Long noncoding RNA HNF1A‐AS1 regulates proliferation and apoptosis of glioma through activation of the JNK signaling pathway via miR‐363‐3p/MAP2K4

Long noncoding RNAs (lncRNAs) have been proven to exert important functions in the various biological processes of human cancers. It has been reported that lncRNA HNF1 homeobox A antisense RNA 1 (HNF1A‐AS1) was abnormally expressed and played a role in the initiation and development of various human cancers. In this study, we confirmed that the expression level of HNF1A‐AS1 was increased in glioma tissues and cells. Knockdown of HNF1A‐AS1 inhibited cell proliferation and promoted cell apoptosis in glioma. Then, we disclosed the downregulation of miR‐363‐3p in glioma tissues and cell lines. The interaction between HNF1A‐AS1 and miR‐363‐3p was identified in glioma cells. Furthermore, an inverse correlation between HNF1A‐AS1 and miR‐363‐3p was observed in glioma tissues. Afterwards, we recognized that MAP2K4 was a direct target of miR‐363‐3p. The expression of MAP2K4 was negatively correlated with miR‐363‐3p while positively related to HNF1A‐AS1 in glioma tissues. We also found the regulatory effect of HNF1A‐AS1 on the MAP2K4‐dependent JNK signaling pathway. All findings indicated that HNF1A‐AS1 induces the upregulation of MAP2K4 to activate the JNK signaling pathway to promote glioma cell growth by acting as a miR‐363‐3p sponge.     

Bi-FoRe:an efficient bidirectional knockin strategy to generate pairwise conditional alleles with fluorescent indicators

Gene expression labeling and conditional manipulation of gene function are important for elaborate dissection of gene function.However,contemporary generation of pairwise dual-function knockin alleles to achieve both conditional and geno-tagging effects with a single donor has not been reported.Here we first developed a strategy based on a flipping donor named FoRe to generate conditional knockout alleles coupled with fluorescent allele-labeling through NHEJ-mediated unidirectional targeted insertion in zebrafish facilitated by the CRISPR/Cas system.We demonstrated the feasibility of this strategy at sox10 and isl1 loci,and successfully achieved Cre-induced conditional knockout of target gene function and simultaneous switch of the fluorescent reporter,allowing generation of genetic mosaics for lineage tracing.We then improved the donor design enabling efficient one-step bidirectional knockin to generate paired positive and negative conditional alleles,both tagged with two different fluorescent reporters.By introducing Cre recombinase,these alleles could be used to achieve both conditional knockout and conditional gene restoration in parallel;furthermore,differential fluorescent labeling of the positive and negative alleles enables simple,early and efficient realtime discrimination of individual live embryos bearing different genotypes prior to the emergence of morphologically visible phenotypes.We named our improved donor as Bi-FoRe and demonstrated its feasibility at the sox10 locus.Furthermore,we eliminated the undesirable bacterial backbone in the donor using minicircle DNA technology.Our system could easily be expanded for other applications or to other organisms,and coupling fluorescent labeling of gene expression and conditional manipulation of gene function will provide unique opportunities to fully reveal the power of emerging single-cell sequencing technologies.     

Genetic tracing of HCoV-19 for the re-emerging outbreak of COVID-19 in Beijing,China

The ongoing pandemic of coronavirus disease 2019(COVID-19)caused by a novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2,also named as 2019-nCoV or HCoV-19)poses an unprecedented threat to public health(Zhu et al.,2020;Wang et al.,2020;Jiang et al.,2020).The novel HCoV-19 virus has rapidly spread into multiple countries across the world since it was first reported in December 2019.The World Health Organization(WHO)declared COVID-19 as a pandemic on 11th March 2020.As of 4th July,over 10 million confirmed COVID-19 cases have been reported in over 200 countries/regions with more than 0.5 million deaths,including 85,287 documented cases and 4,648 deaths in China(WHO,2020a).     

上海苏州河治理中鱼类多样性及群落结构变化

为了评估近20年来上海苏州河环境综合整治过程中鱼类多样性的变化状况, 本文于2019年6月(夏季)和9月(秋季)对苏州河13个断面的鱼类样本进行了采集, 对鱼类多样性和群落结构作了分析。结果显示, 2次采集共获得鱼类样本10,102号, 隶属于8目15科37属45种。夏季和秋季, 上游8个断面的鱼类均为36种, 下游5个断面则为12种和15种。从上游到下游, Shannon-Wiener多样性指数(H')、Margalef种类丰富度指数(D)和Simpson优势度指数(C)总体呈逐渐降低的趋势。相对重要性指数(IRI)显示, 夏秋两季上游断面共同的优势种为似鳊(Pseudobrama simoni), 下游为鲫(Carassius auratus)和泥鳅(Misgurnus anguillicaudatus)。丰度生物量曲线表明, 全河段鱼类群落结构总体上并不稳定, 特别是夏季的下游河段。Cluster聚类和非参数多维标度排序分析可明显将鱼类群落分为上游群组(I)与下游群组(II), 似鳊、泥鳅、鲫、光泽黄颡鱼(Pelteobagrus nitidus)和兴凯鱊(Acheilognathus chankaensis)等是造成群组间差异性的主要分歧种。与2001年的43种、2006年的28种相比, 本次调查的物种数出现了明显回升, 特别是下游河段。这种上游鱼类向下游迁移的趋势, 预示着下游中心城区与上游郊区河段的水质差别正在缩小, 水生态系统恢复迹象明显。本文认为, 上下游之间鱼类群落结构差异的缩小以及翘嘴鲌(Culter alburnus)、红鳍原鲌(Cultrichthys erythropterus)、棒花鱼(Abbottina rivularis)、子陵吻虾虎鱼(Rhinogobius giurinus)等在下游河段的出现, 可作为苏州河综合整治效果的重要生态标志。     

IgA肾病患者与健康人肠道菌群的比较

目的通过16S rRNA高通量基因测序方法对IgA肾病患者与健康人的肠道菌群进行比较。方法纳入生活于同一地区的40例IgA肾病患者与10例健康人,收集研究对象的新鲜粪便样本,提取粪便细菌总DNA,通过PCR扩增后上机测序,然后进行可操作分类单元聚类、物种分类分析及Alpha多样性分析、Beta多样性分析,最后比较两组之间的肠道菌群差异。结果与健康人相比,IgA肾病患者肠道菌群丰富度指数(Ace、Chao1)下降(u=2.308,P=0.033;u=2.259,P=0.039),多样性指数(Shannon、Simpson)升高(u=5.370,P0.001;u=4.601,P=0.007);相对丰度方面,IgA肾病患者的厚壁菌门、拟杆菌门、放线菌门细菌数量增加(t=2.301,P=0.037;t=6.729,P=0.005;t=5.285,P=0.006),而变形菌门细菌数量减少(t=4.138,P=0.009);拟杆菌属、链球菌属细菌数量增加(t=9.037,P=0.003;t=6.001,P=0.008),而unidentified_Enterobacteriaceae数量减少(t=2.198,P=0.033)。PCoA图提示两组肠道菌群有显著差异。LDA差异贡献分析发现两组之间共有15个物种存在显著差异,其中造成显著差异影响力最大的5个物种依次是γ-变形菌纲、unidentified_Enterobacteriaceae、肠杆菌科、肠杆菌目、变形菌门(t=9.930,P=0.002;t=2.198,P=0.033;t=2.604,P=0.015;t=2.393,P=0.021;t=4.138,P=0.009),它们刚好落在同一个进化树上,在IgA肾病组的相对丰度显著降低。结论 IgA肾病患者存在肠道菌群失调,显著减少的肠杆菌科的未知属可能是IgA肾病的特征菌,其对机体免疫的影响及在IgA肾病发生发展中的作用尚不清楚,进一步研究可能为IgA肾病的防治提供新的靶点。     

A Metabonomics Study of Guan-Xin-Shu-Tong Capsule against Diet-Induced Hyperlipidemia in Rats

Russian Journal of Bioorganic Chemistry - Guan-Xin-Shu-Tong capsule is a widely used traditional Chinese medicine for the treatment of cardiovascular diseases. However, little knowledge about the...     

The protective effect of alpha lipoic acid against traumatic brain injury in rats

Traumatic brain injury (TBI) was induced by a weight-drop device using 300 g–1 m weight-height impact. The study groups were: control, alpha-lipoic acid (LA) (100 mg/kg, po), TBI, and TBI + LA (100 mg/kg, po). Forty-eight hours after the injury, neurological scores were measured and brain samples were taken for histological examination or determination of thiobarbituric acid reactive substances (TBARS) and glutathione (GSH) levels, myeloperoxidase (MPO) and Na⁺-K⁺ ATPase activities, whereas cytokines (TNF-α, IL-1β) were determined in blood. Brain oedema was evaluated by wet–dry weight method and blood–brain barrier (BBB) permeability was evaluated by Evans Blue (EB) extravasation. As a result, neurological scores mildly increased in trauma groups. Moreover, TBI caused a significant decrease in brain GSH and Na⁺-K⁺ ATPase activity, which was accompanied with significant increases in TBARS level, MPO activity and plasma proinflammatory cytokines. LA treatment reversed all these biochemical indices as well as histopathological alterations. TBI also caused a significant increase in brain water content and EB extravasation which were partially reversed by LA treatment. These findings suggest that LA exerts neuroprotection by preserving BBB permeability and by reducing brain oedema probably by its anti-inflammatory and antioxidant properties in the TBI model.     

Age-related changes in antioxidant enzyme activities and lipid peroxidation in lungs of control and sulfur dioxide exposed rats

Antioxidant defenses within the lung are pivotal in preventing damage from oxidative toxicants. There have also been several reports with conflicting results on the antioxidant system during aging. In this study, we attempted to investigate age-related alterations in both antioxidant enzyme activities and thiobarbituric acid-reactive substances (TBARS), a product of lipid peroxidation, in the whole lung of control and sulfur dioxide (SO₂) exposed rats of different age groups (3-, 12-, and 24-months-old). Swiss-Albino Male rats were exposed to 10 ppm SO₂ 1 hr/day, 7 days/week for 6 weeks. The antioxidant enzymes examined include Cu,Zn-superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and glutathione S-transferase (GST). A mixed pattern of age-associated alterations in antioxidant activities was observed. SOD, GSH-Px and GST activities were increased with age, but CAT activity was decreased. Lung SOD, GSH-Px and GST activities were also increased in response to SO₂. The level of TBARS was increased with age. SO₂ exposure stimulated lipid peroxide formation in the lung as indicated by an increase in the level of TBARS. These findings suggest that both aging and SO₂ exposure may impose an oxidative stress to the body. We conclude that the increase in the activities of the antioxidant enzymes of the lung during aging, could be interpreted as a positive feedback mechanism in response to rising lipid peroxidation.     

Multiple gene genealogical analyses of a nematophagous fungus Paecilomyces lilacinus from China

Paecilomyces lilacinus is a geographically widespread nematophagous fungus and a promising biological control agent against plant parasitic nematodes. However, relatively little is known about its patterns of genetic variation through its broad geographic and ecological contexts. In this study, we analyzed the genetic variation of 2 virulence-associated genes (PLS and PLC) and 4 housekeeping gene fragments (ITS, RPB1, RPB2, and β-tubulin) among 80 P. lilacinus specimens collected from 7 locations in China. Various degrees of polymorphism and haplotype diversity were observed among the six gene fragments. However, no genetic differentiation was observed among the geographic populations, consistent with extensive gene flow among these geographic populations of P. lilacinus in China. Our analysis also suggested that clonal reproduction was the predominant mode of reproduction in natural populations of P. lilacinus.