| 1 | miR-23a/b suppress cGAS-mediated innate and autoimmunity显示文摘Cyclic GMP-AMP synthase(cGAS),a key sensor of intracellular DNA,is essential for eliciting innate immunity against infection,whereas aberrant activation of cGAS by endogenous DNA promotes severe autoimmune diseases.However,it is largely unknown how cGAS expression is regulated during pathogen infection and autoimmunity.Here,we report that during herpes simplex virus type 1(HSV-1)infection,two microRNAs(miR-23a and miR-23b)whose levels significantly decrease due to their interaction with the lncRNA Oasl2-209 directly regulate the expression of cGAS.Overexpression of miR-23a/b markedly dampens cytosolic DNA-induced innate immune responses,whereas inhibition of miR-23a/b enhances these responses.Mice treated with miR-23a/b agomirs exhibit increased susceptibility to HSV-1 infection.Moreover,cGAS is significantly upregulated in the Trex1^(−/−)mouse autoimmune disease model.Administration of miR-23a/b blunts self DNA-induced autoinflammatory responses in Trex1^(−/−)mice.Collectively,our study not only reveals a novel regulatory mechanism of cGAS expression by miRNAs but also identifies a potential therapy for cGAS-related autoimmune diseases. | Qiuya Yu Lei Chu Yongxing Li Quanyi Wang Juanjuan Zhu Chen Wang Shufang Cui | 2021 | Cellular & Molecular Immunology2021，18，5： | 2 |
| 2 | Cloning,expression and improvement of catalytic activity of alginate lyase by site-directed mutation显示文摘Alginate lyase mainly produces active alginate oligosaccharides(AOS)by degrading alginate viaβ-elimination process.In this study,the Pseudoalteromonas sp.Alg6B alginate lyase-encoding gene alg6B-7 from polysaccharide lyase(PL)-7 family was successfully cloned,sequenced,expressed in Escherichia coli.Based on rational design and amino acid sequence alignment of the alginate lyase from various sources,four positive mutants were obtained.The specific enzyme activities of four mutants I62A,A99K,V132S,and L157T were 38.84%,42.85%,75.8%and 51.83%higher than that of the wild enzyme,respectively.The K_(cat)/K_(m) values of the four mutants were both increased,and the catalytic efficiency of V132S was 1.92-fold higher than that of the wild enzyme,especially.The rational design that was employed in this study achieved the dramatic improvement of catalytic activity,which may provide the application potential in industrial production. | Yu Lu Jianli Zhou Qiuya Gu Wenhua Yang Liu Yang Xiaobin Yu | 2022 | Systems Microbiology and Biomanufacturing2022，2，3： | 0 |
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