Sirt3 Protects Against Ischemic Stroke Injury by Regulating HIF-1α/VEGF Signaling and Blood–Brain Barrier Integrity

Sirtuin 3 (Sirt3) is a member of the Sirtuin family proteins and known to regulate multiple physiological processes such as metabolism and aging. As stroke is an aging-related disease, in this work, we attempt to examine the role and potential mechanism of Sirt3 in regulating ischemic stroke by using a permanent middle cerebral artery occlusion (pMCAO) model in wild type (WT) and Sirt3 knockout (KO) mice, coupled with oxygen glucose deprivation (OGD) experiments in cultured primary astrocytes. Sirt3 deficiency aggravated neuronal cell apoptosis and neurological deficits after brain ischemia. In addition, Sirt3 KO mice showed more severe blood–brain barrier (BBB) disruption and inflammatory responses compared with WT group in the acute phase. Furthermore, specific overexpression of Sirt3 in astrocytes by injecting glial fibrillary acidic protein (GFAP)::Sirt3 virus in ischemic region showed protective effect against stroke-induced damage. Mechanistically, Sirt3 could regulate vascular endothelial growth factor (VEGF) expression by inhibiting hypoxia inducible factor-1α (HIF-1α) signaling after ischemia (OGD). Our results have shown that Sirt3 plays a protective role in ischemic stroke via regulating HIF-1α/VEGF signaling in astrocytes, and reversal of the Sirt3 expression at the acute phase could be a worthy direction for stroke therapy.

     

Independent component analysis based gene co-expression network inference (ICAnet) to decipher functional modules for better single-cell clustering and batch integration

With the tremendous increase of publicly available single-cell RNA-sequencing (scRNA-seq) datasets, bioinformatics methods based on gene co-expression network are becoming efficient tools for analyzing scRNA-seq data, improving cell type prediction accuracy and in turn facilitating biological discovery. However, the current methods are mainly based on overall co-expression correlation and overlook co-expression that exists in only a subset of cells, thus fail to discover certain rare cell types and sensitive to batch effect. Here, we developed independent component analysis-based gene co-expression network inference (ICAnet) that decomposed scRNA-seq data into a series of independent gene expression components and inferred co-expression modules, which improved cell clustering and rare cell-type discovery. ICAnet showed efficient performance for cell clustering and batch integration using scRNA-seq datasets spanning multiple cells/tissues/donors/library types. It works stably on datasets produced by different library construction strategies and with different sequencing depths and cell numbers. We demonstrated the capability of ICAnet to discover rare cell types in multiple independent scRNA-seq datasets from different sources. Importantly, the identified modules activated in acute myeloid leukemia scRNA-seq datasets have the potential to serve as new diagnostic markers. Thus, ICAnet is a competitive tool for cell clustering and biological interpretations of single-cell RNA-seq data analysis.     

The Role of Human LRRK2 in Acute Methylmercury Toxicity in Caenorhabditis elegans

Neurochemical Research - Methylmercury (MeHg) exposure and its harmful effects on the developing brain continue to be a global environmental health concern. Decline in mitochondrial function is...     

The Neurotrophic Effects and Mechanism of Action for FK1706 in Neurorrhaphy Rat Models and SH-SY5Y Cells

FK1706 is a novel non-immunosuppressive immunophilin ligand with neurotrophic activity and exerts its neurotrophic effect through NGF. The present study aimed to elaborate on the neurotrophic activity and the mechanism of action of FK1706 in end-to-side neurorrhaphy rats and SH-SY5Y cells. In the regenerating nerves of neurorrhaphy rats, FK1706 increased the thickness of myelin sheath and the level of nerve regeneration-related proteins. The mechanism of action of FK1706 on neurite regrowth was elucidated in vitro by incubating SH-SY5Y cells in different conditions (Control, NGF, FK1706, NGF?+?FK1706, NGF?+?FK1706?+?geldanamycin). Under the conditions where NGF was used, the phosphorylation level of major proteins (Raf-1 and ERK) in the Ras/Raf/MAPK/ERK signaling pathway related to SH-SY5Y cell proliferation was significantly enhanced following the application of FK1706. The number of viable cells, cell viability and neurite length of SH-SY5Y cells was maximal when NGF and FK1706 were used simultaneously. The binding level of HSP90 and Raf-1 in FK1706 group was the highest. These results indicated that FK1706 could significantly promote nerve regeneration after neurorrhaphy. The putative mechanism of action stated that FK1706 could promote the binding of HSP90 and Raf-1, make Raf-1 continue to be activated, thereby affecting key proteins in the Ras/Raf/MAPK/ERK signaling pathway related to the neurotrophic effects of NGF to promote the proliferation and neurite regrowth of nerve cells.

     

鸡粪有机肥对设施菜地土壤重金属和微生物群落结构的影响

通过田间试验,研究在设施菜地上施用不同剂量的鸡粪有机肥对土壤-植物系统中重金属的累积、重金属有效性和土壤微生物群落结构的影响,进一步探讨土壤微生物群落结构与土壤重金属之间的相关关系。结果表明,与对照相比,施用有机肥可提高小白菜地上部生物量,其中施肥量为60 t/hm²时值最大,增幅为59.92%;小白菜地上部Cd、Cr、Cu、Zn和As含量均大幅增加,但Pb含量无明显变化。土壤重金属Cd、Cr、Cu、Zn和As的全量均随鸡粪有机肥施加量的增加而增大,最高增幅分别为21.30%、21.58%、17.40%、19.40%和17.43%,出现明显的累积现象;施用有机肥均增加了土壤Cd、Cr、Cu、Zn和As的有效态含量,而Pb的全量和有效态含量无显著变化;除重金属Pb外,不同重金属元素全量与有效态含量均显著正相关,其中元素Zn的全量与有效态含量相关性最强。磷脂脂肪酸（PLFA）分析结果表明,土壤中含量较高的PLFA为16：0、18：1ω7c、10Me16：0和18：1ω9c,土壤微生物总PLFA和各类群PLFA含量均呈现M0.5 > M1 > CK > M2 > M4;相关性分析结果表明,土壤Cu、As全量和Cd、Cr、Cu、As有效态含量与微生物总PLFA和各类群PLFA含量均呈现显著负相关关系,其中有效态Cr和Cu含量对微生物群落结构的影响最为显著。     

野生藏酋猴冬季食物组成及营养成分

觅食是获取营养物质和能量的重要途经。对于栖息在四季分明地区的灵长类动物而言,低温以及食物资源相对匮乏的冬季是其生存和生长发育的瓶颈期。本研究以安徽黄山的野生藏酋猴（Macaca thibetana）天湖山群为对象,于2019年11月至2020年1月采用瞬时扫描取样法（Instantaneous scan sampling）采集猴群觅食行为数据,并分析其冬季食物组成及食物中各化学成分含量对取食的影响。结果显示,野生藏酋猴在冬季共取食23科31属34种植物,主要包括壳斗科（Fagaceae,21.62%）、樟科（Lauraceae,17.57%）、蔷薇科（Rosaceae,8.11%）的植物,取食部位以叶片（66.22%）和果实（种子）（24.32%）为主。不同取食部位的水分、总糖、淀粉、脂肪、单宁等成分存在显著差异。其中,叶片的水分含量高于果实（种子）、茎和芽,茎和果实（种子）含有较高的总糖,果实（种子）的淀粉和脂肪含量最高,芽的单宁含量最高。此外,取食植物中的总糖含量高于非取食植物。结果表明,野生藏酋猴适应寒冷冬季与食物匮乏的觅食策略是对植物种类、植物部位及其主要营养成分的综合结果。     

一株氯霉素降解细菌的分离鉴定与代谢特性研究

微生物是介导环境中氯霉素降解转化的主要驱动者,但高效降解矿化菌株资源匮乏,氧化反应介导的代谢途径不清。为研究微生物介导下氯霉素的环境归趋过程,为氯霉素污染环境强化修复提供菌株资源,文中以受氯霉素污染的活性污泥为接种源,首先富集获得一个由红球菌Rhodococcus主导 (相对丰度>70%) 的氯霉素高效降解菌群,并从中分离获得一株能够高效降解氯霉素的菌株CAP-2,通过16S rRNA基因分析鉴定为红球菌Rhodococcus sp.。菌株CAP-2能在不同营养条件下高效降解氯霉素。基于菌株CAP-2对检测到的代谢产物对硝基苯甲酸和已报道的代谢产物对硝基苯甲醛和原儿茶酸的生物转化特征,提出其降解途径是由氯霉素侧链氧化断裂生成对硝基苯甲醛,进一步氧化为对硝基苯甲酸的新型氧化降解途径。该菌株对于氯霉素分解代谢的分子机制研究以及受氯霉素污染环境的原位生物修复应用具有巨大潜力。     

肠道菌群对耐碳青霉烯类肠杆菌科细菌定殖抗性的研究进展

耐碳青霉烯类肠杆菌科细菌(carbapenem-resistant Enterobacteriaceae,CRE)在肠腔中定殖通常先于或并存于CRE的感染。正常情况下,定殖的CRE、肠道菌群和宿主相互作用,处于稳定平衡的状态,当肠道菌群出现失调时,肠道正常菌群失去对定殖CRE的抵抗力,增加CRE感染的风险。大量研究表明通过肠道共生菌群对CRE的定殖抗性不仅可以预防感染,而且也可以降低医疗环境中患者间相互传播的风险。本文就CRE的流行现状、肠杆菌科细菌定殖机制以及肠道共生菌群对CRE定殖抗性机制作一综述,以期为CRE感染的防控工作提供新思路和新方法。