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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

《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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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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流感与COVID-19患者的免疫球蛋白G糖基化差异 Article

Hadžibegović, Barbara Radovani, Ivana Jurin, Lovorka Đerek, Eva Huljev, Alemka Markotić, Ivica Lukšić, Irena Trbojević-Akmačić, Gordan Lauc, Ivan Gudelj, Rok Čivljak

《工程（英文）》 2023年第26卷第7期页码 54-62 doi: 10.1016/j.eng.2022.08.007

摘要：

The essential role of immunoglobulin G (IgG) in immune system regulation and combatting infectious diseases cannot be fully recognized without an understanding of the changes in its N-glycans attached to the asparagine 297 of the Fc domain that occur under such circumstances. These glycans impact the antibody stability, half-life, secretion, immunogenicity, and effector functions. Therefore, in this study, we analyzed and compared the total IgG glycome—at the level of individual glycan structures and derived glycosylation traits (sialylation, galactosylation, fucosylation, and bisecting N-acetylglucosamine (GlcNAc))—of 64 patients with influenza, 77 patients with coronavirus disease 2019 (COVID-19), and 56 healthy controls. Our study revealed a significant decrease in IgG galactosylation, sialylation, and bisecting GlcNAc (where the latter shows the most significant decrease) in deceased COVID-19 patients, whereas IgG fucosylation was increased. On the other hand, IgG galactosylation remained stable in influenza patients and COVID-19 survivors. IgG glycosylation in influenza patients was more time-dependent: In the first seven days of the disease, sialylation increased and fucosylation and bisecting GlcNAc decreased; in the next 21 days, sialylation decreased and fucosylation increased (while bisecting GlcNAc remained stable). The similarity of IgG glycosylation changes in COVID-19 survivors and influenza patients may be the consequence of an adequate immune response to enveloped viruses, while the observed changes in deceased COVID-19 patients may indicate its deviation.

关键词：流行性感冒 COVID-19 病毒感染糖基化免疫球蛋白G 肺炎

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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Ni>-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Ni>-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。另外，我们还发现了S蛋白和hACE2的多个甲基化修饰位点，以及hACE2的多个羟脯氨酸修饰位点。通过在最近发表的冷冻电镜（cryo-EM）结构的基础上加入Ni>-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。本研究揭示的HCoV-19 S蛋白和hACE2的PTM及糖基化图谱为研究病毒的宿主黏附、免疫反应，以及相关药物和疫苗的研发提供了更多的蛋白质结构细节。

关键词： Ni>-糖基化 COVID-19 棘突蛋白 hACE2 蛋白结构

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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

《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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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糖基化与代谢特征之间的双向因果关联。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（glycan-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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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

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A highly efficient methodology for the preparation of

Yongxin Zhang, Shucheng Wang, Yaodong Huang

《化学科学与工程前沿（英文）》 2021年第15卷第3期页码 679-686 doi: 10.1007/s11705-020-1979-9

摘要： A convenient and highly efficient method is described for the synthesis of -methoxycarbazole derivatives, including those with sterically demanding, benzannulated, or strongly electron-donating or -withdrawing substituents. Various -methoxycarbazole derivatives were directly prepared in good-to-moderate yields by the Pd (dba) CHCl /9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene-catalyzed reactions of the corresponding dibromobiphenyl compounds and methoxya-mine. Based on this methodology, the first total synthesis of 3,3′-[oxybis(methylene)]bis(9-methoxy-9 -carbazole), an antimicrobial dimeric carbazole alkaloid previously isolated from the stem bark of , was achieved in 18% yield over seven steps from 1,2-dibromobenzene.

关键词： N-methoxyl carbazole dimeric N-methoxyl carbazole alkaloid total synthesis double N-arylation of methoxyamine

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Inhibition of NO emission by adding antioxidant mixture in

A. PRABU,R. B. ANAND

《能源前沿（英文）》 2015年第9卷第2期页码 238-245 doi: 10.1007/s11708-015-0356-8

摘要： In this paper, the effect of adding an antioxidant mixture in biodiesel as fuel, in a single cylinder, direct injection compression ignition engine was experimentally investigated and the level of pollutants in the exhaust and performance characteristics of the engine were analyzed. Nine test fuels were prepared with three antioxidants, namely, Succinimide (C H NO ), , dimethyl- -phenylenediamine-dihydrochloride (C H Cl N ), and -phenyl- -phenylenediamine (C H NHC H NH ) added to neat biodiesel at 500 parts per million (ppm), 1000 ppm and 2000 ppm and the observed experimental results were compared with those of neat biodiesel and neat diesel as base fuels. The comparison showed that NO emission was reduced drastically for the test fuels with the antioxidant addition of 2000 ppm. The maximum reduction of 10% of NO emission was observed for the antioxidant mixture in neat biodiesel, with a slight increase in unburned HC, CO and smoke opacity. In addition, the obtained experimental results reveal that the addition of two antioxidants as mixture in neat biodiesel caused improved NO emission reduction for all test fuels.

关键词： NO emission antioxidants Succinimide N N-dimethyl-p-phenylenediamine-dihydrochloride N-phenyl-p-phenylenediamine

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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。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。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。有意义的是，IgG2或IgG3/4的唾液酸化和半乳糖基化改变与HD的临床标志物密切相关。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

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Thermogravimetric kinetic analysis of

SUKARNI,SUDJITO,Nurkholis HAMIDI,Uun YANUHAR,I.N.G. WARDANA

《能源前沿（英文）》 2015年第9卷第2期页码 125-133 doi: 10.1007/s11708-015-0346-x

摘要： The thermal behavior of combustion in air atmosphere were investigated by performing experiments on STA PT1600 Thermal Analyzer at heating rates of 10°C/min, 40°C/min and 70°C/min and range of temperatures from room temperature to 1200°C. The kinetic parameters were evaluated by using Kissinger and Ozawa methods. The result showed that combustion occurred in five stages. Started with initial devolatilization, the main thermal decomposition and combustion process, transition stage, the combustion of char and the last stage was the slow burning reaction of residual char. In line with increasing heating rate, the mass loss rate increased as well, but it delayed the thermal decomposition processes toward higher temperatures. The average activation energy at the main thermal decomposition stage and the stage of char combustion were approximately 251 kJ/mol and 178 kJ/mol, respectively.

关键词： Nannochloropsis oculata combustion kinetic parameters air atmosphere thermogravimetric

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Ni>-Positive ion activated rapid addition and mitochondrial targeting ratiometric fluorescent probesfor in vivoi> cell H₂S imaging

Yan Shi, Fangjun Huo, Yongkang Yue, Caixia Yin

《化学科学与工程前沿（英文）》 2022年第16卷第1期页码 64-71 doi: 10.1007/s11705-021-2048-8

摘要： Heterocyclic compound quinoline and its derivatives exist in natural compounds and have a broad spectrum of biological activity. They play an important role in the design of new structural entities for medical applications. Similarly, indoles and their derivatives are found widely in nature. Amino acids, alkaloids and auxin are all derivatives of indoles, as are dyes, and their condensation with aldehydes makes it easy to construct reaction sites for nucleophilic addition agents. In this work, we combine these two groups organically to construct a rapid response site (within 30 s) for H S, and at the same time, a ratiometric fluorescence response is presented throughout the process of H S detection. As such, the lower detection limit can reach 55.7 nmol/L for H S. In addition, cell imaging shows that this probe can be used for the mitochondrial targeted detection of endogenous and exogenous H S. Finally, this probe application was verified by imaging H S in nude mice.

关键词： heterocyclic compound hydrogen sulfide ratiometric mitochondrial targeted

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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。/em>-糖基构成。与健康对照组相比，EC、GC、CRC和PC患者的唾液酸化和半乳糖基化水平降低，而二等分乙酰葡萄糖胺基化水平在消化道癌症患者中升高。此外，只有胰腺癌患者具有低水平的岩藻糖基化。IgG N-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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Accounting for the uncertainties in the estimation of average shear wave velocity using – correlations

《结构与土木工程前沿（英文）》 2021年第15卷第5期页码 1199-1208 doi: 10.1007/s11709-021-0749-1

摘要： Site-specific seismic hazard analysis is crucial for designing earthquake resistance structures, particularly in seismically active regions. Shear wave velocity ( V _S) is a key parameter in such analysis, although the economy and other factors restrict its direct field measurement in many cases. Various V _S–SPT– N correlations are routinely incorporated in seismic hazard analysis to estimate the value of V _S. However, many uncertainties question the reliability of these estimated V _S values. This paper comes up with a statistical approach to take care of such uncertainties involved in V _S calculations. The measured SPT– N values from all the critical boreholes were converted into statistical parameters and passed through various correlations to estimate V _S at different depths. The effect of different soil layers in the boreholes on the Vs estimation was also taken into account. Further, the average shear wave velocity of the top 30 m soil cover ( V _S30) is estimated after accounting for various epistemic and aleatoric uncertainties. The scattering nature of the V _S values estimated using different V _S– N correlations was reduced significantly with the application of the methodology. Study results further clearly demonstrated the potential of the approach to eliminate various uncertainties involved in the estimation of V _S30 using general and soil-specific correlations.

关键词： uncertainties V _S– N correlations V _S30 SPT data statistical methodology

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Hydroxyl radical intensified Cu

Wenyue Li, Min Chen, Zhaoxiang Zhong, Ming Zhou, Weihong Xing

《环境科学与工程前沿（英文）》 2020年第14卷第6期 doi: 10.1007/s11783-020-1281-6

摘要： Abstract • Cu2O NPs/H2O2 Fenton process was intensified by membrane dispersion. • DMAc removal was enhanced to 98% for initial DMAc of 14000 mg/L. • Analyzed time-resolved degradation pathway of DMAc under ·OH attack. High-concentration industrial wastewater containing N,N-dimethylacetamide (DMAc) from polymeric membrane manufacturer was degraded in Cu2O NPs/H2O2 Fenton process. In the membrane-assisted Fenton process DMAc removal rate was up to 98% with 120 min which was increased by 23% over the batch reactor. It was found that ·OH quench time was extended by 20 min and the maximum ·OH productivity was notably 88.7% higher at 40 min. The degradation reaction rate constant was enhanced by 2.2 times with membrane dispersion (k = 0.0349 min−1). DMAc initial concentration (C0) and H2O2 flux (Jp) had major influence on mass transfer and kinetics, meanwhile, membrane pore size (rp) and length (Lm) also affected the reaction rate. The intensified radical yield, fast mass transfer and nanoparticles high activity all contributed to improve pollutant degradation efficiency. Time-resolved DMAc degradation pathway was analyzed as hydroxylation, demethylation and oxidation leading to the final products of CO2, H2O and NO3− (rather than NH3 from biodegradation). Continuous process was operated in the dual-membrane configuration with in situ reaction and separation. After five cycling tests, DMAc removal was all above 95% for the initial [DMAc]0 = 14,000 mg/L in wastewater and stability of the catalyst and the membrane maintained well.

关键词： Ceramic membrane reactor N N-dimethylacetamide Fenton process Cu₂O Wastewater treatment

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标题作者时间类型操作

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

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

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