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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: 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。使用机器学习递归特征消除和惩罚回归算法逐步筛选特征糖基,并开发IgG N-糖基化心血管年龄(GlyCage)指数,以反映归因于心血管风险的与真实年龄间的偏差。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    

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    

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    

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    

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    

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。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。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    

Catalysis and deactivation of montmorillonite K10 in the aryl O -glycosylation of glycosyl trichloroacetoimidates

Xiaoliu LI, Xinhao YAN, Zhiwei LI, Hua CHEN, Pingzhu ZHANG,

《化学科学与工程前沿(英文)》 2010年 第4卷 第3期   页码 342-347 doi: 10.1007/s11705-009-0279-1

摘要: The catalysis of montmorillonite K10 (MK10) for aryl -glycosylation of glycosyl trichloroacetimidates was investigated. It was found that the catalyst MK10 is deactivated gradually in the recycle glycosylation. The fresh and the deactivated catalysts were characterized by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), Thermogravimetric analysis (TGA), and N adsorption-desorption. The results show that the eliminated trichloroacetamide molecule deposits on the MK10, which blocks and poisons the active sites, resulting in the deactivation of the catalyst. The regeneration of the deactivated MK10 by calcination was studied preliminarily.

关键词: photoelectron spectroscopy     adsorption-desorption     glycosylation     deactivated     diffraction    

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    

Emerging roles of podoplanin in vascular development and homeostasis

null

《医学前沿(英文)》 2015年 第9卷 第4期   页码 421-430 doi: 10.1007/s11684-015-0424-9

摘要:

Podoplanin (PDPN) is a mucin-type O-glycoprotein expressed in diverse cell types, such as lymphatic endothelial cells (LECs) in the vascular system and fibroblastic reticular cells (FRCs) in lymph nodes. PDPN on LECs or FRCs activates CLEC-2 in platelets, triggering platelet activation and/or aggregation through downstream signaling events, including activation of Syk kinase. This mechanism is required to initiate and maintain separation of blood and lymphatic vessels and to stabilize high endothelial venule integrity within lymph nodes. In the vascular system, normal expression of PDPN at the LEC surface requires transcriptional activation of Pdpn by Prox1 and modification of PDPN with core 1-derived O-glycans. This review provides a comprehensive overview of the roles of PDPN in vascular development and lymphoid organ maintenance and discusses the mechanisms that regulate PDPN expression related to its function.

关键词: podoplanin     CLEC-2     Prox1     O-glycosylation     lymphatic vascular development and maintenance     lymphoid organ homeostasis    

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

摘要: 质谱分析(MS)发现,在HCoV-19 S蛋白的21个潜在糖基化修饰位点中,有20个位点完全被N-糖链占据,其糖型以低聚甘露糖为主。人血管紧张素转换酶2(hACE2)的7个糖基化位点完全被复合型N-糖链占据。然而,糖基化修饰并不能直接影响HCoV-19 S蛋白与hACE2之间的结合亲和力。通过在最近发表的冷冻电镜(cryo-EM)结构的基础上加入N-糖链和蛋白质翻译后修饰(PTM),我们构建了HCoV-19 S蛋白和hACE2的精细结构模型。

关键词: N-糖基化     COVID-19     棘突蛋白     hACE2     蛋白结构    

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    

Effect of Cu-ZSM-5 catalysts with different CuO particle size on selective catalytic oxidation of N,N-Dimethylformamide

《环境科学与工程前沿(英文)》 2022年 第16卷 第10期 doi: 10.1007/s11783-022-1557-0

摘要:

● A series of Cu-ZSM-5 catalysts were tested for DMF selective catalytic oxidation.

关键词: N     N-Dimethylformamide     Selective catalytic oxidation     Cu-ZSM-5     CuO particle size    

Enhancing the efficiency of nitrogen removing bacterial population to a wide range of C:N ratio (1.5:1 to 14:1) for simultaneous C & N removal

《环境科学与工程前沿(英文)》 2022年 第16卷 第8期 doi: 10.1007/s11783-022-1522-y

摘要:

• Simultaneous C & N removal in Methammox occurs at wide C:N ratio.

关键词: Methanogens     Biological Nitrogen Removal (BNR)     Simultaneous     Methammox     C:N ratio    

Effect of fly ash and slag on concrete: Properties and emission analyses

TAM, Khoa N. LE, Ana Catarina Jorge EVANGELISTA, Anthony BUTERA, Cuong N. N. TRAN, Ashraf TEARA

《工程管理前沿(英文)》 2019年 第6卷 第3期   页码 395-405 doi: 10.1007/s42524-019-0019-2

摘要: Recycled concrete is a material with the potential to create a sustainable construction industry. However, recycled concrete presents heterogeneous properties, thereby reducing its applications for some structural purposes and enhancing its application in pavements. This paper provides an insight into a solution in the deformation control for recycled concrete by adding supplementary cementitious materials fly ash and blast furnace slag. Results of this study indicated that the 50% fly ash replacement of Portland cement increased the rupture modulus of the recycled concrete. Conversely, a mixture with over 50% cement replacement by either fly ash or slag or a combination of both exhibited detrimental effect on the compressive strength, rupture modulus, and drying shrinkage. The combined analysis of environmental impacts and mechanical properties of recycled concrete demonstrated the possibility of optimizing the selection of recycled concrete because the best scenario in this study was obtained with the concrete mixture M8 (50% of fly ash+ 100% recycled coarse aggregate).

关键词: recycled aggregate     recycled concrete     fly ash and slag    

Endemicity of H9N2 and H5N1 avian influenza viruses in poultry in China poses a serious threat to poultry

Jiao HU,Xiufan LIU

《农业科学与工程前沿(英文)》 2016年 第3卷 第1期   页码 11-24 doi: 10.15302/J-FASE-2016092

摘要: The H9N2 and H5N1 avian influenza viruses (AIVs) have been circulating in poultry in China and become endemic since 1998 and 2004, respectively. Currently, they are prevalent in poultry throughout China. This endemicity makes them actively involved in the emergence of the novel lineages of other subtypes of influenza viruses, such as the well-known viruses of the highly pathogenic avian influenza (HPAI) H5N2 and the 2013 novel H7N7, H7N9 and H10N8 subtypes, thereby threatening both the poultry industry and public health. Here, we will review briefly the prevalence and evolution, pathogenicity, transmission, and disease control of these two subtypes and also discuss the possibility of emergence of potentially virulent and highly transmissible AIVs to humans.

关键词: avian influenza virus     H9N2     H5N1     novel viruses     public health    

标题 作者 时间 类型 操作

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

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

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

人类蛋白质N-糖基化的十二年全基因组关联研究

Anna Timoshchuk, Sodbo Sharapov, Yurii S. Aulchenko

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

基于正交质谱的N-糖组谱揭示哈夫病潜在病原学

刘思, 刘圆圆, 林佳静, 刘笔锋, 何振宇, 吴晓旻, 刘欣

期刊论文

Catalysis and deactivation of montmorillonite K10 in the aryl O -glycosylation of glycosyl trichloroacetoimidates

Xiaoliu LI, Xinhao YAN, Zhiwei LI, Hua CHEN, Pingzhu ZHANG,

期刊论文

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

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

期刊论文

Emerging roles of podoplanin in vascular development and homeostasis

null

期刊论文

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

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

期刊论文

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

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Effect of Cu-ZSM-5 catalysts with different CuO particle size on selective catalytic oxidation of N,N-Dimethylformamide

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Enhancing the efficiency of nitrogen removing bacterial population to a wide range of C:N ratio (1.5:1 to 14:1) for simultaneous C & N removal

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Effect of fly ash and slag on concrete: Properties and emission analyses

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Endemicity of H9N2 and H5N1 avian influenza viruses in poultry in China poses a serious threat to poultry

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