Changes in Human Parechovirus Profiles in Hospitalized Children with Acute Gastroenteritis after a Three-Year Interval in Lanzhou,China

The changing profile of infection over time for Human Parechoviruses (HPeVs) is not well known and no detailed study has been reported to date in China. This investigation on HPeV infection in hospitalized children in Lanzhou, China revealed variations in epidemiological characteristics after a three-year interval. To assess the changes that had occurred, epidemiological and clinical characteristics of HPeVs were characterized and compared with previously reported data by our group. A comparable positivity rate (25.3%, 73/289) was revealed after the three-year interval with the majority of the infected children (95.9%, 70/73) being younger than two years of age. While a temporal change in the seasonal distribution was noted in the current study, HPeVs were more frequently detected during July to November compared to September to December in the previous study. Changes in HPeV genotypes patterns, a temporal change in the prevalence of HPeV1, a younger susceptible age to HPeV3 compared with HPeV1 and a tendency of older children to be infected with HPeV4 are in contrast to our previous report. HPeV2, a rarely reported genotype, was identified for the first time in China. In addition, an exclusive trinucleotide (GAT) insertion in the HPeV4 nucleotide sequence was identified. However, the profiles of co-infection with other enteric related viruses were similar to our previous findings. In summary, these data suggest temporal variation in the seasonal distribution of HPeV and changing patterns of HPeV genotypes over time in the study region.     

NSFC微生物学学科工作回顾与展望

1　ＮＳＦＣ成立以来微生物学学科资助项目的整体概况自ＮＳＦＣ成立的 1 986年至 2 0 0 2年的 1 7年里 ,微生物学学科共资助各类项目 1 1 0 7项 ,使用经费1 1 663 6万元 (表 1 )。 2 0 0 2年内 ,截止到 9月底 ,已批准使用经费 2 2 0 8万元 ;今年面上项目平均强度达到1 9万元。随着ＮＳＦＣ经费总量的不断增加 ,面上项目经费强度还会逐年增加。“十五”期间 ,ＮＳＦＣ的总经费将超过 1 0 0亿。表 1　本学科各分支学科 1 7年里经费使用情况各分支学科使用经费 万元占总经费比例 %微生物资源、分类与生态 2 1 39.3 1 8.3微生物代谢与生理生化 …     

The role of the CD134-CD134 ligand costimulatory pathway in alloimmune responses in vivo

The CD134-CD134 ligand (CD134L) costimulatory pathway has been shown to be critical for both T and B cell activation; however, its role in regulating the alloimmune response remains unexplored. Furthermore, its interactions with other costimulatory pathways and immunosuppressive agents are unclear. We investigated the effect of CD134-CD134L pathway blockade on allograft rejection in fully MHC-mismatched rat cardiac and skin transplantation models. CD134L blockade alone did not prolong graft survival compared with that of untreated recipients, and in combination with donor-specific transfusion, cyclosporine, or rapamycin, was less effective than B7 blockade in prolonging allograft survival. However, in combination with B7 blockade, long-term allograft survival was achieved in all recipients (>200 days). Moreover, this was synergistic in reducing the frequency of IFN-gamma-producing alloreactive lymphocytes and inhibiting the generation of activated/effector lymphocytes. Most impressively, this combination prevented rejection in a presensitized model using adoptive transfer of primed lymphocytes into athymic heart transplant recipients. In comparison to untreated recipients (mean survival time (MST): 5.3 +/- 0.5 days), anti-CD134L mAb alone modestly prolonged allograft survival (MST: 14 +/- 2.8 days) as did CTLA4Ig (MST: 21.5 +/- 1.7 days), but all grafts were rejected within 24 days. Importantly, combined blockade further and significantly prolonged allograft survival (MST: 75.3 +/- 12.7 days) and prevented the expansion and/or persistence of primed/effector alloreactive T cells. Our data suggest that CD134-CD134L is a critical pathway in alloimmune responses, especially recall/primed responses, and is synergistic with CD28-B7 in mediating T cell effector responses during allograft rejection. Understanding the mechanisms of collaboration between these different pathways is important for the development of novel strategies to promote long-term allograft survival.     

Psoralen attenuates bleomycin‐induced pulmonary fibrosis in mice through inhibiting myofibroblast activation and collagen deposition

Idiopathic pulmonary fibrosis (IPF) is a progressive disease characterized by excessive deposition of extracellular matrix (ECM) and chronic inflammation with limited therapeutic options. Psoralen, a major active component extracted from Psoralea corylifolia L. seed, has several biological effects. However, the role of psoralen in IPF is still unclear. Here, we hypothesized that psoralen played an essential role in IPF in the inhibition of fibroblast proliferation and inflammatory response. A murine model of IPF was established by injecting bleomycin (BLM) intratracheally, and psoralen was administered for 14 days from the 7^th to 21^st day after BLM injection. Our results demonstrated that psoralen treatment reduced body weight loss and improved the survival rate of mice with IPF. Histological and immunofluorescent examination showed that psoralen alleviated BLM‐induced lung parenchymal inflammatory and fibrotic alteration. Furthermore, psoralen inhibited proliferation and collagen synthesis of mouse fibroblasts and partially reversed BLM‐induced expression of α‐smooth muscle actin at both the tissue and cell level. Moreover, psoralen decreased the expression of transforming growth factor‐β1, interleukin‐1β, and tumor necrosis factor‐α in the lungs of BLM‐stimulated mice. Our results reveale for the first time that psoralen exerts therapeutic effects against IPF in a BLM‐induced murine model.     

MicroRNA-29a-3p regulates abdominal aortic aneurysm development and progression via direct interaction with PTEN

Various research studies have been conducted in deducing the role of microRNAs (miRNAs) in the pathogenesis and physiological processes of various systematic diseases. This study aims at demonstration of the important role played by miR-29a-3p, through association with phosphatase and tensin homolog (PTEN), in the regulation of abdominal aortic aneurysm development and progression. Quantitative real-time polymerase chain reaction (RT-qPCR) examined miRNA-19a-3p and PMEPA1 expression in multiplied vascular smooth muscle cells (VSMCs). Cell transfection upregulated or downregulated the genes and cell counting kit-8 assay determined cellular viability. RT-qPCR detected cellular proliferation and cell death using the cell proliferation and apoptosis biomarkers Ki87 and proliferating cell nuclear antigen, caspase-8 and caspase-3, respectively. Furthermore, luciferase assay analyzed the luciferase activity and western blot analysis determined miRNA-19a-3p and PMEPA1 protein expression in proliferation and apoptosis biomarkers. TargetScan 4.2 online software ( www.targetscan.org ) was used to perform the bioinformatics analysis so as to forecast the putative targets of miR-29a-3p and PTEN. The results inferred that there was an increased expression of miRNA-29a-3p found in AAA-mimic cells with increased cellular viability and significant pathological apoptosis. Further, when the expression of miRNA-29a-3p was downregulated, it reduced the cell viability of AAA cells. On the basis of the gene interplays, it can be understood that the PTEN was directly targeted by miRNA-29a-3p so as to regulate the AAA progression. Thus, PTEN was found to strengthen the proliferation effect of miRNA-29a-3p in AAA cells. The current study thus shed more insights about the molecular mechanistic roles of miRNA-29a-3p and PTEN, opening doors for novel therapeutic approach to AAA.     

氟中毒抑制大鼠泌鼠的实验研究

The effect of fluorosis on lactation, lactotroph function and ultrastructure were studied in lactating rats. The results were as follows: 1) Inhibition of lactation in lactating rats with chronic fluorosis was assessed by stunting growth of pups and decrease in the amount of milk suckled by pups in 30 min. Metoclopramide, a blocker of dopamine receptor, could improve lactation in these rats. 2) During chronic fluorosis serum PRL level was decreased, however, PRL content in pituitary was increased. Electronmicroscopic examination showed accumulation of large mature secretory granules and appearance of extremely large abnormal secretory granules in lactotroph cytoplasma. These findings indicate that hormone release of pituitary lactotrophs is obstructed in lactating rats with fluorosis, and the toxic effect of fluoride is mediated by an enhanced function of dopaminergic system in hypothalamus.     

不同抗性苹果品种应答轮纹病菌胁迫的差异蛋白质组分析

为鉴定不同抗性苹果(Malus domestica)品种响应轮纹病菌胁迫的抗性相关蛋白表达差异, 以抗病品种华月及易感品种金冠为试材, 采用高通量同位素标记定量(IBT)技术结合液相色谱-串联质谱(LC-MS)鉴定技术, 对病原菌处理前后抗、感病品种叶片的蛋白质组差异表达进行分析, 共鉴定出171个差异表达蛋白(DEPs)。GO富集及KEGG通路分析表明, 在细胞组分、分子功能和生物过程3类中共注释到686个GO条目, 其中52个DEPs注释于KEGG通路的18个显著差异途径(P<0.05)。亚细胞定位预测分析表明, 171个DEPs中有170个分别定位于8类细胞器。蛋白功能注释分析表明, 46个DEPs注释于7类抗性相关蛋白, 包括类甜蛋白、过氧化物酶、多酚氧化酶、过敏原蛋白、几丁质酶、内切葡聚糖酶以及主乳胶蛋白。此外, 还对抗性相关蛋白的表达特点及基因定量结果进行了分析。该研究结果可为进一步解析抗、感病苹果品种应答轮纹病菌胁迫的抗性机制提供参考。     

Cooperative DNA binding mediated by KicGAS/ORF52 oligomerization allows inhibition of DNA-induced phase separation and activation of cGAS

Cyclic GMP-AMP synthase (cGAS) is a key DNA sensor that detects aberrant cytosolic DNA arising from pathogen invasions or genotoxic stresses. Upon binding to DNA, cGAS is activated and catalyzes the synthesis of cyclic GMP-AMP (cGAMP), which induces potent antimicrobial and antitumor responses. Kaposi sarcoma-associated herpesvirus (KSHV) is a human DNA tumor virus that causes Kaposi sarcoma and several other malignancies. We previously reported that KSHV inhibitor of cGAS (KicGAS) encoded by ORF52, inhibits cGAS enzymatic activity, but the underlying mechanisms remained unclear. To define the inhibitory mechanisms, here we performed in-depth biochemical and functional characterizations of KicGAS, and mapped its functional domains. We found KicGAS self-oligomerizes and binds to double stranded DNA cooperatively. This self-oligomerization is essential for its DNA binding and cGAS inhibition. Interestingly, KicGAS forms liquid droplets upon binding to DNA, which requires collective multivalent interactions with DNA mediated by both structured and disordered domains coordinated through the self-oligomerization of KicGAS. We also observed that KicGAS inhibits the DNA-induced phase separation and activation of cGAS. Our findings reveal a novel mechanism by which DNA viruses target the host protein phase separation for suppression of the host sensing of viral nucleic acids.     

Long non-coding RNA-ATB promotes EMT during silica-induced pulmonary fibrosis by competitively binding miR-200c

Long non-coding RNAs (lncRNAs) are important signal transduction regulators that act by various patterns. However, little is known about the molecular mechanisms of lncRNA related pathways in occupational lung fibrosis. Our previous study found that epithelial-mesenchymal transition (EMT) was one of the key events in silica-induced pulmonary fibrosis. This study showed that the lncRNA-ATB promoted EMT by acting as a miR-200c sponge. miR-200c was identified by miRNA array as a potential target of lncRNA-ATB and verified by dual luciferase reporter gene together with RNA pull-down assays. Moreover, our findings demonstrated that lncRNA-ATB is abundantly expressed during EMT of lung epithelial cells, which contributes to decreased levels of miR-200c. miR-200c targeted ZEB1 to relief silicosis by blocking EMT in vivo and in vitro. The results also suggested M2 macrophages secreted transforming growth factor-β1 (TGF-β1) to induce EMT process by activating lncRNA-ATB in epithelial cells. Collectively, silica-stimulated macrophages secreted TGF-β1 to induce lncRNA-ATB in epithelia cells, promoting EMT by binding with miR-200c and releasing ZEB1. These observations provide further understanding of the regulatory network of silica-induced pulmonary fibrosis and identify new therapeutic targets hopefully.