1981～2005年中国H1N1甲型流感病毒血凝素基因的HA1演变特征

为了解1981~2005年我国H1N1甲型流感病毒血凝素基因的HA1演变特征,选取H1N1甲型流感病毒370株,提取病毒RNA,经逆转录和聚合酶链反应扩增HA1并测序,测定的序列用生物信息软件分析,与GenBank中相关序列比较,并对推导的编码氨基酸序列进行基因特性分析。结果表明:HA1氨基酸的变异表现为抗原决定簇4个区均有变异,Sb区和Ca区变化较大;HA1受体结合位点(RBS)的前壁130环的第134位赖氨酸从1991年起在部分毒株HA1序列上开始缺失,以后缺失株逐步增多,自2000年起测定的所有毒株上该氨基酸全部缺失,同时这些缺失株的第137位氨基酸也全部由苏氨酸替换为丝氨酸;糖基化位点从增多到减少,最后稳定在7个;1981~2004年我国H1N1甲型流感病毒血凝素HA1编码的氨基酸在种系发育树上同年代基本呈现集中分布,与时间和地域无关,2005年毒株分成两个分支在时间上有明显差异。     

云南脂松香制备光学纯去氢枞酸的研究

以松节油作反应溶剂,在硫、碘的催化作用下云南脂松香经催化异构化、脱氢成为脱氢松香酸,通过进一步的提取、纯化等步骤可直接得到纯度高达96%以上的光学纯的去氢枞酸,其收率为26.6g/100g(松香)。     

药用真菌金耳的rDNA ITS序列分析与鉴别

研究了两个居群的金耳Tremella aurantialba以及近似品的rDNAITS区碱基全序列的特征及其差异,首次报道了金耳的ITS和5.8SrDNA完整序列,序列总长度为467~468,长度变异较少。聚类分析表明两个居群金耳亲缘关系非常密切,金耳药材和近似品金黄银耳形成一个稳定的独立分支,近似品黄金银耳形成另一个分支。ITS序列的差异为金耳的鉴别提供了可靠的分子标记,为金耳菌类药材基原入药建立了遗传基础。     

越鞠丸石油醚提取物的气相色谱-质谱分析

采用气相色谱-质谱联用技术对中药复方越鞠丸石油醚提取物中的成分进行鉴定,共鉴定出60种成分,并采用峰面积归一化法确定了各成分的相对含量。     

哺乳动物早期胚胎端粒和端粒酶重编程

端粒位于真核染色体末端,是稳定染色体末端的重要元件。端粒酶(TER)是一种特殊的细胞核糖核蛋白(RNP)反转录酶(RT),其核心酶包括蛋白亚基和RNA元件。在DNA复制过程中的端粒丢失可以被有活性的端粒酶修复回来。哺乳动物端粒酶在发育中受调控,端粒的重编程可能是由于早期胚胎不同时期的端粒酶活性而造成的。因此,研究端粒和端粒酶重编程在早期胚胎发育中是非常重要的。该文综述了端粒和端粒酶的结构和功能,及其与哺乳动物早期胚胎发育的关系,并在此基础上展望了端粒和端粒酶在克隆动物胚胎发育的基础研究。     

旋覆花素抑制血管内皮剥脱诱导的粘附分子表达

目的观察旋覆花素对内皮剥脱诱导的新生内膜形成过程中血管壁粘附分子OPN、ICAM-1、ILK表达的影响,为寻找该药物抑制新生内膜形成的作用靶标提供实验依据。方法采用主动脉球囊损伤后血管狭窄动物模型,用免疫组织化学和Western Blot方法分别检测血管壁中骨桥蛋白(osteopontin,OPN)、细胞间粘附分子-1(intercellular adhesion molecule-1,ICAM-1)、整合素偶联激酶(integrin-linked kinase,ILK)的表达变化及旋覆花素对其的影响。结果血管内皮剥脱可诱导血管壁平滑肌细胞大量增生,新生内膜呈弥漫性增厚,血管损伤局部组织中OPN、ICAM-1、ILK的表达均比正常对照组明显升高(P<0.05)。旋覆花素治疗组在球囊损伤后,血管内膜增生程度显著减轻,血管壁OPN、ICAM-1、ILK的表达均比模型组明显降低(P<0.05)。结论旋覆花素减缓新生内膜形成的效应与其抑制粘附分子的表达、阻断粘附分子信号传递有关。     

Inhibitors of HCV NS5B polymerase: synthesis and structure-activity relationships of unsymmetrical 1-hydroxy-4,4-dialkyl-3-oxo-3,4-dihydronaphthalene benzothiadiazine derivatives

Substituted 1-hydroxy-4,4-dialkyl-3-oxo-3,4-dihydronaphthalene benzothiadiazine derivatives were investigated as inhibitors of genotype 1 HCV polymerase. Structure-activity relationship patterns for this class of compounds are discussed. It was found that the saturated alkane dialkyl units provided the most active analogs.     

Discovery of selective imidazole-based inhibitors of mammalian 15-lipoxygenase: highly potent against human enzyme within a cellular environment

A series of 2,4,5-tri-substituted imidazoles has proven to be highly potent in inhibiting mammalian 15-lipoxygenase (15-LO) with excellent selectivity over human isozymes 5- and P-12-LO. Non-symmetrical sulfamides (e.g., 21a-n) were found to be suitable replacements for the earlier arylsulfonamide-containing members of this series (e.g., 2, 14a-p). Several members of these series also demonstrated potent inhibition of human 15-LO in a cell-based assay.     

Synthesis and characterization of pyrrolidine derivatives as potent agonists of the human melanocortin-4 receptor

A series of trans-4-phenylpyrrolidine-3-carboxamides were synthesized and characterized as potent ligands of the human melanocortin-4 receptor. Interestingly, a pair of diastereoisomers 20f-1 and 20f-2 displayed potent functional agonist and antagonist activity, respectively. Thus, the 3S,4R-compound 20f-1 possessed a K(i) of 11nM and an EC(50) of 24nM, while its 3R,4S-isomer 20f-2 exhibited a K(i) of 8.6 and an IC(50) of 65nM. Both compounds were highly selective over other melanocortin receptor subtypes. The MC4R agonist 20f-1 also demonstrated efficacy in diet-induced obese rats.     

Synthesis and structure-activity relationships of spirohydantoin-derived small-molecule antagonists of the melanin-concentrating hormone receptor-1 (MCH-R1)

The design, synthesis, and SAR of a series of substituted spirohydantoins are described. Optimization of an in-house screening hit gave compounds that exhibited potent binding affinity and functional activity at MCH-R1.