重金属复合污染对土壤植物系统的生态效应Ⅱ.对作物、苜蓿、树木吸收元素的影响

研究Cd、Pb、Cu、Zn、As 5元素复合污染对农作物、苜蓿、树木吸收元素的影响,供试污染物浓度以接近国内外土壤环境标准值作为高剂量处理,结果表明,5种元素间存在交互作用,可提高作物对Cd、Pb、Zn吸收系数,籽实超出粮食卫生标准的超标率在低剂量处理时Cd为16.6～42.85%,高剂量时达16.6～71.42%.苜蓿茎叶中Cd、Pb含量超出饲料卫生标准,树叶中含量也有所增加,在中、酸性土壤上尤甚.     

Design and synthesis of 4,5,6,7‐tetrahydro‐1H‐1,2‐diazepin‐7‐one derivatives as a new series of Phosphodiesterase 4 (PDE4) inhibitors

Phosphodiesterase 4 (PDE4) inhibitors have attractive therapeutic potential in respiratory, inflammatory, metabolic and CNS disorders. The present work details the design, chemical exploration and biological profile of a novel PDE4 inhibitor chemotype. A diazepinone ring was identified as an under-represented heterocyclic system fulfilling a set of PDE4 structure-based design hypotheses. Rapid exploration of the structure activity relationships for the series was enabled by robust and scalable two/three-steps parallel chemistry protocols. The resulting compounds demonstrated PDE4 inhibitory activity in cell free and cell-based assays comparable to the Zardaverine control used, suggesting potential avenues for their further development.     

麦套不同熟性棉复合群体的生产力及生理生态特性

1　引　　言为了进一步提高棉花单产 ,针对解决短季棉夏播晚熟和麦套高产棉田中后期群体过大 ,脱落严重等问题 ,有人从种植方式上进行了短季棉提早套种密矮早模式和短季棉与中熟棉间作模式的研究和探索[8,9,13 ] ,指出适宜的间套方式可获得显著增产 .研究表明 ,塑造具有更高生产潜力的优质群体 ,促使棉花群体早发快长 ,早现蕾早开花 ,延长开花结铃期 ,提高有效ＬＡＩ ,并延长其持续期 ,实现棉花高能期与高光能季节同步早、同步期长 ,是进一步提高棉花单产的关键[1,7,10 ,11] .本文试图通过 6 2 2式春季麦套早熟棉 ,麦收后再在麦畦上移栽两…     

实验性大鼠溃疡性结肠炎菌群失调的诊断及复方树舌的治疗观察

目的探讨对溃疡性结肠炎厌氧菌菌群失调简便检查方法,寻找有效治疗溃疡性结肠炎的中药合剂。方法用冰乙酸诱发大鼠结肠炎模型,用复方树舌中药治疗,在治疗期间分别检测每组大鼠厌氧菌代谢产物、挥发性脂肪酸的含量、了解肠厌氧菌群改变,一般切片行HE染色,观察病理变化。结果（1）模型组大鼠挥发性脂肪酸明显低于正常组（P〈0．05）;pH从第2天起升高明显高于正常对照组（P〈0．05）,各治疗组与自然恢复组比较差异有显著性（P〈0．05）。（2）自然恢复组与各用药组间的炎症评分比较P〈0．01,各治疗组间比较,树舌加丽珠肠乐组组织损伤评分小（P〈0．05）。结论（1）测定厌氧菌的代谢产物挥发性脂肪酸含量,即可对肠内厌氧菌菌群失调做出判断。（2）实验证明,复方树舌中药可作为益生元调节肠道菌群失调及黏膜的修复,对溃疡性结肠炎疗效显著。     

Improving Compound Quality through in vitro and in silico Physicochemical Profiling

Many compounds entering clinical studies do not survive the numerous hurdles for a good pharmacological lead to a drug on the market. The reasons for attrition have been widely studied which resulted in more early attention to compound quality related to physical chemistry, drug metabolism and pharmacokinetics (DMPK), and toxicology/safety. This paper will briefly review current physicochemical in vitro assays and in silico predictions to support compound and library design through to lead optimization. The most important physicochemical properties include lipophilicity (log P/D), pK_a, solubility, and permeability. These drive key ADMET properties such as absorption, cell penetration, access to the brain, volume of distribution, plasma protein binding, metabolism, and toxicity, as well as biopharmaceutical behavior. Much data are now available from medium‐ to high‐throughput physchem and ADMET in vitro assays, either in the public domain (see, e.g., PubChem, PubMed) or in drug companies' in‐house databases. Such data are increasingly being computer‐modelled and used in predictive chemistry. New pipelining technology makes it easier to build and update QSAR models so that such models can use the latest available data to produce robust local and global predictive in silico ADMET models.     

家族性高胆固醇血症患者低密度脂蛋白受体基因复合杂合突变分析

目的:对1例临床确诊为纯合型家族性高胆固醇血症(FH)先证者及其核心家系成员进行基因检测分析,探讨患儿发病的分子病理基础.方法:收集先证者及父母血标本及临床资料,酚氯仿法提取基因组DNA,DNA直接测序方法检测低密度脂蛋白受体(LDL-R)基因18个外显子和启动子及载脂蛋白B(ApoB100)R3500Q位点,核苷酸序列分析结果与Gen Bank比对寻找突变.结果:(1)先证者三尖瓣轻度关闭不全,先证者父母双侧颈总动脉内-中膜增厚,先证者母亲左侧颈内动脉起始处后壁多发混合回声斑块(2)该家系排除ApoB100基因R3500Q突变;(3)先证者LDL-R基因第13外显子发生A606T和D601Y复合杂合突变,前者第1879位G→A碱基置换,导致丙氨酸改变为苏氨酸,后者为1864位G>T碱基置换,导致天冬氨酸改变为酪氨酸,其父为携带A606T突变的杂合子,其母为携带D601Y突变的杂合子.结论:先证者LDL-R基因存在A606T和D601Y复合杂合突变,它们分别来源于父系及母系遗传.     

Effect of H4R antagonist N-(2-aminoethyl)-5-chloro-1H-indol-2-carboxamides and 5-chloro-2-(piperazin-1-ylmethyl)-1H-benzimidazole on histamine and 4-methylhistamine-induced mast cell response

Context: The histamine plays a decisive role in acute and chronic inflammatory responses and is regulated through its four types of distinct receptors designated from H1 to H4. Recently histamine 4 receptor (H4R) antagonists have been reported to possess various pharmacological effects against various allergic diseases.

Objective: To investigate the inhibitory effect of N-(2-aminoethyl)-5-chloro-1H-indol-2-carboxamide (Compound A) and 5-chloro-2-(piperazin-1-ylmethyl)-1H-benzimidazole (Compound L) on H4R-mediated calcium mobilization, cytokine IL-13 production, ERK1/2, Akt and NF-κB activation in human mastocytoma cells-1 (HMC-1).

Materials and methods: Compounds A and L were synthesized chemically and their inhibitory effect on intracellular calcium release was analyzed by Fluo-4 calcium assay, cytokine measurement through ELISA and activation of signaling molecules by western blot.

Results: Pre-treatment with compounds A and L significantly reduced the H4R-mediated intracellular calcium release. Histamine and 4-methylhistamine (4-MH) induced Th2 cytokine IL-13 production in HMC-1 cells, was inhibited by compound A (77.61%, 74.25% at 1?μM concentration) and compound L (79.63%, 81.70% at 1?μM concentration). Furthermore, histamine induced the phosphorylation of ERK1/2, Akt and NF-κB was suppressed by compounds A and L at varying levels, ERK1/2 (88%, 86%), Akt (88%, 89%) and NF-κB (89%, 87%) in HMC-1 cells.

Discussion and conclusions: Taken together these data demonstrate that compound A and compound L may block H4R-mediated downstream signaling events.     

EP-1 不育剂对长爪沙鼠野生种群增长的控制作用

长爪沙鼠在内蒙古地区的分布非常广泛,长期以来由其造成的“鼠害” 不仅给农牧业生产带来危害,而且还传播疾病。2009 年3 ～ 10 月,在内蒙古鄂尔多斯荒漠草原,利用复合不育剂左炔诺孕酮- 炔雌醚(EP-1)
对长爪沙鼠野生种群进行了不育控制试验研究。结果表明,复合不育剂EP-1 对长爪沙鼠种群结构和种群密度均有显著影响,在5 月和6 月两个繁殖高峰期,不育剂EP-1 显著降低了幼体出生的数量,实验区与对照区幼体组
成差异和成体组成差异均达到极显著(P < 0.01)。在8 ～ 10 月,实验区和对照区种群结构组成中,幼体之间、成体之间差异均达到显著和极显著(P < 0.05, P < 0.01)。在整个发育生长期,实验区长爪沙鼠幼体种群从6 月
份开始出现,9 月达到数量最高值,幼体种群全年呈现下降趋势。而对照区幼体种群从5 月份开始出现,且数量在5 月份达到全年的最高值,幼体种群与实验区相反呈增长趋势。实验区种群总体数量全年呈下降趋势,而对
照区相反,呈增长趋势。因此,复合不育剂EP-1 显著降低了长爪沙鼠种群的繁殖率、幼体出生比例和种群密度,可以对长爪沙鼠野生种群起到有效的繁殖控制作用,进而降低该鼠对农牧业生产的危害和对人类疾病传播
的风险。