Small molecule biaryl FSH receptor agonists. Part 1: Lead discovery via encoded combinatorial synthesis

High-throughput screening of two million compounds in 37 distinct encoded combinatorial libraries using FSH receptor transfected cells provided small molecule agonists such as 1 (EC(50)=3 microM) and 2 (EC(50)=3.9 microM), based on which a focused combinatorial library with a total of 31372 compounds was designed, synthesized, and screened to reveal 72 novel biaryl FSH receptor agonists such as 8a-c as well as a unique combinatorial SAR.     

区域土地整理生态环境评价及其时空配置

土地整理生态环境评价及其时空配置是进行区域土地整理的科学基础.文中以山东省青州市为例,在深入分析土地整理特点和青州市自然社会条件的基础上,构建了土地整理生态环境评价指标体系和评价模型;运用综合指数法和GIS技术取得各评价单元综合得分,在此基础上进行了区域土地整理时空配置.结果表明,青州市耕地和未利用地共1 446 km²,近期土地生态环境整理区主要分布于平原区的西北部,占耕地和未利用地总面积的15.35%,中期整理区分布于平原区的西北部和中部,占13.58%,远期整理区分布在平原区的北部,40.71%,不整理区分布于丘陵区,占30.36%.研究结果可为青州土地整理规划和实施提供科学依据.     

小黑瓢虫与两种猎物作用系统研究:选择捕食作用

研究了小黑瓢虫与烟粉虱及红蜘蛛两种猎物作用系统中 ,小黑瓢虫雌成虫对两种猎物卵的选择捕食作用。结果表明 :当两种猎物共存时 ,小黑瓢虫雌成虫对烟粉虱卵在低密度下不表现喜好性 ,而在中等密度和高密度下表现正喜好性 ,对红蜘蛛卵在各密度下均不表现喜好性。对烟粉虱卵的转换效应会由于总猎物密度的不同而呈现不同的效应 ,即在低密度 (15 0粒 )时无转换行为 ,在中等密度 (30 0粒 )时有负转换行为 ,在高密度 (6 0 0粒 )时有正转换行为。而对红蜘蛛卵则在各总猎物密度下均呈现负转换效应。同时组建了两种猎物共存时 ,小黑瓢虫雌成虫对猎物的总捕食作用方程及对每一种猎物类型的捕食作用方程 ,分析了两种猎物共存时 ,小黑瓢虫雌成虫对各猎物寻找效应的变化情况。     

miR-135b Contributes to the Radioresistance by Targeting GSK3β in Human Glioblastoma Multiforme Cells

Radioresistance remains a major challenge in the treatment of glioblastoma multiforme (GBM). Recent data strongly suggests the important role of miRNAs in cancer progression and therapeutic response. Here, we have established a radioresistant human GBM cell line U87R derived from parental U87 and found miR-135b expression was upregulated in U87R cells. miR-135b knockdown reversed radioresistance of U87R cells, and miR-135b overexpression enhanced radioresistance of U87 cells. Mechanically, bioinformatics analysis combined with experimental analysis demonstrated GSK3β (Glycogen synthase kinase 3 beta) was a novel direct target of miR-135b. Moreover, GSK3β protein expression was downregulated in U87R cells and restored expression of GSK3β increased radiosensitivity of U87R cells. In addition, clinical data indicated that the expression of miR-135b or GSK3β was significantly association with IR resistance of GBM samples. Our findings suggest miR-135b is involved in the radioresistance of human GBM cells and miR-135b-GSK3β axis may be a novel candidate for developing rational therapeutic strategies for human GBM treatment.     

Role of Sciellin in gallbladder cancer proliferation and formation of neutrophil extracellular traps

Apart from primary tumor development and metastasis, cancer-associated thrombosis is the second cause of cancer death in solid tumor malignancy. However, the mechanistic insight into the development of gallbladder cancer (GBC) and cancer-associated thrombosis remains unclear. This study aimed to investigate the mechanistic role of Sciellin (SCEL) in GBC cell proliferation and the development of venous thromboembolism. The expression level of SCEL was determined by immunohistochemical staining. Roles of SCEL in gallbladder cancer cell were determined by molecular and cell biology methods. SCEL was markedly upregulated in GBC and associated with advanced TNM stages and a poor prognosis. Furthermore, SCEL interacted with EGFR and stabilized EGFR expression that activates downstream PI3K and Akt pathway, leading to cell proliferation. In addition, SCEL induces tumor cell IL-8 production that stimulates the formation of neutrophil extracellular traps (NETs), accelerating thromboembolism. In xenografts, SCEL-expressing GBCs developed larger tumors and thrombosis compared with control cells. The present results indicate that SCEL promotes GBC cell proliferation and induces NET-associated thrombosis, thus serving as a potential therapeutic target.Subject terms: Cancer microenvironment, Tumour biomarkers