal of BDE-209 using nano-scaled titanium(IV) oxide.The residual PBDE congeners after photocatalytical degradation of BDE-209 by TiO 2 were analysed by gas chromatography-mass spectrometry(GC-MS).It was found that the degradability of BDE-209 by TiO 2 was attributed to its photocatalytic activity but not the small size of the particles.The half-life of removing BDE-209 by TiO 2 was 3.05 days under visible light.Tetra-and penta-BDEs were the major degraded products of BDE-209.Optimum conditions for photocatalytical degradation of BDE-209 was found to be at pH 12(93% ± 1%),5,10,20 mg/L(93.0% ± 1.70%,91.6% ± 3.21%,91.9% ± 0.952%,respectively),respectively of humic acid and in the form of anatase/rutile TiO 2(82% ± 3%).Hence,the efficiency of removing BDE-209 can be maximized while being cost effective at the said operating conditions. | Ka Lai Chow Yu Bon Man Jin Shu Zheng Yan Liang Nora Fung Yee Tam Ming Hung Wong | 2012 | Journal of Environmental Sciences2012，24，9： | 8 |
| 8 | Allogeneic Vγ9Vδ2 T-cell immunotherapy exhibits promising clinical safety and prolongs the survival of patients with late-stage lung or liver cancer显示文摘Vγ9Vδ2 T cells are promising candidates for cellular tumor immunotherapy.Due to their HLA-independent mode of action,allogeneic Vγ9Vδ2 T cells can be considered for clinical application.To apply allogeneic Vγ9Vδ2 T cells in adoptive immunotherapy,the methodology used to obtain adequate cell numbers with optimal effector function in vitro needs to be optimized,and clinical safety and efficacy also need to be proven.Therefore,we developed a novel formula to improve the expansion of peripheralγδT cells from healthy donors.Then,we used a humanized mouse model to validate the therapeutic efficacy of expandedγδT cells in vivo;furthermore,the expandedγδT cells were adoptively transferred into late-stage liver and lung cancer patients.We found that the expanded cells possessed significantly improved immune effector functions,including proliferation,differentiation,and cancer cell killing,both in vitro and in the humanized mouse model.Furthermore,a phase I clinical trial in 132 late-stage cancer patients with a total of 414 cell infusions unequivocally validated the clinical safety of allogeneic Vγ9Vδ2 T cells.Among these 132 patients,8 liver cancer patients and 10 lung cancer patients who received≥5 cell infusions showed greatly prolonged survival,which preliminarily verified the efficacy of allogeneic Vγ9Vδ2 T-cell therapy.Our clinical studies underscore the safety and efficacy of allogeneic Vγ9Vδ2 T-cell immunotherapy,which will inspire further clinical investigations and eventually benefit cancer patients. | Yan Xu Zheng Xiang Mohammed Alnaggar Léonce Kouakanou Jiawei Li Junyi He Jiashuang Yang Yi Hu Yan Chen Li Lin Jianlei Hao Jingxia Li Jibing Chen Man Li Qingling Wu Christian Peters Qinghua Zhou Jianshuang Li Yingqing Liang Xiaohua Wang Baohui Han Meili Ma Dieter Kabelitz Kecheng Xu Wenwei Tu Yangzhe Wu Zhinan Yin | 2021 | Cellular & Molecular Immunology2021，18，2： | 8 |
| 9 | Surface free energy of copper-zinc alloy for energy-saving of boiler显示文摘Cu-Zn, Cu-Zn-Sn, Cu-Zn-Ni alloys were melted by vacuum smelter. The effect factors to the surface free energy of the alloys such as chemical composition, crystal structure and surface crystal lattice distortion etc. were investigated by OCA30 automatic contact angle test instrument, metallography microscope and XRD instrument etc. Results suggests: adding alloy element to Cu may increase its surface free energy, and the more kinds of alloy elements are added, the more surface free energy increases; the alloy element Sn an increase the surface free energy of Cu-Zn alloy; Cu-Zn alloy with fir-tree crystal structure, great phase discrepancy and obvious composition aliquation has greater surface free energy; Cu-Zn alloy with compounds and serious surface crystal lattice distortion has greater surface free energy. | WANG Man LIANG Jinsheng TANG Qingguo MING Xing MENG Junping DING Yan | 2006 | Rare Metals2006，25，z1： | 6 |
| 10 | Excavation of underground research laboratory ramp in granite using tunnel boring machine: Feasibility study显示文摘Underground research laboratory(URL)plays an important role in safe disposal of high-level radioactive waste(HLW).At present,the Xinchang site,located in Gansu Province of China,has been selected as the final site for China’s first URL,named Beishan URL.For this,a preliminary design of the Beishan URL has been proposed,including one spiral ramp,three shafts and two experimental levels.With advantages of fast advancing and limited disturbance to surrounding rock mass,the tunnel boring machine(TBM)method could be one of the excavation methods considered for the URL ramp.This paper introduces the feasibility study on using TBM to excavation of the Beishan URL ramp.The technical challenges for using TBM in Beishan URL are identified on the base of geological condition and specific layout of the spiral ramp.Then,the technical feasibility study on the specific issues,i.e.extremely hard rock mass,high abrasiveness,TBM operation,muck transportation,water drainage and material transportation,is investigated.This study demonstrates that TBM technology is a feasible method for the Beishan URL excavation.The results can also provide a reference for the design and construction of HLW disposal engineering in similar geological conditions.2020 Institute of Rock and Soil Mechanics,Chinese Academy of Sciences.Production and hosting by Elsevier B.V.This is an open access article under the CC BY-NC-ND license(http://gffzzeb6f7f563f66445dhk9xnn50xpkxb66fv.ffgz.tsg.suse.edu.cn/licenses/by-nc-nd/4.0/). | Hongsu Ma Ju Wang Ke Man Liang Chen Qiuming Gong Xingguang Zhao | 2020 | Journal of Rock Mechanics and Geotechnical Engineering2020，12，6： | 6 |
| 11 | Triptolide suppresses pancreatic cancer cell proliferation by inhibiting hedgehog signaling pathway activity显示文摘Dear Editor,Pancreatic cancer (PCa) is a high-grade gastrointestinal malignancy more commonly occurring in elderly populations with lower than 5% overall 5-year survival rate (Hidalgo, 2010). PCa responds poorly to most chemotherapeutic agents, and therefore it is imperative to develop novel therapeutic agents that have anti-cancer activities against PCa. | Juanjuan Feng Mingjin Rao Man Wang Lin Liang Zhi Chen Xiufeng Pang Weiqiang Lu Zhenliang Sun | 2019 | Science China(Life Sciences)2019，62，10： | 6 |
| 12 | The Immunity of Evolvable Digital Circuits to ESD Interference显示文摘 | Shanghe Liu Menghua Man Zhengquan Ju Xiaolong Chang Jie Chu Liang Yuan | 2012 | Journal of Bionic Engineering2012，9，3： | 6 |
| 13 | Experimental and Modeling Study of the Regular Polygon Angle-spiral Liner in Ball Mills显示文摘Load behavior is one of the most critical factors affecting mills' energy consumption and grinding efficiency,and is greatly affected by the liner profiles. Generally, as liner profiles vary, the ball mill performances are extremely different. In order to study the performance of the ball mill with regular polygon angle-spiral liners(RPASLs), experimental and numerical studies on three types of RPASLs, including regular quadrilateral, pentagonal and hexagonal, are carried out. For the fine product of desired size, two critical parameters are analyzed: the energy input to the mill per unit mass of the fine product, E*, and the rate of production of the fine product, F*. Results show that the optimal structure of RPASLs is Quadrilateral ASL with an assembled angle of 50°. Under this condition, the specific energy consumption E* has the minimum value of 303 J per fine product and the production rate F* has the maximum value of 0.323. The production rate F* in the experimental result is consistent with the specific collision energy intensity to total collision energy intensity ratio E_s/E_t in the simulation. The relations between the production rate F* and the specific energy consumption E* with collision energy intensity E_s and E_t are obtained. The simulation result reveals the essential reason for the experimental phenomenon and correlates the mill performance parameter to the collision energy between balls,which could guide the practical application for Quadrilateral ASL. | Yi SUN Man LIANG Xiaohang JIN Pengpeng JI Jihong SHAN | 2017 | Chinese Journal of Mechanical Engineering2017，30，2： | 4 |
| 14 | Mea6 controls VLDL transport through the coordinated regulation of COPil assembly显示文摘 | Yaqing Wang Liang Liu Hongsheng Zhang Junwan Fan FengZhang Mei Yu Lei Shi Lin Yang Sin Man Lam Huimin Wang Xiaowei Chen Yingchun Wang Fei Gao Guanghou Shui Zhiheng Xu | 2016 | Cell Research2016，26，7： | 4 |
| 15 | Synthesis and Characterization of a Novel Compound SnDy2O4显示文摘A new phase, the rare earth complex oxide SnDy2O4 was synthesized by the thermal decomposition of its oxalate precursor that was prepared by rheological phase reaction method. TG, IR, XRD and EPS were used to prove the formation of the compound SnDy2O4. The structure of SnDy2O4 was refined by Rietveld analysis. SnDy2O4 is cubic, a = 7.40366 ? V = 405.82 ?, Z = 4. | Yong ZHANG, Ke Li ZHANG*, Man Ke JIA, Hao TANG, Ju Tang SUN, Liang Jie YUAN College of Chemistry and Molecular science, Department of Chemistry, Wuhan University, Wuhan 430072 | 2002 | Chinese Chemical Letters2002，13，6： | 4 |
| 16 | Surface modification of PGP for a neutrophil–nanoparticle co-vehicle to enhance the anti-depressant effect of baicalein显示文摘Exploiting cells as vehicles combined with nanoparticles combined with therapy has attracted increasing attention in the world recently. Red blood cells, leukocytes and stem cells have been used for tumor immunotherapy, tissue regeneration and inflammatory disorders, and it is known that neutrophils can accumulate in brain lesions in many brain diseases including depression. N-Acetyl Pro–Gly–Pro(PGP) peptide shows high specific binding affinity to neutrophils through the CXCR2 receptor. In this study, PGP was used to modify baicalein-loaded solid lipid nanoparticles(PGP-SLNs) to facilitate binding to neutrophils in vivo. Brain-targeted delivery to the basolateral amygdala(BLA) was demonstrated by enhanced concentration of baicalein in the BLA. An enhanced anti-depressant effect was observed in vitro and in vivo. The mechanism involved inhibition of apoptosis and a decrease in lactate dehydrogenase release. Behavioral evaluation carried out with rats demonstrated that anti-depression outcomes were achieved. The results indicate that PGP-SLNs decrease immobility time, increase swimming time and climbing time and attenuate locomotion in olfactory-bulbectomized(OB) rats. In conclusion, PGP modification is a strategy for targeting the brain with a cell–nanoparticle delivery system for depression therapy. | Baoyu Chen Man Luo Jianming Liang Chun Zhang Caifang Gao Jue Wang Jianxin Wang Yongji Li Desheng Xu Lina Liu Ning Zhang Huijun Chen Jing Qin | 2018 | Acta Pharmaceutica Sinica B2018，8，1： | 4 |
| 17 | Bio-Inspired Electromagnetic Protection Based on Neural Information Processing显示文摘 | Xiaolong Chang Shanghe Liu Menghua Man Weihua Han Jie Chu Liang Yuan | 2014 | Journal of Bionic Engineering2014，11，1： | 4 |
| 18 | Preparation of DHA-and EPA-enriched Glycerides by Enzymatic Interesterification Using Tuna Oil and Capric Acid显示文摘This study focused on the preparation of docosahexaenoic acid(DHA) and eicosapentaenoic acid(EPA)enriched-triacylglycerols by enzymatic interesterification using tuna oil and capric acid. The content of DHA+EPA is 26.86% in the tuna oil used in this study. A response surface methodology(RSM) was used to optimize the reaction parameters(reaction temperature, substrate molar ratio, enzyme amount and reaction time), and the optimized conditions were determined to be: reaction temperature 58℃, substrate molar ratio(capric acid : tuna oil) 4:1, enzyme amount 4%, and reaction time 7.5 h. Under the optimized conditions, the content of DHA+EPA in the glycerides was 40.03%, which is 13.17% higher than that in raw tuna oil. In addition,the MLM-type structured lipids containing medium chain fatty acids(capric acid) at positions sn-1,3 and a long chain fatty acid(DHA/EPA) at the position sn-2 may have many health benefits for humans. | LIANG Shaohua WANG Mengyuan ZHU Lijie ZHANG Man YANG Ming | 2018 | Grain & Oil Science and Technology2018，1，2： | 4 |
| 19 | Dynamic mechanical loading facilitated chondrogenic differentiation of rabbit BMSCs in collagen scaffolds显示文摘Mechanical signals have been played close attention to regulate chondrogenic differentiation of bone marrow mesenchymal stem cells(BMSCs).In this study,dynamic mechanical loading simulation with natural frequencies and intensities were applied to the 3D cultured BMSCs–collagen scaffold constructs.We investigated the effects of dynamic mechanical loading on cell adhesion,uniform distribution,proliferation,secretion of extracellular matrix(ECM)and chondrogenic differentiation of BMSCs–collagen scaffold constructs.The results indicated that dynamic mechanical loading facilitated the BMSCs adhesion,uniform distribution,proliferation and secretion of ECM with a slight contraction,which significantly improved the mechanical strength of the BMSCs–collagen scaffold constructs for better mimicking the structure and function of a native cartilage.Gene expression results indicated that dynamic mechanical loading contributed to the chondrogenic differentiation of BMSCs with higher levels of AGG,COL2A1 and SOX9 genes,and prevented of hypertrophic process with lower levels of COL10A1,and reduced the possibility of fibrocartilage formation due to down-regulated COL1A2.In conclusion,this study emphasized the important role of dynamic mechanical loading on promoting BMSCs chondrogenic differentiation and maintaining the cartilage phenotype for in vitro reconstruction of tissue-engineered cartilage,which provided an attractive prospect and a feasibility strategy for cartilage repair. | Wanxu Cao Weimin Lin Hanxu Cai Yafang Chen Yi Man Jie Liang Qiguang Wang Yong Sun Yujiang Fan Xingdong Zhang | 2019 | Regenerative Biomaterials2019，6，2： | 3 |
| 20 | Aberrant cholesterol metabolic signaling impairs antitumor immunosurveillance through natural killer T cell dysfunction in obese liver显示文摘Obesity is a major risk factor for cancers including hepatocellular carcinoma(HCC)that develops from a background of non-alcoholic fatty liver disease(NAFLD).Hypercholesterolemia is a common comorbidity of obesity.Although cholesterol biosynthesis mainly occurs in the liver,its role in HCC development of obese people remains obscure.Using high-fat high-carbohydrate diet-associated orthotopic and spontaneous NAFLD-HCC mouse models,we found that hepatic cholesterol accumulation in obesity selectively suppressed natural killer T(NKT)cell-mediated antitumor immunosurveillance.Transcriptome analysis of human liver revealed aberrant cholesterol metabolism and NKT cell dysfunction in NAFLD patients.Notably,cholesterol-lowering rosuvastatin restored NKT expansion and cytotoxicity to prevent obesogenic diet-promoted HCC development.Moreover,suppression of hepatic cholesterol biosynthesis by a mammalian target of rapamycin(mTOR)inhibitor vistusertib preceded tumor regression,which was abolished by NKT inactivation but not CD8^(+)T cell depletion.Mechanistically,sterol regulatory element-binding protein 2(SREBP2)-driven excessive cholesterol production from hepatocytes induced lipid peroxide accumulation and deficient cytotoxicity in NKT cells,which were supported by findings in people with obesity,NAFLD and NAFLD-HCC.This study highlights mTORC1/SREBP2/cholesterol-mediated NKT dysfunction in the tumor-promoting NAFLD liver microenvironment,providing intervention strategies that invigorating NKT cells to control HCC in the obesity epidemic. | Wenshu Tang Jingying Zhou Weiqin Yang Yu Feng Haoran Wu Myth T.S.Mok Lingyun Zhang Zhixian Liang Xiaoyu Liu Zhewen Xiong Xuezhen Zeng Jing Wang Jiahuan Lu Jingqing Li Hanyong Sun Xiaoyu Tian Philip Chun Yeung Yong Hou Heung Man Lee Candice C.H.Lam Howard H.W.Leung Anthony W.H.Chan Ka Fai To John Wong Paul B.S.Lai Kelvin K.C.Ng Simon K.H.Wong Vincent W.S.Wong Alice P.S.Kong Joseph J.Y.Sung Alfred S.L.Cheng | 2022 | Cellular & Molecular Immunology2022，19，7： | 3 |
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