Streptococcus pneumoniae aminopeptidase N contributes to bacterial virulence and elicits a strong innate immune response through MAPK and PI3K/AKT signaling

Streptococcus pneumoniae is a Gram-positive pathogen with high morbidity and mortality globally but some of its pathogenesis remains unknown. Previous research has provided evidence that aminopeptidase N (PepN) is most likely a virulence factor of S. pneumoniae. However, its role in S. pneumoniae virulence and its interaction with the host remains to be confirmed. We generated a pepN gene deficient mutant strain and found that its virulence for mice was significantly attenuated as were in vitro adhesion and invasion of host cells. The PepN protein could induce a strong innate immune response in vivo and in vitro and induced secretion of IL-6 and TNF-α by primary peritoneal macrophages via the rapid phosphorylation of MAPK and PI3K/AKT signaling pathways and this was confirmed using specific pathway inhibitors. In conclusion, PepN is a novel virulence factor that is essential for the virulence of S. pneumoniae and induces host innate immunity via MAPK and PI3K/AKT signaling.

     

落叶松针叶化学成分研究

该研究采用硅胶柱色谱、半制备型高效液相色谱和重结晶等方法对落叶松针叶乙酸乙酯萃取物进行分离纯化,利用NMR、MS现代波谱技术结合相关文献报道对分离得到的化合物进行结构鉴定,并对提取浸膏的抑菌活性进行了测试。结果表明:从落叶松针叶乙酸乙酯萃取物中分离得到15个化合物,分别鉴定为Larixol (1)、(2R)-5,4'-二羟基-6-甲基-7-甲氧基-黄酮(2)、2',4'-二羟基-4,6'-二甲氧基二氢查尔酮(3)、2',4-二羟基-4',6'-二甲氧基查尔酮(4)、2',4'-二羟基-4,6'-二甲氧基查尔酮(5)、异鼠李素(6)、4',5-二羟基-7-甲氧基-8-甲基黄酮(7)、山奈酚(8)、β-谷甾醇(9)、豆甾醇(10)、胡萝卜苷(11)、香草酸(12)、对羟基苯甲酸(13)、二甲基罗汉松脂素(14)、15-二十九烷醇(15)。其中,化合物2,4,5和7为首次从该属植物中分离得到。抑菌活性实验结果显示,乙酸乙酯萃取浸膏在浓度为5~100 mg·mL-1时对大肠杆菌、枯草芽孢杆菌、蜡样芽孢杆菌和金黄色葡萄球菌的抑菌率分别为55%~70%、53%~72%、61%~71%和33%~65%。上述结果为更加深入探究落叶松针叶化学成分和药理活性提供了一定理论依据。     

大鼠肝纤维化相关microRNA及其候选靶基因的筛选

microRNAs (miRNAs)是一类功能性非编码RNA,在多种生物过程中具有重要作用.然而,miRNA的表达模式、调控网络以及参与肝纤维化的miRNA仍有待阐明.为了探讨与肝纤维化相关的miRNA及其靶基因的功能,为临床肝纤维化治疗提供理论依据,本研究前期已采用胆管结扎法(BDL)建立大鼠胆汁淤积性肝纤维化模型.从大鼠肝脏中提取总RNA,应用基因芯片技术对胆汁淤积性肝纤维化肝组织中miRNA和mRNA表达谱进行综合分析;结合生物信息方法分析在胆汁淤积性肝纤维化中差异表达miRNA可能的靶基因;实时荧光定量PCR技术检测TGF-β1处理人肝星状细胞LX-2细胞中miR-29a-3p、miR-194-5p和miR-22-3p相对表达水平.结果 表明,与正常肝组织相比,纤维化肝组织中有48个差异表达miRNA (FC＞2,P＜0.05),其中36个上调,12个下调;筛选出18个预测靶基因参与与纤维化相关的生物过程;TGF-β1处理LX-2细胞中miR-29a-3p、miR-194-5p和miR-22-3p相对表达水平显著下调(P＜0.05).本研究筛选的差异表达miRNAs通过调节靶基因的表达在肝纤维化中可能发挥重要作用,将为miRNA在肝纤维化中的作用提供新的见解.     

Fecal Influenza in Mammals: Selection of Novel Variants

In aquatic birds, influenza A viruses mainly replicate in the intestinal tract without significantly affecting the health of the host, but in mammals, they replicate in the respiratory tract and often cause disease. Occasionally, influenza viruses have been detected in stool samples of hospitalized patients and in rectal swabs of naturally or experimentally infected mammals. In this study, we compared the biological and molecular differences among four wild-type avian H1N1 influenza viruses and their corresponding fecal and lung isolates in DBA/2J and BALB/cJ mice. All fecal and lung isolates were more pathogenic than the original wild-type viruses, when inoculated into mice of both strains. The increased virulence was associated with the acquisition of genetic mutations. Most of the novel genotypes emerged as PB2^E627K, HA^F128V, HA^F454L, or HA^H300P variations, and double mutations frequently occurred in the same isolate. However, influenza virus strain- and host-specific differences were also observed in terms of selected variants. The avian H1N1 virus of shorebird origin appeared to be unique in its ability to rapidly adapt to BALB/cJ mice via the fecal route, compared to the adaptability of the H1N1 virus of mallard origin. Furthermore, a bimodal distribution in fecal shedding was observed in mice infected with the fecal isolates, while a normal distribution was observed after infection with the lung isolates or wild-type virus. Fecal isolates contained HA mutations that increased the activation pH of the HA protein. We conclude that influenza virus variants that emerge in fecal isolates in mammals might influence viral transmission, adaptation to mammals, and viral ecology or evolution.     

A simple and biosafe method for isolation of human umbilical vein endothelial cells

Human umbilical vein endothelial cells (HUVEC_S) are used as an irreplaceable tool for the study of vascular diseases. However, the technicians who isolate HUVECs are largely exposed to potential infectious threats. Here we report the development of a specialized instrument to protect researchers from known or unknown infectious agents when they operate on human umbilical cords. This instrument can be assembled by common laboratory supplies and adapted to accommodate umbilical cords of different lengths. When the cord is enclosed within the instrument, the risk of sample contamination and operator infection is greatly reduced. Using our instrument, endothelial cells were successfully isolated from human umbilical veins without contamination. The cells were verified by their cobblestone-like morphology and by immunofluorescence staining (Factor VIII and CD31 positivity and α-SMA negativity). Our instrument simplifies and optimizes the cell extraction process, and most importantly elevates the biosafety to a higher level during the isolation of human umbilical vein endothelial cells.     

生物多样性与稳定性机制研究进展

随着全球生物多样性的迅速丧失,生物多样性与生态系统稳定性的关系已成为人类面临的重要科学问题。许多研究表明生物多样性与稳定性存在正相互关系,但其内在机制尚不能被很好地理解并且存在争议。对生物多样性与稳定性的研究历史做简短的回顾,然后根据时间稳定性的计算方法将时间稳定性分为平均值、方差之和以及协方差之和3个统计组成部分,在此基础上对现在常见的生物多样性-稳定性机制进行分类和详细介绍。并对现在生物多样性和稳定研究的争论进行总结。建议未来生物多样性稳定性关系的研究应该建立更加综合的理论,增加实验时间,应用整合分析(meta-analysis)对已发表实验结果进行综合分析,此外,应多关注非生物量/多度的属性,控制物种属性而不是仅仅控制物种的数量。     

Design,synthesis and biological evaluation of hypolipidemic compounds based on BRD4 inhibitor RVX-208

Bromodomain-containing protein 4 (BRD4) is a new therapeutic target for the treatment of diseases including cardiovascular diseases, cancer, inflammation and central nervous system (CNS) disorders. In this study, we introduced the pharmacophore of fibrates to a BRD4 inhibitor, RVX-208, to design dual-active hypolipidemic compounds, and found that some of new analogues showed favorable hypolipidemic activities. Synthetic accessibility towards this class of compounds optimized RVX-208 as well as would supply more thoughts on hypolipidemic drugs.