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低蛋白日粮中添加亮氨酸通过雷帕霉素靶蛋白信号通路增加成年大鼠骨骼肌重量及蛋白质合成
张博, 楚丽翠, 刘宏, 谢春元, 谯仕彦, 曾祥芳
《工程（英文）》 2017年 第3卷 第5期 页码 760-765 doi: 10.1016/J.ENG.2017.03.008
低蛋白日粮会减少动物组织中蛋白质沉积，影响骨骼肌增重。本文旨在研究低蛋白日粮中添加亮氨酸对成年大鼠骨骼肌重量和蛋白质合成的影响。试验第11天，所有大鼠大剂量一次性腹腔注射L-[ring-2H5]苯丙氨酸注射液，测定血清中的氨基酸含量、比目鱼肌和腓肠肌重量、蛋白质合成速率及mTOR信号通路相关分子的表达。结果表明，在3个处理中，RL组血清亮氨酸含量最高（P < 0.05），而异亮氨酸含量最低（P < 0.05）；CON组的缬氨酸含量低于R和RL组（P < 0.05），但采食量、蛋白质合成速度和与R组相比，RL组可以增加腓肠肌重量（P < 0.05），促进S6K1磷酸化（P < 0.05），增加骨骼肌蛋白质合成（P < 0.05）。本文结论如下，在成年大鼠长期采食低蛋白日粮的情况下，日粮中添加亮氨酸可以改善大鼠的生长性能，通过提高mTOR通路中S6K1磷酸化水平，促进大鼠骨骼肌蛋白质合成，抑制蛋白质降解。
通过蛋白质工程提高聚酯水解酶对PET 塑料的降解效率 Article
马渊, 姚明东, 李炳志, 丁明珠, 何博, 陈思, 周晓, 元英进
《工程（英文）》 2018年 第4卷 第6期 页码 888-893 doi: 10.1016/j.eng.2018.09.007
来自Ideonella sakaiensis 的聚对苯二甲酸乙二醇酯水解酶（PETase）在室温下具有很强的降解聚对苯二甲酸乙二醇酯（PET）的能力，因此被认为是解决聚酯塑料污染问题的潜在工具为了更加快速地筛选突变体酶的活性，本研究利用无细胞蛋白表达体系对设计的PETase 突变体进行高通量的表达和验证。因此，本研究通过蛋白质工程对PETase 的关键疏水位点进行设计和改造，获得了降解效果提高的酶突变体，并进一步证实了其生物降解塑料的潜力。
时间序列多组学整合分析揭示原代肝细胞体外培养去分化过程伴随非降解性泛素化修饰的增加 Article
姜正一, 孙泽宇, 欧阳晓希, 赵亚磊, 周梦豪, 王保红, 李启睿, 范林骁, 张赛男, 李兰娟
《工程（英文）》 2020年 第6卷 第11期 页码 1302-1314 doi: 10.1016/j.eng.2020.02.011
人类蛋白质N-糖基化的十二年全基因组关联研究 Review
Anna Timoshchuk, Sodbo Sharapov, Yurii S. Aulchenko
《工程（英文）》 2023年 第26卷 第7期 页码 17-31 doi: 10.1016/j.eng.2023.03.013
Most human-secreted and membrane-bound proteins have covalently attached oligosaccharide chains, or glycans. Glycosylation influences the physical and chemical properties of proteins, as well as their biological functions. Unsurprisingly, alterations in protein glycosylation have been implicated in a growing number of human diseases, and glycans are increasingly being considered as potential therapeutic targets, an essential part of therapeutics, and biomarkers. Although glycosylation pathways are biochemically well-studied, little is known about the networks of genes that guide the cell- and tissue-specific regulation of these biochemical reactions in humans in vivo. The lack of a detailed understanding of the mechanisms regulating glycome variation and linking the glycome to human health and disease is slowing progress in clinical applications of human glycobiology. Two of the tools that can provide much sought-after knowledge of human in vivo glycobiology are human genetics and genomics, which offer a powerful data-driven agnostic approach for dissecting the biology of complex traits. This review summarizes the current state of human populational glycogenomics. In Section 1, we provide a brief overview of the N-glycan's structural organization, and in Section 2, we give a description of the major blood plasma glycoproteins. Next, in Section 3, we summarize, systemize, and generalize the results from current N-glycosylation genome-wide association studies (GWASs) that provide novel knowledge of the genetic regulation of the populational variation of glycosylation. Until now, such studies have been limited to an analysis of the human blood plasma N-glycome and the N-glycosylation of immunoglobulin G and transferrin. While these three glycomes make up a rather limited set compared with the enormous multitude of glycomes of different tissues and glycoproteins, the study of these three does allow for powerful analysis and generalization. Finally, in Section 4, we turn to genes in the established loci, paying particular attention to genes with strong support in Section 5. At the end of the review, in Sections 6 and 7, we describe special cases of interest in light of new discoveries, focusing on possible mechanisms of action and biological targets of genetic variation that have been implicated in human protein N-glycosylation.
门可佩
《中国工程科学》 2009年 第11卷 第6期 页码 82-88
许尔琪
《中国工程科学》 2018年 第20卷 第5期 页码 57-62 doi: 10.15302/J-SSCAE-2018.05.009
中东呼吸综合征病毒（MERS-CoV）蛋白的分子特征、功能及其致病性 Review
李艳华, 胡晨雨, 吴南屏, 姚航平, 李兰娟
《工程（英文）》 2019年 第5卷 第5期 页码 940-947 doi: 10.1016/j.eng.2018.11.035
转录因子HNF1A、HNF4A和FOXA2调节肝细胞蛋白质N-糖基化 Article
Vedrana Vičić Bočkor,Nika Foglar,Goran Josipović,Marija Klasić,Ana Vujić,Branimir Plavša,Toma Keser,Samira Smajlović,Aleksandar Vojta,Vlatka Zoldoš
《工程（英文）》 2024年 第32卷 第1期 页码 58-69 doi: 10.1016/j.eng.2023.09.019
Hepatocyte nuclear factor 1 alpha (HNF1A), hepatocyte nuclear factor 4 alpha (HNF4A), and forkhead box protein A2 (FOXA2) are key transcription factors that regulate a complex gene network in the liver, creating a regulatory transcriptional loop. The Encode and ChIP-Atlas databases identify the recognition sites of these transcription factors in many glycosyltransferase genes. Our in silico analysis of HNF1A, HNF4A, and FOXA2 binding to the 10 candidate glyco-genes studied in this work confirms a significant enrichment of these transcription factors specifically in the liver. Our previous studies identified HNF1A as a master regulator of fucosylation, glycan branching, and galactosylation of plasma glycoproteins. Here, we aimed to functionally validate the role of the three transcription factors on downstream glyco-gene transcriptional expression and the possible effect on glycan phenotype. We used the state-of-the-art clustered regularly interspaced short palindromic repeats/dead Cas9 (CRISPR/dCas9) molecular tool for the downregulation of the HNF1A, HNF4A, and FOXA2 genes in HepG2 cells—a human liver cancer cell line. The results show that the downregulation of all three genes individually and in pairs affects the transcriptional activity of many glyco-genes, although downregulation of glyco-genes was not always followed by an unambiguous change in the corresponding glycan structures. The effect is better seen as an overall change in the total HepG2 N-glycome, primarily due to the extension of biantennary glycans. We propose an alternative way to evaluate the N-glycome composition via estimating the overall complexity of the glycome by quantifying the number of monomers in each glycan structure. We also propose a model showing feedback loops with the mutual activation of HNF1A–FOXA2 and HNF4A–FOXA2 affecting glyco-genes and protein glycosylation in HepG2 cells.
关键词： Clustered regularly interspaced short palindromic repeats/dead Cas9 (CRISPR/dCas9) Epigenetics Hepatocyte nuclear factor 1 alpha (HNF1A) Hepatocyte nuclear factor 4 alpha (HNF4A) Forkhead box protein A2 (FOXA2) N-glycosylation HepG2 cells
向小东
《中国工程科学》 2008年 第10卷 第11期 页码 89-92
根据时间序列近期数据较远期数据包含有更多未来信息的思想，对最小二乘支持向量机预测方法进行了扩展，得到了更具一般性的最小二乘支持向量机预测模型，给出了扩展后的预测模型具体算法。两个时间序列的预测实例表明，扩展后的预测方法获得了更好的预测效果，提升了最小二乘支持向量机预测方法的价值。
普列克底物蛋白同源物样结构域家族A成员1蛋白——导致代谢疾病的多方面细胞存活因素 Review
Tamana Yousof, Jae Hyun Byun, Jack Chen, Richard C. Austin
《工程（英文）》 2023年 第20卷 第1期 页码 9-18 doi: 10.1016/j.eng.2022.05.014
普列克底物蛋白同源物样结构域家族A成员1（PHLDA1）是多作用的胞内蛋白，属于进化上保守的普列克底物蛋白同源相关结构域家族。本文综述了PHLDA1基因及蛋白调控、定位和功能方面的现有知识。本文重点介绍了PHLDA1促凋亡和抗凋亡，进而导致代谢性疾病的作用。
标题 作者 时间 类型 操作
卢云峰：纳米胶囊：新型蛋白质药物投递技术平台（2019年9月18日）
2021年08月16日
会议视频
转录因子HNF1A、HNF4A和FOXA2调节肝细胞蛋白质N-糖基化
Vedrana Vičić Bočkor,Nika Foglar,Goran Josipović,Marija Klasić,Ana Vujić,Branimir Plavša,Toma Keser,Samira Smajlović,Aleksandar Vojta,Vlatka Zoldoš
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