肺炎链球菌感染早期IFN-β通过调节巨噬细胞炎症反应保护宿主

该文旨在探讨干扰素-β(interferon-β,IFN-β)在肺炎链球菌(Streptococcus pneumoniae,S.pn)感染早期对宿主炎症免疫的影响.使用外源重组IFN-β蛋白(recombinant IFN-β,rIFN-β)预处理WT小鼠及其腹腔渗出巨噬细胞(peritoneal exudate m...     

预防造影剂肾病水化时机选择的Meta分析

目的 评价预防造影剂肾病(CIN)不同口服水化时机选择的效果,为降低CIN发生率提供依据.方法 运用计算机检索PubMed、EMbase、The Cochrane Library、中国知网、万方数据库、维普数据库以及中国生物医学文献数据库关于口服水化预防造影剂肾病的随机对照试验(RCT),检索时间从建库至2020年9月...     

微嗜酸寡养单胞菌中的漆酶对黄曲霉毒素B1降解脱毒的生物活性

[目的]探究微嗜酸寡养单胞菌中的漆酶对AFB1的降解活性,并确定漆酶在菌株CW117降解代谢AFB1过程中的贡献.[方法]从微嗜酸寡养单胞菌基因组中,共筛选到两个漆酶基因lc1和lc2,并用大肠杆菌BL21外源表达蛋白rLC1和rLC2,在体外检测其对AFB1的降解活性.同时参考前人报道,研究了氧化性辅剂对漆酶AFB1...     

Association of ischemic stroke onset time with presenting severity,acute progression,and long-term outcome: A cohort study

BackgroundPreclinical data suggest circadian variation in ischemic stroke progression, with more active cell death and infarct growth in rodent models with inactive phase (daytime) than active phase (nighttime) stroke onset. We aimed to examine the association of stroke onset time with presenting severity, early neurological deterioration (END), and long-term functional outcome in human ischemic stroke.Methods and findingsIn a Korean nationwide multicenter observational cohort study from May 2011 to July 2020, we assessed circadian effects on initial stroke severity (National Institutes of Health Stroke Scale [NIHSS] score at admission), END, and favorable functional outcome (3-month modified Rankin Scale [mRS] score 0 to 2 versus 3 to 6). We included 17,461 consecutive patients with witnessed ischemic stroke within 6 hours of onset. Stroke onset time was divided into 2 groups (day-onset [06:00 to 18:00] versus night-onset [18:00 to 06:00]) and into 6 groups by 4-hour intervals. We used mixed-effects ordered or logistic regression models while accounting for clustering by hospitals. Mean age was 66.9 (SD 13.4) years, and 6,900 (39.5%) were women. END occurred in 2,219 (12.7%) patients. After adjusting for covariates including age, sex, previous stroke, prestroke mRS score, admission NIHSS score, hypertension, diabetes, hyperlipidemia, smoking, atrial fibrillation, prestroke antiplatelet use, prestroke statin use, revascularization, season of stroke onset, and time from onset to hospital arrival, night-onset stroke was more prone to END (adjusted incidence 14.4% versus 12.8%, p = 0.006) and had a lower likelihood of favorable outcome (adjusted odds ratio, 0.88 [95% CI, 0.79 to 0.98]; p = 0.03) compared with day-onset stroke. When stroke onset times were grouped by 4-hour intervals, a monotonic gradient in presenting NIHSS score was noted, rising from a nadir in 06:00 to 10:00 to a peak in 02:00 to 06:00. The 18:00 to 22:00 and 22:00 to 02:00 onset stroke patients were more likely to experience END than the 06:00 to 10:00 onset stroke patients. At 3 months, there was a monotonic gradient in the rate of favorable functional outcome, falling from a peak at 06:00 to 10:00 to a nadir at 22:00 to 02:00. Study limitations include the lack of information on sleep disorders and patient work/activity schedules.ConclusionsNight-onset strokes, compared with day-onset strokes, are associated with higher presenting neurologic severity, more frequent END, and worse 3-month functional outcome. These findings suggest that circadian time of onset is an important additional variable for inclusion in epidemiologic natural history studies and in treatment trials of neuroprotective and reperfusion agents for acute ischemic stroke.

Wi-Sun Ryu and colleagues investigate the association of stroke onset time with presenting severity, early neurological deterioration (END), and long-term functional outcome in ischemic stroke.     

哺乳动物毛色调控机制及其适应性进化研究进展

哺乳动物类群呈现出的丰富毛色是引人注目的一种生物现象,是研究和理解哺乳动物适应性进化的理想模型之一.哺乳动物的毛色多态在躲避天敌、捕食、求偶及抵御紫外线等方面都具有重要作用.哺乳动物毛发的色素化过程由体内黑色素的数量、质量和分布状况所决定.黑色素的形成过程复杂,包括黑素细胞的分化、成熟,黑素体等细胞器的形态发生及黑色素...     

Structural determinants of the dominant conformational epitopes of phospholipase A2 receptor in primary membranous nephropathy

Anti-phospholipase A2 receptor autoantibody (PLA2R-Ab) plays a critical role in the pathogenesis of primary membranous nephropathy (PMN), an autoimmune kidney disease characterized by immune deposits in the glomerular subepithelial spaces and proteinuria. However, the mechanism of how PLA2R-Abs interact with the conformational epitope(s) of PLA2R has remained elusive. PLA2R is a single transmembrane helix receptor containing ten extracellular domains that begin with a CysR domain followed by a FnII and eight CTLD domains. Here, we examined the interactions of PLA2R-Ab with the full PLA2R protein, N-terminal domain truncations, and C-terminal domain deletions under either denaturing or physiological conditions. Our data demonstrate that the PLA2R-Abs against the dominant epitope (the N-terminal CysR-CTLD1 triple domain) possess weak cross-reactivities to the C-terminal domains beyond CTLD1. Moreover, both the CysR and CTLD1 domains are required to form a conformational epitope for PLA2R-Ab interaction, with FnII serving as a linker domain. Upon close examination, we also observed that patients with newly diagnosed PMN carry two populations of PLA2R-Abs in sera that react to the denatured CysR-CTLD3 (the PLA2R-Ab₁) and denatured CysR-CTLD1 (the PLA2R-Ab₂) domain complexes on Western blots, respectively. Furthermore, the PLA2R-Ab₁ appeared at an earlier time point than PLA2R-Ab₂ in patients, whereas the increased levels of PLA2R-Ab₂ coincided with the worsening of proteinuria. In summary, our data support that an integrated folding of the three PLA2R N-terminal domains, CysR, FnII, and CTLD1, is a prerequisite to forming the PLA2R conformational epitope and that the dominant epitope-reactive PLA2R-Ab₂ plays a critical role in PMN clinical progression.     

四吡咯化合物生物合成研究进展

四吡咯化合物是存在于生物体中一类具有重要功能的化合物,已经广泛应用于农业、食品和医药等领域.由于化学合成法的烦琐流程和高昂成本以及动植物提取法存在品质不均一等缺点,大幅度限制了其工业化生产与相关应用.近年来,合成生物学的快速发展为微生物利用可再生生物质资源高效合成四吡咯化合物提供了新的技术手段.针对四吡咯化合物生物合成...     

非洲猪瘟病毒E248R蛋白抑制cGAS-STING介导的天然免疫

为了探究ASFV E248R蛋白调控cGAS-STING信号通路的机制,利用双荧光素酶报告系统验证ASFV E248R蛋白够剂量依赖性地抑制cGAS-STING和HT-DNA诱导的IFN-β的产生。通过相对定量PCR技术验证,过表达E248R抑制IFNB1、RANTES、IL-6和TNF-αβ基因的转录水平。免疫共沉淀和激光共聚焦试验结果表明,E248R与STING相互作用。通过蛋白印迹试验证实,过表达E248R可抑制STING的表达。研究表明ASFV E248R蛋白通过抑制STING的表达拮抗天然免疫应答。该结果将扩展对ASF免疫逃逸的认知,为疫苗的研制提供新的思路。