17-[3,6-二氧杂-8-N-(取代肉桂酰基)辛二胺]-17-去甲氧基格尔德霉素新颖衍生物的合成

格尔德霉素(geldanamycin,GA)是一个以热休克蛋白90(Hsp90)为靶点的高效抗肿瘤先导物,但其临床应用受到了肝脏毒性的限制.目前通常对其C-17位进行修饰,以保留活性和降低肝毒性.本研究提出了一种GA结构修饰的新思路,即在GA的C-17位引入烷胺基链,进而接入保肝基团肉桂酰基.报道了26个17-(3,6-二氧杂-8-N-(取代肉桂酰基)辛二胺)-17-去甲氧基GA新颖衍生物的合成;体外人乳腺癌细胞株MDA-MB-231生长抑制实验和靶点亲和实验结果表明,化合物3u有明显细胞毒性和靶点选择性(IC50=1.5μmol/L,Kd=1.14μmol/L);并对该类衍生物的构效关系进行了讨论,对深入开展GA结构修饰的相关研究有参考价值.     

三种复苏液治疗失血性休克的血气指标定量分析数学模型

针对三种复苏液治疗失血性休克的血气指标,利用机理分析方法建立了血气指标的微分模型,给出血气指标的指数曲线表达式,并结合试验数据进行了曲线拟合,得到了指数曲线的具体形式,结果与试验数据高度吻合同时分析了用药的效果.利用统计分析方法给出三种复苏液治疗失血性休克的动脉血、静脉血和肠系膜静脉血的血气指标间的回归曲线关系式.     

鱼类HSP70的研究进展

HSP70是含量最丰富的一大家族HSPs,具有高度保守的序列,作为分子伴侣在协助新生多肽链折叠,蛋白质复合体的装配,以及调节、修复和降解变性的蛋白质方面起着重要作用,也是目前鱼类上研究最广泛的热休克蛋白.多种鱼类编码热应激蛋白的基因序列也己经被克隆和检测,HSP70的表达主要在转录水平进行调控,目前对HSP70在应激反应中的合成机制仍不是很清楚.本文综述了它的研究概况以及应用前景.     

氧氟沙星的不良反应

综述了氧氟沙星的不良反应,包括：致过敏休克,致过敏反应,气喘,致全身瘙痒与静脉炎,致发热,致震颤麻痹,对神经系统、血液、肾功能的影响等。氧氟沙星对个别个体存在不同的不良反应。     

泥蚶多倍体胚胎的激发诱导：Ⅰ.低温与秋水仙素的诱导

用Ｌ９（３）＾４正交设计的低温休克诱导泥蚶三倍体的试验,结果表明,８－１２℃低温刺激均能获得三倍体胚胎,其中优化组合为处理温度８℃,处理时机在受精５ｍｉｎ后,处理时间为１ｍｉｎ,最高三倍体率为３８．２％。     

Differential Expression of Molecular Chaperones in PC12 Cells Treated with PSI

<正>Parkinson's disease(PD) is a common neurodegenerative disorder whose primary pathology features are the degeneration of dopaminergic neurons in the substantia nigra pars compacta(SNc) and the presence of eosinophilic inclusions called Lewy body in the cytoplasm of the remained neurons.Growing evidence suggests that dysfunction of the ubiquitin-proteasome system(UPS) is involved in the etiopathogenesis of PD.In order to investigate the pathogenetic mechanism of ubiquitin-proteasome dysfunction in PD,2D-differential gel electrophoresis (2D-DIGE) and MALDI-TOF Pro MS were used to determine the proteins,which were differentially expressed,in PC12 cells that had undergone a synthetic proteasomal inhibitor PSI(10μmol/L) treatment for 24 h.Forty-six protein spots were differentially expressed in response to PSI administration,of which 34 were increased and 12 decreased. Six of these were identified as molecular charperones:endoplasmin precursor(GRP94),heat shock protein 105(HSP105),HSC-70-psl,glucose ruglated protein 75(GRP75),glucose ruglated protein 58(GRP58) and heat shock 27000 protein 1(HSP27).The results suggest that the molecular chaperones play an important role in the PD model induced by proteasomal inhibitor.     

基于抗肿瘤活性化合物MED烟酸类衍生物的设计及作用靶点

通过变性荧光素酶的再复性实验发现真菌环氧二烯(Mycoepoxydiene,MED)对热休克蛋白(Heat shock protein 90,Hsp90)具有抑制作用.Western Blot实验结果表明,MED影响人宫颈癌细胞株HeLa中Hsp70及Hsp90的客户蛋白质(Akt,Raf-1)的表达,表明MED是Hsp90的抑制剂.通过靶向对接技术预测了MED与人Hsp90 N端ATP结合位点的结合情况,并在此基础上发现,MED的烟酸类衍生物4-NDM与Hsp90的结合具有比MED与Hsp90更强的亲和作用.体外实验结果证明,MED的烟酸类衍生物4-NDM及3-NDM对HeLa细胞表现出比MED更强的细胞毒活性;可通过上调Hsp70,并下调Akt和Raf-1而影响HeLa细胞中Hsp90相关蛋白质的表达.由此推测,MED及其烟酸类衍生物可以通过抑制Hsp90,而使其客户蛋白Akt或Raf-1发生降解,发挥其抗肿瘤作用.     

Ion Acceleration in Laser-Plasma Interaction： Shock, Sheath, and Scaling

Some notes and comments on ion acceleration in laser-plasma interaction is given, in particular for the implication of shock, sheath and sealing. A simple model is proposed for ion acceleration by the combination of shock and sheath. The obtained scaling relations between the maximum ion energy and laser parameters （power, pulse duration） as well plasma parameter （plasma density）for example α PL 7/12 Eion,max α TL1/3 and Eion,max α ne2/3,are compared to the previous works. Some deficiencies and implications of model and results are discussed.     

Simulation Study of Shock Reaction on Porous Material

Direct modeling of porous materials under shock is a complex issue. We investigate such a system via the newly developed material-point method. The effects of shock strength and porosity size are the main concerns. For the same porosity, the effects of mean-void-size are checked. It is found that local turbulence mixing and volume dissipation are two important mechanisms for transformation of kinetic energy to heat. When the porosity is very small, the shocked portion may arrive at a dynamical steady state; the voids in the downstream portion reflect back rarefactive waves and result in slight oscillations of mean density and pressure; for the same value of porosity, a larger mean-void-size makes a higher mean temperature. When the porosity becomes large, hydrodynamic quantities vary with time during the whole shock-loading procedure： after the initial stage, the mean density and pressure decrease, but the temperature increases with a higher rate. The distributions of local density, pressure, temperature and particle-velocity are generally non-Gaussian and vary with time. The changing rates depend on the porosity value, mean-void-size and shock strength. The stronger the loaded shock, the stronger the porosity effects. This work provides a supplement to experiments for the very quick procedures and reveals more fundamental mechanisms in energy and momentum transportation.     

热休克处理应用于直投式发酵剂对酸奶品质改善作用的研究

为研究热休克处理应用于直投式发酵剂对酸奶品质的改善作用, 通过保加利亚乳杆菌、嗜热链球菌和嗜酸乳杆菌制备直投式发酵剂, 比较3种菌的热休克处理实验组与未热休克处理对照组在冷冻干燥后的存活率及酸奶发酵性能. 结果显示: 热休克处理组发酵剂存活率极显著增加, 酸奶pH下降速度显著加快(P<0.01), 双乙酰、乙醛含量均显著升高(P<0.05), 蛋白质、活菌数含量均显著提升(P<0.01), 且使用经热休克处理制备发酵剂生产的酸奶在感官评价上优于未热休克处理组. 结果表明, 在冷冻干燥前进行热休克处理可以提高直投式发酵剂中乳酸菌的存活率、产酸产香等发酵性能, 改善酸奶的风味和品质, 为提升酸奶发酵剂的品质提供了一种新的方法.