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| 1 | The association between the genetic polymorphisms of LMP2/LMP7 and the outcomes of HCV infection among drug users显示文摘Objective:To investigate a possible association of LMP2/LMP7 genes with chronic hepatitis C virus(HCV) infection,and to assess whether LMP2/LMP7 genes could influence the outcomes of HCV infection among drug users.Methods:Genomic DNAs of 362 anti-HCV sero-positive drug users and 225 control drug users were extracted from the peripheral blood leukocytes.The sero-positive patients were divided into those who had persistent infection and those who had spontaneously cleared the infection.Polymorphisms of LMP genes were determined by PCR combined with restriction fragment length polymorphism(RFLP).Results:The distribution of LMP2 genotypes among the control,persistent infection and spontaneous clearance groups were not different.However,the LMP7 codon 145 Gln/Lys,Lys/Lys,and Gln/Lys+Lys/Lys genotypes were found significantly more frequent in the persistent infection group than in control group(OR=1.75,95%CI=1.06~2.90;OR=3.16,95%CI=1.23-8.12;OR=1.94,95%CI=1.21-3.12,respectively).Similarly,the frequencies of the codon 145 Gln/Lys,Lys/Lys,and Gln/Lys+Lys/Lys genotypes were found significantly more frequent in the persistent infection group than in the spontaneous clearance group(OR=1.64,95%CI=1.04-2.57;OR=2.40,95%CI=1.09-5.28;OR=1.76,95%CI=1.152.69,respectively).Stratified analysis indicated that combined genotype Gln/Lys+Lys/Lys of the LMP7 gene was related to an increasing susceptibility to HCV infection(OR=1.91,95%CI=1.02-3.55;OR=2.19,95%CI=1.243.89;OR=1.91,95%CI=1.05-3.48,OR=2.86,95%CI=1.41-5.78,respectively)and the risk of persistent HCV infection(OR=1.94,95%CI=1.12-3.34;OR=2.02,95%CI=1.21-3.38;OR=1.78,95%CI=1.12-2.85,OR=2.23,95%CI=1.09-4.58,respectively)among>30-year-old,males,the injection drug user(IDU)subjects and/or the shorter duration drug users(≤5 y).Conclusion:These results suggest that polymorphism of the LMP7 gene may have an influence on the outcomes of HCV infection,and is one of the factors accounting for the genetic susceptibility to HCV infection among drug users. | Qian Cui Yongxiang Zhang Jing Su Chao Shi Na Lei Keqin Ding Jun Li Rongbin Yu L u Wang Ning Wang | 2010 | The Journal of Biomedical Research2010，24，5： | 6 |
| 2 | Evolutionary trace analysis of eukaryotic DNA topoisomerase I superfamily: Identification of novel antitumor drug binding site显示文摘The studies of novel inhibitors of DNA topoisomerase I (Topo I) have already be-come very promising in cancer chemotherapy. Identifying the new drug-binding residues is playing an important role in the design and optimization of Topo I inhibitors. The designed com-pounds may have novel scaffolds, thus will be helpful to overcome the toxicities of current camptothecin (CPT) drugs and may provide a solution to cross resistance with these drugs. Mul-tiple sequence alignments were performed on eukaryotic DNA topoisomerase I superfamily and thus the evolutionary tree was constructed. The Evolutionary Trace method was applied to iden-tify functionally important residues of human Topo I. It has been demonstrated that class-specific hydrophobic residues Ala351, Met428, Pro431 are located around the 7,9-position of CPT, indi-cating suitable substitution of hydrophobic group on CPT will increase antitumor activity. The conservative residue Lys436 in the superfamily is of particular interest and new CPT derivatives designed based on this residue may greatly increase water solubility of such drugs. It has also been demonstrated that the residues Asn352 and Arg364 were conservative in the superfamily, whose mutation will render CPT resistance. As our molecular docking studies demonstrated they did not make any direct interaction with CPT, they are important drug-binding site residues for future design of novel non-camptothecin lead compounds. This work provided a strong basis for the design and synthesis of novel highly potent CPT derivatives and virtual screening for novel lead compounds. | SONG Yunlong QI Yunpeng ZHANG Wannian SHENG Chunquan ZHANG Min YAO Jianzhong YU Jianxin MIAO Zhenyuan ZHOU Youjun ZHU Ju L(U) Jiaguo | 2005 | Science China(Life Sciences)2005，48，4： | 5 |
| 3 | Critical function of DNA methyltransferase 1 in tomato development and regulation of the DNA methylome and transcriptome显示文摘DNA methylation confers epigenetic regulation on gene expression and thereby on various biological processes.Tomato has emerged as an excellent system to study the function of DNA methylation in plant development.To date,regulation and function of DNA methylation maintenance remains unclear in tomato plants.Here,we report the critical function of tomato(Solanum lycopersicum)Methyltransferase 1(Sl MET1)in plant development and DNA methylome and transcriptome regulation.Using CRISPR-Cas9 gene editing,we generated slmet1 mutants and observed severe developmental defects with a frame-shift mutation,including small and curly leaves,defective inflorescence,and parthenocarpy.In leaf tissues,mutations in Sl MET1 caused CG hypomethylation and CHH hypermethylationon a whole-genome scale,leading to a disturbed transcriptome including ectopic expression of many RIN target genes such as ACC2 in leaf tissues,which are normally expressed in fruits.Neither the CG hypomethylation nor CHH hypermethylation in the slmet1 mutants is related to tissue culture.Meanwhile,tissue culture induces non-CG hypomethylation,which occurs more frequently at gene regions than at TE regions.Our results depict Sl MET1-and tissue culture-dependent tomato DNA methylomes,and that Sl MET1 is required for maintaining a normal transcriptome and normal development of tomato. | Yu Yang Kai Tang Tatsiana U Datsenka Wenshan Liu Suhui Lv Zhaobo Lang Xingang Wang Jinghui Gao Wei Wang Wenfeng Nie Zhaoqing Chu Heng Zhang Avtar K HANDa Jian-Kang Zhu Huiming Zhang | 2019 | Journal of Integrative Plant Biology2019，61，12： | 3 |
| 4 | Increased circulating level of interleukin-6 and CD8+T cell exhaustion are associated with progression of COVID-19显示文摘Background: Coronavirus disease 2019(COVID-19)is pandemic.It is critical to identify COVID-19 patients who are most likely to develop a severe disease.This study was designed to determine the clinical and epidemiological features of COVID-19 patients associated with the development of pneumonia and factors associated with disease progression.Methods:: Seventy consecutive patients with etiologically confirmed COVID-19 admitted to PLA General Hospital in Beijing,China from December 27,2019 to March 12,2020 were enrolled in this study and followed-up to March 16,2020.Differences in clinical and laboratory findings between COVID-19 patients with pneumonia and those without were determined by theχ2 test or the Fisher exact test(categorical variables)and independent group t test or Mann–Whitney U test(continuous variables).The Cox proportional hazard model and Generalized Estimating Equations were applied to evaluate factors that predicted the progression of COVID-19.Results: The mean incubation was 8.67(95%confidence interval,6.78–10.56)days.Mean duration from the first test severe acute respiratory syndrome coronavirus 2-positive to conversion was 11.38(9.86–12.90)days.Compared to pneumonia-free patients,pneumonia patients were 16.5 years older and had higher frequencies of having hypertension,fever,and cough and higher circulating levels of neutrophil proportion,interleukin-6,low count(<190/µl)of CD8+T cells,and neutrophil/lymphocyte ratio.Thirteen patients deteriorated during hospitalization.Cox regression analysis indicated that older age and higher serum levels of interleukin-6,C-reactive protein,procalcitonin,and lactate at admission significantly predicted the progression of COVID-19.During hospitalization,circulating counts of T lymphocytes,CD4+T cells,and CD8+T cells were lower,whereas neutrophil proportion,neutrophil/lymphocyte ratio,and the circulating levels of interleukin-6,C-reactive protein,and procalcitonin were higher,in pneumonia patients than in pneumonia-free patients.CD8+lymphocyte count in pneumonia patients did not recover when discharged.Conclusions: Older age and higher levels of C-reactive protein,procalcitionin,interleukin-6,and lactate might predict COVID-19 progression.T lymphocyte,especially CD8+cell-mediated immunity is critical in recovery of COVID-19.This study may help in predicting disease progression and designing immunotherapy for COVID-19. | Peng-Hui Yang Yi-Bo Ding Zhe Xu Rui Pu Ping U Jin Yan Ji-Luo Liu Fan-Ping Meng Lei Huang Lei Shi Tian-Jun Jiang En-Qiang Qin Min Zhao Da-Wei Zhang Peng Zhao Ling-Xiang Yu Zhao-Hai Wang Zhi-Xian Hong Zhao-Hui Xiao Qing Xi De-Xi Zhao Peng Yu Cai-Zhong Zhu Zhu Chen Shao-Geng Zhang Jun-Sheng Ji Fu-Sheng Wang Guang-Wen Cao | 2020 | Infectious Diseases of Poverty2020，9，6： | 3 |
| 5 | Requirement for cyclin D3 in germinal center formation and function显示文摘第二等的淋巴的纸巾的幼芽的中心(GC ) 对装高亲密关系的体液的有免疫力的回答批评。当多样化他们的抗体基因时,在 GC 以内的 B 房间经历快速的同种细胞的扩大和选择。尽管 GC B 房间采用一个唯一的 proliferative 程序提供这些进程,这通常被相信,很少联系 GC 的房间周期怎么被安排被知道。D 类型 cyclins 组成使房间能对生理的变化作出回应的房间周期引擎的一个重要部件。房间类型 -- 并且 D 类型 cyclins 的发展阶段特定的角色被描述了,但是 cyclin D 要求没在 GC 反应期间被探讨。在这研究,我们报导 cyclin D3 为切换的增长和 Ig 班大部分是非必需的在 vitro 激活的 B 房间。相反,在 Ccnd3 的 GC 开发 ?/ ?老鼠显著地被损害,作为是 T 房间依赖者抗体反应。在 GC 以内,尽管切换, unswitched B 房间被 cyclin D3 inactivation 影响, IgM?水池更严重地被减少。有趣地尽管有 cyclin D2 表示的补偿增加, Ccnd3 的一个重要数字 ?/ ?GC B 房间处于静止 G0 状态积累。最后,尽管 cyclin D3 inactivation 没在 GC B 房间破坏 BCL6 表示,支持 BCL6 overexpression 的效果完全堵住了 GC,建议 cyclin D3 调整 GC 形成的 BCL6 下游地行动。这是 cyclin D3 玩的第一示范在 B 房间开发的 GC 阶段的一个重要、唯一的角色。 | Jonathan U Peled J Jessica Yu Jeganathan Venkatesh Enguang Bi B Belinda Ding Melissa Krupski-Downs Rita Shaknovich Piotr Sicinski Betty Diamond Matthew D Scharff B Hilda Ye | 2010 | Cell Research2010，20，6： | 3 |
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