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| 1 | A structural view of the antibiotic degradation enzyme NDM-1 from a superbug显示文摘Gram-negative Enterobacteriaceae with resistance to carbapenem conferred by New Delhi metallo-β-lactamase 1(NDM-1)are a type of newly discovered antibioticresistant bacteria.The rapid pandemic spread of NDM-1 bacteria worldwide(spreading to India,Pakistan,Europe,America,and Chinese Taiwan)in less than 2 months characterizes these microbes as a potentially major global health problem.The drug resistance of NDM-1 bacteria is largely due to plasmids containing the blaNDM-1 gene shuttling through bacterial populations.The NDM-1 enzyme encoded by the blaNDM-1 gene hydrolyzes β-lactam antibiotics,allowing the bacteria to escape the action of antibiotics.Although the biological functions and structural features of NDM-1 have been proposed according to results from functional and structural investigation of its homologues,the precise molecular characteristics and mechanism of action of NDM-1 have not been clarified.Here,we report the threedimensional structure of NDM-1 with two catalytic zinc ions in its active site.Biological and mass spectroscopy results revealed that D-captopril can effectively inhibit the enzymatic activity of NDM-1 by binding to its active site with high binding affinity.The unique features concerning the primary sequence and structural conformation of the active site distinguish NDM-1 from other reported metallo-β-lactamases(MBLs)and implicate its role in wide spectrum drug resistance.We also discuss the molecular mechanism of NDM-1 action and its essential role in the pandemic of drug-resistant NDM-1 bacteria.Our results will provide helpful information for future drug discovery targeting drug resistance caused by NDM-1 and related metallo-β-lactamases. | Yu Guo Jing Wang Guojun Niu Wenqing Shui Yuna Sun Honggang Zhou Yaozhou Zhang Cheng Yang Zhiyong Lou Zihe Rao | 2011 | Protein & Cell2011，2，5： | 16 |
| 2 | Rice Ferredoxin-Dependent Glutamate Synthase Regulates Nitrogen-Carbon Metabolomes and Is Genetically Differentiated between japonica and indica Subspecies显示文摘当通过夫酸安 synthetase/glutamine:2-oxoglutarate amidotransferase (GS/GOGAT ) 的 Gln 和 Glu 骑车,植物吸收从土壤吸收进器官的形式的无机的氮。而 GS 从 Glu 和氨催化 Gln 的形成, GOGAT 从 Gln 催化一个酰胺组的转移到 2-oxoglutarate 生产 Glu 的二个分子。然而,处于碳氮平衡的 GS/GOGAT 周期的规章的角色很好没被理解。这里,我们报导米饭的功能的描述反常细胞激动素反应 1 (ABC1 ) 编码一个铁氧化还原蛋白依赖者(Fd ) 的基因 -GOGAT。弱变异的等位基因 abc1-1 异种显示出典型氮缺乏的症候群,而 T-DNA insertional 异种 abc1-2 是幼苗致命。Metabolomics 分析在 abc1-1 在 tricarboxylic 酸周期与高 N/C 比率(Gln 和 Asn ) 和几中介揭示了氨基酸的过多的数量的累积,建议 ABC1 起在氮吸收和碳氮平衡的一个关键作用。五非同义的单个核苷酸的多型性在编码区域的 ABC1 被识别并且作为三不同 haplotypes 描绘了,它高度并且明确地在装饰用的梨树和 indica 亚种之间被区分了。一起,这些结果建议 ABC1/OsFd-GOGAT 由 modulating 氮吸收和碳氮平衡为植物生长和开发是必要的。 | Xiaolu Yang Jinqiang Nian Qincliun xie Jian Feng Fengxia Zhang Hongwei Jing Jian Zhang Guojun Dong Yan Liang Juli Peng GuodongWang Qian Qian Jianru Zuo | 2016 | Molecular Plant2016，9，11： | 14 |
| 3 | Lithospheric structure and faulting characteristics of the Helan Mountains and Yinchuan Basin: Results of deep seismic reflection profiling显示文摘The Helan Mountains and Yinchuan Basin(HM-YB) are located at the northern end of the North-South tectonic belt,and form an intraplate tectonic deformation zone in the western margin of the North China Craton(NCC).The HM-YB has a complicated history of formation and evolution,and is tectonically active at the present day.It has played a dominant role in the complex geological structure and modern earthquake activities of the region.A 135-km-long deep seismic reflection profile across the HM-YB was acquired in early 2014,which provides detailed information of the lithospheric structure and faulting characteristics from near-surface to various depths in the region.The results show that the Moho gradually deepens from east to west in the depth range of 40-48 km along the profile.Significant differences are present in the crustal structure of different tectonic units,including in the distribution of seismic velocities,depths of intra-crustal discontinuities and undulation pattern of the Moho.The deep seismic reflection profile further reveals distinct structural characteristics on the opposite sides of the Helan Mountains.To the east,The Yellow River fault,the eastern piedmont fault of the Helan Mountains,as well as multiple buried faults within the Yinchuan Basin are all normal faults and still active since the Quaternary.These faults have controlled the Cenozoic sedimentation of the basin,and display a 'negative-flower' structure in the profile.To the west,the Bayanhaote fault and the western piedmont fault of the Helan Mountains are east-dipping thrust faults,which caused folding,thrusting,and structural deformation in the Mesozoic stratum of the Helan Mountains uplift zone.A deep-penetrating fault is identified in the western side of the Yinchuan Basin.It has a steep inclination cutting through the middle-lower crust and the Moho,and may be connected to the two groups of faults in the upper crust.This set of deep and shallow fault system consists of both strike-slip,thrust,and normal faults formed over different eras,and provides the key tectonic conditions for the basin-mountains coupling,crustal deformation and crust-mantle interactions in the region.The other important phenomenon revealed from the results of deep seismic reflection profiling is the presence of a strong upper mantle reflection(UMR) at a depth of 82-92 km beneath the HM-YB,indicating the existence of a rapid velocity variation or a velocity discontinuity in that depth range.This is possibly a sign of vertical structural inhomogeneity in the upper mantle of the region.The seismic results presented here provide new clues and observational bases for further study of the deep structure,structural differences among various blocks and the tectonic relationship between deep and shallow processes in the western NCC. | LIU BaoJin FENG ShaoYing JI JiFa WANG ShuaiJun ZHANG JianShi YUAN HongKe YANG GuoJun | 2017 | Science China Earth Sciences2017，60，3： | 11 |
| 4 | Impending HRT wave precursors to the Wenchuan M_s8.0 earthquake and methods of earthquake impending prediction by using HRT wave显示文摘We deployed four geo-electric monitoring stations in Sichuan and Yunnan provinces from 2004, using the new generation of equipment (PS-100) and technologies to capture the HRT wave earthquake precursor. Before the Wenchuan Ms8.0 earthquake, we recorded the HRT wave precursor at the only operating station in Hongge (HG, Δ=465 km) and found that significant impending signal had been recorded at the station in the early morning ( 0―5 am) of 12th of May, 2008. The precursor for this earthquake is consistent with precursors recorded for other strong earthquakes. The measured physical properties (geo-resistivity and telluric-current) show tidal wave period oscillations from several days to several months before the earthquakes and the amplitude of such HT oscillation increases significantly towards the occurrence of an earthquake. These HT and RT waves from the epicenter have a causal relationship with the earthquakes that happened several days later. The arrival time of two RT waves is proportional to the distance from the station to the epicenter. The estimated natural decay of the amplitude is correlated with the natural period (T0) of the earthquake fault, which is proportional to the fault length. From this relationship, we can predict the earthquake magnitude. For magnitude 6―9 earthquakes, the natural period is about 1―6 hours. Such oscillation comes from the epicenter area and they can propagate several thousand kilometers in the Earth's crust. Before a strong earthquake in the shallow crust, the conductive pore fluid will experience major changes before the fault rapture. Such fluid change will emit an oscillation in the pore fluid pressure. This is the mechanism for the HRT wave generation. Since the China Earthquake Administration funded the HRT wave short-term earth-quake prediction project in 2003, the first record of HRT precursor wave has been recorded from the 2004-12-26 Sumatra Mw9.0 earthquake with the largest epicentre distance Δ=2900 km. Thereafter, we have captured HRT waves from more than twenty strong earthquakes, which are well-matched and show repeatability, consistency and regularity. All our observation with the HRT waves demonstrate that HRT wave precursors to earthquakes indeed exist. Strong earthquakes can be predicted and short-term and impending earthquake prediction is achievable in the very near future. From all the observations, including the ones at HG station from Wenchuan Ms8.0 earthquake, we conclude that using HRT wave to predict earthquakes is feasible. | QIAN FuYe ZHAO BiRu QIAN Wei ZHAO Jian HE ShiGen ZHANG HongKui LI ShiYu LI ShaoKun YAN GuLiang WANG ChengMin SUN ZhenKai ZHANG DongNing LU Jun ZHANG Ping YANG GuoJun SUN JiaLin GUO ChunSheng TANG YuXiong XU JianMing XIA KunTao JU Hang YIN BangHong LI Ming YANG DongSheng QI WeiLuo HE TaiMing GUAN HuaPing ZHAO YuLin | 2009 | Science China Earth Sciences2009，52，10： | 8 |
| 5 | Characterization and fine mapping of an early senescence mutant (es-t) in Oryza sativa L.显示文摘An es-t (early senescence-temporary) mutant, produced by ethylene methylsulfonate treatment of strain Nipponbare, was identified in rice. The leaves of es-t appeared yellow at the seedling stage, and had decreased chlorophyll content. Rust spots were found during growth in es-t, especially at the leaf margin and tip. The plants showed a typical early-senescence phenotype at the milky stage. The leaf surface of es-t appeared smoother than wild-type leaves under a scanning electron microscope, because the leaves lack siliceous protuberances around the stoma. Chloroplasts grow abnormally and are filled with many starch grains in es-t. Paraffin section analysis showed that the development of the sclerenchyma cells and vascular bundles were also abnormal in es-t. Genetic analysis indicated that es-t was controlled by a recessive gene, which was finely mapped to a 42-kb interval on chromosome 5. These results will facilitate the positional cloning and functional studies of the gene. | YANG YaoLong RAO YuChun LIU HuiJuan FANG YunXia DONG GuoJun HUANG LiChao LENG YuJia GUO LonBiao ZHANG GuangHeng HU Jiang GAO ZhenYu QIAN Qian ZENG DaLi | 2011 | Chinese Science Bulletin2011，56，23： | 8 |
| 6 | Development of nutritious rice with high zinc/selenium and low cadmium in grains through QTL pyramiding显示文摘Enriching zinc(Zn) and selenium(Se) levels,while reducing cadmium(Cd) concentration in rice grains is of great benefit for human diet and health.Large natural variations in grain Zn, Se, and Cd concentrations in different rice accessions enable Zn/Sebiofortification and Cd-minimization through molecular breeding. Here, we report the development of new elite varieties by pyramiding major quantitative trait loci(QTLs) that significantly contribute to high Zn/Se and low Cd accumulation in grains. A chromosome segment substitution line CSSLGCC7 with the PA64s-derived GCC7 allele in the 93-11 background, exhibited steadily higher Mn and lower Cd concentrations in grains than those of 93-11. This elite chromosome segment substitution line(CSSL) was used as the core breeding material to cross with CSSLs harboring other major QTLs for essential mineral elements, especially CSSLGZC6 for grain Zn concentration and CSSLGSC5 for grain Se concentration. The CSSLGCC7+GZC6 and CSSLGCC7+GSC5 exhibited lower Cd concentration with higher Zn and Se concentrations in grains, respectively. Our study thus provides elite materials for rice breeding targeting high Zn/Se and low Cd concentrations in grains. | Chaolei Liu Shilin Ding Anpeng Zhang Kai Hong Hongzhen Jiang Shenglong Yang Banpu Ruan Bin Zhang Guojun Dong Longbiao Guo Dali Zeng Qian Qian Zhenyu Gao | 2020 | Journal of Integrative Plant Biology2020，62，3： | 7 |
| 7 | Analytical validation of GMEX rapid point- of care CYP2C19 genotyping system for the CHANCE-2 trial显示文摘Background and purpose Rapid genotyping is useful for guiding early antiplatelet therapy in patients with high-risk nondisabling ischaemic cerebrovascular events(HR-NICE).Conventional genetic testing methods used in CYP2C19 genotype-guided antiplatelet therapy for patients with HR-NICE did not satisfy the needs of the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events(CHANCE)-2 trial.Therefore,we developed the rapid-genotyping GMEX(point-of care)system to meet the needs of the CHANCE-2 trial.Methods Healthy individuals and patients with history of cardiovascular diseases(n=408)were enrolled from six centres of the CHANCE-2 trial.We compared the laboratory-based genomic test results with Sanger sequencing test results for accuracy verification.Next,we demonstrated the accuracy,timeliness and clinical operability of the GMEX system compared with laboratory-based technology(YZY Kit)to verify whether the GMEX system satisfies the needs of the CHANCE-2 trial.Results Genotypes reported by the GMEX system showed 100%agreement with those determined by using the YZY Kit and Sanger sequencing for all three CYP2C19 alleles(*2,*3 and*17)tested.The average result’s turnaround times for the GMEX and YZY Kit methods were 85.0(IQR:85.0-86.0)and 1630.0(IQR:354.0-7594.0)min(p<0.001),respectively.Conclusions Our data suggest that the GMEX system is a reliable and feasible point-of care system for rapid CYP2C19 genotyping for the CHANCE-2 trial or related clinical and research applications. | Xia Meng Anxin Wang Guojun Zhang Siying Niu Wei Li Sifei Han Fang Fang Xingquan Zhao Kehui Dong Zening Jin Huaguang Zheng Kelin Chen Hao Li Chengyuan Yang Yongjun Wang | 2021 | Stroke & Vascular Neurology2021，6，2： | 7 |
| 8 | Upregulated KPNA2 promotes hepatocellular carcinoma progression and indicates prognostic significance across human cancer types显示文摘Hepatocellular carcinoma(HCC)is one of the most aggressive cancers worldwide.Identification of the molecular mechanisms underlying the development and progression of HCC is particularly important.Here,we demonstrated the expression pattern,clinical significance,and function of Karyopherin α2(KPNA2)in HCC.The expression of KPNA2 was upregulated in tumor tissue and negatively associated with the survival time,and a significant correlation between KPNA2 expression and aggressive clinical characteristics was established.Both in vitro and in vivo experiments demonstrated that knockdown of KPNA2 reduced migration and proliferation capacities of HCC cells,while over-expression of KPNA2 increased these malignant characteristics.The analysis of the Cancer Genome Atlas cohorts also reveals that high-KPNA2 expression is associated with poor outcome in multiple cancer types.In addition,gene sets enrichment analysis exhibited cell cycle and DNA replication as the top altered pathways in the high-KPNA2 expression group in HCC and other two cancer types.Overall,this study identified KPNA2 as a potential diagnostic and prognostic biomarker in HCC and other neoplasms,probably by regulating cell cycle and DNA replication. | Xinggang Guo Zhiheng Wang Jianing Zhang Qingguo Xu Guojun Hou Yuan Yang Chuanpeng Dong Gang Liu Chenhua Liang Lei Liu Weiping Zhou Hui Liu | 2019 | Acta Biochimica et Biophysica Sinica2019，51，3： | 6 |
| 9 | Rational development of a human antibody cocktail that deploys multiple functions to confer Pan-SARS-CoVs protection显示文摘Structural principles underlying the composition and synergistic mechanisms of protective monoclonal antibody cocktails are poorly defined.Here,we exploited antibody cooperativity to develop a therapeutic antibody cocktail against SARS-CoV-2.On the basis of our previously identified humanized cross-neutralizing antibody H014,we systematically an a lyzed a fully human n aive antibody library and rationally identified a potent neutralizing antibody partner,P17,which confers effective protection in animal model.Cryo-EM studies dissected the nature of the P17 epitope,which is SARS-CoV-2 specific and distinctly different from that of HOI4.High-resolution structure of the SARS-CoV-2 spike in complex with HOM and P17,together with functional investigations revealed that in a two-antibody cocktail,synergistic neutralization was achieved by S1 shielding and conformational locking,thereby blocking receptor attachment and viral membrane fusion,conferring high potency as well as robustness against viral mutation escape.Furthermore,cluster analysis identified a hypothetical 3rd antibody partner for further reinforcing the cocktail as pan-SARS-CoVs therapeutics. | Hangping Yao Yao Sun Yong-Qiang Deng Nan Wang Yongcong Tan Na-Na Zhang Xiao-Feng Li Chao Kong Yan-Peng Xuc Qi Chen Tian-Shu Cao Hui Zhao Xintian Yan Lei Cao Zhe Lv Dandan Zhu Rui Feng Nanping Wu Wenhai Zhang Yuhao Hu Keda Chen Rong-Rong Zhang Qingyu Lv Shihui Sun Yunhua Zhou Run Yan Guan Yang Xinglu Chanjuan Liu Xiangyun Lu Linfang Cheng Hongying Qiu Xing-Yao Huang Tianhao Weng Danrong Shi Weidong Jiang Junbin Shao Lei Wang Jie Zhang Tao Jiang Guojun Lang Cheng-Feng Qinc Lanjuan Li Xiangxi Wang | 2021 | Cell Research2021，31，1： | 5 |
| 10 | Bevacizumab biosimilar LY01008 compared with bevacizumab(Avastin)as first-line treatment for Chinese patients with unresectable,metastatic,or recurrent non-squamous non-small-cell lung cancer:A multicenter,randomized,double-blinded,phase Ⅲ trial显示文摘Background:Previous studies have demonstrated the preclinical pharmacological and toxicological consistency,and clinical pharmacokinetic equivalence of bevacizumab biosimilar LY01008 with reference bevacizumab(Avastin).This randomized controlled trial aimed to compare the efficacy and safety of LY01008 with Avastin in first-line treatment of Chinese patients with advanced or recurrent non-squamous non-small cell lung cancer(NSCLC).Methods:StageⅢB-ⅣNSCLC patients with evaluable lesions,good physical status,and adequate organ functions from 67 centers across China were randomized in a ratio of 1:1 to receive LY01008 or Avastin 15 mg/kg intravenously in combination with paclitaxel/carboplatin(combined treatment)for 4-6 cycles,followed by maintenance monotherapy with LY01008 until disease progression,intolerable toxicity,or death.The primary endpoint was objective response rate(ORR)in accordance with Response Evaluation Criteria in Solid Tumors(RECIST)version 1.1 confirmed by independent radiological review committees(IRRC).Secondary endpoints included disease control rate(DCR),duration of response(DoR),progression-free survival(PFS),overall survival(OS),and safety.This study was registered in Clinical Trials.gov(NCT03533127).Results:Between December 15^(th),2017,and May 15^(th),2019,a total of 649 patients were randomized to the LY01008(n=324)or Avastin(n=325)group.As of September 25th,2019 for primary endpoint analysis,589 patients received ORR evaluation,with a median number of combined treatment cycles of 5(range 1-6)andmedian duration of treatment of 3.0(range 0.0-5.1)months.ORRof responseevaluable patients in the LY01008 and Avastin groups were 48.5% and 53.0%,respectively.The stratified ORR ratio was 0.91(90%CI 0.80-1.04,within the prespecified equivalence margin of 0.75-1.33).Up to May 15^(th),2020,with a median follow-up of 13.6(range 0.8-28.4)months,no notable differences in DCR,median DoR,median PFS,median OS,and 1-year OS rate were observed between the LY01008 and Avastin groups.There were no clinically meaningful differences in safety and immunogenicity across treatment groups.Conclusions:LY01008 demonstrated similarity to Avastin in terms of efficacy and safety in Chinese patients with advanced or recurrent non-squamous NSCLC.LY01008 combined with paclitaxel/carboplatin is expected to become a new treatment option for unresectable,metastatic,LY01008 and Avastin groups.There were no clinically meaningful differences in safety and immunogenicity across treatment groups.Conclusions:LY01008 demonstrated similarity to Avastin in terms of efficacy and safety in Chinese patients with advanced or recurrent non-squamous NSCLC.LY01008 combined with paclitaxel/carboplatin is expected to become a new treatment option for unresectable,metastatic,or recurrent non-squamous NSCLC patients in the first-line setting. | Yuankai Shi Kaijian Lei Yuming Jia Bingqiang Ni Zhiyong He Minghong Bi Xicheng Wang Jianhua Shi Ming Zhou Qian Sun Guolei Wang Dongji Chen Yongqian Shu Lianke Liu Zhongliang Guo Yong Liu Junquan Yang Ke Wang Ke Xiao LinWu Tienan Yi Debin Sun Mafei Kang Tianjiang Ma Yimin Mao Jinsheng Shi Tiegang Tang Yan Wang Puyuan Xing Dongqing Lv Wangjun Liao Zhiguo Luo Bin Wang Xiaohong Wu Xiaoli Zhu Shuhua Han Qisen Guo Rongyu Liu Zhiwei Lu Jianyong Zhang Jian Fang Changlu Hu Yinghua Ji Guolong Liu Hong Lu Dedong Wu Junhong Zhang Shuyang Zhu Zheng Liu Wensheng Qiu Feng Ye Yan Yu Yanqiu Zhao Qinhong Zheng Jun Chen Zhanyu Pan Yiping Zhang Wenjuan Lian Bo Jiang Bo Qiu Guojun Zhang Hua Zhang Yanju Chen Yuan Chen Hongbing Duan Manxiang Li Shengming Liu Lijun Ma Hongming Pan Xia Yuan Xueli Yuan Yulong Zheng Emei Gao Li Zhao Shumin Wang Can Wu | 2021 | Cancer Communications2021，41，9： | 5 |
| 11 | Sin1/mTORC2 regulate B cell growth and metabolism by activating mTORC1 and Myc显示文摘Proper control of B cell growth and metabolism is crucial for B-cell-mediated immunity,but the underlying molecular mechanisms remain incompletely understood.In this study,Sin1,a key component of mTOR complex 2(mTORC2),specifically regulates B cell growth and metabolism.Genetic ablation of Sin1 in B cells reduces the cell size at either the transitional stage or upon antigen stimulation and severely impairs metabolism.Sin1 deficiency also severely impairs B-cell proliferation,antibody responses,and anti-viral immunity.At the molecular level,Sin1 controls the expression and stability of the c-Myc protein and maintains the activity of mTORC1 through the Akt-dependent inactivation of GSK3 and TSC1/2,respectively.Therefore,our study reveals a novel and specific role for Sin1 in coordinating the activation of mTORC2 and mTORC1 to control B cell growth and metabolism. | Man Li Adam S.Lazorchak Xinxing Ouyang Huihui Zhang Hongzhi Liu Omotooke A.Arojo Lichong Yan Jingsi Jin Yuheng Han Guojun Qu Yuhong Fu Xiaocao Xu Xiaobo Liu Wenqian Zhang Zhengfeng Yang Chuan Ruan Qijun Wang Dou Liu Chuanxin Huang Lu Lu Shibo Jiang Fubin Li Bing Su | 2019 | Cellular & Molecular Immunology2019，16，9： | 4 |
| 12 | QTL mapping and QTL × environment interaction analysis of multi-seed pod in cultivated peanut(Arachis hypogaea L.)显示文摘To dissect the genetic mechanism of multi-seed pod in peanut, we explored the QTL/gene controlling multi-seed pod and analyzed the interaction effect of QTL and environment. Two hundred and forty eight recombinant inbred lines(RIL) from cross Silihong × Jinonghei 3 were used as experimental materials planted in 8 environments from 2012 to 2017. Three methods of analysis were performed. These included individual environment analysis, joint analysis in multiple environments, and epistatic interaction analysis for multi-seed pod QTL. Phenotypic data and best linear unbiased prediction(BLUP) value of the ratio of multi-seed pods per plant(RMSP) were used for QTL mapping. Seven QTL detected by the individual environmental mapping analysis and were distributed on linkage groups 1, 6, 9, 14, 19(2), and 21. Each QTL explained 4.42%–11.51% of the phenotypic variation in multi-seed pod, and synergistic alleles of5 QTL were from the Silihong parent. One QTL, explaining 4.93% of the phenotypic variation was detected using BLUP data, and this QTL mapped in the same interval as q RMSP19.1 detected in the individual environment analysis. Seventeen additive QTL were identified by joint analysis across multiple environments. A total of 43 epistatic QTL were detected by ICIM-EPI mapping in the multiple environment trials(MET) module, and involved 57 loci. Two main-effect QTL related to multi-seed pod in peanut were filtered. We also found that RMSP had a highly significant positive correlation with pod yield per plant(PY), and epistatic effects were much more important than additive effects. These results provide theoretical guidance for the genetic improvement of germplasm resources and further fine mapping of related genes in peanut. | Liang Wang Xinlei Yang Shunli Cui Guojun Mu Xingming Sun Lifeng Liu Zichao Li | 2019 | The Crop Journal2019，7，2： | 4 |
| 13 | Sortilin promotes macrophage cholesterol accumulation and aortic atherosclerosis through lysosomal degradation of ATP-binding cassette transporter A1 protein显示文摘Sortilin is closely associated with hyperlipidemia and the risk of atherosclerosis(AS).The role of sortilin and the underlying mechanism in peripheral macrophage are not fully understood.In this study,we investigated the effect of macrophage sortilin on ATP-binding cassette transporter A1(ABCA1)expression,ABCA1-mediated cholesterol efflux,and aortic AS.Macrophage sortilin expression was upregulated by oxidized low-density lipoproteins(ox-LDLs)in both concentration-and time-dependent manners.Its expression reached the peak level when cells were incubated with 50μg/ml ox-LDL for 24 h.Overexpression of sortilin in macrophage reduced cholesterol efflux,leading to an increase in intracellular total cholesterol,free cholesterol,and cholesterol ester.Sortilin was found to bind with ABCA1 protein and suppress macrophage ABCA1 expression,resulting in a decrease in cholesterol efflux from macrophages.The inhibitory effect of sortilin in cholesterol efflux was partially reversed by treatment with chloroquine,a lysosomal inhibitor.On the contrary,the ABCA1 protein level and ABCA1-mediated cholesterol efflux is increased by sortilin short hairpin RNA transfection.The fecal and biliary cholesterol 3H-sterol from cholesterol-laden mouse peritoneal macrophage was reduced by sortilin overexpression through lentivirus vector(LV)-sortilin in low-density lipoprotein receptor knockout mice,which was prevented by co-treatment with chloroquine.Treatment with LV-sortilin reduced plasma high-density lipoprotein and increased plasma ox-LDL levels.Accordingly,aortic lipid deposition and plaque area were exacerbated,and ABCA1 expression was reduced in mice in response to infection with LV-sortilin alone.These effects of LV-sortilin were partially reversed by chloroquine.Sortilin enhances lysosomal degradation of ABCA1 protein and suppresses ABCA1-mediated cholesterol efflux from macrophages,leading to foam cell formation and AS development. | Yuncheng Lv Jing Yang Anbo Gao Sha Sun Xilong Zheng Xi Chen Wei Wan Chaoke Tang Wei Xie Suyun Li Dongming Guo Tianhong Peng Guojun Zhao Liyuan Zhong | 2019 | Acta Biochimica et Biophysica Sinica2019，51，5： | 4 |
| 14 | Effect of the exposure to suspended solids on the enzymatic activity in the bivalve Sinonovacula constricta显示文摘Aquatic animals are susceptible to sudden changes of their living environment but they adopt strategies to cope with adverse environmental challenges.Contamination by suspended solids,often associated with a dramatic change in the concentrations of important water-quality variables is a frequent occurrence in China's coastal waters and estuaries.Here we studied the impact of suspended solids on the activities of the antioxidant enzymes superoxide dismutase(SOD)and catalase(CAT),as well as adenosine triphosphates(including Na^(+)K^(+)-ATPase,Mg^(++)-ATPase,Ca^(++)-ATPase)and H^(+)K^(+)-ATPase in the gills and visceral mass tissues of the molluscan bivalve Sinonovacula constricta exposed(4,8,12,16,20,and 24 days)to various concentrations of suspended solids.Our results showed that the antioxidant enzymes cooperated closely to effectively scavenge superoxide anion free radicals and H2O2(which can ultimately inhibit gill activity)through the modification of SOD and/or CAT enzymatic activities.ATPases activity(considered to be a sensitive indicator of toxicity)could play an effective role in the maintenance of functional integrity of the plasma membranes as well as some other intracellular functions.After the exposure,a decrease in the Nat K^(+)-ATPase,Mg^(++)-ATPase,and Ca^(++)-ATPase activity of the gills was observed suggesting that they were inhibited by the treatments.These results also indicated that,from day 4 to day 16,exposure to high concentrations of suspended solids had an inhibitory effect on the activity of H^(+)-K^(+)-ATPase in the visceral mass of S.constricta.However,after a period of adaptation the H^(+)-K^(+)-ATPase activity was restored to original levels.Our results suggest that long-term exposure to high levels of suspended solids disturb osmoregulation,gastric acid secretion and digestion,cause oxidative damage,as a consequence of antioxidant enzymes inactivation which eventually damages the gills,affect the food intake and transformation,ultimately resulting in systems failure and eventually death. | Guojun Yang Lun Song Xiaoqian Lu Nianbin Wang Yang Li | 2017 | Aquaculture and Fisheries2017，2，1： | 3 |
| 15 | Seasonal Variation of Environmental Variables and Phytoplankton Community Structure and Their Relationship in Liaodong Bay of Bohai Sea,China显示文摘In this paper, systematic studies on the changes in concentrations of the environmental factors and the net-phytoplankton community, and the relationship between them in the Liaodong Bay, Bohai Sea during 2013 are presented. The PCA results showed that higher levels of nutrients and dissolved heavy metals in the river-estuary-bay system were closely related to the river runoff. Since the influences of industrial and anthropogenic activities, the Liaodong Bay coastal areas are facing a huge environmental challenge of nutrients and heavy metal pollution. Net-phytoplankton community structure showed obvious seasonal succession, among which the dominant and(or) key species were the main factors affecting community structure change and stability. Under certain environmental conditions, the dominant species and(or) key species dominated the phytoplankton community structure succession. The Bio-ENV results suggested that the seawater temperature, nutrient, Cu, Pb, Zn, and Cd in Liaodong Bay are important environmental variables that affect the phytoplankton community structure. Anthropogenic activities have significantly contributed to the changes in concentrations of environmental factors and the net-phytoplankton community structure and stability, and the relationship between them. | YANG Guojun WU Zhongxin SONG Lun LU Xiaoqian | 2018 | Journal of Ocean University of China2018，17，4： | 3 |
| 16 | Efficacy of Rebixiao Chinese herbal tablets and Chinese formula granules in acute gout arthritis patients:a randomized,multicenter,double-blind,controlled trial显示文摘OBJECTIVE:To evaluate the clinical efficacy and safety of Rebixiao(RBX)Chinese herbal tablets(CHT)and Chinese formula granules(CFG)in the treatment of acute gout arthritis(AGA).METHODS:This randomized,multicenter,double-blind,controlled trial included 165 AGA patients with the damp-heat symptom pattern who were randomly divided into an RBX CHT group and an RBX CFG group and treated for 7 d at three centers.The total effective rates of the joint symptom score,Traditional Chinese Medicine(TCM)symptoms score,erythrocyte sedimentation rate(ESR),and C-reactive protein(CRP)were used to evaluate the clinical efficacy.Safety assessments were also performed.RESULTS:Of the 165 enrolled patients,147 completed the clinical observation.There was no difference in baseline between the two groups.The total effective rates of the joint symptom score were 94.36%and 97.36%,and the total effective rates of the TCM symptoms score were 95.77%and 97.36%in the CFG group and CHT group,respectively.No statistical difference was found between the two groups(P>0.05).Additionally,ESR and CRP were similar in both groups(P>0.05).Furthermore,treatment efficacy regarding TCM and joint symptoms,the ESR,and CRP were consistent within each center and among the different centers(P>0.05).In addition,the incidence of adverse events was 4.22%and 2.63%in the CFG group and CHT group,respectively,and no difference was observed between the two groups(P>0.05).CONCLUSION:RBX CFG and CHT have significant and similar efficacy in the treatment of AGA,and CFG did not increase adverse side effects. | Wang Shasha Zhang Ying Dai Min Yang Min Leng Wenfei Peng Xiufeng Li Guojun Yang Jinbing Gan Jianping Zhu Fenglin Li Yanping Wu Bin | 2020 | Journal of Traditional Chinese Medicine2020，40，4： | 3 |
| 17 | Genome-wide association study and transcriptome analysis reveal new QTL and candidate genes for nitrogen-deficiency tolerance in rice显示文摘The development of rice cultivars with improved nitrogen use efficiency(NUE)is desirable for sustainable agriculture.Achieving this goal depends in part on understanding how rice responds to low soil nitrogen(N)and identifying causative genes underlying this trait.To identify quantitative trait loci(QTL)or genes associated with low N response,we conducted a genome-wide association study(GWAS)using a diverse panel of 230 rice accessions and performed a transcriptomic investigation of rice accessions with differential responses to low N stress at two N levels.We detected 411 GWAS-associated genes in 5 QTL and 2722 differentially expressed genes in response to low N,of which 24 were identified by both methods and ranked according to gene annotations,literature queries,gene expression,and genetic diversity analysis.The large-scale datasets obtained from this study reveal low N-responsive characteristics and provide insights towards understanding the regulatory mechanisms of N-deficiency tolerance in rice,and the candidate genes or QTL would be valuable resources for increasing rice NUE via molecular biotechnology. | Qing Li Xueli Lu Changjian Wang Lan Shen Liping Dai Jinli He Long Yang Peiyuan Li Yifeng Hong Qiang Zhang Guojun Dong Jiang Hu Guangheng Zhang Deyong Ren Zhenyu Gao Longbiao Guo Qian Qian Li Zhu Dali Zeng | 2022 | The Crop Journal2022，10，4： | 3 |
| 18 | Greenhouse gas emissions from oilfield-produced water in Shengli Oilfield,Eastern China显示文摘Greenhouse gas(GHG) emissions from oil and gas systems are an important component of the GHG emission inventory. To assess the carbon emissions from oilfield-produced water under atmospheric conditions correctly, in situ detection and simulation experiments were developed to study the natural release of GHG into the atmosphere in the Shengli Oilfield,the second largest oilfield in China. The results showed that methane(CH4) and carbon dioxide(CO2) were the primary gases released naturally from the oilfield-produced water.The atmospheric temperature and release time played important roles in determining the CH4 and CO2emissions under atmospheric conditions. Higher temperatures enhanced the carbon emissions. The emissions of both CH4 and CO2from oilfield-produced water were highest at 27°C and lowest at 3°C. The bulk of CH4 and CO2was released from the oilfield-produced water during the first release period, 0–2 hr, for each temperature, with a maximum average emission rate of 0.415 g CH4/(m3·hr) and 3.934 g CO2/(m3·hr), respectively. Then the carbon emissions at other time periods gradually decreased with the extension of time. The higher solubility of CO2 in water than CH4 results in a higher emission rate of CH4 than CO2over the same release duration. The simulation proved that oilfield-produced water is one of the potential emission sources that should be given great attention in oil and gas systems. | Shuang Yang Wei Yang Guojun Chen Xuan Fang Chengfu Lv Jiaai Zhong Lianhua Xue | 2016 | Journal of Environmental Sciences2016，28，8： | 2 |
| 19 | Bacteroides ovatus-mediated CD27^(−)MAIT cell activation is associated with obesity-related T2D progression显示文摘Type 2 diabetes(T2D)is highly associated with obesity.However,the factors that drive the transition from excessive weight gain to glucose metabolism disruption are still uncertain and seem to revolve around systemic immune disorder.Mucosal-associated invariant T(MAIT)cells,which are innate-like T cells that recognize bacterial metabolites,have been reported to be altered in obese people and to lead to metabolic dysfunction during obesity.By studying the immunophenotypes of blood MAIT cells from a cross-sectional cohort of obese participants with/without T2D,we found an elevation in CD27^(-)negative(CD27−)MAIT cells producing a high level of IL-17 under T2D obese conditions,which could be positively correlated with impaired glucose metabolism in obese people.We further explored microbial translocation caused by gut barrier dysfunction in obese people as a triggering factor of MAIT cell abnormalities.Specifically,accumulation of the bacterial strain Bacteroides ovatus in the peripheral blood drove IL-17^(-)producing CD27−MAIT cell expansion and could be associated with T2D risk in obese individuals.Overall,these results suggest that an aberrant gut microbiota–immune axis in obese people may drive or exacerbate T2D.Importantly,CD27−MAIT cell subsets and Bacteroides ovatus could represent targets for novel interventional strategies.Our findings extend current knowledge regarding the clinical relevance of body mass index(BMI)-associated variation in circulating MAIT cells to reveal the role of these cells in obesity-related T2D progression and the underlying cellular mechanisms. | Yue Li Yi Yang Jin Wang Peihong Cai Mei Li Xixiang Tang Ying Tan Yuchan Wang Fan Zhang Xiaofeng Wen Qiaoxing Liang Yuanpeng Nie Tufeng Chen Xiang Peng Xuemin He Yanhua Zhu Guojun Shi Wai WCheung Lai Wei Yanming Chen Yan Lu | 2022 | Cellular & Molecular Immunology2022，19，7： | 2 |
| 20 | The function of three indigenous plasmids in Mesorhizobium huakuii 2020 and its symbiotic inter-action with Sym pJB5JI of Rhizobium leguminosarum显示文摘A Mesorhizobium huakuii strain 2020, isolated from a rice-growing field in southern China, contains three indigenous plasmids named p2020a, p2020b and p2020c, respectively. The plasmids were deleted via Tn5-sacB insertion, and two cured derivatives were obtained. Interestingly, the mutant 2020D29 curing of p2020c could significantly enhance the capacity of symbiotic nitrogen fixation. But the mutant 2020D8 curing of p2020b lost the ability to nodulate Astragalus sinicus. Furthermore, the third plasmid p2020a could be hardly eliminated, suggesting that some house-keeping genes necessary for strain growth located on this plasmid. Then the Sym plasmid pJB5JI of R. leguminosarum bv. viciae was transferred into 2020 and its cured derivatives. The pot plant test showed that the ability of competition and symbiotic nitrogen fixation of transconjugant 2020-137 (pJB5JI) was increased evidently in con-trast to 2020. pJB5JI could not restore the ability of 2020D8 to nodulate Astragalus sinicus. 2020D8-8 (pJB5JI) could form ineffective nodules on peas, which implied that the symbiotic plasmid pJB5JI could express its function at the chromosomal background of Mesorhizobium huakuii 2020. The plas-mid stability was checked in transconjugants under free-living and during symbiosis. The results indi-cated that pJB5JI failed to be detected in some nodule isolates. That Km resistance gene could be am-plified from all transconjugants and nodule isolates suggested that pJB5JI was fully or partially inte-grated into the chromosome of recipients. | YANG ChengYun, LI YouGuo, WEI Li, CHENG GuoJun & ZHOU JunChu State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China | 2008 | Science China(Life Sciences)2008，51，4： | 2 |
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