Viral infections

病毒感染
  • 文章类型: Journal Article
    选择性自噬是一种由进化保守的选择性自噬受体(SARs)介导的蛋白质清除机制,特别是降解错误折叠,组装错误,或代谢调节的蛋白质。SARs通过降解病毒蛋白帮助宿主抑制病毒感染。然而,病毒已经进化出复杂的机制来抵消,逃避,或者选择自噬过程,从而促进病毒复制。因此,这篇综述旨在总结SARs参与病毒感染的复杂机制,特别关注病毒如何利用策略来调节选择性自噬。我们提出了对SARs在病毒发病机理中的各种关键作用的最新理解。此外,讨论了新发现的病毒逃避策略,并提出泛素化-自噬-先天免疫调节轴是控制病毒感染的关键途径。这篇综述强调了SARs在病毒感染中的显着灵活性和可塑性。
    Selective autophagy is a protein clearance mechanism mediated by evolutionarily conserved selective autophagy receptors (SARs), which specifically degrades misfolded, misassembled, or metabolically regulated proteins. SARs help the host to suppress viral infections by degrading viral proteins. However, viruses have evolved sophisticated mechanisms to counteract, evade, or co-opt autophagic processes, thereby facilitating viral replication. Therefore, this review aims to summarize the complex mechanisms of SARs involved in viral infections, specifically focusing on how viruses exploit strategies to regulate selective autophagy. We present an updated understanding of the various critical roles of SARs in viral pathogenesis. Furthermore, newly discovered evasion strategies employed by viruses are discussed and the ubiquitination-autophagy-innate immune regulatory axis is proposed to be a crucial pathway to control viral infections. This review highlights the remarkable flexibility and plasticity of SARs in viral infections.
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  • 文章类型: Journal Article
    背景:鉴于病毒感染会增加不良妊娠结局的风险,比如自发性流产,早产胎膜早破,和早产,COVID-19是一种在全球迅速传播的新型冠状病毒疾病,对妊娠结局的重视.
    方法:我们对过去五年(2019年12月至2023年4月)与感染SARS-CoV-2的孕妇有关的研究进行了回顾,利用PubMed等搜索引擎,WebofScience,和中国国家知识基础设施(CNKI)。本研究在PROSPERO注册,ID:CRD42024540849。
    结果:共筛选了218篇文章,有15项研究符合这项研究的纳入标准,包括12项队列研究,一项横断面研究,一项病例对照研究,一个案例系列。6项研究发现感染组早产率高于对照组;5项研究表明感染组剖宫产率高于对照组;3项研究发现对照组新生儿APGAR评分高于感染组;3项研究表明感染组新生儿死亡率高于对照组。
    结论:我们的回顾性研究表明,与未感染SARS-CoV-2的孕妇相比,被诊断为COVID-19的孕妇更有可能出现早产等不良结局,剖宫产,新生儿出生体重低。
    Given that viral infections can increase the risk of adverse pregnancy outcomes, such as spontaneous miscarriage, preterm premature rupture of membranes, and preterm birth, the effects of COVID-19, a novel emerging coronavirus disease rapidly spreading globally, on pregnancy outcomes have garnered significant attention.
    We conducted a review of studies related to pregnant women infected with SARS-CoV-2 over the past five years (December 2019 to April 2023), utilizing search engines such as PubMed, Web of Science, and the China National Knowledge Infrastructure (CNKI). This study was registered with PROSPERO with ID: CRD42024540849.
    A total of 218 articles were screened, with 15 studies meeting the inclusion criteria for this research, including 12 cohort studies, one cross-sectional study, one case-control study, and one case series. Six studies found that the preterm birth rate was higher in the infected group compared to the control group; five studies showed that the cesarean section rate was higher in the infected group; three studies found that the APGAR scores of newborns were higher in the control group than in the infected group; three studies indicated that the mortality rate of newborns in the infected group was higher than that in the control group.
    Our retrospective review suggests that compared to pregnant women not infected with SARS-CoV-2, those diagnosed with COVID-19 are more likely to experience adverse outcomes such as preterm birth, cesarean delivery, and low birth weight in newborns.
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  • 文章类型: Journal Article
    背景:病毒感染与结直肠癌(CRC)风险之间的遗传易感性关系尚未确定。
    方法:我们使用全基因组关联研究(GWAS)数据进行了双样本孟德尔随机化(MR)分析。除了传统的MR方法,我们采用了其他几种方法,包括CML,ConMix,MR-RAPS,和DIVW,全面评估因果效应。还进行了灵敏度分析以确保结果的稳健性。
    结果:经过敏感性分析,与感冒疮感染易感性增加相关的SNP的存在可降低CRC的风险(OR:0.73,95%CI:0.57-0.93,P=0.01).在亚组分析中,存在与病毒性肝炎易感性增加相关的SNP(OR:0.89,95%CI:0.81-0.98,P=0.02)和传染性单核细胞增多症(OR:0.91,95%CI:0.84-0.98,P=0.02)与结肠癌风险降低相关,而麻疹病毒(OR:1.41,95%CI:1.07~1.85,P=0.01)与结肠癌风险增加相关。存在与带状疱疹易感性增加相关的SNP(OR:1.26,95%CI:1.05-1.52,P=0.01)与直肠癌风险增加相关,而传染性单核细胞增多症(OR:0.809,95%CI:0.80-0.98,P=0.02)与风险降低相关。
    结论:该研究提供了不同病毒感染与CRC之间遗传易感性关联的第一个证据,增强我们对CRC病因的理解。
    BACKGROUND: The genetic susceptibility association between viral infection and the risk of colorectal cancer (CRC) has not been established.
    METHODS: We conducted two-sample Mendelian randomization (MR) analysis using genome-wide association study (GWAS) data. In addition to traditional MR methods, we employed several other approaches, including cML, ConMix, MR-RAPS, and dIVW, to comprehensively assess causal effects. Sensitivity analyses were also performed to ensure the robustness of the results.
    RESULTS: After sensitivity analysis, presence of SNPs linked to increased susceptibility to cold sores infection was found to decrease the risk of CRC (OR: 0.73, 95% CI: 0.57-0.93, P = 0.01). In subgroup analysis, presence of SNPs linked to increased susceptibility to viral hepatitis (OR: 0.89, 95% CI: 0.81-0.98, P = 0.02) and infectious mononucleosis (OR: 0.91, 95% CI: 0.84-0.98, P = 0.02) were associated with a decreased risk of colon cancer, while measles virus (OR: 1.41, 95% CI: 1.07-1.85, P = 0.01) was associated with an increased risk of colon cancer. Presence of SNPs linked to increased susceptibility to herpes zoster (OR: 1.26, 95% CI: 1.05-1.52, P = 0.01) was associated with an increased risk of rectal cancer, while infectious mononucleosis (OR: 0.809, 95% CI: 0.80-0.98, P = 0.02) was associated with a decreased risk.
    CONCLUSIONS: The study provides the first evidence of the genetic susceptibility associations between different viral infections and CRC, enhancing our understanding of the etiology of CRC.
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  • 文章类型: Journal Article
    泛素化,一个关键的翻译后修饰,在几乎所有的生理过程中发挥作用。其功能执行取决于一系列涉及许多蛋白酶的催化反应。TRIM26,一种属于TRIM家族的蛋白质,由于其RING结构域而表现出E3泛素连接酶活性,并存在于不同的细胞谱系中。在过去的几十年里,TRIM26已被证明参与许多生理和病理过程作为控制器,展示了各种各样的生物学角色。尽管对TRIM26的研究兴趣越来越大,但在现有的综述中,对研究蛋白质的结构和功能的关注有限。这篇综述首先简要概述了TRIM26的组成和定位,然后继续研究其在免疫应答中的作用。病毒入侵,和炎症过程。同时,我们证明了TRIM26对各种疾病进展的贡献,包括许多恶性肿瘤和神经系统疾病。最后,我们调查了TRIM26未来研究的潜在领域.
    Ubiquitination, a crucial post-translational modification, plays a role in nearly all physiological processes. Its functional execution depends on a series of catalytic reactions involving numerous proteases. TRIM26, a protein belonging to the TRIM family, exhibits E3 ubiquitin ligase activity because of its RING structural domain, and is present in diverse cell lineages. Over the last few decades, TRIM26 has been documented to engage in numerous physiological and pathological processes as a controller, demonstrating a diverse array of biological roles. Despite the growing research interest in TRIM26, there has been limited attention given to examining the protein\'s structure and function in existing reviews. This review begins with a concise overview of the composition and positioning of TRIM26 and then proceeds to examine its roles in immune response, viral invasion, and inflammatory processes. Simultaneously, we demonstrate the contribution of TRIM26 to the progression of various diseases, encompassing numerous malignancies and neurologic conditions. Finally, we have investigated the potential areas for future research on TRIM26.
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  • 文章类型: Journal Article
    病毒感染被认为是喉癌的危险因素。鉴于2019年冠状病毒病(COVID-19)对喉组织的可能影响,我们采用双样本孟德尔随机化(MR)方法研究了COVID-19与喉癌之间的因果关系.
    我们利用了来自COVID-19宿主遗传学倡议(2021年1月18日发布)的第五次全基因组关联研究(GWAS)版的遗传数据和大规模喉癌GWAS,包括180例病例和218,612个欧洲血统对照。我们应用了方差逆加权,Egger先生,和加权中位数方法来推断因果关系。我们使用“留一法”进行了敏感性分析,以验证稳健性。
    我们没有发现基因预测的COVID-19与喉癌之间存在因果关系的证据[赔率(OR)=0.24(95%置信区间(CI),0.05-1.26),P=0.09]。然而,我们观察到基因预测的COVID-19住院率之间的显着负相关[OR=0.51(95%CI,0.28-0.95),P=0.03]和重症患者[OR=0.62(95%CI,0.43-0.90),P=0.01]和喉癌。值得注意的是,这项研究发现了重要的遗传变异,如rs13050728,调节干扰素α受体2(IFNAR2)的表达,表明免疫应答途径在COVID-19和癌症中的可能作用。
    这项研究揭示了COVID-19严重程度之间的潜在相互作用,遗传因素,喉癌,强调在这两种情况下研究免疫应答机制的重要性。这些发现有助于理解COVID-19与喉癌之间的复杂相互作用,并可能指导未来对免疫反应作用的研究。特别是涉及IFNAR2。
    UNASSIGNED: Viral infections have been implicated as a risk factor for laryngeal cancer. Given the possible effects of Corona virus disease 2019 (COVID-19) on the laryngeal tissue, we investigated the causal link between COVID-19 and laryngeal cancer using a two-sample Mendelian randomization (MR) approach.
    UNASSIGNED: We utilized genetic data from the 5th Genome-wide association studies (GWAS) edition of the COVID-19 Host Genetics Initiative (published on January 18, 2021) and a large-scale laryngeal cancer GWAS comprising 180 cases and 218,612 controls of European ancestry. We applied inverse variance weighting, MR Egger, and weighted median methods to infer causality. We performed sensitivity analysis using the \"leave-one-out\" method to verify robustness.
    UNASSIGNED: We found no evidence of a causal association between gene-predicted COVID-19 and laryngeal cancer [Odds ratio (OR)=0.24 (95% Confidence intervals (CI), 0.05-1.26), P=0.09]. However, we observed significant inverse associations between gene-predicted COVID-19 hospitalization [OR=0.51 (95% CI, 0.28-0.95), P=0.03] and severe patients [OR=0.62 (95% CI, 0.43-0.90), P=0.01] and laryngeal cancer. Notably, the study detected important genetic variants, such as rs13050728, that modulate the expression of interferon alpha receptor 2 (IFNAR2), indicating possible roles for immune response pathways in both COVID-19 and cancer.
    UNASSIGNED: This study reveals a potential interaction between COVID-19 severity, genetic factors, and laryngeal cancer, underscoring the importance of investigating the immune response mechanisms in both conditions. These findings contribute to the understanding of the complex interactions between COVID-19 and laryngeal cancer and may guide future research on the role of immune response, particularly involving IFNAR2.
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  • 文章类型: Journal Article
    模式识别受体是免疫系统的重要组成部分,检测病原体相关分子模式(PAMPs)和损伤相关分子模式(DAMPs),并帮助塑造先天和适应性免疫反应。当dsDNA存在时,环状GMP-AMP合成酶(cGAS)产生称为环状GMP-AMP(cGAMP)的第二信使,然后触发一种叫做STING的衔接蛋白,并最终激活免疫细胞中I型干扰素(IFN)和促炎细胞因子的表达。cGAS-STING信号通路作为重要的免疫监视介质近来受到了广泛的关注。在这次审查中,我们总结了cGAS-STING信号通路在病毒感染和炎症性疾病中的研究现状,以及自身免疫性疾病。cGAS-STING信号通路的调节为治疗病毒感染提供了潜在的策略,炎症性疾病,和自身免疫性疾病。
    Pattern recognition receptors are an essential part of the immune system, which detect pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) and help shape both innate and adaptive immune responses. When dsDNA is present, cyclic GMP-AMP Synthase (cGAS) produces a second messenger called cyclic GMP-AMP (cGAMP), which then triggers an adaptor protein called STING, and eventually activates the expression of type I interferon (IFN) and pro-inflammatory cytokines in immune cells. The cGAS-STING signaling pathway has been receiving a lot of attention lately as a key immune-surveillance mediator. In this review, we summarize the present circumstances of the cGAS-STING signaling pathway in viral infections and inflammatory diseases, as well as autoimmune diseases. Modulation of the cGAS-STING signaling pathway provides potential strategies for treating viral infections, inflammatory diseases, and autoimmune diseases.
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  • 文章类型: Journal Article
    背景:冠状病毒(COVID-19)是一种新型呼吸道病毒感染,导致相对大量的死亡,特别是在患有慢性阻塞性肺疾病和哮喘等肺部疾病的人中,人类仍然遭受有限的测试能力。在这篇文章中,提出了一种通过分析呼出气体来检测COVID-19病毒感染的解决方案,即,一氧化氮,一种由呼吸道上皮释放的重要生物标志物,作为一种非侵入性和节省时间的方法。这里,我们设计了一种新颖且低成本的N和P共掺杂C60富勒烯的呼吸分析仪,用于检测从呼吸道上皮细胞呼出的NO气体。该呼吸测醉器通过直接将NO转化为NO2而无需通过任何能垒(0kcal/mol活化能),对NO气体的检测显示出快速反应。呼吸测醉器的恢复时间很短(0.98×103s),而它对CO2和H2O气体混合物中的NO传感具有高度选择性。该研究为低成本的合成提供了思路(与以前报道的Au原子修饰的纳米结构和金属基呼吸测醉器相比),高效,以及高选择性N和P共掺杂C60富勒烯的呼吸测醉器,用于COVID-19检测。
    方法:使用自旋极化密度泛函理论计算模拟了N和P掺杂的系统和气体分子的几何形状。
    BACKGROUND: Coronavirus (COVID-19) is a novel respiratory viral infection, causing a relatively large number of deaths especially in people who underly lung diseases such as chronic obstructive pulmonary and asthma, and humans are still suffering from the limited testing capacity. In this article, a solution is proposed for the detection of COVID-19 viral infections through the analysis of exhaled breath gasses, i.e., nitric oxide, a prominent biomarker released by respiratory epithelial, as a non-invasive and time-saving approach. Here, we designed a novel and low-cost N and P co-doped C60 fullerene-based breathalyzer for the detection of NO gas exhaled from the respiratory epithelial cells. This breathalyzer shows a quick response to the detection of NO gas by directly converting NO to NO2 without passing any energy barrier (0 kcal/mol activation energy). The recovery time of breathalyzer is very short (0.98 × 103 s), whereas it is highly selective for NO sensing in the mixture of CO2 and H2O gasses. The study provides an idea for the synthesis of low-cost (compared to previously reported Au atom decorated nanostructure and metal-based breathalyzer), efficient, and highly selective N and P co-doped C60 fullerene-based breathalyzer for COVID-19 detection.
    METHODS: The geometries of N and P-doped systems and gas molecules are simulated using spin-polarized density functional theory calculations.
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  • 文章类型: Journal Article
    支气管肺发育不良(BPD)是极早产儿(VPI)或极低出生体重(VLBW)婴儿最常见的严重并发症。研究表明病毒感染在病因发生中。本研究的目的是通过系统评价和荟萃分析总结病毒感染与BPD之间的关系。我们搜索了PubMed,Embase,WebofScience核心合集,和2023年12月19日的Cochrane数据库。我们纳入了观察性研究,这些研究检查了早产儿病毒感染与BPD之间的关系。我们提取了研究方法的数据,参与者特征,暴露评估,和结果措施。我们使用纽卡斯尔-渥太华量表(NOS)评估研究偏倚风险。我们在定性综述和荟萃分析中纳入了17项和15项研究,分别。荟萃分析显示病毒感染与月经后36周龄诊断的BPD之间存在显着关联(优势比(OR):2.42,95%置信区间:1.89-3.09,13项研究,证据的确定性非常低)。在特定病毒的亚组分析中,巨细胞病毒(CMV)被证明与月经后36周龄时诊断的BPD显着相关(OR:2.34,95%置信区间:1.80-3.05,11项研究)。我们没有发现病毒感染和出生后第28天诊断的BPD之间的关联,可能是由于纳入的前瞻性研究样本量小。结论:病毒感染,尤其是CMV,与早产儿BPD风险增加相关。需要具有大样本的方法可靠的前瞻性研究来验证我们的结论,需要高质量的随机对照研究来探讨预防或治疗病毒感染对BPD发病率的影响。研究试图确定早产儿的病毒感染和支气管肺发育不良;然而,结果不一致。新增内容:•系统证明病毒感染,特别是巨细胞病毒,与月经后第36周龄早产儿诊断的支气管肺发育不良呈正相关。•筛查早产儿病毒感染的重要性,尤其是巨细胞病毒.未来应进行更多高质量的研究,以研究病毒感染与支气管肺发育不良之间的因果关系。
    Bronchopulmonary dysplasia (BPD) is the most common serious complication of very preterm infants (VPI) or very low birth weight (VLBW) infants. Studies implicate viral infections in etiopathogenesis. The aim of this study was to summarize the relationship between viral infections and BPD through a systematic review and meta-analysis. We searched PubMed, Embase, the Web of Science Core Collection, and the Cochrane Database on December 19, 2023. We included observational studies that examined the association between viral infections and BPD in preterm infants. We extracted data on study methods, participant characteristics, exposure assessment, and outcome measures. We assessed study risk of bias using the Newcastle-Ottawa Scale (NOS). We included 17 and 15 studies in the qualitative review and meta-analysis, respectively. The meta-analysis showed a significant association between viral infection and BPD diagnosed at 36 weeks postmenstrual age (odds ratio (OR): 2.42, 95% confidence interval: 1.89-3.09, 13 studies, very low certainty of evidence). In a subgroup analysis of specific viruses, cytomegalovirus (CMV) proved to be significantly associated with BPD diagnosed at 36 weeks postmenstrual age (OR: 2.34, 95% confidence interval: 1.80-3.05, 11 studies). We did not find an association between viral infection and BPD diagnosed on the 28th day of life, probably due to the small sample size of the included prospective studies.  Conclusion: Viral infections, especially CMV, are associated with an increased risk of BPD in preterm infants. Methodologically reliable prospective studies with large samples are needed to validate our conclusions, and high-quality randomized controlled studies are needed to explore the effect of prevention or treatment of viral infections on the incidence of BPD. What is Known: • Studies have attempted to identify viral infections and bronchopulmonary dysplasia in preterm infants; however, results have been inconsistent. What is New: • Systematic demonstration that viral infections, particularly cytomegalovirus, are positively associated with bronchopulmonary dysplasia diagnosed in preterm infants at the 36th week of postmenstrual age. • The importance of screening for viral infections in preterm infants, especially cytomegalovirus. More high-quality studies should be produced in the future to investigate the causal relationship between viral infections and bronchopulmonary dysplasia.
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  • 文章类型: Journal Article
    背景:儿童和青少年是急性病毒性肝炎(AVH)的高危人群,但是针对它们的流行病学研究已经被成人慢性B和C所掩盖。我们提供全球,区域,以及国家对1990年至2019年20岁以下人群的AVH负担及其趋势的估计。
    方法:使用来自全球疾病负担研究(GBD)2019的AVH数据。计算了发病率和残疾调整寿命年(DALYs),用估计的年度百分比变化(EAPC)和Joinpoint回归分析趋势。
    结果:2019年,全球儿童和青少年中报告了156.39(95%不确定区间145.20-167.16)百万新的AVH病例,产生1.98(1.50-2.55)百万DALYs。幼儿发病率(<5岁),年龄较大的儿童(5-9岁),青少年(10-19岁)为12,799(11,068-14,513),5,108(4829-5411),和3020(2724-3339)每100,000人口,分别。全球AVH发病率显示线性下降,EAPC为-0.66(-0.68至-0.65)。高发地区包括撒哈拉以南非洲,大洋洲,南亚,中亚,印度,巴基斯坦,尼日利亚面临最大的负担。主要原因是甲型肝炎,其次是戊型肝炎,B,所有类型的肝炎都呈下降趋势,尤其是乙型肝炎。此外,我们证实了AVH发病率和社会经济学之间的关联,疫苗,和晚期肝病。
    结论:有效的乙型和丙型肝炎疫苗和治疗提供了根除的机会。扩大诊断和治疗覆盖面对于解决为儿童和青少年提供服务的差距至关重要。
    BACKGROUND: Children and adolescents are at high risk for acute viral hepatitis (AVH), but epidemiological research focusing on them has been overshadowed by adult chronic B and C. We provide global, regional, and national estimates of the AVH burden and their trends on people under 20 years from 1990 to 2019.
    METHODS: AVH data from Global Burden of Disease Study (GBD) 2019 was used. Incidence and disability-adjusted life years (DALYs) were calculated, analyzing trends with estimated annual percentage change (EAPC) and Joinpoint regression.
    RESULTS: In 2019, 156.39 (95% uncertainty interval 145.20-167.16) million new cases of AVH were reported among children and adolescents globally, resulting in 1.98 (1.50-2.55) million DALYs. Incidence rates for young children (< 5 years), older children (5-9 years), and adolescents (10-19 years) were 12,799 (11,068-14,513), 5,108 (4829-5411), and 3020 (2724-3339) per 100,000 population, respectively. The global AVH incidence displayed a linear decline with an EAPC of - 0.66 (- 0.68 to - 0.65). High-incidence regions included sub-Saharan Africa, Oceania, South Asia, and Central Asia, with India, Pakistan, and Nigeria facing the greatest burden. Leading causes were hepatitis A, followed by hepatitis E, B, and C. All hepatitis types showed declining trends, especially hepatitis B. Furthermore, we confirmed the association between the AVH incidence and the socioeconomics, vaccine, and advanced liver diseases.
    CONCLUSIONS: Effective vaccines and treatments for hepatitis B and C offer eradication opportunities. Broadening diagnostic and therapeutic coverage is vital to address disparities in service provision for children and adolescents.
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  • 文章类型: Video-Audio Media
    相分离现象在细胞中相当普遍,它参与了生命活动的多个过程。然而,目前关于蛋白质修饰与相分离之间的相关性以及对相分离趋势的干扰的研究存在一定的局限性。在这里,我们专注于蛋白质的几种翻译后修饰,包括多个位点的蛋白质磷酸化修饰,甲基化修饰,乙酰化改性,泛素化修饰,磺酰化改性,等。,通过多价相互作用调节相分离的形成和相分离结构的稳定性。这种调节作用与神经退行性疾病的发生发展密切相关,肿瘤,病毒感染,和其他疾病,并在环境压力中发挥重要作用,DNA损伤修复,转录调控,信号转导,和生物体的细胞稳态,这为探索新型蛋白质翻译后修饰与相分离之间的相互作用提供了思路。视频摘要。
    The phenomenon of phase separation is quite common in cells, and it is involved in multiple processes of life activities. However, the current research on the correlation between protein modifications and phase separation and the interference with the tendency of phase separation has some limitations. Here we focus on several post-translational modifications of proteins, including protein phosphorylation modification at multiple sites, methylation modification, acetylation modification, ubiquitination modification, SUMOylation modification, etc., which regulate the formation of phase separation and the stability of phase separation structure through multivalent interactions. This regulatory role is closely related to the development of neurodegenerative diseases, tumors, viral infections, and other diseases, and also plays essential functions in environmental stress, DNA damage repair, transcriptional regulation, signal transduction, and cell homeostasis of living organisms, which provides an idea to explore the interaction between novel protein post-translational modifications and phase separation. Video Abstract.
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