Pantolactams as androgen receptor antagonists for the topical suppression of sebum production

A series of pantolactam based compounds were identified as potent antagonists for the androgen receptor (AR). Those that possessed properties suitable for topical delivery were evaluated in the validated Hamster Ear Model. Several compounds were found to be efficacious in reducing wax esters, a major component of sebum, initiating further preclinical work on these compounds.     

Mode of action investigation for the antibacterial cationic anthraquinone analogs

Reported previously by our group, we have developed a novel class of antibacterial cationic anthraquinone analogs with superb potency (MIC <1μg/mL) against Gram positive (G+) pathogens including Methicillin-resistant Staphylococcus aureus (MRSA). However, most of these compounds only manifest modest antibacterial activity against Gram negative (G-) bacteria. Further investigation on the antibacterial mode of action using fluorogenic dyes reveals that these compounds exert two different modes of action that account for the difference in their antibacterial profile. It was found that most of the compounds exert their antibacterial activity by disrupting the redox processes of bacteria. At high concentration, these compounds can also act as membrane disrupting agents. This information can help to design new therapeutics against various bacteria.     

Total synthesis of solamargine

Solamargine, (25R)-3β-{O-α-l-rhamnopyranosyl-(1→2)-[O-α-l-rhamnopyranosyl-(1→4)]-β-d-glucopyranosyloxy}-22α-N-spirosol-5-ene, has been synthesized in 13 steps in a 10.5% overall yield starting from the naturally abundant diosgenin. Condensation of a partially protected glucopyranosyl donor with an oxaza-spiro moiety, which was formed in one-pot azido reduction, significantly improved the synthesis of desired molecule. The target compound exhibited good cytotoxic activities against tumor cells HeLa, A549, MCF-7, K562, HCT116, U87, and HepG2 with IC₅₀ ranging from 2.1 to 8.0 μM.     

晋西黄土区辽东栎、山杨树干液流比较研究

于2009年生长季(4—10月),应用TDP (Thermal Dissipation Probe) 热扩散探针技术,并结合同步测定的太阳辐射、大气温度、空气饱和水汽压差及大气相对湿度等气象因子,分析了晋西黄土区15年生辽东栎、山杨树干液流的昼夜变化及季节变化规律,建立了液流速率与气象因子的关系模型。结果表明：辽东栎和山杨树干液流速率昼夜变化显著,4月份和7月份峰值出现的时间不一致。4月份两个树种的峰值出现在清晨或夜间,而7月份树种树干液流速率于中午前后达到高峰。4月份两个树种夜间的树干液流速率明显大于白天,山杨的树干液流于中午前后接近于零。4月份,辽东栎和山杨树干液流速率的峰值分别为2.808 cm/h和1.188 cm/h,最小值为0.218 cm/h和0 cm/h,日平均液流速率为1.440 cm/h 和0.516 cm/h; 7月份,辽东栎和山杨树干液流速率的峰值分别为12.276 cm/h和 20.448 cm/h,最小值为0.144 cm/h和0.288 cm/h,日平均液流速率为3.656 cm/h 和6.328 cm/h。7月份阴雨天时,辽东栎的液流速率峰值较晴天小,日平均液流速率是晴天的0.95倍,对山杨是0.75倍。4月份两树种树干液流速率的月平均值最低,只有1.106 cm/h和0.626 cm/h;6月份达最高值5.112 cm/h和8.214 cm/h,分别是4月份的4.62倍和13.12倍。生长季(4—10月)的林分林木总蒸腾耗水量对于辽东栎林为201.14 mm,山杨林为56.43 mm,辽东栎林为山杨林的3.56倍。统计分析表明,影响树干液流速率的主要因子对辽东栎是大气温度和太阳辐射,对山杨是太阳辐射和空气饱和水汽压差。     

环境因子和干扰强度对高寒草甸植物多样性空间分异的影响

采用样带与样地结合的方法在三江源自然保护区的核心区沿海拔梯度在阴坡、阳坡分别进行草本植被调查,通过因子分析和偏相关分析研究丰富度指数、多样性指数与环境梯度（包括海拔梯度、裸斑面积、坡度、土壤总碳、总氮含量、土壤pH值、土壤总可溶性盐含量）和干扰强度（鼠类干扰强度、放牧强度）之间的关系。研究结果表明：杂类草丰富度指数（DMa杂）与总物种丰富度指数（DMa总）极显著相关（P<0.01）;阳坡DMa杂和DMa总均呈现“中海拔膨胀”现象,阴坡DMa杂和DMa总与海拔梯度呈正相关,莎草科和禾本科的丰富度指数（DMa莎和DMa禾）随海拔升高并无明显规律;通过主成分分析,及偏相关分析,第一主成分（裸斑面积、鼠类干扰和放牧强度）与除莎草科Margalef丰富度指数、禾本科Simpson指数和禾本科Pielou均匀度指数外的其他草地多样性指数均显著相关,是影响阳坡草地植物多样性的主要因子,土壤总碳、总氮含量对阳坡禾本科类群的多样性指数和均匀度指数有极显著影响,土壤pH值、TDS含量和坡度对阳坡莎草科类群的丰富度有显著影响;海拔梯度、土壤总碳、总氮以及pH值对阴坡草本植物群落的多样性影响较大。研究结论认为,植物群落生物多样性的空间分异特征是地理环境、土壤环境以及干扰强度等因素综合作用的结果。无干扰或干扰较弱时,物种多样性主要受土壤环境状况所影响;而在强干扰存在条件下,干扰强度对物种丰富度和多样性的影响比环境因子更显著;遏制高寒草甸植物多样性降低应首先控制放牧及鼠类等强干扰活动。     

噬菌体展示HIV-1 Tat38-61碱性区51和55位随机突变体文库的构建

为了构建噬菌体展示Tat38-61(51N/55N) 碱性区突变体文库,进一步研究HIV-1 Tat38-61表位的分子进化筛选,采用含随机核苷酸序列的引物,通过Overlap PCR的方法获得51和55位氨基酸随机突变的全长Tat编码序列,再以此为模板PCR扩增出两端含有Xba I识别序列的Tat38-61突变体片段HIV-1 Tat38-61(51N/55N),克隆至噬菌体展示载体pCANTAB5S上,转化大肠杆菌TG1,经M13K07辅助噬菌体拯救,构建噬菌体展示Tat38-61(51N/55N) 碱性区突变体文库。结果显示文库的库容量为5.0×106,滴度为2.65×1012 TU/mL,阳性克隆率为56.50％;序列分析显示文库中51、55位核苷酸与氨基酸均呈随机性分布,达到了对文库进行分子进化筛选的要求,为获得可用作疫苗候选物的新型Tat突变体奠定基础。     

Ellipticines and 9-acridinylamines as inhibitors of D-alanine:D-alanine ligase

D-Alanine:D-alanine ligase (Ddl), an intracellular bacterial enzyme essential for cell wall biosynthesis, is an attractive target for development of novel antimicrobial drugs. This study focused on an extensive evaluation of two families of Ddl inhibitors encountered in our previous research. New members of both families were obtained through similarity search and synthesis. Ellipticines and 9-acridinylamines were both found to possess inhibitory activity against Ddl from Escherichia coli and antimicrobial activity against E. coli and Staphylococcus aureus. Ellipticines with a quaternary methylpyridinium moiety were the most potent among all studied compounds, with MIC values as low as 2 mg/L in strains with intact efflux mechanisms. Antimicrobial activity of the studied compounds was connected to membrane damage, making their development as antibacterial drug candidates unlikely unless analogues devoid of this nonspecific effect can be discovered.     

基于地表温度-植被指数关系的地表温度降尺度方法研究

地表温度(Land Surface Temperature, LST)在空间上和时间上均存在很大的差异性。而通过卫星遥感技术来监测地表温度存在着空间分辨率和时间分辨率上的矛盾:空间分辨率高的卫星时间分辨率低,反之亦然。为了解决这个矛盾,首先利用TsHARP (An algorithm for sharpening thermal imagery)温度降尺度方法将LST_MODIS,1km(1km MODIS(Moderate-resolution Imaging Spectroradiometer)地表温度)图像(2004年9月9日上午)降尺度为LST_MODIS,500m(500m MODIS地表温度)图像。为了对降尺度LST_MODIS,500m图像进行验证,对研究区内同一天(2004年9月9日上午)的ETM图像的第6波段的辐亮度值升尺度到500m后,再利用Sobrino ETM(Enhanced Thematic Mapper)温度反演方法反演得到LST_ETM,500m(500m ETM地表温度)图像,将LST_ETM,500m图像作为当日地表温度的实测值,对降尺度LST_MODIS,500m图像的降尺度效果进行验证。对比结果表明降尺度LST_MODIS,500m图像更加精细刻画LST_MODIS,1km图像在空间上的分布格局;定量对比3种降尺度LST_MODIS,500m和LST_ETM,500m的RMSE分别为0.786、1.002,0.754℃,降尺度结果达到预期效果。     

BST-2抑制HIV-1病毒样颗粒释放的研究

BST-2是最近发现的可以抑制成熟HIV-1(human immunodeficiency virus,HIV)病毒颗粒从哺乳动物细胞表面释放的宿主因子,随之发现其也可以抑制多种包膜病毒的释放。本研究采用密码子优化的表达HIV-1 gag和gag-pol蛋白的质粒所形成的病毒样颗粒作为研究对象,观测BST-2对这两种病毒样颗粒(Virus-like particle,VLP)的释放抑制情况及其作用机制。结果发现,瞬时表达和稳定表达的BST-2均可以显著抑制病毒样颗粒从哺乳动物细胞释放,同时发现这两种病毒样颗粒(gag/gag-pol)的释放都可以被BST-2抑制;而且,HIV-1中Vpu蛋白可以拮抗BST-2抑制HIV病毒样颗粒释放的作用,另外,通过化学试剂和酶学方法处理,确证BST-2可以被包装进病毒样颗粒中。     

Sp1真核表达载体的构建及对USP22基因转录活性的影响

目的 克隆人sp1基因,构建真核表细胞达载体pVAX-Sp1,研究其对USP22基因转录活性的影响.方法 Trizol试剂快速提取人肝癌细胞株HepG2总RNA,经RT-PCR扩增Sp1基因序列,与pVAX1真核表达载体连接;测序、酶切鉴定重组载体;pVAX1-Sp1与含USP22启动子的萤光素酶报告质粒共转染HepG2细胞,双萤光素酶报告系统检测萤光素酶活性表达.结果 测序及酶切结果显示重组质粒pVAX1-Sp1构建成功;高表达sp1可使USP22启动子的转录活性降低（P＜0.01）.结论 成功构建了sp1真核表达质粒,sp1对USP22启动子具有转录抑制作用.