Pharmacokinetic,metabolic stability,plasma protein binding and CYP450s inhibition/induction assessment studies of N-(2-pyridylmethyl)-2-hydroxiymethyl-1-pyrrolidinyl-4-(3-chloro-4-methoxy-benzylamino)-5-pyrimidine-carboxamide as potential type 5 phosphodiesterase inhibitors

N-(2-pyridylmethyl)-2-hydroxiymethyl-1-pyrrolidinyl-4-(3-chloro-4-methoxy-benzylamino)-5-pyrimidine-carboxamide (NHPPC) is a new potential of type 5 phosphodiesterase (PDE5) inhibitors, synthesized from the avanafil analogue for the treatment of erectile dysfunction. The targets of this article were to assess plasma protein binding, liver microsomal metabolic stability, inhibition and induction on cytochrome P450 isozymes and the pharmacokinetics of NHPPC. Equilibrium dialysis technique was applied to determine Plasma protein binding (PPB) and NHPPC was evaluated in male Sprague–Dawley rats and Beagle dogs in vivo pharmacokinetic. The NHPPC was highly bound to plasma proteins in rats, dogs and human tested and the mean values for PPB rate were 96.2%, 99.6% and 99.4%, respectively. After in vitro liver microsomes incubated for 60?min, the percent remaining of NHPPC was 42.8%, 0.8% and 42.0% in rats, dogs and human, respectively. In vitro intrinsic clearance was found to be 0.0233, 0.1204 and 0.0214 mL/min/mg protein in rat, dog and human liver microsomes of NHPPC, respectively. NHPPC showed no significant inhibitory effects on major CYP450 enzymes, and had no significant induction potential on CYP1A2 and CYP3A4. Following oral administration in rats and dogs, t_max was 6 and 0.5?h, respectively. The clearance for NHPPC was 1.19 and 1.46?L/h/kg in rats and dogs, respectively. And absolute bioavailability in rat and dog were approximately 34.5% and 53.1%, respectively. These results showed that NHPPC has a good development prospect.     

油藏嗜热菌与膨润土的相互作用及其对储层防膨的意义

[目的]本文从胜利油田沾3区块的高温油藏的原油采出液中分离得到一株嗜热菌,通过其与膨润土的相互作用,尝试探讨油藏微生物作为油藏储层中水敏性矿物（如蒙皂石）改性剂的可能性。[意义]研究结果将在降低水敏矿物的膨胀性能,为解决水驱采油中遇到的水敏效应的瓶颈问题提供微生物的新途径。[结果]所得菌株为革兰氏阳性菌,呈杆状,具芽孢,兼性厌氧,鉴定为Geobacillus icigianus SL-1。菌株SL-1在厌氧条件下能够还原蒙皂石的结构铁。扫描电镜（SEM）结果显示,无菌对照体系中,蒙皂石呈不规则薄片状。而经微生物作用后,除薄片状蒙皂石外,另有板状次生矿物的生成。进一步能谱（EDS）分析表明,与薄片状蒙皂石相比,板状矿物含有较高的Al/Si比值,且含有明显的K⁺信号。XRD结果显示,经过微生物作用后,固相物质中蒙皂石的百分比下降至47.7%,伊利石百分比上升至29.1%,而无菌对照组中蒙皂石的百分含量则为70.4%,伊利石的百分比则为19.8%。XRD物相分析和EDS结果均证实经过微生物作用后,部分蒙皂石转化成了伊利石。膨胀性能的分析进一步揭示菌株SL-1作用后,矿物膨胀性较初始矿物显著降低,缩膨率达到25.9%。以上结果为油藏储层防膨提供了重要的实验依据。     

慢性乙型肝炎舌红苔黄和舌淡苔白不同舌象的尿代谢组研究

目的：探索慢性乙型肝炎舌红苔黄和舌淡苔白不同舌象者的尿代谢差异指标,为中医舌象生物学物质基础微观辨证提供证据。方法：采用气相色谱／质谱联用（GC／MS ）技术方法获取慢性乙型肝炎舌红苔黄和舌淡苔白不同舌象者的尿液样本代谢指纹谱,用无监督的学习模式进行多变量统计分析,观察不同组别的人群之间是否存在“自然”的分类结构。利用有监督的学习模式进行数据分类模型的建立和检验,寻找造成样本聚集和离散的主要差异变量。利用商业化的代谢物谱库以及标准品数据库,进行物质鉴定。结果：慢性乙型肝炎舌红苔黄和舌淡苔白者在有监督的学习模式下具有良好的分开趋势,慢乙肝不同舌象者较健康者的差异代谢物谱主要与能量代谢、氨基酸代谢、核苷酸代谢以及肠道菌群代谢相关。结论：舌象是机体变化的重要窗口,不同舌象的外在表观潜在体内的代谢差异。     

Investigation on the Tribological Behavior and Wear Mechanism of Five Different Veneering Porcelains

Objectives

The primary aim of this research was to investigate the wear behavior and wear mechanism of five different veneering porcelains.

Methods

Five kinds of veneering porcelains were selected in this research. The surface microhardness of all the samples was measured with a microhardness tester. Wear tests were performed on a ball-on-flat PLINT fretting wear machine, with lubrication of artificial saliva at 37°C. The friction coefficients were recorded by the testing system. The microstructure features, wear volume, and damage morphologies were recorded and analyzed with a confocal laser scanning microscope and a scanning electron microscope. The wear mechanism was then elucidated.

Results

The friction coefficients of the five veneering porcelains differ significantly. No significant correlation between hardness and wear volume was found for these veneering porcelains. Under lubrication of artificial saliva, the porcelain with higher leucite crystal content exhibited greater wear resistance. Additionally, leucite crystal size and distribution in glass matrix influenced wear behavior. The wear mechanisms for these porcelains were similar: abrasive wear dominates the early stage, whereas delamination was the main damage mode at the later stage. Furthermore, delamination was more prominent for porcelains with larger crystal sizes.

Significance

Wear compatibility between porcelain and natural teeth is important for dental restorative materials. Investigation on crystal content, size, and distribution in glass matrix can provide insight for the selection of dental porcelains in clinical settings.     

Phosphorylation of Pkp1 by RIPK4 regulates epidermal differentiation and skin tumorigenesis

Tissue homeostasis of skin is sustained by epidermal progenitor cells localized within the basal layer of the skin epithelium. Post‐translational modification of the proteome, such as protein phosphorylation, plays a fundamental role in the regulation of stemness and differentiation of somatic stem cells. However, it remains unclear how phosphoproteomic changes occur and contribute to epidermal differentiation. In this study, we survey the epidermal cell differentiation in a systematic manner by combining quantitative phosphoproteomics with mammalian kinome cDNA library screen. This approach identified a key signaling event, phosphorylation of a desmosome component, PKP1 (plakophilin‐1) by RIPK4 (receptor‐interacting serine–threonine kinase 4) during epidermal differentiation. With genome‐editing and mouse genetics approach, we show that loss of function of either Pkp1 or Ripk4 impairs skin differentiation and enhances epidermal carcinogenesis in vivo. Phosphorylation of PKP1's N‐terminal domain by RIPK4 is essential for their role in epidermal differentiation. Taken together, our study presents a global view of phosphoproteomic changes that occur during epidermal differentiation, and identifies RIPK‐PKP1 signaling as novel axis involved in skin stratification and tumorigenesis.     

Design of novel analogues of short antimicrobial peptide anoplin with improved antimicrobial activity

Currently, novel antibiotics are urgently required to combat the emergence of drug‐resistant bacteria. Antimicrobial peptides with membrane‐lytic mechanism of action have attracted considerable interest. Anoplin, a natural α‐helical amphiphilic antimicrobial peptide, is an ideal research template because of its short sequence. In this study, we designed and synthesized a group of analogues of anoplin. Among these analogues, anoplin‐4 composed of d ‐amino acids displayed the highest antimicrobial activity due to increased charge, hydrophobicity and amphiphilicity. Gratifyingly, anoplin‐4 showed low toxicity to host cells, indicating high bacterial selectivity. Furthermore, the mortality rate of mice infected with Escherichia coli was significantly reduced by anoplin‐4 treatment relative to anoplin. In conclusion, anoplin‐4 is a novel anoplin analogue with high antimicrobial activity and enzymatic stability, which may represent a potent agent for the treatment of infection. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.     

北京地区油松人工林不同演替类型空间结构对林下植被及土壤的影响

以北京地区油松(Pinus tabuliformis)人工林不同演替类型林分为研究对象,研究油松纯林、油松-栓皮栎(Quercus variabilis)混交林和栓皮栎纯林三种不同演替类型林分的空间结构、林下植被和土壤水分的变化规律及其相互作用关系。结果表明：(1)林分水平及垂直空间结构、草本层物种多样性、更新幼树生长、土壤持水和透气性能等指标在三种不同演替类型林分间差异显著(P<0.05),林分空间结构参数中的角尺度、林层指数和开敞度显著影响了各类型林分的灌草多样性,混交度、林层指数和大小比数显著影响了更新幼树的生长,混交度和林层指数显著影响了土壤水分的变化(P<0.05)。(2)松栎混交林灌草生物量、天然更新幼树的生长以及土壤水分物理状况均好于纯林,并主要受林分混交度和林层指数的共同作用。(3)各演替类型林分内均存在栓皮栎更新幼树,混交林栓皮栎更新幼树数量最多、长势最好,对林地资源的竞争最为激烈。因此,可以通过调整林分空间结构实现种间关系及林地资源的调控,以充分发挥森林生态系统的各项功能与价值。     

探讨我国森林野生动物红外相机监测规范

野生动物多样性是生物多样性监测与保护管理评价的关键指标, 因此对野生动物进行长期监测是中国森林生物多样性监测网络(CForBio)等大尺度生物多样性监测研究计划的一个重要组成部分。2011年以来, CForBio网络陆续在多个森林动态监测样地开展以红外相机来监测野生动物多样性。随着我国野生动物红外相机监测网络的初步形成, 亟待建立和执行基于红外相机技术的统一监测规范。基于3年来在我国森林动态监测样地红外相机监测的进展情况, 以及热带生态评价与监测网络针对陆生脊椎动物(兽类和鸟类)所提出的红外相机监测规范, 本文从监测规范和监测注意事项等方面探讨了我国森林野生动物红外相机监测的现状和未来。     

RNAi转基因作物安全评价研究进展

在秀丽隐杆线虫中首次发现双链RNA(dsRNA)能特异性地导致基因沉默(RNAi)现象后,人们开始大量地研究RNAi技术,并将其应用于功能基因的研究,来提高作物的抗性和改良遗传育种等。本文详细介绍了RNAi的技术原理,并且对RNAi技术与传统转基因技术的区别进行分析,阐述了该技术具有重要的生物学意义,以及在农作物害虫防治领域的占据独特优势。基于RNAi技术存在的潜在脱靶效应,从改良植物、靶标生物和生态环境的3个方面具体分析该技术可能存在的风险,为RNAi技术的风险评估提供参考。由于RNAi技术仍存在风险,为了维护生态多样性和保障人们的人身安全,应尽快建立起符合实际需求的安全性评价方法,本文针对RNAi转基因作物的环境安全和食用安全2个方面的评估方案进行概述。RNAi技术对减少害虫数量、提高水稻产量、降低种植成本以及减少化学农药污染、促进农业可持续发展来说具有重要意义,但该技术仍存在风险,需要进一步监管和研究,建立完善的生态评价系统,让RNAi技术在农业生产上发挥作用。