秦岭山区中国大鲵生境因子的选择

通过对秦岭山区中国大鲵(Andrias davidianus)栖息地生境因子调查、统计,利用R语言分析了各因子与大鲵生境选择的相关性,得出研究结果:秦岭山区影响大鲵生存的主要因子为栖息地类型(相关系数r=0.98),其次是水温(相关系数r=-0.8)、河岸坡度(r=-0.6)和p H (r=-0.6);浊度(相关系数r=0.5)、电导率(r=0.49)、DO(r=0.4)、人为干扰(r=0.35)和海拔(r=0.31)对大鲵分布影响不大。研究结果为探讨中国大鲵对野生环境的适应性选择提供了参考。     

Vegetation and environment changes inferred from pollen records since 3000 cal. yr BP in Kanas wetland,Xinjiang

Aims Climate change can significantly affect the vegetation worldwide. Thus, paleovegetation and paleoclimate reconstruction should consider the quantitative relationship between modern vegetation and climate. The specific objectives of this study were (i) to assess the influence of environmental variables on pollen assemblages in the Kanas region, (ii) to reconstruct the evolution of vegetation over the past 3000 years using pollen records and (iii) to quantify historical climate change (including mean annual temperature and total annual precipitation) using a weighted averaging partial least squares regression method (WAPLS) applied to fossil pollen data from the Kanas wetland in Xinjiang, China.     

Design,synthesis and biological evaluation of novel human monoamine oxidase B inhibitors based on a fragment in an X-ray crystal structure

Herein we report our efforts of developing reversible selective hMAO-B inhibitors based on isatin, a fragment in an X-ray crystal structure. Five different scaffolds were designed and many compounds were synthesized. Among them, compound A3 demonstrated very high potency and isoform selectivity against hMAO-B, 11 and 13 times more potent (IC₅₀?=?3?nM) and 23.64 and 6.8 times more selective than the marked drugs, selegiline and safinamide. However, the endeavors to modify the polar 3-one group of isatin, that is in a hydrophobic environment in the binding site of hMAO-B, to small nonpolar hydrophobic groups did not bring about improved hMAO-B inhibitors, which may challenge our understanding of molecular interactions and molecular recognition in biological systems.     

Synthesis and biological evaluation of BMS-986120 and its deuterated derivatives as PAR4 antagonists

BMS-986120 is a PAR4 antagonist that is being investigated as an antiplatelet agent in phase I clinical trial. An improved synthesis of BMS-986120 has been developed. Based on the novel synthetic approach to BMS-986120, a series of deuterated derivatives of BMS-986120 have been synthesized and biologically evaluated to search for more potent antiplatelet agents. The in vitro antiplatelet assay by turbidimetry demonstrated that PC-2 and PC-6 had IC₅₀ values of 6.30?nM and 6.97?nM, respectively, versus BMS-986120 with an IC₅₀ of 7.80?nM. The result of in vitro metabolic stability study showed that all of the deuterated compounds had similar half-life (T_1/2) and intrinsic clearance (Clint) in comparison with BMS-986120. Further probing the metabolic profile of BMS-986120 is worth being conducted.     

Leucine ureido derivatives as aminopeptidase N inhibitors using click chemistry. Part II

Aminopeptidase N (APN) has been proved to be deeply associated with cancer angiogenesis, metastasis and invasion. Therefore, APN gains increasing attention as a promising anti-tumor target. In the current study, we report the design, synthesis, biological evaluation and structure-activity relationship of one new series of leucine ureido derivatives containing the 1,2,3-triazole moiety. Among them, compound 31f was identified as the best APN inhibitor with IC₅₀ value being two orders of magnitude lower than that of the positive control bestatin. Compound 31f possessed selective cytotoxicity to several tumor cell lines over the normal cell line human umbilical vein endothelial cells (HUVECs). Notably, when combined with 5-fluorouracil (5-Fu), 31f exhibited synergistic anti-proliferation effect against several tumor cell lines. At the same concentration, 31f exhibited much better anti-angiogenesis activities than bestatin in the HUVECs capillary tube formation assay and the rat thoracic aorta rings test. In the in vitro anti-invasion assay, 31f also exhibited superior potency over bestatin. Moreover, considerable in vivo antitumor potencies of 31f alone or in combination with 5-Fu were observed without significant toxic signs in a mouse heptoma H22 tumor transplant model.     

粘合材料及其在生物医学中的应用：进展与展望

粘合材料作为一种重要的辅助材料,在工业包装、海洋工程以及生物医药等多个领域都有广泛的应用需求。天然存在的粘合剂如贻贝足丝粘合蛋白等具有良好的生物相容性和生物可降解性,但因其来源受限及在生理环境下较弱的粘合性能,因此在生物医药领域的应用受到了限制。从自然生物的粘合现象中汲取灵感,各种利用化学或生物合成方法制备的仿生粘合材料应运而生,针对生物医药领域的特定需求,一些新兴粘合材料在生物相容性、生物可降解性以及组织粘附等方面都表现出在医药领域应用的潜力。展望未来,受自然粘合材料兼具环境响应、自我再生和自修复等特征的启迪,各种生物灵感和生物仿生粘合材料的开发势必是未来的发展热点,而合成生物学技术为创建具有上述特征的活体粘合材料提供了新的可能。     

裂解系统在细菌载体疫苗中的应用

重组细菌载体疫苗因其能够诱导机体产生粘膜免疫、体液免疫和细胞免疫的特点,已经被广泛用作递送保护性抗原和核酸疫苗的载体来预防某些传染病。但是重组到细菌载体疫苗中的保护性抗原和核酸难以穿越细菌细胞壁释放到宿主细胞内发挥作用,残留在动物或畜禽产品中的疫苗菌株还可能造成环境的污染和疫苗菌株的传播。而有效解决这些问题的方法是构建一种细菌自动裂解系统,使疫苗菌株能够在体外培养时正常生长而在体内环境中自动裂解死亡。目前主要应用的细菌裂解系统包括:基于调控延迟肽聚糖合成的裂解系统、基于噬菌体裂解蛋白调控的裂解系统、基于毒素-抗毒素系统(Toxin-antitoxin system)的裂解系统。此外,一种潜在的基于细菌Ⅵ型分泌系统(Type Ⅵ secretion system,T6SS)的裂解系统也有望成为构建自动裂解菌株的新方法。文中将着重对这几种裂解系统的调控机制进行阐述。