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N-糖基化 3

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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

摘要：

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.

关键词：糖组学聚糖 N-糖基化基因组学遗传学全基因组关联研究

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血清N-聚糖生物标志物诊断ALT水平正常慢性乙型肝炎患者显著肝纤维化和肝硬化的临床意义 Article

王林, 刘艺琪, 顾启馨, 张驰, 徐蕾, 王蕾, 陈翠英, 刘学恩, 赵鸿, 庄辉

《工程（英文）》 2023年第26卷第7期页码 151-158 doi: 10.1016/j.eng.2023.03.008

摘要：

本研究目的是探讨血清N-聚糖模型在285例丙氨酸转移酶（alanine aminotransferase, ALT）水平正常应用基于DNA测序仪的荧光糖电泳技术检测患者血清N-聚糖图谱，每例患者的血清样本中共鉴定出9个N-聚糖峰。），并比较血清N-聚糖模型和其他纤维化标志物的诊断效能。在诊断肝硬化（≥F5）时，血清N-聚糖RF-B模型的AUROC为0.97，与肝组织活检的符合率为88.94%。在ALT水平正常的慢性乙肝患者中，血清N-聚糖模型可作为诊断显著肝纤维化或肝硬化的潜在生物标志物。

关键词：肝纤维化慢性乙型肝炎血清N-聚糖 N-聚糖模型丙氨酸转移酶

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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

摘要：

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.

关键词：糖蛋白 N-聚糖可逆标签亲水相互作用液相色谱法毛细管凝胶电泳质谱法

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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

摘要：

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。

关键词：孟德尔随机化研究免疫球蛋白 G N-糖基化代谢特征数量性状位点双向因果关联

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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

摘要： The effect of the urease inhibitor, N-(n-butyl) thiophosphoric triamide (NBPT) at a range of application rates on rice production was examined in a field experiment at Jinxian County, Jiangxi Province, China. The normalized difference vegetation index (NDVI) was measured at key growth stages in both early and late rice. The results showed that the grain yield increased significantly when urea was applied with NBPT, with the highest yield observed at 1.00% NBPT (wt/wt). NDVI differed with the growth stage of rice; it remained steady from the heading to the filling stage. Rice yield could be predicted from the NDVI taken at key rice growing stages, with ranging from 0.34 to 0.69 in early rice and 0.49 to 0.70 in late rice. The validation test showed that RMSE (t·hm ) values were 0.77 and 0.87 in early and late rice, respectively. Therefore, it was feasible to estimate rice yield for different amounts of urease inhibitor using NDVI.

关键词： normalized difference vegetation index (NDVI) N-(n-butyl) thiophosphoric triamide (NBPT) rice grain yield

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Detecting

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

摘要： nitrosodimethylamine (NDMA) and several other nitrosamines have been detected as disinfection by-products in drinking waters in many countries around the world. An ultra-performance liquid chromatography-tandem mass spectrometry method with solid phase extraction sample preparation was developed to study the occurrence of nitrosamines in several water treatment plants and distribution systems in China. Isotope labeled nitrosodi- propylamine-d14 (NDPA-d14) was selected as the internal standard for quantification. The solid phase extraction procedures including pH, enrichment process and MS/MS parameters including capillary voltage, cone gas flow, cone voltage, collision energy were optimized to give average recoveries of 26% to 112% for nine nitrosamine species. The instrument detection limits were estimated to range from 0.5 to 5 μg·L for the nine nitrosamine species. NDMA and several other nitrosamines were found at fairly high concentrations in several water treatment plants and distribution systems. NDMA was found in all locations, and the highest concentrations in cities B, G, T, and W were 3.0, 35.7, 21.3, and 19.7 ng·L , respectively. A wide range of nitrosamines concentrations and species were observed in different locations. Higher concentrations of nitrosamines were detected in distribution systems that were further away from the treatment plants, suggesting that the contact time between the residual disinfectant and natural organic matter may play an important role in the formation of these compounds.

关键词： N-nitrosamines water treatment plant distribution system ultra-performance liquid chromatography-tandem mass spectrometry

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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

摘要：

亚临床动脉粥样硬化和代谢紊乱是心血管健康的重要风险因素，应用免疫球蛋白G（IgG）N-聚糖模式作为炎症指标表征其发病风险已有研究报道然而，对于IgG N-糖基谱在心血管疾病（CVD）风险分层中的能力仍然未知。本研究旨在利用IgG N-糖基标志物开发追踪心血管疾病风险的年龄指数。结果显示，对GlyCage指数贡献最大的是具有双分叉N-乙酰葡萄糖胺（GlcNAc）的岩藻糖基化N-聚糖（GP6, FA2B）和具有双分叉GlcNAc的双半乳糖基化N-聚糖（GP13, A2BG2）。因此，本研究开发的GlyCage指数利用IgG N-糖基谱追踪心血管健康水平。GlyCage和真实年龄之间的差距能够独立地表征心血管风险，提示IgG N-糖基化在心血管疾病的发病机制中起作用。

关键词： IgG N-糖基心血管年龄心血管年龄免疫球蛋白G 糖基化炎症特征选择机器学习

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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

摘要： N-糖组的剖析将促进破译疾病的分子机制，而HD相关的糖基化从未被探索过。2019—2020年期间，本研究团队招募了来自武汉市疾病预防控制中心的90份HD患者和对照组血清样本。本文中，采用基于高通量的正交质谱对HD中血清和血清衍生的IgG的N-糖组谱进行了表征。数据显示，HD与总血清糖蛋白的核心岩藻糖基化和单半乳糖醇化升高有关。血清IgG水平是HD患者的良好指标。此外，IgG的差异半乳糖基化和唾液酸化与HD密切相关。值得注意的是，IgG1和IgG2的半乳糖基化和唾液酸化的变化具有亚类特异性。本研究表明差异化IgG N-糖基化与HD的关联，为这种罕见疾病的病因提供了新的见解。

关键词：哈夫病全血清 IgG抗体糖基化疾病病原学

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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

摘要：本文对一些不同特性的纳米多孔碳材料促进剂（NCP）进行了合成和表征，并将其作为N,N-二乙基乙醇胺（DEEA）水溶液吸收CO₂的加速剂。

关键词：二氧化碳吸收纳米流体 N N-二乙基乙醇胺纳米多孔碳促进剂聚胺功能化

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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

摘要：

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.

关键词： N-糖基化免疫球蛋白G 月经周期女性性激素雌激素孕酮睾酮妇女

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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

摘要：

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

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人体前列腺特异性抗原携带含酮基-脱氧壬酮糖酸的N-聚糖 Article

Wei Wang, Tao Zhang, Jan Nouta, Peter A. van Veelen, Noortje de Haan, Theo M. de Reijke, Manfred Wuhrer, Guinevere S.M. Lageveen-Kammeijer

《工程（英文）》 2023年第26卷第7期页码 119-131 doi: 10.1016/j.eng.2023.02.009

摘要：

Ketodeoxynononic acid (Kdn) is a rather uncommon class of sialic acid in mammals. However, associations have been found between elevated concentrations of free or conjugated Kdn in relation to human cancer progression. Hitherto, there has been a lack of conclusive evidence that Kdn occurs on (specific) human glycoproteins (conjugated Kdn). Here, we report for the first time that Kdn is expressed on prostate-specific antigen (PSA) N-linked glycans derived from human seminal plasma and urine. Interestingly, Kdn was found only in an α2,3-linkage configuration on an antennary galactose, indicating a highly specific biosynthesis. This unusual glycosylation feature was also identified in a urinary PSA cohort in relation to prostate cancer (PCa), although no differences were found between PCa and non-PCa patients. Further research is needed to investigate the occurrence, biosynthesis, biological role, and biomarker potential of both free and conjugated Kdn in humans.

关键词：酮基-脱氧壬酮糖酸 Kdn 糖基化前列腺癌前列腺特异性抗原

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鲆鲽类主要病原菌抗血清的制备及应用

甘玲玲,王蔚芳,高淳仁,雷霁霖

《中国工程科学》 2014年第16卷第9期页码 21-25

摘要： em>)、迟缓爱德华菌(Edwardsiella tarda)、鮰爱德华菌(Edwardsiella ictaluri)，制备成灭活疫苗后肌肉注射大菱鲆获得各病原菌抗血清结果显示，抗鳗弧菌血清、抗哈维弧菌血清、抗豚鼠气单胞菌血清、抗鮰爱德华菌效价为1:6 400，抗创伤弧菌血清、抗溶藻弧菌血清、抗嗜水气单胞菌血清效价为1:12 800，抗迟缓爱德华菌血清效价为1:102应用ELISA分析各抗血清与8 种病原菌及迟缓爱德华菌蛋白的免疫交叉反应，结果显示，各病原菌与其本身的抗血清反应最为强烈，而与其他抗血清间有程度不等的交叉反应；菌蛋白与其相应的菌抗血清反应最为强烈，与其他病原菌抗血清反应较弱本研究所制备的病原菌抗血清效价较高，且具有特异性，可应用于鲆鲽类病原菌的检测。

关键词：鲆鲽类疫苗抗血清病原菌

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血清免疫球蛋白G N-糖基的高通量分析——一种消化道癌症的非侵入性生物标志物 Article

刘鹏程, 王小兵, 顿爱社, 李昱潼, 李厚强, 王璐, 张怡春, 李灿灿, 张金霞, 张晓雨, 马立兴, 侯海峰

《工程（英文）》 2023年第26卷第7期页码 44-53 doi: 10.1016/j.eng.2023.02.008

摘要：

免疫球蛋白G (Immunoglobulin G, IgG) 的 N-糖基化在炎症性疾病的发展中起着重要作用。本研究旨在评价IgG N-糖基在消化道癌症亚型中的诊断效能。interaction liquid chromatography using ultra-performance liquid chromatography, HILIC-UPLC）分析血浆中IgG的 NN-糖基的组成与炎症因子相关 (r = 0.556)。这些研究结果表明，IgG N-糖基在调节消化道肿瘤的发病机制中发挥了重要作用。血清IgG N-糖基可以作为潜在的非侵入性辅助消化道癌症临床诊断的方法。

关键词：消化道癌症糖基化免疫球蛋白 G 诊断生物标志物

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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

摘要：目前已有的SLE血清生物标志物灵敏度或特异性有限，使得SLE的早期精准诊断存在困难。在本研究中，通过对389例SLE患者及304例健康对照者进行深入的糖组学分析，鉴定出血清免疫球蛋白G（IgG）上的两种N-糖链能够作为SLE的诊断生物标志物。在其他易与SLE混淆的系统性自身免疫性疾病（如类风湿性关节炎、原发性干燥综合征或系统性硬化症）中，这两种生物标志物没有出现显著变化，提示这两种N-糖链生物标志物对诊断SLE具有特异性。值得注意的是，这两种N-糖链生物标志物被证明是自身抗体非依赖性的，并且适用于所有阶段的SLE患者。基于片段特异性糖链分析和糖肽分析，发现这两种N-糖链生物标志物位于IgG上的Fc区域，并与疾病活动性密切相关。而酶学分析结果则提示，SLE患者体内一系列糖转移酶的失调可能是观察到的糖链产生变化的原因。

关键词：系统性红斑狼疮 N-糖链诊断指标