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171.
Shi Y O'Connor SP Sitkoff D Zhang J Shi M Bisaha SN Wang Y Li C Ruan Z Lawrence RM Klei HE Kish K Liu EC Seiler SM Schweizer L Steinbacher TE Schumacher WA Robl JA Macor JE Atwal KS Stein PD 《Bioorganic & medicinal chemistry letters》2011,21(24):7516-7521
The design, synthesis and SAR of a novel class of valerolactam-based arylsulfonamides as potent and selective FXa inhibitors is reported. The arylsulfonamide–valerolactam scaffold was derived based on the proposed bioisosterism to the arylcyanoguanidine-caprolactam core in known FXa inhibitors. The SAR study led to compound 46 as the most potent FXa inhibitor in this series, with an IC50 of 7 nM and EC2×PT of 1.7 μM. The X-ray structure of compound 40 bound to FXa shows that the sulfonamide–valerolactam scaffold anchors the aryl group in the S1 and the novel acylcytisine pharmacophore in the S4 pockets. 相似文献
172.
为了研究季节性流感裂解疫苗在小鼠中针对甲型流感病毒同型同株、同型异株、异型异株攻击的免疫保护效力及其与诱发的血凝抑制(HI)抗体滴度的关系,本研究使用我国2008~2009年度季节性流感裂解疫苗中不同剂量的甲1型流感病毒H1N1(疫苗株病毒A/Brisbane/59/2007(H1N1)-like)和甲3型流感病毒的H3N2(疫苗株病毒A/Brisbane/10/2007(H3N2)-like)疫苗组分免疫BALB/c小鼠,首先确定了能在小鼠中诱发血HI抗体滴度达到40的疫苗免疫剂量;然后以此剂量免疫小鼠,分别使用同型同株流感病毒(鼠肺适应株A/Brisbane/59/2007(H1N1)-like virus(MA))(简称A1)和同型异株流感病毒(鼠肺适应株A/Purto Rico/8/34(H1N1))(简称PR8)攻击H1N1疫苗免疫小鼠,使用异型异株流感病毒A1攻击H3N2疫苗免疫小鼠,通过体重变化和存活率情况,探讨季节性流感疫苗在小鼠中针对甲型流感病毒同型同株、同型异株、异型异株攻击的保护效力。结果显示,季节性流感裂解疫苗H1N1和H3N2组分按照HA不同剂量0.15μg、0.5μg、1.5μg、5μg和15μg免疫小鼠后,所诱发的HI抗体滴度随免疫剂量的增加而增强,1.5μgHA即可以诱发免疫小鼠HI抗体滴度达到40;以此剂量免疫小鼠,分别使用3LD50、10LD50、30LD50、100LD50、300LD50、1 000LD50和3 000LD50的同型同株流感病毒A1进行攻击,1.5μgH1N1疫苗可以100%保护小鼠抵御高至1000LD50同型同株流感病毒A1的攻击,15μg甚至可以100%保护3 000LD50同型同株流感病毒A1的攻击,但是这两个剂量免疫的小鼠在低至3LD50同型异株流感病毒PR8的攻击后都全部死亡;使用可以诱发HI抗体滴度达到140的15μg H3N2疫苗免疫小鼠,在低至3LD50异型异株流感病毒A1的攻击后亦全部死亡。以上结果表明,季节性流感疫苗可使小鼠HI抗体滴度达到40的疫苗免疫剂量为1.5μg,该免疫剂量可以有效保护小鼠抵御同型同株流感病毒的攻击,但是难以保护小鼠抵御同型异株与异型异株流感病毒的攻击,这一结果为建立以季节性流感疫苗为参考的免疫保护评价体系提供了实验依据。 相似文献
173.
目的探讨医疗设备绩效管理的新模式,提高医疗设备的经济效益。方法研制医疗器械成本效益分析评价模型,对医疗设备使用中影响成本的元素进行分析,并提出合理的改善方法。结果通过开展医疗设备使用效益分析,为决策提供可靠的数字依据,对医疗设备的投资及使用进行监督核算。 相似文献
174.
175.
Song-Lin Ruan Hua-Sheng Ma Shi-Heng Wang Ya-Ping Fu Ya Xin Wen-Zhen Liu Fang Wang Jian-Xin Tong Shu-Zhen Wang Hui-Zhe Chen 《BMC plant biology》2011,11(1):34
Background
High Salinity is a major environmental stress influencing growth and development of rice. Comparative proteomic analysis of hybrid rice shoot proteins from Shanyou 10 seedlings, a salt-tolerant hybrid variety, and Liangyoupeijiu seedlings, a salt-sensitive hybrid variety, was performed to identify new components involved in salt-stress signaling. 相似文献176.
Cytoglobin, generated using genetic engineering method, is a kind of recombinant human stellate cell activation-associated
protein. We speculate that it could influence the development of hepatic fibrosis like Sellate cell activation-associated
protein which was discovered by Kawada et al. Therefore, we investigated its anti-fibrosis effect on liver both in vivo and
in vitro. During our research, we found that cytoglobin showed obvious effect compared with the control group on Thioacetamide-induced
liver fibrosis in SD rats, including significantly decrease in aspartate aminotransferase, Hyaluronic acid, laminin and collagen
I(Col I) levels in serum and hydroxyproline in livers, which are the important indices reflecting the degree of hepatic fibrosis.
Meanwhile, the viability of rat hepatic stellate cell line T6 (HSC-T6) cells was inhibited by cytoglobin and the apoptosis
induced by cytoglobin in HSC-T6 cells was detected by Annexin V/PI double staining. Activation of the caspase cascade including
caspase-3 for the intrinsic pathways was demonstrated. The results also showed that the expression of Bcl-2 protein decreased
whereas that of Bax protein increased, leading to an increase of the Bax/Bcl-2 ratio. Our results demonstrated that cytoglobin
exhibited anti-fibrosis activity on livers in vivo and in vitro, involving apoptosis induction. 相似文献
177.
178.
Carvalheiro LG Veldtman R Shenkute AG Tesfay GB Pirk CW Donaldson JS Nicolson SW 《Ecology letters》2011,14(3):251-259
Ongoing expansion of large-scale agriculture critically threatens natural habitats and the pollination services they offer. Creating patches with high plant diversity within farmland is commonly suggested as a measure to benefit pollinators. However, farmers rarely adopt such practice, instead removing naturally occurring plants (weeds). By combining pollinator exclusion experiments with analysis of honeybee behaviour and flower-visitation webs, we found that the presence of weeds allowed pollinators to persist within sunflower fields, maximizing the benefits of the remaining patches of natural habitat to productivity of this large-scale crop. Weed diversity increased flower visitor diversity, hence ameliorating the measured negative effects of isolation from natural habitat. Although honeybees were the most abundant visitors, diversity of flower visitors enhanced honeybee movement, being the main factor influencing productivity. Conservation of natural patches combined with promoting flowering plants within crops can maximize productivity and, therefore, reduce the need for cropland expansion, contributing towards sustainable agriculture. 相似文献
179.
Background
The latent membrane protein 1 (LMP1) encoded by EBV is expressed in the majority of EBV-associated human malignancies and has been suggested to be one of the major oncogenic factors in EBV-mediated carcinogenesis. In previous studies we experimentally demonstrated that down-regulation of LMP1 expression by DNAzymes could increase radiosensitivity both in cells and in a xenograft NPC model in mice.Results
In this study we explored the molecular mechanisms underlying the radiosensitization caused by the down-regulation of LMP1 in nasopharyngeal carcinoma. It was confirmed that LMP1 could up-regulate ATM expression in NPCs. Bioinformatic analysis of the ATM ptomoter region revealed three tentative binding sites for NF-κB. By using a specific inhibitor of NF-κB signaling and the dominant negative mutant of IkappaB, it was shown that the ATM expression in CNE1-LMP1 cells could be efficiently suppressed. Inhibition of LMP1 expression by the DNAzyme led to attenuation of the NF-κB DNA binding activity. We further showed that the silence of ATM expression by ATM-targeted siRNA could enhance the radiosensitivity in LMP1 positive NPC cells.Conclusions
Together, our results indicate that ATM expression can be regulated by LMP1 via the NF-κB pathways through direct promoter binding, which resulted in the change of radiosensitivity in NPCs. 相似文献180.