Human chromosome 21-derived miRNAs are overexpressed in down syndrome brains and hearts

Down syndrome (DS), or Trisomy 21, is the most common genetic cause of cognitive impairment and congenital heart defects in the human population. To date, the contribution of microRNAs (miRNAs) in DS has not been investigated. Bioinformatic analyses demonstrate that human chromosome 21 (Hsa21) harbors five miRNA genes; miR-99a, let-7c, miR-125b-2, miR-155, and miR-802. MiRNA expression profiling, miRNA RT-PCR, and miRNA in situ hybridization experiments demonstrate that these miRNAs are overexpressed in fetal brain and heart specimens from individuals with DS when compared with age- and sex-matched controls. We hypothesize that trisomic 21 gene dosage overexpression of Hsa21-derived miRNAs results in the decreased expression of specific target proteins and contribute, in part, to features of the neuronal and cardiac DS phenotype. Importantly, Hsa21-derived miRNAs may provide novel therapeutic targets in the treatment of individuals with DS.     

中国大陆地区曲霉病流行现状分析

目的了解中国大陆地区曲霉病流行状况及诊治现状。方法通过CNKI及Pubmed搜索1991年来中国大陆地区曲霉病及曲霉相关文献,进行数据统计和总结。结果 1991年1月～2009年10月报道曲霉病1457例,其中481例有病原学证据,258例进行菌种鉴定,其中烟曲霉153例。感染部位最常见于肺,为1047例。病原学诊断依据主要是镜检和培养;菌种鉴定主要依赖形态学特征,仅4例进行分子生物学鉴定;仅少数进行半乳甘露聚糖及葡聚糖检测;体外药敏试验少,仅报道2株黄曲霉对两性霉素B耐药,2株烟曲霉多药耐药。伊曲康唑为侵袭性曲霉感染经验治疗(抢先治疗)的首选药物。过敏性支气管肺曲霉病则多单用糖皮质激素或联合伊曲康唑,大部分慢性及腐生型曲霉病及鼻窦曲霉病患者行手术治疗。结论中国大陆地区曲霉病流行趋势与国际一致,非烟曲霉感染有所增加,感染部位仍以肺为主。应提高菌种形态学和分子生物学鉴定水平,积极开展非培养检测手段,保证正确和及时地诊断;加强药敏监测,为临床治疗提供有效信息。     

华北大黑鳃金龟中肠丝氨酸蛋白酶cDNA克隆、 序列分析及表达

丝氨酸蛋白酶是昆虫体内一类重要的消化酶, 为了了解该类酶的分子特性及功能, 本研究利用粉纹夜蛾Trichoplusia ni围食膜蛋白多克隆抗体筛选华北大黑鳃金龟Holotrichia oblita中肠cDNA表达文库, 首次得到编码华北大黑鳃金龟丝氨酸蛋白酶cDNA序列, 命名为HoSP1（GenBank登录号为FJ573146）。序列分析表明, 该基因长902 bp, 开放阅读框（ORF）长783 bp, 编码260个氨基酸, 推测分子量和pI值分别为26.7 kDa和4.19, 不含有N-糖基化位点, 但在Thr₁₅₇处有一个O-糖基化位点, 含有6个保守的半胱氨酸残基, 组成3对二硫键, 对于维持蛋白质的三级结构起着重要的作用。通过与几种丝氨酸蛋白酶的比对发现, 该酶具有组氨酸（His）、 天冬氨酸（Asp）、 丝氨酸（Ser）催化中心, 与褐新西兰肋翅鳃金龟Costelytra zealandica的14种丝氨酸蛋白酶有明显的相似性, 其中与CzSP3的序列一致性最高, 为52.47%。把该基因与pET21b载体重组后, 进行体外表达, 以BTEE为底物, 测得该酶的活力为0.0378 μmol/mg·min。HoSP1基因的克隆及体外表达为进一步研究该酶在华北大黑鳃金龟体内的表达及功能提供了依据。     

Bioleaching and bioprecipitation of nickel and iron from laterites

Abstract: Leaching of silicate ores, particularly nickel laterites, with the aid of heterotrophic organisms has been briefly reviewed. Samples of laterite ores from Greece were characterised mineralogically and a number of microorganisms isolated from them. One of these organisms (code FI) was successfully acclimatized to 6400 ppm nickel. Samples of the high-grade Greek Kastoria nickel laterite were leached with sulphuric acid and a number of organic acids. Sulphuric and citric acids extracted over 60 and 40% of the contained nickel, respectively, but the other acids employed were less efficient leachants. Oxalic acid precipitated nickel oxalate. Roughly the same extraction of iron was observed. The main leaching parameter was confirmed to be hydrogen ion concentration, although complexation with organic anions was a contributor. Organism FI (a strain of Penicillium ) was used in comparison with organisms from various culture collections to bioleach nickel from samples of the low-grade Greek Litharakia nickel laterite. The organisms were cultivated in a mixture of a sugar-based nutrient mineral medium and finely ground ore. Several penicillia and aspergilli leached 55–60% of the contained nickel and cobalt, and 25–35% of the iron when sucrose was the carbon source, but FI was not efficient. However, in molasses medium, Fl extracted nearly 40% of the nickel. Biosorption and bioprecipitation reactions were observed. The mechanism of bioleaching or in situ leaching is discussed in terms of close physical and chemical association between the fungal hyphae and mineral phases in the ore. This accounted for the low overall hydrogen ion concentration observed during bioleaching.     

体外诊断试剂防腐剂的选择策略

对体外诊断试剂中防腐剂的作用机理及选择原则进行了阐述,并对目前常用的防腐剂如叠氮钠、庆大霉素、硫柳汞、异噻唑啉酮类等的性能进行了比较,为体外诊断试剂的研究开发及生产中防腐剂的使用提供有益指导。     

Quantitative structure–activity relationship analysis using deep learning based on a novel molecular image input technique

Quantitative structure–activity relationship (QSAR) analysis uses structural, quantum chemical, and physicochemical features calculated from molecular geometry as explanatory variables predicting physiological activity. Recently, deep learning based on advanced artificial neural networks has demonstrated excellent performance in the discipline of QSAR research. While it has properties of feature representation learning that directly calculate feature values from molecular structure, the use of this potential function is limited in QSAR modeling. The present study applied this function of feature representation learning to QSAR analysis by incorporating 360° images of molecular conformations into deep learning. Accordingly, I successfully constructed a highly versatile identification model for chemical compounds that induce mitochondrial membrane potential disruption with the external validation area under the receiver operating characteristic curve of ≥0.9.     

着床期小鼠子宫内膜中EGF及其受体转录和表达状况的研究

为探讨表皮生长因子（epidermal growth factor,EGF)在胚泡着床过程中的作用。本文应用原位杂交和免疫组织化学方法,检测了EGE及其受体在胚泡着床前后小鼠子宫内膜中的转录和表达。结果显示：未孕和受精后第4-5天,子宫内膜表面上皮和腺上皮细胞仍呈EGF,EGFR原位杂交和免疫组化阴性着色,受精后第4-5天子宫内膜基质细胞EGF及其受体转录和表达较未孕期增强,受精后第6天,EGF及其受体免疫组化和原位杂交阳性着色主要分布于初级蜕膜带（primary decidual zone,PDZ);随着胚泡植入的进行,PDZ区蜕膜细胞EGF及其受体的转录和表达明显减少,而PDZ周围蜕膜细胞EGF及其受体的转录和表达增强,结果提示,EGF是小鼠胚泡着床过程中的一个重要调节因子。     

α-Glucosidase inhibition by flavonoids: an in vitro and in silico structure–activity relationship study

α-Glucosidase inhibitors are described as the most effective in reducing post-prandial hyperglycaemia (PPHG) from all available anti-diabetic drugs used in the management of type 2 diabetes mellitus. As flavonoids are promising modulators of this enzyme’s activity, a panel of 44 flavonoids, organised in five groups, was screened for their inhibitory activity of α-glucosidase, based on in vitro structure–activity relationship studies. Inhibitory kinetic analysis and molecular docking calculations were also applied for selected compounds. A flavonoid with two catechol groups in A- and B-rings, together with a 3-OH group at C-ring, was the most active, presenting an IC₅₀ much lower than the one found for the most widely prescribed α-glucosidase inhibitor, acarbose. The present work suggests that several of the studied flavonoids have the potential to be used as alternatives for the regulation of PPHG.     

含铬重组液激活部分缺失金属原子簇的钼铁蛋白的研究

棕色固氮菌（Ａｚｏｔｏｂａｃｔｅｒ ｖｉｎｅｌａｎｄｉｉ）固氮酶钼铁蛋白经邻菲口罗啉和Ｏ２ 处理后,变为部分缺失ＦｅＭｏｃｏ 和Ｐ－ｃｌｕｓｔｅｒ的失活蛋白。与由Ｋ２ＣｒＯ４、高柠檬酸铁、Ｎａ２Ｓ和二硫苏糖醇组成的重组液保温后,处理蛋白对乙炔和质子还原的活性都得以显著恢复;然而,它的吸收光谱和圆二色谱虽有明显恢复,但仍与还原钼铁蛋白有所不同。这表明,激活蛋白中也许存在功能与钼铁蛋白相似,而结构则有所差异的含铬（ＣｒＦｅ）蛋白