Bone marrow mesenchymal stem cell-derived extracellular vesicles containing miR-181d protect rats against renal fibrosis by inhibiting KLF6 and the NF-κB signaling pathway

Recent studies have investigated the ability of extracellular vesicles (EVs) in regulating neighboring cells by transferring signaling molecules, such as microRNAs (miRs) in renal fibrosis. EVs released by bone marrow mesenchymal stem cells (BMSCs) contain miR-181d, which may represent a potential therapy for renal fibrosis. miR-181d has been speculated to regulate Krüppel-like factor 6 (KLF6), which activates the nuclear factor-kappa B (NF-κB) signaling pathway. Luciferase assays were performed to confirm the relationship between miR-181d and KLF6. Gain- and loss-of-function studies in vivo and in vitro were performed to assess the effect of BMSC-derived EVs (BMSC-EVs), which contained miR-181d, on KLF6, NF-κB, and renal fibrosis. Transforming growth factor-β (TGF-β)-induced renal tubular epithelial HK-2 cells were treated with EVs derived from BMSCs followed by evaluation of collagen type IV α1 (Col4α1), Collagen I and α-smooth muscle actin (α-SMA) as indicators of the extent of renal fibrosis. Renal fibrosis was induced in rats by unilateral ureteral obstruction (UUO) followed by the subsequent analysis of fibrotic markers. BMSC-EVs had higher miR-181d expression. Overexpression of miR-181d correlated with a decrease in KLF6 expression as well as the levels of IκBα phosphorylation, α-SMA, Col4α1, TGF-βR1 and collagen I in HK-2 cells. In vivo, treatment with miR-181d-containing BMSC-derived EVs was able to restrict the progression of fibrosis in UUO-induced rats. Together, BMSC-EVs suppress fibrosis in vitro and in vivo by delivering miR-181d to neighboring cells, where it targets KLF6 and inhibits the NF-κB signaling pathway.Subject terms: Cell biology, Biotechnology     

人重组IL6／IL2融合蛋白的变性、复性及纯化

经超声破碎,分离已表达CH925包涵体,较系统地研究变性剂浓度、融合蛋白浓度对蛋白折叠的影响.在还原型及氧化型谷胱甘肽复性条件下,成功地将融合蛋白CH925折叠成具有IL6及IL2双活性蛋白,IL6的比活为2.3×10⁸U/mg, IL2比活为2.2×10⁶U/mg.经阴离子交换、凝胶过滤层析,获得一定纯度的CH925,配合反相HPLC.洗脱收集蛋白峰,CH925纯度为98%.     

保护三峡工程影响的珍稀濒危生物的经济价值评估

运用条件价值评估法, 基于三峡工程对珍稀濒危生物影响的现状和采取的保护措施, 设计了支付卡式调查问卷。通过调查我国31个省(自治区、直辖市)以国有单位为主的职工的支付意愿, 评估了保护三峡工程影响的珍稀濒危生物白鳍豚(Lipotes vexillifer)、白鲟(Psephurus gladius)、达氏鲟(Acipenser dabryanus)、胭脂鱼(Myxocyprinus asiaticus)、中华鲟(Acipenser sinensis)和荷叶铁线蕨(Adiantum reniforme var. sinense)、疏花水柏枝(Myricaria laxiflora)、川明参(Chuanminshen violaceum)的经济价值。回收有效问卷1,036份, 有70.08%的有效问卷反馈者愿意为保护三峡工程影响的这些珍稀濒危生物而支付费用, 平均支付意愿值为127.82元/年。同时采用列联表及卡方独立性检验方法重点分析了总样本各因素对支付意愿值的影响, 结果显示年龄、文化程度、从事职业、个人收入、对三峡工程的了解、对三峡工程的关注、对三峡工程对生物影响的了解等因素与支付意愿值显著相关。最后计算得出保护三峡工程影响的这些珍稀濒危生物的经济价值为82.19×10⁸元/年。以上结果为进一步制定相关保护政策提供了依据。     

松材线虫伴生细菌多样性的宏基组分析

摘要：【目的】松材线虫是松材线虫病的病原,且与其伴生细菌之间存在互作关系,它们构成一个微生态系统。本研究旨在揭示松材线虫-伴生细菌群落细菌多样性。【方法】采用16S rRNA基因文库和454测序对伴生细菌群落的宏基因组进行初步分析。【结果】依据97％序列相似性划分OTU（Operational Taxonomic Unit）,构建的16S rRNA文库包含25个OTU,分别属于Alphaproteobacteria、Betaproteobacteria、Gammaproteobacteria和Bacter     

pLoc_bal-mGpos: Predict subcellular localization of Gram-positive bacterial proteins by quasi-balancing training dataset and PseAAC

Knowledge of protein subcellular localization is vitally important for both basic research and drug development. With the avalanche of protein sequences emerging in the post-genomic age, it is highly desired to develop computational tools for timely and effectively identifying their subcellular localization purely based on the sequence information alone. Recently, a predictor called “pLoc-mGpos” was developed for identifying the subcellular localization of Gram-positive bacterial proteins. Its performance is overwhelmingly better than that of the other predictors for the same purpose, particularly in dealing with multi-label systems in which some proteins, called “multiplex proteins”, may simultaneously occur in two or more subcellular locations. Although it is indeed a very powerful predictor, more efforts are definitely needed to further improve it. This is because pLoc-mGpos was trained by an extremely skewed dataset in which some subset (subcellular location) was over 11 times the size of the other subsets. Accordingly, it cannot avoid the bias consequence caused by such an uneven training dataset. To alleviate such bias consequence, we have developed a new and bias-reducing predictor called pLoc_bal-mGpos by quasi-balancing the training dataset. Rigorous target jackknife tests on exactly the same experiment-confirmed dataset have indicated that the proposed new predictor is remarkably superior to pLoc-mGpos, the existing state-of-the-art predictor in identifying the subcellular localization of Gram-positive bacterial proteins. To maximize the convenience for most experimental scientists, a user-friendly web-server for the new predictor has been established at http://www.jci-bioinfo.cn/pLoc_bal-mGpos/, by which users can easily get their desired results without the need to go through the detailed mathematics.     

Big‐sized trees overrule remaining trees' attributes and species richness as determinants of aboveground biomass in tropical forests

Large‐diameter, tall‐stature, and big‐crown trees are the main stand structures of forests, generally contributing a large fraction of aboveground biomass, and hence play an important role in climate change mitigation strategies. Here, we hypothesized that the effects of large‐diameter, tall‐stature, and big‐crown trees overrule the effects of species richness and remaining trees attributes on aboveground biomass in tropical forests (i.e., we term the “big‐sized trees hypothesis”). Specifically, we assessed the importance of: (a) the “top 1% big‐sized trees effect” relative to species richness; (b) the “99% remaining trees effect” relative to species richness; and (c) the “top 1% big‐sized trees effect” relative to the “99% remaining trees effect” and species richness on aboveground biomass. Using environmental factor and forest inventory datasets from 712 tropical forest plots in Hainan Island of southern China, we tested several structural equation models for disentangling the relative effects of big‐sized trees, remaining trees attributes, and species richness on aboveground biomass, while considering for the full (indirect effects only) and partial (direct and indirect effects) mediation effects of climatic and soil conditions, as well as interactions between species richness and trees attributes. We found that top 1% big‐sized trees attributes strongly increased aboveground biomass (i.e., explained 55%–70% of the accounted variation) compared to species richness (2%–18%) and 99% remaining trees attributes (6%–10%). In addition, species richness increased aboveground biomass indirectly via increasing big‐sized trees but via decreasing remaining trees. Hence, we show that the “big‐sized trees effect” overrides the effects of remaining trees attributes and species richness on aboveground biomass in tropical forests. This study also indicates that big‐sized trees may be more susceptible to atmospheric drought. We argue that the effects of big‐sized trees on species richness and aboveground biomass should be tested for better understanding of the ecological mechanisms underlying forest functioning.     

非线性映射和聚类分析在中风病证候分类中的应用

本文用非线性映射和聚类分析方法,给出了中风病的四个类型,为中风病的证候分类提供了分析方法和信息．     

The association between common genetic variant of microRNA-146a and cancer susceptibility

Published data on the association between microRNA-146a (miR-146a) G/C polymorphism and cancer susceptibility are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 23 studies including 10,585 cases and 12,183 controls were used in the meta-analysis. Overall, no significant associations were found between miR-146a G/C polymorphism and cancer risk when all studies pooled into the meta-analysis (GC vs. CC: OR=1.08, 95% CI=0.94-1.24; GG vs. CC: OR=1.13, 95% CI=0.93-1.37; dominant model: OR=1.09, 95% CI=0.94-1.26). In the subgroup analysis by ethnicity, still no significant associations were found. In the subgroup analysis by cancer type, statistically significantly increased risks were found for papillary thyroid carcinoma (GC vs. CC: OR=3.44, 95% CI=1.86-6.34; GG vs. CC: OR=2.20, 95% CI=1.22-3.99; dominant model: OR=2.68, 95% CI=1.48-4.83). In the subgroup analysis by population-based controls or hospital-based controls, no statistically significantly increased risks were found. Despite some limitations, this meta-analysis suggests that the miR-146a G allele is a low-penetrant risk factor for papillary thyroid carcinoma development.     

Refolding of the hyperthermophilic protein Ssh10b involves a kinetic dimeric intermediate

The α/β-mixed dimeric protein Ssh10b from the hyperthermophile Sulfolobus shibatae is a member of the Sac10b family that is thought to be involved in chromosomal organization or DNA repair/recombination. The equilibrium unfolding/refolding of Ssh10b induced by denaturants and heat was fully reversible, suggesting that Ssh10b could serve as a good model for folding/unfolding studies of protein dimers. Here, we investigate the folding/unfolding kinetics of Ssh10b in detail by stopped-flow circular dichroism (SF-CD) and using GdnHCl as denaturant. In unfolding reactions, the native Ssh10b turned rapidly into fully unfolded monomers within the stopped-flow dead time with no detectable kinetic intermediate, agreeing well with the results of equilibrium unfolding experiments. In refolding reactions, two unfolded monomers associate in the burst phase to form a dimeric intermediate that undergoes a further, slower, first-order folding process to form the native dimer. Our results demonstrate that the dimerization is essential for maintaining the native tertiary interactions of the protein Ssh10b. In addition, folding mechanisms of Ssh10b and several other α/β-mixed or pure β-sheet proteins are compared.     

原生质体融合技术选育分解草酸乳酸菌菌株的研究

将具有草酸分解能力的乳双歧杆菌和具有耐氧特性的嗜酸乳杆菌进行原生质体融合,其最佳条件为:50%的PEG6000,融合温度30℃,融合时间为7 min,CaCl2浓度为0.02 mol/L,MgCl2浓度为0.5 mol/L,在此条件下融合率可达7.6%。从中筛选出同时具有耐氧特性和草酸分解能力的融合子,草酸分解率为13.4%。