Biotransformation of 4‐fluoro‐N‐(1‐{2‐[(propan‐2‐yl)phenoxy]ethyl}‐8‐azabicyclo[3.2.1]octan‐3‐yl)‐benzenesulfonamide,a novel potent 5‐HT7 receptor antagonist with antidepressant‐like and anxiolytic properties: In vitro and in silico approach

The aim of the study was to investigate the metabolism of 4‐fluoro‐N‐(1‐{2‐[(propan‐2‐yl)phenoxy]ethyl}‐8‐azabicyclo[3.2.1]octan‐3‐yl)‐benzenesulfonamide (PZ‐1150), a novel 5‐HT₇ receptor antagonist with antidepressant‐like and anxiolytic properties, by the following three ways: in vitro with microsomes; in vitro employing Cunninghamella echinulata, and in silico using MetaSite. Biotransformation of PZ‐1150 with microsomes resulted in five metabolites, while transformation with C. echinulata afforded two metabolites. In both models, the predominant metabolite occurred due to hydroxylation of benzene ring. In silico data coincide with in vitro experiments, as three MetaSite metabolites matched compounds identified in microsomal samples. In human liver microsomes PZ‐1150 exhibited in vitro half‐life of 64 min, with microsomal intrinsic clearance of 54.1 μL/min/mg and intrinsic clearance of 48.7 mL/min/kg. Therefore, PZ‐1150 is predicted to be a high‐clearance agent. The study demonstrated the applicability of using microsomal model coupled with microbial model to elucidate the metabolic pathways of compounds and comparison with in silico metabolite predictions.     

基于韧性理念的中国城市雨洪管理研究热点与趋势

在中国洪涝灾害频发的背景下,海绵城市等雨洪管理实践有助于灾害的缓解,提高城市应对雨洪的“韧性”。韧性城市作为应对灾害风险的城市规划理念,已被应用于一些国家的雨洪风险管理中。本文基于韧性理念,运用科学计量分析工具CiteSpace梳理中国雨洪研究现状,从生态、工程、社会雨洪韧性3方面分析了雨洪管理热点与相关技术,发现在跨领域的雨洪系统管理、区域到街区间不同空间尺度用地调蓄管理方面存在不足,提出未来应构建以“生态-工程-社会”为核心,涵盖“区域-城市-街区”尺度,多技术集成为支撑的自适应韧性雨洪管理体系。     

A green and effective method for the determination of metalaxyl enantiomers in tobacco and soil by supercritical fluid chromatography–tandem mass spectrometry

We reported a new methodology for the stereoselective determination of metalaxyl enantiomers in tobacco and soil. The QuEChERS (quick, easy, cheap, effective, rugged, and safe) method was used for the extraction and clean-up of the tobacco and soil samples. Separation of the metalaxyl enantiomers was performed on an ACQUITY UPC2 Trefoil CEL1 chiral column coupled with supercritical fluid chromatography with tandem mass spectrometry (SFC-MS/MS), and the run time was only 5 minutes. Under the optimized conditions, the recoveries for the enantiomers were between 78.2% and 93.3% with intraday relative standard deviations (RSDs) ranging from 1.1% to 5.4%. The limit of detection (LOD) for the enantiomers in tobacco and soil varied from 0.005 to 0.007 mg/kg, and the limit of quantitation (LOQ) ranged from 0.017 to 0.020 mg/kg. In this method, only a small amount of methanol was consumed to obtain a rapid stereoselective separation. This proposed method showed good accuracy and precision and might be suitable for fast enantioselective determination of metalaxyl in food and environmental samples. The developed method was further validated by application to the analysis of authentic samples.     

Testing hypotheses driving genetic structure in the cooperatively breeding Brown‐headed Nuthatch Sitta pusilla

Habitat fragmentation has often been implicated in the decline of many species. For habitat specialists and/or sedentary species, loss of habitat can result in population isolation and lead to negative genetic effects. However, factors other than fragmentation can often be important and also need to be considered when assessing the genetic structure of a species. We genotyped individuals from 13 populations of the cooperatively breeding Brown‐headed Nuthatch Sitta pusilla in Florida to test three alternative hypotheses regarding the effects that habitat fragmentation might have on genetic structure. A map of potential habitat developed from recent satellite imagery suggested that Brown‐headed Nuthatch populations in southern Florida occupied smaller and more isolated habitat patches (i.e. were more fragmented) than populations in northern Florida. We also genotyped individuals from a small, isolated Brown‐headed Nuthatch population on Grand Bahama Island. We found that populations associated with more fragmented habitat in southern Florida had lower allelic richness than populations in northern Florida (P = 0.02), although there were no differences in heterozygosity. Although pairwise estimates of F_ST were low overall, values among southern populations were generally higher than northern populations. Population assignment tests identified K = 3 clusters corresponding to a northern cluster, a southern cluster and a unique population in southeast Florida; using sampling localities as prior information revealed K = 7 clusters, with greater structure only among southern Florida populations. The Bahamas population showed moderate to high differentiation compared with Florida populations. Overall, our results suggest that fragmentation could affect gene flow in Brown‐headed Nuthatch populations and is likely to become more pronounced over time.     

肾素-血管紧张素系统在调节肾脏活动和慢性肾功能不全中的作用

一、肾内RAS的组成、生物学特征及肾内分布;(一)有关RAS的研究进展;(二)肾脏组织局部的RAS;(三)AngⅡ受体的亚型及其在肾内的分布;二、AngⅡ对肾脏血流动力学的影响;三、AngⅡ对肾脏的非血流动力学效应;(一)AngⅡ的促生长作用及促纤维生成效应;(二)AngⅡ作为促炎症因子的作用;四、有关RAS在肾功能不全中的临床研究     

陕西宝鸡发现喜山鼠耳蝠

2011年4和8月及2014年4月在陕西省宝鸡市太白县分别采集到2只、1只和1只共4只蝙蝠个体,标本保存于陕西省动物研究所标本馆(标本编号为TB0001、TB0002、TB0017和TB0042)。其主要形态特征为：体型小,头体长34.59 ~ 43.86 mm(n = 4);耳较小,黑色;耳前缘近凸圆,耳后缘在基部有一浅的缺刻;耳屏细长,约为耳长的一半;后足不及胫长的一半;背部毛基黑色,毛尖为赤褐色;腹部毛基为黑色,毛尖为灰褐色;翼膜起始于后足外趾的基部。以上特征均与喜山鼠耳蝠moupinensis亚种(Myotis muricola moupinensis)相符。结合线粒体Cyt b基因序列,构建其系统发生关系,与基因库中宽吻蝠属未定种(Submyotodon sp.)序列聚为较高支持度的一支。综合形态与系统发育证据,参考目前最新的中国兽类物种分类和分布信息,将采集到的标本初步鉴定为喜山鼠耳蝠moupinensis亚种,此次发现是陕西省境内该物种的首次记录,拓展了对其在我国分布范围的认识。     

贵州六盘水发现东阳江麝鼩

在贵州省六盘水市杨梅乡慕尼克村,利用陷阱法捕捉到3号麝鼩属(Crocidura)标本。本次采集标本的体形较小,头体长(49.0 ± 0.8)mm,尾长[(41.8 ± 4.2)mm]略短于头体长(尾长/头体长为85%)。背毛呈浅灰褐色,腹毛颜色浅于背毛,呈灰色。尾部双色,背侧黑褐色,腹侧淡于背侧。前足背部白色,后足则为淡灰色。尾近乎裸露,尾基约1/3着生稀疏白色长毛。颅全长(15.92 ± 0.55)mm,脑颅高(4.75 ± 0.18)mm。上门齿1枚,有一长而大的前尖和一小而矮的后尖。上单尖齿3枚,第1单尖齿最大,第2单尖齿略大于第3单尖齿,1枚第四前臼齿(P4),3枚臼齿。上述特征与东阳江麝鼩(C. dongyangjiangensis)模式标本的描述和鉴定特征基本一致,因此将3号采集标本鉴定为东阳江麝鼩。基于Cyt b基因进行分子系统发育分析,采集标本与麝鼩属物种中的东阳江麝鼩遗传距离最近,在0.004 ~ 0.027之间。系统发生树显示,3号标本与东阳江麝鼩构成一个单系进化分支,进一步证实本次采集的3号标本是东阳江麝鼩,为贵州省分布新记录种。     

A sensitive signal-on assay for MTase activity based on methylation-responsive hairpin-capture DNA probe

This work develops a simple, sensitive and signal-on electrochemical sensor for methyltransferase (MTase) activity analysis. The sensor is composed of a methylene blue-modi?ed "signaling DNA probe" and a "capture DNA probe" tethered methylation-responsive hairpin DNA (hairpin-capture DNA probe). The thiol- modified hairpin-capture DNA probe at 5' end was firstly self-assembled on gold electrode via Au-S bonding. Methylation-induced scission of hairpin-capture DNA probe would displace the hairpin section and remain the "capture DNA probe" section on the gold electrode. Subsequently, the remained "capture DNA probe" on the gold electrode can hybridize with the methylene blue-modi?ed "signaling DNA probe", mediating methylene blue onto the gold electrode surface to generate redox current. It was eT on state. The developed facile signal-on electrochemical sensing system showed a linear response to concentration of Dam MTase range from 0.1 to 1.0 U/mL. The detection limit of Dam MTase activity was determined to be 0.07 U/mL and the total detection time is 7h. The sensor also has the ability to provide information about the dynamics of methylation process. Furthermore, we demonstrated that this sensor could be utilized to screen inhibitors or drugs for Dam MTase.