1株多重耐药肺炎克雷伯菌耐药基因和整合子、转座子遗传标记研究

目的 了解多重耐药肺炎克雷伯菌的耐药基因存在状况和遗传学背景。方法 聚合酶链反应(RCR)法对多重耐药的肺炎克雷伯菌进行β-内酰胺酶基因、氨基糖苷类修饰酶基因、质粒AmpC酶基因、qacEΔ1-sull耐消毒剂和磺胺基因、整合子遗传标记(整合酶基因)、Tn21/Tn501转座子遗传标记(汞离子还原酶基因)检测。结果 TEM、SHV型β-内酰胺酶基因, DHA型质粒AmpC酶基因,aac(6′)-1型氮基糖苷类修饰酶基因,qacEΔ1-sul1耐消毒剂和磺胺基因,整合子遗传标记(intI1整合酶基因),Tn21/Tn501转座子遗传标记(merA汞离子还原酶基因)检测阳性。结论 多重耐药肺炎克雷伯菌存在多种耐药基因和Ⅰ类整合子、Tn21/Tn501转座子。     

青藏高原主要植被类型生物生产量的比较研究

以１８种群落类型的实测为数据和１０１３块森林测树样地的估算数据为基础,首次系统地分析和比较了青藏高原主要植被类型生物生产量的构成规律及分布格局。亚高山暗针叶 生物量一般在３００ｔ／ｈｍ＾２以上,最高可达约１６００ｔ／ｈｍ＾２,叶生物量８～３９ｔ／ｈｍ＾２,根茎比０．１～０．２,生产量８～１３ｔ／ｈｍ＾２．ａ;高山灌丛类型生物量２０～４０ｔ／ｈｍ＾２,叶生物量３～６ｔ／ｈｍ＾２,根茎比０．４～０．８     

高通量药物筛选技术的研究现状及光学编码技术在其中的应用

高通量药物筛选是创新药物研究的重要内容,本文综合介绍了高通量药物筛选的研究现状及发展趋势,及目前遇到的一些问题,如随着样品的体积达到微升量级时,目前所采用的孔板筛选遇到了一些难以克服的障碍,使化合物和药物靶点的相互作用难以进行等。针对这些问题,本文介绍了一种新的以自编码光谱识别微球为基础的新型高通量药物筛选技术在高通量药物筛选中的应用,同时简要介绍了我们目前所做的一些工作。     

藏酋猴精液深低温冻存的研究──不同的冷冻程序、冷冻稀释保存液冻存效果的比较

以存活率（ＳＲ）、复苏运动度（ＲＭ）、ＳＰＡ为精子活力检测指标，对四种冷冻程序ＰＳＦ、Ｈ３Ｐ、ＬＰ、ＭＤＰ和卵黄的、无卵黄的冷冻稀释保存液进行了藏酋猴（Ｍａｃａｃａ ｔｈｉｂｅｔａｎａ）精液冻存比较研究。 ＰＳＦ的ＳＲ为９０．１±１．９％，ＲＭ为６３．８±２．８％，显著高于其他三种冷冻程序（Ｐ＜０．０１）。卵黄冷冻稀释保存液（ＭＤＭ）的ＳＲ（９５． ４±１．３％）和ＲＭ（８８．０±１０．２％）显著高于无卵黄防冻液（ＦＣＳ－Ｇ／ＴＨ）的ＳＲ（９０．１±１．９％）和ＲＭ（６３．６±２．８％），但前者在复苏一小时后，ＲＭ（１２．５±１．６％）明显低于后者的ＲＭ（５４． ７±２． ２％）。用 ＦＣＳ～Ｇ／ＴＨ冻存的精液经 ＳＰＡ检测，其穿透率为新鲜精子的 ５１． ９％。结果提示：１）慢速降温冷冻程序适于藏酋猴精液冻存；２）卵黄冷冻稀释保存液能较好地保存藏酋猴精液的活动度；而无卵黄防冻液则有利于延长其冷冻精子的运动寿命。这可能与两者的稀释液及所含的脂蛋白不同有关。     

循环包装回收技术在筛选肝癌细胞相关耐药基因中的应用

肝癌先天性多表达多药耐药基因,严重影响肝癌的化疗效果,筛选肝癌细胞中的耐药基因,研究其耐药机制有助于提高肝癌化疗效果,提高肝癌的治愈率。首先构建肝癌细胞逆转录病毒的cDNA文库,感染成纤维细胞,使得逆转录病毒基因整合进细胞,加药筛选,存活细胞中的基因再次包装成病毒,用于下一轮筛选。采用循环包装回收(Cyclical packaging rescue,CPR)技术进行肝癌细胞耐药基因的筛选即是通过病毒包装将基因从细胞中钓取出来,相比于常规筛选方法,仅通过一轮筛选可能会出现很多假阳性基因,采用CPR技术则是通过多轮筛选,很大程度减少了假阳性细胞的出现。通过该方法经过四轮筛选获得核糖体蛋白S11(RPS11)、核糖体蛋白L6(RPL6)、核糖体蛋白L11(RPL11)、核糖体蛋白L24(RPL24)等几种基因,经初步检测,增加了细胞的耐药性。     

青藏公路沿线白昼交通运输等人类活动对藏羚羊迁徙的影响

To study effects of traffic during daytime and other human activities, we conducted surveys on the migration of Tibetan antelope Pantholops hodgsoni along the Qinghai-Tibet highway between Kunlun Mountain Pass to Wudaoliang,using line transects (LT) from June to September in 2001 and 2002, Data were collected for 64 days with 17 days in 2001, and 47days in 2002. The Stationary Observation Method (SOM) was also adopted for the investigation of status of the disturbance from traffic when antelopes passing the highway and the traffic situation from August 6 to 28 (6 : 30-19: 00), 4 to 20 (6: 00- 18: 00) and from December 21 to 29 (9：00- 19: 00) in 2002. The results showed that,the period of migration in 2002 was more prolonged than in 2001, and it took at least 45 min for each group to cross the highway, with success ratio of only 30.2 %, and the traffic flow of summer daytime was 76/h, while the winter‘s traffic flow was 29/h. Highway and rail traffic should be managed during daylight hours from June to August, to allow for the migration of the antelopes. Also conservation education and a further survey should be emphasized for the protection on the species [Acta Zoologica Sinica 50 (4) : 669-674, 2004].     

去甲基化药物治疗肿瘤新进展

人类肿瘤的发生是多基因、多步骤共同作用的结果,抑癌基因在这一进程中扮演着重要的角色。最新研究表明,在肿瘤形成过程中,启动子区异常高甲基化的抑癌基因（包括几个关键基因）始终保持沉默、功能丧失,而启动子区去甲基化后抑癌基因则可以重新激活,其产物恢复表达。据此,人们开发出了去甲基化药物,并已应用于临床治疗及研究,结果证实去甲基化药物是一类安全、有效的抗肿瘤新药。随着研究的不断深入,必将有更多的去甲基化药物问世。     

Modification of a novel angiogenic peptide, AG30, for the development of novel therapeutic agents

We previously identified a novel angiogenic peptide, AG30, with antibacterial effects that could serve as a foundation molecule for the design of wound-healing drugs. Toward clinical application, in this study we have developed a modified version of the AG30 peptide characterized by improved antibacterial and angiogenic action, thus establishing a lead compound for a feasibility study. Because AG30 has an α-helix structure with a number of hydrophobic and cationic amino acids, we designed a modified AG30 peptide by replacing several of the amino acids. The replacement of cationic amino acids (yielding a new molecule, AG30/5C), but not hydrophobic amino acids, increased both the angiogenic and the antimicrobial properties of the peptide. AG30/5C was also effective against methicillin-resistant Staphylococcus aureus (MRSA) and antibiotic-resistant Pseudomonas aeruginosa. In a diabetic mouse wound-healing model, the topical application of AG30/5C accelerated wound healing with increased angiogenesis and attenuated MRSA infection. To facilitate the eventual clinical investigation/application of these compounds, we developed a large-scale procedure for the synthesis of AG30/5C that employed the conventional solution method and met Good Manufacturing Practice guidelines. In the evaluation of stability of this peptide in saline solution, RP-HPLC analysis revealed that AG30/5C was fairly stable under 5°C for 12 months. Therefore, we propose the use of AG30/5C as a wound-healing drug with antibacterial and angiogenic actions.     

Current and emerging commercial optical biosensors.

The field of commercial optical biosensors is rapidly evolving, with new systems and detection methods being developed each year. This review outlines the currently available biosensor hardware and highlights unique features of each platform. Affinity-based biosensor technology, with its high sensitivity, wide versatility and high throughput, is playing a significant role in basic research, pharmaceutical development, and the food and environmental sciences. Likewise, the increasing popularity of biosensors is prompting manufacturers to develop new instrumentation for dedicated applications. We provide a preview of some of the emerging commercial systems that are dedicated to drug discovery, proteomics, clinical diagnostics and routine biomolecular interaction analysis.     

Diffusional interaction behavior of NSAIDs in lipid bilayer membrane using molecular dynamics (MD) simulation: Aspirin and Ibuprofen

In this research, for the first time, molecular dynamics (MD) method was used to simulate aspirin and ibuprofen at various concentrations and in neutral and charged states. Effects of the concentration (dosage), charge state, and existence of an integral protein in the membrane on the diffusion rate of drug molecules into lipid bilayer membrane were investigated on 11 systems, for which the parameters indicating diffusion rate and those affecting the rate were evaluated. Considering the diffusion rate, a suitable score was assigned to each system, based on which, analysis of variance (ANOVA) was performed. By calculating the effect size of the indicative parameters and total scores, an optimum system with the highest diffusion rate was determined. Consequently, diffusion rate controlling parameters were obtained: the drug–water hydrogen bond in protein-free systems and protein–drug hydrogen bond in the systems containing protein.