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Joint analysis of three genome-wide association studies of esophageal squamous cell carcinoma in Chinese populations Wu, Chen | Wang, Zhaoming | Song, Xin | Feng, Xiao-Shan | Abnet, Christian C. | He, Jie | Hu, Nan | Zuo, Xian-Bo | Tan, Wen | Zhan, Qimin | Hu, Zhibin | He, Zhonghu | Jia, Weihua | Zhou, Yifeng | Yu, Kai | Shu, Xiao-Ou | Yuan, Jian-Min | Zheng, Wei | Zhao, Xue-Ke | Gao, She-Gan | Yuan, Zhi-Qing | Zhou, Fu-You | Fan, Zong-Min | Cui, Ji-Li | Lin, Hong-Li | Han, Xue-Na | Li, Bei | Chen, Xi | Dawsey, Sanford M. | Liao, Linda | Lee, Maxwell P. | Ding, Ti | Qiao, You-Lin | Liu, Zhihua | Liu, Yu | Yu, Dianke | Chang, Jiang | Wei, Lixuan | Gao, Yu-Tang | Koh, Woon-Puay | Xiang, Yong-Bing | Tang, Ze-Zhong | Fan, Jin-Hu | Han, Jing-Jing | Zhou, Sheng-Li | Zhang, Peng | Zhang, Dong-Yun | Yuan, Yuan | Huang, Ying | Liu, Chunling | Zhai, Kan | Qiao, Yan | Jin, Guangfu | Guo, Chuanhai | Fu, Jianhua | Miao, Xiaoping | Lu, Changdong | Yang, Haijun | Wang, Chaoyu | Wheeler, William A. | Gail, Mitchell | Yeager, Meredith | Yuenger, Jeff | Guo, Er-Tao | Li, Ai-Li | Zhang, Wei | Li, Xue-Min | Sun, Liang-Dan | Ma, Bao-Gen | Li, Yan | Tang, Sa | Peng, Xiu-Qing | Liu, Jing | Hutchinson, Amy | Jacobs, Kevin | Giffen, Carol | Burdette, Laurie | Fraumeni, Joseph F. | Shen, Hongbing | Ke, Yang | Zeng, Yixin | Wu, Tangchun | Kraft, Peter | Chung, Charles C. | Tucker, Margaret A. | Hou, Zhi-Chao | Liu, Ya-Li | Hu, Yan-Long | Liu, Yu | Wang, Li | Yuan, Guo | Chen, Li-Sha | Liu, Xiao | Ma, Teng | Meng, Hui | Sun, Li | Li, Xin-Min | Li, Xiu-Min | Ku, Jian-Wei | Zhou, Ying-Fa | Yang, Liu-Qin | Wang, Zhou | Li, Yin | Qige, Qirenwang | Yang, Wen-Jun | Lei, Guang-Yan | Chen, Long-Qi | Li, En-Min | Yuan, Ling | Yue, Wen-Bin | Wang, Ran | Wang, Lu-Wen | Fan, Xue-Ping | Zhu, Fang-Heng | Zhao, Wei-Xing | Mao, Yi-Min | Zhang, Mei | Xing, Guo-Lan | Li, Ji-Lin | Han, Min | Ren, Jing-Li | Liu, Bin | Ren, Shu-Wei | Kong, Qing-Peng | Li, Feng | Sheyhidin, Ilyar | Wei, Wu | Zhang, Yan-Rui | Feng, Chang-Wei | Wang, Jin | Yang, Yu-Hua | Hao, Hong-Zhang | Bao, Qi-De | Liu, Bao-Chi | Wu, Ai-Qun | Xie, Dong | Yang, Wan-Cai | Wang, Liang | Zhao, Xiao-Hang | Chen, Shu-Qing | Hong, Jun-Yan | Zhang, Xue-Jun | Freedman, Neal D | Goldstein, Alisa M. | Lin, Dongxin | Taylor, Philip R. | Wang, Li-Dong | Chanock, Stephen J.\nNature genetics 2014;46(9):1001-1006.\nWe conducted a joint (pooled) analysis of three genome-wide association studies (GWAS) 1-3 of esophageal squamous cell carcinoma (ESCC) in ethnic Chinese (5,337 ESCC cases and 5,787 controls) with 9,654 ESCC cases and 10,058 controls for follow-up. In a logistic regression model adjusted for age, sex, study, and two eigenvectors, two new loci achieved genome-wide significance, marked by rs7447927 at 5q31.2 (per-allele odds ratio (OR) = 0.85, 95% CI 0.82-0.88; P=7.72x10−20) and rs1642764 at 17p13.1 (per-allele OR= 0.88, 95% CI 0.85-0.91; P=3.10x10−13). rs7447927 is a synonymous single nucleotide polymorphism (SNP) in TMEM173 and rs1642764 is an intronic SNP in ATP1B2, near TP53. Furthermore, a locus in the HLA class II region at 6p21.32 (rs35597309) achieved genome-wide significance in the two populations at highest risk for ESSC (OR=1.33, 95% CI 1.22-1.46; P=1.99x10−10). Our joint analysis identified new ESCC susceptibility loci overall as well as a new locus unique to the ESCC high risk Taihang Mountain region.\n2. Genotypic variants at 2q33 and risk of esophageal squamous cell carcinoma in China: a meta-analysis of genome-wide association studies Abnet, Christian C. | Wang, Zhaoming | Song, Xin | Hu, Nan | Zhou, Fu-You | Freedman, Neal D. | Li, Xue-Min | Yu, Kai | Shu, Xiao-Ou | Yuan, Jian-Min | Zheng, Wei | Dawsey, Sanford M. | Liao, Linda M. | Lee, Maxwell P. | Ding, Ti | Qiao, You-Lin | Gao, Yu-Tang | Koh, Woon-Puay | Xiang, Yong-Bing | Tang, Ze-Zhong | Fan, Jin-Hu | Chung, Charles C. | Wang, Chaoyu | Wheeler, William | Yeager, Meredith | Yuenger, Jeff | Hutchinson, Amy | Jacobs, Kevin B. | Giffen, Carol A. | Burdett, Laurie | Fraumeni, Joseph F. | Tucker, Margaret A. | Chow, Wong-Ho | Zhao, Xue-Ke | Li, Jiang-Man | Li, Ai-Li | Sun, Liang-Dan | Wei, Wu | Li, Ji-Lin | Zhang, Peng | Li, Hong-Lei | Cui, Wen-Yan | Wang, Wei-Peng | Liu, Zhi-Cai | Yang, Xia | Fu, Wen-Jing | Cui, Ji-Li | Lin, Hong-Li | Zhu, Wen-Liang | Liu, Min | Chen, Xi | Chen, Jie | Guo, Li | Han, Jing-Jing | Zhou, Sheng-Li | Huang, Jia | Wu, Yue | Yuan, Chao | Huang, Jing | Ji, Ai-Fang | Kul, Jian-Wei | Fan, Zhong-Min | Wang, Jian-Po | Zhang, Dong-Yun | Zhang, Lian-Qun | Zhang, Wei | Chen, Yuan-Fang | Ren, Jing-Li | Li, Xiu-Min | Dong, Jin-Cheng | Xing, Guo-Lan | Guo, Zhi-Gang | Yang, Jian-Xue | Mao, Yi-Ming | Yuan, Yuan | Guo, Er-Tao | Zhang, Wei | Hou, Zhi-Chao | Liu, Jing | Li, Yan | Tang, Sa | Chang, Jia | Peng, Xiu-Qin | Han, Min | Yin, Wan-Li | Liu, Ya-Li | Hu, Yan-Long | Liu, Yu | Yang, Liu-Qin | Zhu, Fu-Guo | Yang, Xiu-Feng | Feng, Xiao-Shan | Wang, Zhou | Li, Yin | Gao, She-Gan | Liu, Hai-Lin | Yuan, Ling | Jin, Yan | Zhang, Yan-Rui | Sheyhidin, Ilyar | Li, Feng | Chen, Bao-Ping | Ren, Shu-Wei | Liu, Bin | Li, Dan | Zhang, Gao-Fu | Yue, Wen-Bin | Feng, Chang-Wei | Qige, Qirenwang | Zhao, Jian-Ting | Yang, Wen-Jun | Lei, Guang-Yan | Chen, Long-Qi | Li, En-Min | Xu, Li-Yan | Wu, Zhi-Yong | Bao, Zhi-Qin | Chen, Ji-Li | Li, Xian-Chang | Zhuang, Xiang | Zhou, Ying-Fa | Zuo, Xian-Bo | Dong, Zi-Ming | Wang, Lu-Wen | Fan, Xue-Pin | Wang, Jin | Zhou, Qi | Ma, Guo-Shun | Zhang, Qin-Xian | Liu, Hai | Jian, Xin-Ying | Lian, Sin-Yong | Wang, Jin-Sheng | Chang, Fu-Bao | Lu, Chang-Dong | Miao, Jian-Jun | Chen, Zhi-Guo | Wang, Ran | Guo, Ming | Fan, Zeng-Lin | Tao, Ping | Liu, Tai-Jing | Wei, Jin-Chang | Kong, Qing-Peng | Fan, Lei | Wang, Xian-Zeng | Gao, Fu-Sheng | Wang, Tian-Yun | Xie, Dong | Wang, Li | Chen, Shu-Qing | Yang, Wan-Cai | Hong, Jun-Yan | Wang, Liang | Qiu, Song-Liang | Goldstein, Alisa M. | Yuan, Zhi-Qing | Chanock, Stephen J. | Zhang, Xue-Jun | Taylor, Philip R. | Wang, Li-Dong\nHuman Molecular Genetics 2012;21(9):2132-2141.\nGenome-wide association studies have identified susceptibility loci for esophageal squamous cell carcinoma (ESCC). We conducted a meta-analysis of all single-nucleotide polymorphisms (SNPs) that showed nominally significant P-values in two previously published genome-wide scans that included a total of 2961 ESCC cases and 3400 controls. The meta-analysis revealed five SNPs at 2q33 with P< 5 × 10−8, and the strongest signal was rs13016963, with a combined odds ratio (95% confidence interval) of 1.29 (1.19–1.40) and P= 7.63 × 10−10. An imputation analysis of 4304 SNPs at 2q33 suggested a single association signal, and the strongest imputed SNP associations were similar to those from the genotyped SNPs. We conducted an ancestral recombination graph analysis with 53 SNPs to identify one or more haplotypes that harbor the variants directly responsible for the detected association signal. This showed that the five SNPs exist in a single haplotype along with 45 imputed SNPs in strong linkage disequilibrium, and the strongest candidate was rs10201587, one of the genotyped SNPs. Our meta-analysis found genome-wide significant SNPs at 2q33 that map to the CASP8/ALS2CR12/TRAK2 gene region. Variants in CASP8 have been extensively studied across a spectrum of cancers with mixed results. The locus we identified appears to be distinct from the widely studied rs3834129 and rs1045485 SNPs in CASP8. Future studies of esophageal and other cancers should focus on comprehensive sequencing of this 2q33 locus and functional analysis of rs13016963 and rs10201587 and other strongly correlated variants.\n3. The Brassica oleracea genome reveals the asymmetrical evolution of polyploid\ngenomes Liu, Shengyi | Liu, Yumei | Yang, Xinhua | Tong, Chaobo | Edwards, David | Parkin, Isobel A. P. | Zhao, Meixia | Ma, Jianxin | Yu, Jingyin | Huang, Shunmou | Wang, Xiyin | Wang, Junyi | Lu, Kun | Fang, Zhiyuan | Bancroft, Ian | Yang, Tae-Jin | Hu, Qiong | Wang, Xinfa | Yue, Zhen | Li, Haojie | Yang, Linfeng | Wu, Jian | Zhou, Qing | Wang, Wanxin | King, Graham J | Pires, J. Chris | Lu, Changxin | Wu, Zhangyan | Sampath, Perumal | Wang, Zhuo | Guo, Hui | Pan, Shengkai | Yang, Limei | Min, Jiumeng | Zhang, Dong | Jin, Dianchuan | Li, Wanshun | Belcram, Harry | Tu, Jinxing | Guan, Mei | Qi, Cunkou | Du, Dezhi | Li, Jiana | Jiang, Liangcai | Batley, Jacqueline | Sharpe, Andrew G | Park, Beom-Seok | Ruperao, Pradeep | Cheng, Feng | Waminal, Nomar Espinosa | Huang, Yin | Dong, Caihua | Wang, Li | Li, Jingping | Hu, Zhiyong | Zhuang, Mu | Huang, Yi | Huang, Junyan | Shi, Jiaqin | Mei, Desheng | Liu, Jing | Lee, Tae-Ho | Wang, Jinpeng | Jin, Huizhe | Li, Zaiyun | Li, Xun | Zhang, Jiefu | Xiao, Lu | Zhou, Yongming | Liu, Zhongsong | Liu, Xuequn | Qin, Rui | Tang, Xu | Liu, Wenbin | Wang, Yupeng | Zhang, Yangyong | Lee, Jonghoon | Kim, Hyun Hee | Denoeud, France | Xu, Xun | Liang, Xinming | Hua, Wei | Wang, Xiaowu | Wang, Jun | Chalhoub, Boulos | Paterson, Andrew H\nNature Communications 2014;5:3930.\nPolyploidization has provided much genetic variation for plant adaptive evolution,\nbut the mechanisms by which the molecular evolution of polyploid genomes establishes\ngenetic architecture underlying species differentiation are unclear. Brassica\nis an ideal model to increase knowledge of polyploid evolution. Here we describe a\ndraft genome sequence of Brassica oleracea, comparing it with that of its\nsister species B. rapa to reveal numerous chromosome rearrangements and\nasymmetrical gene loss in duplicated genomic blocks, asymmetrical amplification of\ntransposable elements, differential gene co-retention for specific pathways and\nvariation in gene expression, including alternative splicing, among a large number\nof paralogous and orthologous genes. Genes related to the production of anticancer\nphytochemicals and morphological variations illustrate consequences of genome\nduplication and gene divergence, imparting biochemical and morphological variation\nto B. oleracea. This study provides insights into Brassica genome\nevolution and will underpin research into the many important crops in this\nBrassica oleracea is plant species comprising economically important vegetable\ncrops. Here, the authors report the draft genome sequence of B. oleracea and,\nthrough a comparative analysis with the closely related B. rapa, reveal insights\ninto Brassica evolution and divergence of interspecific genomes and intraspecific\n4. Dual-color immunofluorescent labeling with quantum dots of the diabetes-associated proteins aldose reductase and Toll-like receptor 4 in the kidneys of diabetic rats Liu, Xiaomin | Hu, Rui | Lian, Hongwei | Liu, Yang | Liu, Jing | Liu, Jianwei | Lin, Guimiao | Liu, Liwei | Duan, Xiaojian | Yong, Ken-Tye | Ye, Ling\nInternational Journal of Nanomedicine 2015;10:3651-3662.\nDiabetes is one of the major chronic diseases diagnosed worldwide with a common complication of diabetic nephropathy (DN). There are multiple possible mechanisms associated with DN. Aldose reductase (AR) and Toll-like receptor 4 (TLR4) may be involved in the occurrence and development of DN. Here, we describe the distribution of AR and TLR4 in cells and renal tissues of diabetic rats through a quantum dot (QD)-based immunofluorescence technique and conventional immunohistochemistry. As a new type of nanosized fluorophore, QDs have been recognized in imaging applications and have broad prospects in biomedical research. The results of the reported study demonstrate that both the AR and the TLR4 proteins were upregulated in the renal tissues of diabetic rats. Further, to explore the relationship between AR and TLR4 in the pathogenesis of DN, a dual-color immunofluorescent labeling technique based on QDs was applied, where the expressions of AR and TLR4 in the renal tissues of diabetic rats were simultaneously observed – for the first time, as far as we are aware. The optimized QD-based immunofluorescence technique has not only shown a satisfying sensitivity and specificity for the detection of biomarkers in cells and tissues, but also is a valuable supplement of immu-nohistochemistry. The QD-based multiplexed imaging technology provides a new insight into the mechanistic study of the correlation among biological factors as well as having potential applications in the diagnosis and treatment of diseases.\ndiabetic nephropathy; TLR4; immunofluorescence; immunohistochemistry\n5. D-Galactose Induces a Mitochondrial Complex I Deficiency in Mouse Skeletal Muscle: Potential Benefits of Nutrient Combination in Ameliorating Muscle Impairment Chang, Liao | Liu, Xin | Liu, Jing | Li, Hua | Yang, Yanshen | Liu, Jia | Guo, Zihao | Xiao, Ke | Zhang, Chen | Liu, Jiankang | Zhao-Wilson, Xi | Long, Jiangang\nJournal of Medicinal Food 2014;17(3):357-364.\nAccumulating research has shown that chronic D-galactose (D-gal) exposure induces symptoms similar to natural aging in animals. Therefore, rodents chronically exposed to D-gal are increasingly used as a model for aging and delay-of-aging pharmacological research. Mitochondrial dysfunction is thought to play a vital role in aging and age-related diseases; however, whether mitochondrial dysfunction plays a significant role in mice exposed to D-gal remains unknown. In the present study, we investigated cognitive dysfunction, locomotor activity, and mitochondrial dysfunction involved in D-gal exposure in mice. We found that D-gal exposure (125 mg/kg/day, 8 weeks) resulted in a serious impairment in grip strength in mice, whereas spatial memory and locomotor coordination remained intact. Interestingly, muscular mitochondrial complex I deficiency occurred in the skeletal muscle of mice exposed to D-gal. Mitochondrial ultrastructure abnormality was implicated as a contributing factor in D-gal-induced muscular impairment. Moreover, three combinations (A, B, and C) of nutrients applied in this study effectively reversed D-gal-induced muscular impairment. Nutrient formulas B and C were especially effective in reversing complex I dysfunction in both skeletal muscle and heart muscle. These findings suggest the following: (1) chronic exposure to D-gal first results in specific muscular impairment in mice, rather than causing general, premature aging; (2) poor skeletal muscle strength induced by D-gal might be due to the mitochondrial dysfunction caused by complex I deficiency; and (3) the nutrient complexes applied in the study attenuated the skeletal muscle impairment, most likely by improving mitochondrial function.\naging; dietary supplement; mitochondria\n6. The Epidemic Characteristics and Changing Trend of Hemorrhagic Fever with Renal Syndrome in Hubei Province, China Zhang, Yi-Hui | Ge, Liang | Liu, Li | Huo, Xi-Xiang | Xiong, Hai-Rong | Liu, Yuan-Yuan | Liu, Dong-Ying | Luo, Fan | Li, Jin-Lin | Ling, Jia-Xin | Chen, Wen | Liu, Jing | Hou, Wei | Zhang, Yun | Fan, Hong | Yang, Zhan-Qiu\nPLoS ONE 2014;9(3):e92700.\nHemorrhagic fever with renal syndrome (HFRS) is caused by different hantaviruses within the Bunyaviridae family. HFRS is a fulminant, infectious disease that occurs worldwide and is endemic in all 31 provinces of China. Since the first HFRS case in Hubei Province was reported in 1957, the disease has spread across the province and Hubei has become one of the seriously affected areas in China with the greatest number of reported HFRS cases in the 1980's. However, the epidemic characteristics of HFRS in Hubei are still not entirely clear and long-term, systematic investigations of this epidemic area have been very limited.\nThe spatiotemporal distribution of HFRS was investigated using data spanning the years 1980 to 2009. The annual HFRS incidence, fatality rate and seasonal incidence between 1980 and 2009 were calculated and plotted. GIS-based spatial analyses were conducted to detect the spatial distribution and seasonal pattern of HFRS. A spatial statistical analysis, using Kulldorff's spatial scan statistic, was performed to identify clustering of HFRS.\nA total of 104,467 HFRS cases were reported in Hubei Province between 1980 and 2009. Incidence of and mortality due to HFRS declined after the outbreak in 1980s and HFRS cases have been sporadic in recent years. The locations and scale of disease clusters have changed during the three decades. The seasonal epidemic pattern of HFRS was characterized by the shift from the unimodal type (autumn/winter peak) to the bimodal type.\nSocioeconomic development has great influence on the transmission of hantaviruses to humans and new epidemic characteristics have emerged in Hubei Province. It is necessary to reinforce preventative measures against HFRS according to the newly-presented seasonal variation and to intensify these efforts especially in the urban areas of Hubei Province.\n7. Klotho Endows Hepatoma Cells with Resistance to Anoikis via VEGFR2/PAK1 Activation in Hepatocellular Carcinoma Chen, Lin | Liu, Haiou | Liu, Jing | Zhu, Yu | Xu, Le | He, Hongyong | Zhang, Heng | Wang, Shanshan | Wu, Qian | Liu, Weisi | Liu, Yidong | Pan, Deng | Ren, Shifang | Xu, Jiejie | Gu, Jianxin\nPLoS ONE 2013;8(3):e58413.\nKlotho was originally characterized as an aging suppressor gene that predisposed Klotho-deficient mice to premature aging-like syndrome. Although Klotho was recently reported to exhibit tumor suppressive properties during various malignant transformations, the functional role and molecular mechanism of Klotho in hepatocarcinogenesis remains poorly understood. In our present study, immunohistochemical Klotho staining levels in a clinical follow-up of 52 hepatoma patients were significantly associated with liver cirrhosis, tumor multiplicity and venous invasion. The overall survival rate of hepatoma patients with high Klotho expression was significantly lower than those patients with low Klotho expression. Moreover, Klotho overexpression increased cellular migration, anchorage-independent growth, and anoikis resistance in hepatoma cells. Klotho overexpression elevated p21-activated kinase 1 (PAK1) expression and shRNA-mediated PAK1 knockdown and kinase activity inhibition with kinase dead mutant PAK1 K299R coexpression or allosteric inhibitor IPA3 treatment reversed anoikis resistance in Klotho-overexpressed hepatoma cells. More importantly, the pivotal significance of upregulated VEGFR2 protein levels mediated by Klotho expression was confirmed by VEGFR2 inhibitor Axitinib and blocking antibody treatment in hepatoma cells. Axitinib treatment sensitized anoikis was reversed by constitutive active mutant PAK1 T423E coexpression in Klotho-overexpressed hepatoma cells. Conversely, knockdown of Klotho reduced VEGFR2/PAK1 dependent anoikis resistance, which could be reversed by PAK1 T423E. These results revealed a novel oncogenic function of Klotho in promoting anoikis resistance via activating VEGFR2/PAK1 signaling, thus facilitating tumor migration and invasion during hepatoma progression, which could provide a putative molecular mechanism for tumor metastasis.\n8. Overexpression of FRAT1 Is Associated with Malignant Phenotype and Poor Prognosis in Human Gliomas Guo, Geng | Zhong, Cheng-liang | Liu, Yang | Mao, Xing-gang | Zhang, Zheng | Jin, Ji | Liu, Jing | Yang, Liu | Mao, Jin-ming | Guo, Yu-hong | Zhao, Yuan-li\nDisease Markers 2015;2015:289750.\nGlioma is the most common malignancy of the central nervous system. Approximately 40 percent of intracranial tumors are diagnosed as gliomas. Difficulties in treatment are associated closely with the malignant phenotype, which is characterized by excessive proliferation, relentless invasion, and angiogenesis. Although the comprehensive treatment level of brain glioma is continuously progressing, the outcome of this malignancy has not been improved drastically. Therefore, the identification of new biomarkers for diagnosis and therapy of this malignancy is of significant scientific and clinical value. FRAT1 is a positive regulator of the Wnt/β-catenin signaling pathway and is overexpressed in many human tumors. In the present study, we investigated the expression status of FRAT1 in 68 patients with human gliomas and its correlation with the pathologic grade, proliferation, invasion, angiogenesis, and prognostic significance. These findings suggest that FRAT1 may be an important factor in the tumorigenesis and progression of glioma and could be explored as a potential biomarker for pathological diagnosis, an indicator for prognosis, and a target for biological therapy of malignancy.\n9. Cbl-b inhibits P-gp transporter function by preventing its translocation into caveolae in multiple drug-resistant gastric and breast cancers Zhang, Ye | Qu, Xiujuan | Teng, Yuee | Li, Zhi | Xu, Ling | Liu, Jing | Ma, Yanju | Fan, Yibo | Li, Ce | Liu, Shizhou | Wang, Zhenning | Hu, Xuejun | Zhang, Jingdong | Liu, Yunpeng\nThe transport function of P-glycoprotein (P-gp) requires its efficient localization to caveolae, a subset of lipid rafts, and disruption of caveolae suppresses P-gp transport function. However, the regulatory molecules involved in the translocation of P-gp into caveolae remain unknown. In the present study, we showed that c-Src dependent Caveolin-1 phosphorylation promoted the translocation of P-gp into caveolae, resulting in multidrug resistance in adriamycin resistant gastric cancer SGC7901/Adr and breast cancer MCF-7/Adr cells. In a negative feedback loop, the translocation of Cbl-b from the nucleus to the cytoplasm prevented the localization of P-gp to caveolae resulting in the reversal of MDR through the ubiquitination and degradation of c-Src. Clinical data showed a significant positive relationship between Cbl-b expression and survival in P-gp positive breast cancer patients who received anthracycline-based chemotherapy. Our findings identified a new regulatory mechanism of P-gp transport function in multiple drug-resistant gastric and breast cancers.\nCbl-b; P-gp; Caveolae; Multiple Drug-resistant\n10. Discovery of a Potent, Covalent BTK Inhibitor for\nB-Cell Lymphoma Wu, Hong | Wang, Wenchao | Liu, Feiyang | Weisberg, Ellen L. | Tian, Bei | Chen, Yongfei | Li, Binhua | Wang, Aoli | Wang, Beilei | Zhao, Zheng | McMillin, Douglas W. | Hu, Chen | Li, Hong | Wang, Jinhua | Liang, Yanke | Buhrlage, Sara J. | Liang, Junting | Liu, Jing | Yang, Guang | Brown, Jennifer\nR. | Treon, Steven P. | Mitsiades, Constantine S. | Griffin, James D. | Liu, Qingsong | Gray, Nathanael S.\nACS Chemical Biology 2014;9(5):1086-1091.\nBTK is a member of the TEC family\nof non-receptor tyrosine kinases\nwhose deregulation has been implicated in a variety of B-cell-related\ndiseases. We have used structure-based drug design in conjunction\nwith kinome profiling and cellular assays to develop a potent, selective,\nand irreversible BTK kinase inhibitor, QL47, which covalently modifies\nCys481. QL47 inhibits BTK kinase activity with an IC50 of\n7 nM, inhibits autophosphorylation of BTK on Tyr223 in cells with\nan EC50 of 475 nM, and inhibits phosphorylation of a downstream\neffector PLCγ2 (Tyr759) with an EC50 of 318 nM. In\nRamos cells QL47 induces a G1 cell cycle arrest that is associated\nwith pronounced degradation of BTK protein. QL47 inhibits the proliferation\nof B-cell lymphoma cancer cell lines at submicromolar concentrations.\n11. Overendocytosis of gold nanoparticles increases autophagy and apoptosis in hypoxic human renal proximal tubular cells Ding, Fengan | Li, Yiping | Liu, Jing | Liu, Lei | Yu, Wenmin | Wang, Zhi | Ni, Haifeng | Liu, Bicheng | Chen, Pingsheng\nInternational Journal of Nanomedicine 2014;9:4317-4330.\nGold nanoparticles (GNPs) can potentially be used in biomedical fields ranging from therapeutics to diagnostics, and their use will result in increased human exposure. Many studies have demonstrated that GNPs can be deposited in the kidneys, particularly in renal tubular epithelial cells. Chronic hypoxic is inevitable in chronic kidney diseases, and it results in renal tubular epithelial cells that are susceptible to different types of injuries. However, the understanding of the interactions between GNPs and hypoxic renal tubular epithelial cells is still rudimentary. In the present study, we characterized the cytotoxic effects of GNPs in hypoxic renal tubular epithelial cells.\nBoth 5 nm and 13 nm GNPs were synthesized and characterized using various biophysical methods, including transmission electron microscopy, dynamic light scattering, and ultraviolet–visible spectrophotometry. We detected the cytotoxicity of 5 and 13 nm GNPs (0, 1, 25, and 50 nM) to human renal proximal tubular cells (HK-2) by Cell Counting Kit-8 assay and lactate dehydrogenase release assay, but we just found the toxic effect in the 5 nm GNP-treated cells at 50 nM dose under hypoxic condition. Furthermore, the transmission electron microscopy images revealed that GNPs were either localized in vesicles or free in the lysosomes in 5 nm GNPs-treated HK-2 cells, and the cellular uptake of the GNPs in the hypoxic cells was significantly higher than that in normoxic cells. In normoxic HK-2 cells, 5 nm GNPs (50 nM) treatment could cause autophagy and cell survival. However, in hypoxic conditions, the GNP exposure at the same condition led to the production of reactive oxygen species, the loss of mitochondrial membrane potential (ΔΨM), and an increase in apoptosis and autophagic cell death.\nOur results demonstrate that renal tubular epithelial cells presented different responses under normoxic and hypoxic environments, which provide an important basis for understanding the risks associated with GNP use–especially for the potential GNP-related therapies in chronic kidney disease patients.\ngold nanoparticles (GNPs); toxicity; autophagy; apoptosis\n12. CistromeFinder for ChIP-seq and DNase-seq data reuse Sun, Hanfei | Qin, Bo | Liu, Tao | Wang, Qixuan | Liu, Jing | Wang, Juan | Lin, Xueqiu | Yang, Yulin | Taing, Len | Rao, Prakash K. | Brown, Myles | Zhang, Yong | Long, Henry W. | Liu, X. Shirley\nSummary: Chromatin immunoprecipitation and DNase I hypersensitivity assays with high-throughput sequencing have greatly accelerated the understanding of transcriptional and epigenetic regulation, although data reuse for the community of experimental biologists has been challenging. We created a data portal CistromeFinder that can help query, evaluate and visualize publicly available Chromatin immunoprecipitation and DNase I hypersensitivity assays with high-throughput sequencing data in human and mouse. The database currently contains 6378 samples over 4391 datasets, 313 factors and 102 cell lines or cell populations. Each dataset has gone through a consistent analysis and quality control pipeline; therefore, users could evaluate the overall quality of each dataset before examining binding sites near their genes of interest. CistromeFinder is integrated with UCSC genome browser for visualization, Primer3Plus for ChIP-qPCR primer design and CistromeMap for submitting newly available datasets. It also allows users to leave comments to facilitate data evaluation and update.\nxsliu@jimmy.harvard.edu or henry_long@dfci.harvard.edu\n13. Wen-Dan Decoction Improves Negative Emotions in Sleep-Deprived Rats by Regulating Orexin-A and Leptin Expression Wu, Fengzhi | Song, Yuehan | Li, Feng | He, Xin | Ma, Jie | Feng, Ting | Guan, Binghe | Wang, Liye | Li, Sinai | Liu, Xiaolan | Liu, Yan | Mao, Meng | Liu, Jing | Bai, Shijing | Song, Cai\nEvidence-based Complementary and Alternative Medicine : eCAM 2014;2014:872547.\nWen-Dan Decoction (WDD), a formula of traditional Chinese medicine, has been clinically used for treating insomnia for approximately 800 years. However, the therapeutic mechanisms of WDD remain unclear. Orexin-A plays a key role in the sleep-wake cycle, while leptin function is opposite to orexin-A. Thus, orexin-A and leptin may be important factors in sleep disorders. In this study, 48 rats were divided into control, model, WDD-treated, and diazepam-treated groups. The model of insomnia was produced by sleep deprivation (SD) for 14 days. The expressions of orexin-A, leptin, and their receptors in blood serum, prefrontal cortex, and hypothalamus were detected by enzyme-linked immunosorbent assay, immunohistochemistry, and real time PCR. Open field tests showed that SD increased both crossing movement (Cm) and rearing-movement (Rm) times. Orexin-A and leptin levels in blood serum increased after SD but decreased in brain compared to the control group. mRNA expressions of orexin receptor 1 and leptin receptor after SD were decreased in the prefrontal cortex but were increased in hypothalamus. WDD treatment normalized the behavior and upregulated orexin-A, leptin, orexin receptor 1 and leptin receptor in brain. The findings suggest that WDD treatment may regulate SD-induced negative emotions by regulating orexin-A and leptin expression.\n14. A Fungal Insecticide Engineered for Fast Per Os Killing of Caterpillars Has High Field Efficacy and Safety in Full-Season Control of Cabbage Insect Pests Liu, Yong-Jie | Liu, Jing | Ying, Sheng-Hua | Liu, Shu-Sheng | Feng, Ming-Guang\nApplied and Environmental Microbiology 2013;79(20):6452-6458.\nFungal insecticides developed from filamentous pathogens of insects are notorious for their slow killing action through cuticle penetration, depressing commercial interest and practical application. Genetic engineering may accelerate their killing action but cause ecological risk. Here we show that a Beauveria bassiana formulation, HV8 (BbHV8), engineered for fast per os killing of caterpillars by an insect midgut-acting toxin (Vip3Aa1) overexpressed in conidia has both high field efficacy and safety in full-season protection of cabbage from the damage of an insect pest complex dominated by Pieris rapae larvae, followed by Plutella xylostella larvae and aphids. In two fields repeatedly sprayed during summer, BbHV8 resulted in overall mean efficacies of killing of 71% and 75%, which were similar or close to the 70% and 83% efficacies achieved by commercially recommended emamectin benzoate but much higher than the 31% and 48% efficacies achieved by the same formulation of the parental wild-type strain (WT). Both BbHV8 and WT sprays exerted no adverse effect on a nontarget spider community during the trials, and the sprays did not influence saprophytic fungi in soil samples taken from the field plots during 4 months after the last spray. Strikingly, BbHV8 and the WT showed low fitness when they were released into the environment because both were decreasingly recovered from the field lacking native B. bassiana strains (undetectable 5 months after the spray), and the recovered isolates became much less tolerant to high temperature and UV-B irradiation. Our results highlight for the first time that a rationally engineered fungal insecticide can compete with a chemical counterpart to combat insect pests at an affordable cost and with low ecological risk.\n15. Cetuximab-Induced MET Activation Acts as a Novel Resistance Mechanism in Colon Cancer Cells Song, Na | Liu, Shizhou | Zhang, Jingdong | Liu, Jing | Xu, Ling | Liu, Yunpeng | Qu, Xiujuan\nInternational Journal of Molecular Sciences 2014;15(4):5838-5851.\nAberrant MET expression and hepatocyte growth factor (HGF) signaling are implicated in promoting resistance to targeted agents; however, the induced MET activation by epidermal growth factor receptor (EGFR) inhibitors mediating resistance to targeted therapy remains elusive. In this study, we identified that cetuximab-induced MET activation contributed to cetuximab resistance in Caco-2 colon cancer cells. MET inhibition or knockdown sensitized Caco-2 cells to cetuximab-mediated growth inhibition. Additionally, SRC activation promoted cetuximab resistance by interacting with MET. Pretreatment with SRC inhibitors abolished cetuximab-mediated MET activation and rendered Caco-2 cells sensitive to cetuximab. Notably, cetuximab induced MET/SRC/EGFR complex formation. MET inhibitor or SRC inhibitor suppressed phosphorylation of MET and SRC in the complex, and MET inhibitor singly led to disruption of complex formation. These results implicate alternative targeting of MET or SRC as rational strategies for reversing cetuximab resistance in colon cancer.\ncetuximab; MET; EGFR; SRC; colon cancer\n16. Evaluation on Genotoxicity and Teratogenicity of Aqueous Extract from Cyclocarya paliurus Leaves Deng, Lihong | Lei, Jiandu | He, Jing | Liu, Jing | Wang, Luying | Zhang, Rui | Liu, Xinhua | Liu, Yun\nThe Scientific World Journal 2014;2014:498134.\nTremendous attentions have been attracted to the foods labeled with natural, green, organic, and nuisanceless conception of healthy diet. Therefore, it is of great significance to establish relative defining guidance for safe assessment of botanicals. Cyclocarya paliurus (Batal.) Iljinsk (family Cyclocaryaceae), called sweet tea tree, is a well-known edible and medicinal plant, which has been widely used in China as drug formulation for the treatment of hypertension and diabetes. Despite its benefits, no reports have been described on the safe assessment of C. paliurus leaves aqueous extract. In this study, we have conducted the genotoxicity assay (including Ames test, bone marrow polychromatic erythrocyte micronucleus test, and sperm abnormality test in mice) and traditional teratogenicity assay in rats (maternal toxicity, embryo toxicity, and teratogenicity test) to assess the genetic and teratogenic safety of aqueous extracts from C. paliurus leaves. Results of each assay show that the highest dose of C. paliurus leaves aqueous extract is considered relatively nonmutagenic and nonteratogenic, revealing that C. paliurus leaves possess safety and quality as a functional additional ingredient in food.\n17. Conditioned medium of human adipose-derived mesenchymal stem cells mediates protection in neurons following glutamate excitotoxicity by regulating energy metabolism and GAP-43 expression Hao, Peng | Liang, Zhanhua | Piao, Hua | Ji, Xiaofei | Wang, Yachen | Liu, Yong | Liu, Rutao | Liu, Jing\nMetabolic Brain Disease 2014;29(1):193-205.\nGlutamate excitotoxicity has been implicated as one of the pathological mechanisms contributing to neuronal cell death and is involved in many neurological disorders. Stem cell transplantation is a promising approach for the treatment of nervous system damage or diseases. Previous studies have shown that mesenchymal stem cells (MSCs) have important therapeutic effects in experimental animal and preclinical disease model of central nervous system pathology. However, it is not well understood whether neurogenesis of MSCs or MSC conditioned-medium (CM) containing microparticles mediates therapeutic effects. Here, we investigated the neuroprotective effects of human adipose-derived MSCs (AMSCs) on cortical neurons using models of glutamate excitotoxicity. Following exposure to glutamate (100 μM, 15 min), cortical neurons were co-cultured with either AMSCs separated by a semiporous membrane (prohibiting direct cell-cell contact) or with AMSC-CM for 18 h. Compared to untreated control groups, AMSCs and AMSC-CM partially and similarly reduced neuronal cell damages, as indicated by reduced LDH release, a decreased number of trypan-positive cells and a decline in the number of apoptotic nuclei. Protection by CM was associated with increased GAP-43 expression and an elevated number of GAP-43-positive neurites. Furthermore, CM increased levels of ATP, NAD+ and NADH and the ratio of NAD+/NADH, while preventing a glutamate-induced decline in mitochondrial membrane potential. These results demonstrate that AMSC-CM mediates direct neuroprotection by inhibiting neuronal cell damage/apoptosis, promoting nerve regeneration and repair, and restoring bioenergy following energy depletion caused by glutamate excitotoxicity.\nExcitotoxicity; Cortical neurons; AMSCs; Neuroprotection; GAP-43; Energy metabolism\n18. High-Fat-Diet-Induced Weight Gain Ameliorates Bone Loss without Exacerbating AβPP Processing and Cognition in Female APP/PS1 Mice Peng, Yunhua | Liu, Jing | Tang, Ying | Liu, Jianshu | Han, Tingting | Han, Shujun | Li, Hua | Hou, Chen | Liu, Jiankang | Long, Jiangang\nFrontiers in Cellular Neuroscience 2014;8:225.\nOsteoporosis is negatively correlated with body mass, whereas both osteoporosis and weight loss occur at higher incidence during the progression of Alzheimer’s disease (AD) than the age-matched non-dementia individuals. Given that there is no evidence that being overweight is associated with AD-type cognitive dysfunction, we hypothesized that moderate weight gain might have a protective effect on the bone loss in AD without exacerbating cognitive dysfunction. In this study, feeding a high-fat diet (HFD, 45% calorie from fat) to female APP/PS1 transgenic mice, an AD animal model, induced weight gain. The bone mineral density, microarchitecture, and biomechanical properties of the femurs were then evaluated. The results showed that the middle-aged female APP/PS1 transgenic mice were susceptible to osteoporosis of the femoral bones and that weight gain significantly enhanced bone mass and mechanical properties. Notably, HFD was not detrimental to brain insulin signaling and AβPP processing, as well as to exploration ability and working, learning, and memory performance of the transgenic mice measured by T maze and Morris water maze, compared with the mice fed a normal-fat diet (10% calorie from fat). In addition, the circulating levels of leptin but not estradiol were remarkably elevated in HFD-treated mice. These results suggest that a body weight gain induced by the HFD feeding regimen significantly improved bone mass in female APP/PS1 mice with no detriments to exploration ability and spatial memory, most likely via the action of elevated circulating leptin.\nAlzheimer’s disease; osteoporosis; weight gain; bone mineral density; leptin\n19. Disruption of Growth Factor Receptor–Binding Protein 10 in the Pancreas Enhances β-Cell Proliferation and Protects Mice From Streptozotocin-Induced β-Cell Apoptosis Zhang, Jingjing | Zhang, Ning | Liu, Meilian | Li, Xiuling | Zhou, Lijun | Huang, Wei | Xu, Zhipeng | Liu, Jing | Musi, Nicolas | DeFronzo, Ralph A. | Cunningham, John M. | Zhou, Zhiguang | Lu, Xin-Yun | Liu, Feng\nDefects in insulin secretion and reduction in β-cell mass are associated with type 2 diabetes in humans, and understanding the basis for these dysfunctions may reveal strategies for diabetes therapy. In this study, we show that pancreas-specific knockout of growth factor receptor–binding protein 10 (Grb10), which is highly expressed in pancreas and islets, leads to elevated insulin/IGF-1 signaling in islets, enhanced β-cell mass and insulin content, and increased insulin secretion in mice. Pancreas-specific disruption of Grb10 expression also improved glucose tolerance in mice fed with a high-fat diet and protected mice from streptozotocin-induced β-cell apoptosis and body weight loss. Our study has identified Grb10 as an important regulator of β-cell proliferation and demonstrated that reducing the expression level of Grb10 could provide a novel means to increase β-cell mass and reduce β-cell apoptosis. This is critical for effective therapeutic treatment of both type 1 and 2 diabetes.\n20. The long non-coding RNA HOTAIR indicates a poor prognosis and promotes metastasis in non-small cell lung cancer Liu, Xiang-hua | Liu, Zhi-li | Sun, Ming | Liu, Jing | Wang, Zhao-xia | De, Wei\nBMC Cancer 2013;13:464.\nThe identification of cancer-associated long non-coding RNAs and the investigation of their molecular and biological functions are important for understanding the molecular biology and progression of cancer. HOTAIR (HOX transcript antisense intergenic RNA) has been implicated in several cancers; however, its role in non-small cell lung cancer (NSCLC) is unknown. The aim of the present study was to examine the expression pattern of HOTAIR in NSCLC and to evaluate its biological role and clinical significance in tumor progression.\nExpression of HOTAIR was analyzed in 42 NSCLC tissues and four NSCLC cell lines by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Over-expression and RNA interference (RNAi) approaches were used to investigate the biological functions of HOTAIR. The effect of HOTAIR on proliferation was evaluated by MTT and colony formation assays, and cell migration and invasion were evaluated by transwell assays. Tail vein injection of cells was used to study metastasis in nude mice. Protein levels of HOTAIR targets were determined by western blot analysis. Differences between groups were tested for significance using Student’s t-test (two-tailed).\nHOTAIR was highly expressed both in NSCLC samples and cell lines compared with corresponding normal counterparts. HOTAIR upregulation was correlated with NSCLC advanced pathological stage and lymph-node metastasis. Moreover, patients with high levels of HOTAIR expression had a relatively poor prognosis. Inhibition of HOTAIR by RNAi decreased the migration and invasion of NSCLC cells in vitro and impeded cell metastasis in vivo. HOXA5 levels were affected by HOTAIR knockdown or over-expression in vitro.\nOur findings indicate that HOTAIR is significantly up-regulated in NSCLC tissues, and regulates NSCLC cell invasion and metastasis, partially via the down-regulation of HOXA5. Thus, HOTAIR may represent a new marker of poor prognosis and is a potential therapeutic target for NSCLC intervention.\nLong non-coding RNA; HOTAIR; Non-small cell lung cancer; Prognosis; Metastasis\n21. Correction: Inflammation Disrupts the LDL Receptor Pathway and Accelerates the Progression of Vascular Calcification in ESRD Patients Liu, Jing | Ma, Kun Ling | Gao, Min | Wang, Chang Xian | Ni, Jie | Zhang, Yang | Zhang, Xiao Liang | Liu, Hong | Wang, Yan Li | Liu, Bi Cheng\nPLoS ONE 2013;8(8):10.1371/annotation/6d657d25-6835-40ee-9751-3f8fbc40e2b8.\n22. Prevalence of hyperuricemia and its related risk factors in healthy adults from Northern and Northeastern Chinese provinces Qiu, Ling | Cheng, Xin-qi | Wu, Jie | Liu, Jun-ting | Xu, Tao | Ding, Hai-tao | Liu, Yan-hong | Ge, Zeng-mei | Wang, Ya-jing | Han, Hui-juan | Liu, Jing | Zhu, Guang-jin\nBMC Public Health 2013;13:664.\nHyperuricemia (HUA) is a potential risk factor for developing insulin resistance, hypertension, dyslipidemia and cardiovascular disease. Therefore, we studied the prevalence of HUA and associated risk factors in the population of two provinces in northern China.\nBased on the research of Chinese Physiological Constant and Health Conditions conducted in 2008–2010, we enrolled 29,639 subjects in a randomized, stratified study in four sampling areas in Heilongjiang Province and the Inner Mongolia Autonomous Region. We collected 13,140 serum samples to determine biochemical indicators including uric acid(UA), glucose, blood lipids, liver function, and renal function, and finally a representative sample of 8439 aged 18 years and older was determined. We also defined and stratified HUA, hypertension, diabetes, obesity and lipid abnormalities according to international guidelines.\nThere were significant differences in the UA levels between different genders and regions. The total prevalence of HUA is 13.7%. Men had a higher prevalence of HUA than women (21% vs. 7.9%; P < 0.0001). As age increased, HUA prevalence decreased in men but rose in women. The suburbs of big cities had the highest HUA prevalence (18.7%), and in high-prevalence areas the proportion of women with HUA also increased. A stepwise logistic regression model was used to filter out twelve HUA risk factors, including age, gender, residence, hypercholesterolemia, hypertriglyceridemia, impaired fasting glucose, hypertension, obesity, abdominal obesity, CKD, drinking and sleeping. After adjusting for these factors, the odds ratio of HUA was 1.92 times higher in men than in women. Compared with agricultural and pastoral areas, the odds ratio of having HUA was 2.14 for participants in the suburbs of big cities and 1.57 in the center of big cities.\nThe prevalence of HUA is high in northern China. The differences in HUA prevalence by geographic region suggested that unbalanced economic development and health education, therefore HUA prevention measures should be strengthened to improve quality of life and reduce health care costs.\nPrevalence; Hyperuricemia; Risk factors\n23. Synthesis of Luminescent Near-Infrared AgInS2 Nanocrystals as Optical Probes for In Vivo Applications Liu, Liwei | Hu, Rui | Roy, Indrajit | Lin, Guimiao | Ye, Ling | Reynolds, Jessica L. | Liu, Jianwei | Liu, Jing | Schwartz, Stanley A. | Zhang, Xihe | Yong, Ken-Tye\nNear infrared quantum dots have been receiving great attention as fluorescent optical probes for in vivo imaging applications. In this contribution, we report the synthesis and surface functionalization of cadmium free ternary AgInS2 nanocrystals emitting in the near infrared range for successful in vitro and in vivo bioimaging applications. The FDA approved triblock copolymer Pluronic F127 was used to encapsulate the nanocrystals and made them dispersible in aqueous solution. By employing a whole body small animal optical imaging setup, we were able to use the AgInS2 nanocrystals formulation for passive targeted delivery to the tumor site. The ultra-small crystal size, near-infrared emitting luminescence, and high quantum yield make the AgInS2 nanocrystals an attractive candidate as a biological contrast agent for cancer sensing and imaging.\nNear infrared quantum dots; Bioimaging; Surface functionalization; Targeted delivery; Nanotoxicity.\n24. Inflammation Disrupts the LDL Receptor Pathway and Accelerates the Progression of Vascular Calcification in ESRD Patients Liu, Jing | Ma, Kun Ling | Gao, Min | Wang, Chang Xian | Ni, Jie | Zhang, Yang | Zhang, Xiao Liang | Liu, Hong | Wang, Yan Li | Liu, Bi Cheng\nPLoS ONE 2012;7(10):e47217.\nChronic inflammation plays a crucial role in the progression of vascular calcification (VC). This study was designed to investigate whether the low-density lipoprotein receptor (LDLr) pathway is involved in the progression of VC in patients with end-stage renal disease (ESRD) during inflammation.\nTwenty-eight ESRD patients were divided into control and inflamed groups according to plasma C-reactive protein (CRP) level. Surgically removed tissues from the radial arteries of patients receiving arteriovenostomy were used in the experiments. The expression of tumour necrosis factor-α (TNF-α) and monocyte chemotactic protein-1 (MCP-1) of the radial artery were increased in the inflamed group. Hematoxylin-eosin and alizarin red S staining revealed parallel increases in foam cell formation and calcium deposit formation in continuous cross-sections of radial arteries in the inflamed group compared to the control, which were closely correlated with increased LDLr, sterol regulatory element binding protein-2 (SREBP-2), bone morphogenetic proteins-2 (BMP-2), and collagen I protein expression, as shown by immunohistochemical and immunofluorescent staining. Confocal microscopy confirmed that inflammation enhanced the translocation of the SREBP cleavage-activating protein (SCAP)/SREBP-2 complex from the endoplasmic reticulum to the Golgi, thereby activating LDLr gene transcription. Inflammation increased alkaline phosphatase protein expression and reduced α-smooth muscle actin protein expression, contributing to the conversion of the vascular smooth muscle cells in calcified vessels from the fibroblastic to the osteogenic phenotype; osteogenic cells are the main cellular components involved in VC. Further analysis showed that the inflammation-induced disruption of the LDLr pathway was significantly associated with enhanced BMP-2 and collagen I expression.\nInflammation accelerated the progression of VC in ESRD patients by disrupting the LDLr pathway, which may represent a novel mechanism involved in the progression of both VC and atherosclerosis.\n25. An improved allele-specific PCR primer design method for SNP marker analysis and its application Liu, Jing | Huang, Shunmou | Sun, Meiyu | Liu, Shengyi | Liu, Yumei | Wang, Wanxing | Zhang, Xiurong | Wang, Hanzhong | Hua, Wei\nPlant Methods 2012;8:34.\nAlthough Single Nucleotide Polymorphism (SNP) marker is an invaluable tool for positional cloning, association study and evolutionary analysis, low SNP detection efficiency by Allele-Specific PCR (AS-PCR) still restricts its application as molecular marker like other markers such as Simple Sequence Repeat (SSR). To overcome this problem, primers with a single nucleotide artificial mismatch introduced within the three bases closest to the 3’end (SNP site) have been used in AS-PCR. However, for one SNP site, nine possible mismatches can be generated among the three bases and how to select the right one to increase primer specificity is still a challenge.\nIn this study, different from the previous reports which used a limited quantity of primers randomly (several or dozen pairs), we systematically investigated the effects of mismatch base pairs, mismatch sites and SNP types on primer specificity with 2071 primer pairs, which were designed based on SNPs from Brassica oleracea 01-88 and 02-12. According to the statistical results, we (1) found that the primers designed with SNP (A/T), in which the mismatch (CA) in the 3rd nucleotide from the 3’ end, had the highest allele-specificity (81.9%). This information could be used when designing primers from a large quantity of SNP sites; (2) performed the primer design principle which forms the one and only best primer for every SNP type. This is never reported in previous studies. Additionally, we further identified its availability in rapeseed (Brassica napus L.) and sesame (Sesamum indicum). High polymorphism percent (75%) of the designed primers indicated it is a general method and can be applied in other species.\nThe method provided in this study can generate primers more effectively for every SNP site compared to other AS-PCR primer design methods. The high allele-specific efficiency of the SNP primer allows the feasibility for low- to moderate- throughput SNP analyses and is much suitable for gene mapping, map-based cloning, and marker-assisted selection in crops.\nSNP; AS-PCR; Mismatch; Polymorphism; Destabilization


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url: =Model and simulation of electromagnetic compatibility of SAM and decoy dilution jamming--《Journal of Naval University of Engineering》2017年03期\nModel and simulation of electromagnetic compatibility of SAM and decoy dilution jamming\nQIN Jian-dong;WU Xiao-feng;CHENG Zhi-feng;TIAN Bin;College of Electronic Engineering,Naval Univ. of Engineering;School of Mathematics and Statistics,Minnan Normal Univ.;\nResearches are carried out from time,spatial and frequency domain on the basis of analyzing the operation process of SAM and decoy dilution jamming.The electromagnetic compatibility judgment model of SAM and decoy dilution jamming is built and the simulation experiments are carried out.The results show that decoy dilution jamming provides obvious interference with SAM.Thus,in decision-making of a collaborative anti-missile program,the commander shall conduct electromagnetic compatibility testing first and eliminate the possible conflicts ahead of time to ensure the maximum efficiency of the integrated anti-missile capability of SAM and decoy dilution jamming.\n【CateGory Index】： TJ762.33\n1 WU Qi-peng;WANG Bin;Qiu Xin-heng;Unit 92038 of PLA;Electronic Engineering Institute of PLA;;Research on Unintentional Hitting Probability Engendered by Diluting J amming in Anti-missile Campaign of Warship Formation[J];火力与指挥控制;2013-11\n2 QIN Jian-dong,XING Chang-feng,WU Ling(Naval University of Engineering,Wuhan 430033,China);Research on the compatibility of shipboard soft and hard weapons for cooperative anti-missile[J];舰船科学技术;2012-07\n3 GAO Xiao-dong1,WANG Guang-hui2,LI Chuan-shun2(1.Ordnance Branch of NED,Beijing 100841,China;2.Department of Command,NAAU,Yantai Shandong 264001,China);An Improved Acquire Algorithm of Anti-Ship Missile Based on Lead-Point Shoot[J];海军航空工程学院学报;2012-02\n4 ZHOU Shao-leia,YIN Gao-yangb,ZHANG Wen-guanga(Naval Aeronautical and Astronautical University a.Department of Control Engineering;b.Graduate Students' Brigade,Yantai Shandong 264001,China);Simulation of Time Window Calculation Model of Ship-to-Air Missile[J];海军航空工程学院学报;2012-02\n5 ZHOU Xia,LU Qin-fub,YIN Haia,ZHAO Fenga(Naval Command College,a.Postgraduate Team 2;b.Warfare Laboratory,Jiangsu Nanjing 210016,China);Antimissile Compatibility between Chaff Centroid Jamming and Ship to Air Missile[J];现代防御技术;2011-03\n6 WANG Chao,WANG Yi-tao(Dalian Naval Academy,Dalian 116018,China);Research on EMC Judging Model in Warships Formation Cooperative Air Defence[J];火力与指挥控制;2011-06\n7 SU Liang,SONG Jiang-Tao,MAO Ming(Dalian Naval Academy,Liaoning Dalian 116018,China);Study on the Problem of EMC of Integrated Anti-Missile Operation of ECM and SAM[J];现代防御技术;2007-04\n1 Wang Yu;Zheng Jin;No.91404 Unit of PLA;;Study of Electromagnetic Compatibility of in Surface Warship Formation Air Defense Combat[J];兵工自动化;2018-04\n2 Chen Rong;Shen Peizhi;He Yingzheng;School of Aviation Operation & Logistics, Navy Aeronautical University;School of Coast Defense Army, Navy Aeronautical University;;Formation Diluting Jamming Based on Resolution of Anti-ship Missile Radar[J];兵工自动化;2018-02\n3 QIN Jian-dong;WU Xiao-feng;CHENG Zhi-feng;TIAN Bin;College of Electronic Engineering,Naval Univ. of Engineering;School of Mathematics and Statistics,Minnan Normal Univ.;;Model and simulation of electromagnetic compatibility of SAM and decoy dilution jamming[J];海军工程大学学报;2017-03\n4 LU Jun;QIAO Yong-jie;ZHANG Xian-chao;China Academy of Electronics and Information Technology;;On Constructing Theory and Method of Missile Kill Chain[J];中国电子科学研究院学报;2016-04\n5 LI Yu-ling;WANG Xiu-ling;College of Information Engineering,Inner Mongolia Technology University;;Intelligent sensor based on cooperative network on chip and electromagnetic synergistic effect perception[J];传感器与微系统;2016-05\n6 SHEN Pei-zhi;NIE Qi-gang;ZHANG Bang-yu;LI Han;Department of Command,Naval Aeronautical and Astronautical University;Postgraduate Management Department,Naval Aeronautical and Astronautical University;The No.91362nd Troop of PLA;The No.92212nd Troop of PLA;;Target-Catching Strategy of Anti-Ship Missile Based On Game Theory[J];兵器装备工程学报;2016-01\n7 WANG Mu-hong;ZHOU Zhi-chao;LENG Hua-ping;Naval Marine Academy;Naval Command Academy;;Detection and Resolution of Firepower Conflict Between Infrared Decoy and Ship-to-Air Missile[J];电光与控制;2016-02\n8 SUN Yi;HAN Long;No.1 Postgraduate Division,Dalian Naval Academy;;Chaff Centroid Jammingand Shipto Air Missile Anti-missile Cooperation Conflict Prediction[J];舰船电子工程;2015-11\n9 ZHANG Jianqiang;LIU Zhong;YANG Hongmei;Electronics Engineering College,Naval University of Engineering;Air Force Early Warning Academy;;The target acquisition probability modeling method of long-range anti-ship missile based on search theory[J];国防科技大学学报;2015-04\n10 SHEN Pei-zhi;ZHANG Bang-yu;Naval Aeronautical and Astronautical University;;Model on Searching Angle of Anti-ship Missile Terminal Guidance Radar[J];火力与指挥控制;2015-08\n1 LIU Chuanbo1,QIU Zhiming2,WU Ling1,WANG Hangyu1(1.Naval Engineering of University,Wuhan 430033,China;2.Naval Equipment Institute,Beijing 100073,China);Review on Current Status and Prospect of Researches on Dynamic Weapon Target Assignment[J];电光与控制;2010-11\n2 GE Jin-huaa,WANG Hong-junb,CHANG Leia,LIU Wen-zhenga(Dalian Naval Academy a.Postgraduate Team;b.Department of Operation and Command,Dalian 116018,China);Research on Electronic Countermeasure Operational Formation Distance Based on Campaign Forearm[J];电子信息对抗技术;2010-05\n3 QIN Jian-dong,XING Chang-feng,WU Ling(Naval University of Engineering,Wuhan 430033,China);Study on the cooperative control and guidance for SAM in air-defense combat of warship formation[J];舰船科学技术;2010-05\n4 Wang Guanghui1,Song Yanbo1,Wang Weiya1,Xie Yupeng2(1. Department of Command,Naval Aeronautical and Astronautical University,Yantai 264001,China)(2.Graduate Student Brigade,Naval Aeronautical and Astronautical University,Yantai 264001,China);Optimum Search-graph Model of Homing Radar Based on Target Distance[J];航空学报;2010-03\n5 LIU Zhi-xuea,ZHU Shou-leia,XU Chengb,DU Mao-huaa (Naval Aeronautical and Astronautical University a.Graduate Students’ Brigade;b.Department of Airborne Vehicle Engineering,Yantai Shandong 264001,China);The Petri Net Model of the Intelligence Anti-Ship Missile Attack-Defense Operation[J];海军航空工程学院学报;2010-02\n6 LU Fa-xing,WU Ling,DONG Yin-wen(Coll.of Electronic Engineering,Naval Univ.of Engineering,Wuhan 430033,China);Blind launch of anti-ship missiles without route-planning capability[J];系统工程与电子技术;2009-11\n7 LU Fa-xing,WU Ling,DONG Yin-wen (Electronic Engineering College,Naval University of Engineering,Wuhan,Hubei 430033,China);Research on the Attacking Mode for Blind Launch of Anti-Ship Missiles with Route-Planning Capability[J];电子学报;2009-09\n8 ZHONG Zhi-tong1,2,XU De-min1,ZHOU Zhou2 (1.College of marine engineering Northwest Ploytechnical University,Xi'an 710072,China,2.Dailian Navy Academe,Dailian 116018,China);Research on Intercepting Possibility's Calculating Model of Ship-to-air Missile Weapon[J];火力与指挥控制;2009-05\n9 SHI Hong-quan,WANG Chao (Dalian Navy Academy,Dalian 116018,China);Research on Fire Distribution Sequencing Model of Air Target based on Degree of Urgency[J];火力与指挥控制;2008-09\n10 JIANG Yanlin1,CHEN Xuelai1,LIANG Yuan2(1 Naval Arms Command Academy,Guangzhou 510430,China;2 Naval Command Academy,Nanjing 210016,China);Study of Influence of Centroid Disturbing on Millimeter Wave Radar Guidance Anti-ship Missile Homing Flight Status[J];弹箭与制导学报;2008-02


url: =Sun Daguang meets with vice president of China Zheshang Bank_Nanning China\nSun Daguang meets with vice president of China Zheshang Bank\nRecently, Sun Daguang, mayor of Nanning, met with Xu Manxuan, vice president of China Zheshang Bank Co., Ltd., and his delegation in Nanning Municipal People’s Government. The two sides exchanged views on the preparatory work of China Zheshang Bank Nanning Branch.\nSun Daguang gave a warm welcome to Xu Manxuan and his delegation to Nanning and expressed his gratitude to China Zheshang Bank for choosing Nanning to develop its business. He hoped China Zheshang Bank could give full play to its advantages and provide practical guidance for the financial system innovation and cross-border financial comprehensive services in the Nanning Area of China (Guangxi) Pilot Free Trade Zone. Xu Manxuan also expressed his gratitude to Nanning for all its support to China Zheshang Bank, and said that Nanning's outstanding geographical advantages would bring huge development space for the bank to settle down in Nanning for carrying out its financial business.


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url: =China Top 10 Exhibitions Archives - Page 10 of 12 - World Exhibitions\nHome/Tag: China Top 10 Exhibitions (page 10)\n2exhibitions July 19, 2021\tSporting Goods, Trade Fair 4,974\n2exhibitions July 19, 2021\tSporting Goods, Trade Fair 2,776\nInforma PLC July 14, 2021\tArchitecture and Designing, Trade Fair 4,951\nEvent Name: Windoor Expo China Category: Architecture and Designing Event Date: 11 – 13 March, 2022 Frequency: Annual Location: Poly World Trade Center Expo & Nan Fung International Convention & Exhibition Center, Guangzhou, China Organizer: Guangzhou Citiexpo Co., Ltd. Rm1807, Poly World Trade Center, No. 1000, XinGang East Road, Guangzhou 510335 China …\n2exhibitions July 5, 2021\tPlastic, Trade Fair 3,691\n2exhibitions July 3, 2021\tGifts and Handicrafts, Trade Fair 4,484\nEvent Name: Ceramics China Category: Gifts and Handicrafts Date: 27 – 30 June, 2021 Frequency: Annual Location: China Import and Export Fair (Canton Fair Complex), 382 Yuejiang Middle Road, Haizhu Qu Guangzhou Shi, Guangdong Sheng 510310 China Organizer: Unifair Exhibition Service Co. Limited, Room 2501, Guoxin Mansion, No.363 Dongfeng Rd., …\n2exhibitions June 8, 2021\tAutomotive, Trade Fair 8,596\nEvent Name: CITEXPO Shanghai Category: Automotive Event Date: 12 – 14 December, 2022 Frequency: Annual Location: Shanghai World Expo Exhibition & Convention Center – 850 Bocheng Road, Shanghai, China Organizer: Reliable International Exhibition Services Co. Ltd. – Rm 1702, Bldg. 6, SOHO New Town, No. 88, Jianguo Road, Chaoyang District, Beijing …\n2exhibitions March 23, 2020\tComputer and IT, Trade Fair 3,345\n2exhibitions March 18, 2020\tBuilding Construction, Trade Fair 1,863\n2exhibitions January 2, 2020\tIndustrial Goods, Trade Fair 5,332\nCategory: Industrial Goods Date: 15 – 19 September, 2020 Frequency: Annual Location: National Exhibition and Convention Center, Shanghai, China Organizer: Shanghai Industry & Commerce Exhibition Co., Ltd. – 13F, Minmetals Building, No. 757 Guangfu Road, Shanghai 200070 P.R. China Phone: 021-22068388 Email: ciif@shanghaiexpogroup.com Timings: 09:30 AM – 17:00 PM Welcome to …\nMesse Munchen December 9, 2019\tEnvironment and Waste Management, Trade Fair 2,245


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url: =Effects of Small Time-Delays on Dynamic Output Feedbac... CNKI文献\nThis paper is to investigate the effect of a small time-delay on dynamic output feedback control of an offshore steel jacket structure subject to a nonlinear wave-induced selfexcited hydrodynamic for...\nXian-Ming Zhang Qing-Long Han... Proceedings of Joint 48th IEEE Conference on Decision a... 2009-12-16 国际会议\n关键词： Effects / of / Small / Time-Delays\nDynamic Event-Triggered Vehicle Platooning Control: Tr... CNKI文献\nThis paper addresses the co-design problem of event-triggered communication scheduling and cooperative longitudinal control for automated vehicles subject to unknown external disturbances and vehicul...\nXiaohua Ge Qing-Long Han... 第40届中国控制会议论文集（9） 2021-07-26 中国会议\n关键词： Vehicle / platooning / cooperative / adaptive\nFinite-time Stability and Stabilization for a Class of... CNKI文献\nThis paper is concerned with the finite-time stability analysis and state feedback stabilization controller design for a class of nonlinear discrete-time descriptor switched systems with time-varying...\nYou Xu Shuqian Zhu... 第三十三届中国控制会议论文集（D卷） 2014-07-28 国际会议\n关键词： Descriptor / systems / Switched / systems\nA new unidirectional coupling for global synchronizati... CNKI文献\nIn this paper,a new unidirectional coupling for global synchronization of two Hindmarsh-Rose neurons is designed.Compared with existing results,external control for global synchronization is no longe...\nKe Ding Qing-Long Han 第27届中国控制与决策会议论文集 2015-05-23 国际会议\n关键词： Synchronization / Unidirectional / coupling / Hindmarsh-Rose\nHierarchical Distributed Receding Horizon Control for ... CNKI文献\nThis paper is concerned with a hierarchical distributed receding horizon control(HDRHC) approach, by which a global objective of locating the peaks of an unknown environment of interest can be achiev...\nQiang Lu Qing-Long Han... 第三十四届中国控制会议论文集（E卷） 2015-07-28 国际会议\n关键词： Distributed / Receding / Horizon / Multi-Agent\nA Survey of Motion Control for Marine Vehicles CNKI文献\nThe motion control of marine vehicles has attracted much attention from control community. This paper reviews the recent results on the motion control of marine vehicles. The approaches dealing with ...\nAi-Chun Qi Qing-Long Han... 第三十四届中国控制会议论文集（C卷） 2015-07-28 国际会议\n关键词： Marine / Vehicles / Roll / Stabilization\nImpulsive Synchronization of Complex Dynamical Network... CNKI文献\nThis paper investigates synchronization of complex dynamical networks with distributed-delay coupling via impulsive control.Based on the theory of impulsive functional differential equations and the ...\nSumei Chu Wangli He... 第三十三届中国控制会议论文集（A卷） 2014-07-28 国际会议\n关键词： Synchronization / Impulsive / control / Distributed-delay\nSynchronization Criteria for Lur'e Complex Dynamical N... CNKI文献\nThis paper is concerned with synchronization in Lur'e complex dynamical networks with coupling delays. Every identical node in the network can be represented as a Lur'e system. The influence ...\nKe Ding Qing-Long Han Proceedings of Joint 48th IEEE Conference on Decision a... 2009-12-16 国际会议\n关键词： Synchronization / Criteria / for / Lur'e\nNetworked Control Systems:A Survey of Trends and Techn... CNKI文献\nNetworked control systems are spatially distributed systems in which the communication between sensors, actuators,and controllers occurs through a shared band-limited digital communication network. S...\nXian-Ming Zhang Qing-Long Han... 《IEEE/CAA Journal of Automatica Sinica》 2020年01期 期刊\n关键词： Event-triggered / control / networked / control\nDeep Learning Based Attack Detection for Cyber-Physica... CNKI文献\nWith the booming of cyber attacks and cyber criminals against cyber-physical systems(CPSs), detecting these attacks remains challenging. It might be the worst of times, but it might be the best of ti...\nJun Zhang Lei Pan... 《IEEE/CAA Journal of Automatica Sinica》 2022年03期 期刊\n关键词： Cyber-physical / system / cybersecurity / deep\nDynamic Event-Triggered Scheduling and Platooning Cont... CNKI文献\nThis paper deals with the co-design problem of event-triggered communication scheduling and platooning control over vehicular ad-hoc networks(VANETs) subject to finite communication resource. First, ...\nXiaohua Ge Shunyuan Xiao... 《IEEE/CAA Journal of Automatica Sinica》 2022年01期 期刊\n关键词： Automated / vehicles / dynamic / event-triggered\nDynamic Event-triggered Control and Estimation: A Surv... CNKI文献\nThe efficient utilization of computation and communication resources became a critical design issue in a wide range of networked systems due to the finite computation and processing capabilities of s...\nXiaohua Ge Qing-Long Han... 《International Journal of Automation and Computing》 2021年06期 期刊\n关键词： Networked / systems / dynamic / event-triggered\nHow often should one update control and estimation:rev... CNKI文献\nManagement of resources is a constant topic in industrial systems. How to use minimum communication resources is of particular interest for control and estimation of networked systems. It raises the ...\nZhiyong CHEN Qing-Long HAN... 《Science China(Information Sciences)》 2020年05期 期刊\n关键词： event-triggered / control / event-triggered / estimation\nUnmanned Aerial Vehicles: Control Methods and Future C... CNKI文献\nWith the rapid development of computer technology,automatic control technology and communication technology,research on unmanned aerial vehicles(UAVs) has attracted extensive attention from all over ...\nZongyu Zuo Cunjia Liu... 《IEEE/CAA Journal of Automatica Sinica》 2022年04期 期刊\n关键词： Aircraft / control / disturbance / rejection\nDecentralized Dynamic Event-Triggered Communication an... CNKI文献\nThis paper addresses the co-design problem of decentralized dynamic event-triggered communication and active suspension control for an in-wheel motor driven electric vehicle equipped with a dynamic d...\nIftikhar Ahmad Xiaohua Ge... 《IEEE/CAA Journal of Automatica Sinica》 2021年05期 期刊\n关键词： Active / suspension / control / decentralized\nCooperative and Competitive Multi-Agent Systems:From O... CNKI文献\nMulti-agent systems can solve scientific issues related to complex systems that are difficult or impossible for a single agent to solve through mutual collaboration and cooperation optimization. In a...\nJianrui Wang Yitian Hong... 《IEEE/CAA Journal of Automatica Sinica》 2022年05期 期刊\n关键词： Cooperative / games / counterfactual / regret\nNovel Stability Criteria for Linear Time-Delay Systems... CNKI文献\nOne of challenging issues on stability analysis of time-delay systems is how to obtain a stability criterion from a matrix-valued polynomial on a time-varying delay. The first contribution of this pa...\nXian-Ming Zhang Qing-Long Han... 《IEEE/CAA Journal of Automatica Sinica》 2021年01期 期刊\n关键词： Bessel-Legendre / inequality / matrix-valued / polynomial\nAn Ellipsoidal Set-Membership Approach to Distributed ... CNKI文献\nThis paper is concerned with the problem of distributed joint state and sensor fault estimation for autonomous ground vehicles subject to unknown-but-bounded(UBB) external disturbance and measurement...\nEman Mousavinejad Xiaohua Ge... 《IEEE/CAA Journal of Automatica Sinica》 2021年06期 期刊\n关键词： Autonomous / ground / vehicle(AGV) / distributed\nSecure Impulsive Synchronization in Lipschitz-Type Mul... CNKI文献\nCyber attacks pose severe threats on synchronization of multi-agent systems. Deception attack, as a typical type of cyber attack, can bypass the surveillance of the attack detection mechanism silentl...\nWangli He Zekun Mo... 《IEEE/CAA Journal of Automatica Sinica》 2020年05期 期刊\n关键词： Deception / attacks / impulsive / control\nEffects of Small Time-Delays on Dynamic Output Feedback Control o...\nXian-Ming Zhang Qing-Long Han\nDynamic Event-Triggered Vehicle Platooning Control: Trade-off Bet...\nXiaohua Ge Qing-Long Han\nFinite-time Stability and Stabilization for a Class of Nonlinear ...\nYou Xu Shuqian Zhu\nA new unidirectional coupling for global synchronization of two H...\nKe Ding Qing-Long Han\nHierarchical Distributed Receding Horizon Control for a Group of ...\nQiang Lu Qing-Long Han\nA Survey of Motion Control for Marine Vehicles\nAi-Chun Qi Qing-Long Han\nImpulsive Synchronization of Complex Dynamical Networks with Dist...\nSumei Chu Wangli He\nSynchronization Criteria for Lur'e Complex Dynamical Networks wit...\nNetworked Control Systems:A Survey of Trends and Techniques\nDeep Learning Based Attack Detection for Cyber-Physical System Cy...\nJun Zhang Lei Pan\nDynamic Event-Triggered Scheduling and Platooning Control Co-Desi...\nXiaohua Ge Shunyuan Xiao\nHow often should one update control and estimation:review of netw...\nZhiyong CHEN Qing-Long HAN\nZongyu Zuo Cunjia Liu\nDecentralized Dynamic Event-Triggered Communication and Active Su...\nIftikhar Ahmad Xiaohua Ge\nCooperative and Competitive Multi-Agent Systems:From Optimization...\nJianrui Wang Yitian Hong\nNovel Stability Criteria for Linear Time-Delay Systems Using Lyap...\nAn Ellipsoidal Set-Membership Approach to Distributed Joint State...\nEman Mousavinejad Xiaohua Ge\nSecure Impulsive Synchronization in Lipschitz-Type Multi-Agent Sy...\nWangli He Zekun Mo\n学术研究指数分析 Qing-Long Han,Qing-Long Han