Abnormal kynurenine pathway of tryptophan catabolism in cardiovascular diseases

Kynurenine pathway (KP) is the primary path of tryptophan (Trp) catabolism in most mammalian cells. The KP generates several bioactive catabolites, such as kynurenine (Kyn), kynurenic acid (KA), 3-hydroxykynurenine (3-HK), xanthurenic acid (XA), and 3-hydroxyanthranilic acid (3-HAA). Increased catabolite concentrations in serum are associated with several cardiovascular diseases (CVD), including heart disease, atherosclerosis, and endothelial dysfunction, as well as their risk factors, including hypertension, diabetes, obesity, and aging. The first catabolic step in KP is primarily controlled by indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO). Following this first step, the KP has two major branches, one branch is mediated by kynurenine 3-monooxygenase (KMO) and kynureninase (KYNU) and is responsible for the formation of 3-HK, 3-HAA, and quinolinic acid (QA); and another branch is controlled by kynurenine amino-transferase (KAT), which generates KA. Uncontrolled Trp catabolism has been demonstrated in distinct CVD, thus, understanding the underlying mechanisms by which regulates KP enzyme expression and activity is paramount. This review highlights the recent advances on the effect of KP enzyme expression and activity in different tissues on the pathological mechanisms of specific CVD, KP is an inflammatory sensor and modulator in the cardiovascular system, and KP catabolites act as the potential biomarkers for CVD initiation and progression. Moreover, the biochemical features of critical KP enzymes and principles of enzyme inhibitor development are briefly summarized, as well as the therapeutic potential of KP enzyme inhibitors against CVD is briefly discussed.     

试论滇文化青铜贮贝器的“纪念碑性”

中国的青铜时代又可称为“礼制艺术时代”。这一时期的时代特点是用青铜材料铸造各种“礼器”，这些礼器具有逐渐丰富的以政治和宗教为核心的“纪念碑性”，也可视之为另一种意义上的“纪念碑”。青铜贮贝器是滇文化时期的重器，其纪念碑性来源于铜鼓、铜桶等礼器，最初体现了滇人对权力与财富的占有。在此基础上表达了滇人在军事、宗教与社会生活等诸多方面的观念。从贮贝器纪念碑性产生、发展到衰落的历程可看出，滇文化时期的滇池区域也具有中国青铜时代的一般特点。     

中俄（NSFC-RFBR）基础研究合作现状分析和未来合作展望

本文回顾了2003—2012年中俄（NSFC-RFBR）双边合作项目的背景、类别与机制。对双边合作交流项目和双边研讨会项目资助情况进行了统计分析,总结了项目资助成果。针对存在的问题与不足进行了思考,并对加强双方未来合作的途径提出了若干建议。为双方进一步提升合作水平,促进实质性双边合作提供了信息参考。     

钢铁企业订货系统建模与仿真分析

订货模型存在于大多数的公司中，用以根据销售情况组织公司生产。供应链中的企业大多数是根 据销售组织生产的，企业中的订货模型尤为重要。以钢铁企业分销商订货模型为例，运用系统动力学方法分 析了该订货模型，并对现实情况进行了仿真分析，提出了钢铁企业分销商订货策略。     

激光相变热处理对TC４电子束焊缝残余应力的影响

利用CO２激光相变热处理技术对TC４钛合金电子束焊缝进行了处理,研究了激光功率、光斑直径、 辅助气体等激光工艺参数对电子束焊缝残余应力分布的影响。实验结果表明,激光相变热处理改善了焊缝残余 应力的分布,使焊缝表面残余应力由拉应力转变为压应力,其压应力值随着激光功率的增加而增大,随着激光 光斑直径的减小而增加;辅助气体为O２时残余压应力值比辅助气体为N２大３０～４０MPa,激光相变热处理显著 提高了TC４钛合金电子束焊缝的残余压应力及其使用寿命。     

香格里拉区域大气本底站环境特征初探

介绍了香格里拉大气本底站的站址地理分布特征,分析和总结了近年来的基本气象要素特征,通过轨迹-聚类方法分析了影响该站的气流来源.轨迹分析结果表明:香格里拉区域大气本底观测站对于探讨南亚地区的大气成分远距离输送对我国西南地区的环境影响具有独特的作用.     

Crystal structure of the β2 adrenergic receptor-Gs protein complex

G protein-coupled receptors (GPCRs) are responsible for the majority of cellular responses to hormones and neurotransmitters as well as the senses of sight, olfaction and taste. The paradigm of GPCR signalling is the activation of a heterotrimeric GTP binding protein (G protein) by an agonist-occupied receptor. The β(2) adrenergic receptor (β(2)AR) activation of Gs, the stimulatory G protein for adenylyl cyclase, has long been a model system for GPCR signalling. Here we present the crystal structure of the active state ternary complex composed of agonist-occupied monomeric β(2)AR and nucleotide-free Gs heterotrimer. The principal interactions between the β(2)AR and Gs involve the amino- and carboxy-terminal α-helices of Gs, with conformational changes propagating to the nucleotide-binding pocket. The largest conformational changes in the β(2)AR include a 14 ? outward movement at the cytoplasmic end of transmembrane segment 6 (TM6) and an α-helical extension of the cytoplasmic end of TM5. The most surprising observation is a major displacement of the α-helical domain of Gαs relative to the Ras-like GTPase domain. This crystal structure represents the first high-resolution view of transmembrane signalling by a GPCR.     

The Moment of China's Internet Companies Management Method

文章介绍了我国互联网企业的资本结构后,从市场、技术、人力资源3个方面分析了我国互联网企业的管理之道,最后讨论了互联网企业文化建设的不足和原因.以及如何提高策略.     

Identification of susceptibility genes loci associated with type 2 diabetes

In this study, we selected 10 susceptible SNPs loci to investigate their contribution to susceptibility to type 2 diabetes in Han Chinese among Hubei population. We genotyped SNPs rs5219, rs1801282, rs1470579, rs1111875, rs1081661, rs7754840, rs4506565, rs13266634, rs4402960, and rs5643981 by using the method of polymerase chain reaction-ligase detection reaction (PCR-LDR). In a case-control study, we have genotyped the 10 candidate susceptibility SNP loci, and here, we reported that the SNP rs5219 in KCNJ1...     

基于Pro/E的车用CNG气瓶装卸机械设计

针对车用CNG气瓶定检时人工装卸气瓶效率低、安全性差等问题,提出设计一种CNG气瓶装卸机械.该装置包括升降小车和机械抓手两部分,可实现对气瓶的抓取、旋转、升降、进退等动作.基于Pro/Engineer的三维建模功能,建立该机械装置、气瓶及车厢的3D模型,进行模拟装卸的结构干涉分析.结果表明该机械结构简单、操作方便,具有...