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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.
系统性红斑狼疮患者的血清IgG糖链特征 Article
潘胡丹, 王静蓉, 梁勇, 王灿坚, 田瑞敏, 叶华, 张晓, 吴沅皞, 邵苗, 张瑞军, 肖瑶, 李智, 张光峰, 周华, 王艺霖, 王晓双, 栗占国, 刘维, 刘良
《工程（英文）》 2023年 第26卷 第7期 页码 89-98 doi: 10.1016/j.eng.2023.01.006
结直肠癌、基质和正常结肠黏膜显微解剖区域N-糖组的显著多样性 Article
Di Wang, Katarina Madunić , Tao Zhang, Guinevere S.M. Lageveen-Kammeijer, Manfred Wuhrer
《工程（英文）》 2023年 第26卷 第7期 页码 32-43 doi: 10.1016/j.eng.2022.08.016
Aberrant glycosylation is considered to be a hallmark of colorectal cancer (CRC), as demonstrated by various studies. While the N-glycosylation of cell lines and serum has been widely examined, the analysis of cancer-associated N-glycans from tissues has been hampered by the heterogeneity of tumors and the complexity of N-glycan structures. To overcome these obstacles, we present a study using laser capture microdissection that makes it possible to largely deconvolute distinct N-glycomic signatures originating from different regions of heterogeneous tissues including cancerous, stromal, and healthy mucosa cells. N-glycan alditols were analyzed by means of porous graphitized carbon liquid chromatography-electrospray ionization tandem mass spectrometry, enabling the differentiation and structural characterization of isomeric species. In total, 116 N-glycans were identified that showed profound differences in expression among cancer, stroma, and normal mucosa. In comparison with healthy mucosa, the cancer cells showed an increase in α2-6 sialylation and monoantennary N-glycans, as well as a decrease in bisected N-glycans. Moreover, specific sialylated and (sialyl-)LewisA/X antigen-carrying N-glycans were exclusively expressed in cancers. In comparison with cancer, the stroma showed lower levels of oligomannosidic and monoantennary N-glycans, LewisA/X epitopes, and sulfation, as well as increased expression of (core-)fucosylation and α2-3 sialylation. Our study reveals the distinct N-glycomic profiles of different cell types in CRC tumor and control tissues, proving the necessity of their separate analysis for the discovery of cancer-associated glycans.
关键词： 结直肠癌 肿瘤 多孔石墨化碳液相色谱-质谱 N-糖组 抗体反应
免疫球蛋白G N-糖基化与代谢特征之间的双向因果关联——一项孟德尔随机化研究 Article
孟晓妮, 曹维杰, 刘迪, Isinta Elijah Maranga, 邢薇佳, 侯海峰, 徐希柱, 宋曼殳, 王友信
《工程（英文）》 2023年 第26卷 第7期 页码 74-88 doi: 10.1016/j.eng.2022.11.004
既往研究已发现免疫球蛋白 G（immunoglobulin G, IgG）N-糖基化与代谢特征之间存在关联，但它们之间是否存在因果关联尚有待研究在正向MR分析中，通过整合IgG N-糖基-QTL遗传变异与GWAS 数据和代谢特征进行分析，分别发现59个包括影响体质指数（body mass index, BMI）的9个IgG N-糖基（glycanpeaks, GP）（GP1和GP6等）和影响空腹血糖（fasting plasma glucose, FPG）的 7个IgG N-糖基（GP1和GP5等）以及15个[包括影响BMI 的5个IgG N--糖基（GP2 和 GP11 等）和影响FPG的 4个IgG N-糖基（GP1和GP10等）]由遗传决定的 IgG N-糖基在单样本和两样本MR研究中与代谢特征存在因果关联（全部 P综上所述，本研究全面的双向MR分析提供了IgG N-糖基化与代谢特征之间双向因果关联的证据，在一定程度上揭示了 IgG N-糖基化与代谢特征之间的生物学机制。
Estimating the effect of urease inhibitor on rice yield based on NDVI at key growth stages
Kailou LIU,Yazhen LI,Huiwen HU
《农业科学与工程前沿（英文）》 2014年 第1卷 第2期 页码 150-157 doi: 10.15302/J-FASE-2014028
关键词： normalized difference vegetation index (NDVI) N-(n-butyl) thiophosphoric triamide (NBPT) rice grain yield
新型冠状病毒HCoV-19 S蛋白与人ACE2蛋白表面糖链和独特翻译后修饰的质谱分析 Article
孙泽宇, 任科燚, 张兴, 陈景华, 姜正一, 江静, 季飞洋, 欧阳晓希, 李兰娟
《工程（英文）》 2021年 第7卷 第10期 页码 1441-1451 doi: 10.1016/j.eng.2020.07.014
Chengkun WANG, Xiaojian ZHANG, Jun WANG, Chao CHEN
《环境科学与工程前沿（英文）》 2012年 第6卷 第6期 页码 770-777 doi: 10.1007/s11783-012-0412-0
关键词：
IgG N-糖基心血管年龄独立于真实年龄精准表征心血管事件风险 Article
武志远, 郭政, 郑雨露, 王玉涛, 张海平, 潘慧颖, 李志伟, Lois Balmer, 李霞, 陶丽新, 郭秀花, 王嵬
《工程（英文）》 2023年 第26卷 第7期 页码 99-107 doi: 10.1016/j.eng.2022.12.004
可去除染料——N-聚糖多方法深入分析中的缺失环节 Article
Samanta Cajic, René Hennig, Valerian Grote, Udo Reichl, Erdmann Rapp
《工程（英文）》 2023年 第26卷 第7期 页码 132-150 doi: https://doi.org/10.1016/j.eng.2023.02.016
As the roles of glycans in health and disease continue to be unraveled, it is becoming apparent that glycans' immense complexity cannot be ignored. To fully delineate glycan structures, we developed an integrative approach combining a set of cost-effective, widespread, and easy-to-handle analytical methods. The key feature of our workflow is the exploitation of a removable fluorescent label—exemplified by 9-fluorenylmethyl chloroformate (Fmoc)—to bridge the gap between diverse glycoanalytical methods, especially multiplexed capillary gel electrophoresis with laser-induced fluorescence detection (xCGE-LIF) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Through the detailed structural analysis of selected, dauntingly complex N-glycans from chicken ovalbumin, horse serum, and bovine transferrin, we illustrate the capabilities of the presented strategy. Moreover, this approach "visualizes" N-glycans that have been difficult to identify thus far—such as the sulfated glycans on human immunoglobulin A—including minute changes in glycan structures, potentially providing useful new targets for biomarker discovery.
基于正交质谱的N-糖组谱揭示哈夫病潜在病原学 Article
刘思, 刘圆圆, 林佳静, 刘笔锋, 何振宇, 吴晓旻, 刘欣
《工程（英文）》 2023年 第26卷 第7期 页码 63-73 doi: 10.1016/j.eng.2022.09.012
用于提高叔胺的二氧化碳吸收能力的纳米多孔碳材料促进剂的制备 Review
Masood S. Alivand, Omid Mazaheri, Yue Wu, Geoffrey W. Stevens, Colin A. Scholes, Kathryn A. Mumford
《工程（英文）》 2020年 第6卷 第12期 页码 1381-1394 doi: 10.1016/j.eng.2020.05.004
月经周期中免疫球蛋白G N-糖基化的周期性变化 Article
Julija Jurić, Hongli Peng, Manshu Song, Frano Vučković, Jelena Šimunović, Irena Trbojević-Akmačić, Youxin Wang, Jiaonan Liu, Qing Gao, Hao Wang, Qiaoyun Chu, Marija Pezer, Wei Wang, Gordan Lauc
《工程（英文）》 2023年 第26卷 第7期 页码 108-118 doi: 10.1016/j.eng.2022.10.020
Immunoglobulin G (IgG) is the most abundant plasma glycoprotein and a prominent humoral immune mediator. Glycan composition affects the affinity of IgG to ligands and consequent immune responses. The modification of IgG N-glycosylation is considered to be one of the various mechanisms by which sex hormones modulate the immune system. Although the menstrual cycle is the central sex hormone-related physiological process in most women of reproductive age, IgG N-glycosylation dynamics during the menstrual cycle have not yet been investigated. To fill this gap, we profiled the plasma IgG N-glycans of 70 healthy premenopausal women at 12 time points during their menstrual cycles (every 7 days for 3 months) using hydrophilic interaction ultra-performance liquid chromatography (HILIC-UPLC). We observed cyclic periodic changes in the N-glycosylation of IgG in association with the menstrual cycle phase and sex hormone concentration in plasma. On the integrated cohort level, the modeled average menstrual cycle effect on the abundance of IgG N-glycosylation traits was low for each trait, with the highest being 1.1% for agalactosylated N-glycans. However, intrapersonal changes were relatively high in some cases; for example, the largest difference between theminimum and maximum values during themenstrual cycle was up to 21% for sialylated N-glycans. Across all measurements, the menstrual cycle phase could explain up to 0.72% of the variation in the abundance of a single IgG glycosylation trait of monogalactosylation. In contrast, up to 99% of the variation in the abundance of digalactosylation could be attributed to interpersonal differences in IgG N-glycosylation. In conclusion, the average extent of changes in the IgG N-glycopattern that occur during the menstrual cycle is small; thus, the IgG N-glycoprofiling of women in large sample-size studies can be performed regardless of menstrual cycle phase.
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
孙毅,范灵俊,洪学海
《中国工程科学》 2018年 第20卷 第2期 页码 27-32 doi: 10.15302/J-SSCAE-2018.02.005
本文介绍了区块链技术发展和行业应用的现状，对区块链未来大规模应用会面临的技术挑战进行了剖析，综述了区块链体系结构、共识算法、隐私保护、智能合约、跨链通信等关键问题的研究现状，从技术、人才和监管三个方面对我国进一步发展区块链技术及应用的政策提出了建议
标题 作者 时间 类型 操作
系统性红斑狼疮患者的血清IgG糖链特征
潘胡丹, 王静蓉, 梁勇, 王灿坚, 田瑞敏, 叶华, 张晓, 吴沅皞, 邵苗, 张瑞军, 肖瑶, 李智, 张光峰, 周华, 王艺霖, 王晓双, 栗占国, 刘维, 刘良
期刊论文
结直肠癌、基质和正常结肠黏膜显微解剖区域N-糖组的显著多样性
Di Wang, Katarina Madunić , Tao Zhang, Guinevere S.M. Lageveen-Kammeijer, Manfred Wuhrer
期刊论文
免疫球蛋白G N-糖基化与代谢特征之间的双向因果关联——一项孟德尔随机化研究
孟晓妮, 曹维杰, 刘迪, Isinta Elijah Maranga, 邢薇佳, 侯海峰, 徐希柱, 宋曼殳, 王友信
期刊论文
Estimating the effect of urease inhibitor on rice yield based on NDVI at key growth stages
Kailou LIU,Yazhen LI,Huiwen HU
期刊论文
IgG N-糖基心血管年龄独立于真实年龄精准表征心血管事件风险
武志远, 郭政, 郑雨露, 王玉涛, 张海平, 潘慧颖, 李志伟, Lois Balmer, 李霞, 陶丽新, 郭秀花, 王嵬
期刊论文
用于提高叔胺的二氧化碳吸收能力的纳米多孔碳材料促进剂的制备
Masood S. Alivand, Omid Mazaheri, Yue Wu, Geoffrey W. Stevens, Colin A. Scholes, Kathryn A. Mumford
期刊论文
月经周期中免疫球蛋白G N-糖基化的周期性变化
Julija Jurić, Hongli Peng, Manshu Song, Frano Vučković, Jelena Šimunović, Irena Trbojević-Akmačić, Youxin Wang, Jiaonan Liu, Qing Gao, Hao Wang, Qiaoyun Chu, Marija Pezer, Wei Wang, Gordan Lauc
期刊论文
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
期刊论文
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