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111.
Karolina Maciejewska Kamila Czarnecka Pawe Krcisz Dorota Niedziaek Grzegorz Wieczorek Robert Skibiski Pawe Szymaski 《International journal of molecular sciences》2022,23(11)
A series of new cyclopentaquinoline derivatives with 9-acridinecarboxylic acid and a different alkyl chain length were synthesized, and their ability to inhibit cholinesterases was evaluated. All designed compounds, except derivative 3f, exhibited a selectivity for butyrylcholinesterase (BuChE) with IC50 values ranging from 103 to 539 nM. The 3b derivative revealed the highest inhibitory activity towards BuChE (IC50 = 103.73 nM) and a suitable activity against AChE (IC50 = 272.33 nM). The 3f derivative was the most active compound to AChE (IC50 = 113.34 nM) with satisfactory activity towards BuChE (IC50 = 203.52 nM). The potential hepatotoxic effect was evaluated for both 3b and 3f compounds. The 3b and 3f potential antioxidant activity was measured using the ORAC-FL method. The 3b and 3f derivatives revealed a significantly higher antioxidant potency, respectively 35 and 25 higher than tacrine. Theoretical, physicochemical, and pharmacokinetic properties were calculated using ACD Labs Percepta software. Molecular modeling and kinetic study were used to reveal the mechanism of cholinesterase inhibition in the most potent compounds: 3b and 3f. 相似文献
112.
万娟 《南京工业职业技术学院学报》2007,7(1):12-14
美国较早经历了城市无限制增长的危害,因而也较早进行了相应的公共活动并取得了一定的效果,本文介绍了美国增长管理概念,并把城市增长管理与我国的小城镇发展相结合,针对我国小城镇发展中出现的问题,探讨了如何对发展中的小城镇进行管理,以实现小城镇的可持续发展。 相似文献
113.
Tatyana A. Vasilyeva Andrey V. Marakhonov Sergey I. Kutsev Rena A. Zinchenko 《International journal of molecular sciences》2022,23(12)
Genome-wide sequencing metadata allows researchers to infer bias in the relative frequencies of mutational events and to predict putative mutagenic models. In addition, much less data could be useful in the evaluation of the mutational frequency spectrum and the prevalent local mutagenic process. Here we analyzed the PAX6 gene locus for mutational spectra obtained in our own and previous studies and compared them with data on other genes as well as the whole human genome. MLPA and Sanger sequencing were used for mutation searching in a cohort of 199 index patients from Russia with aniridia and aniridia-related phenotypes. The relative frequencies of different categories of PAX6 mutations were consistent with those previously reported by other researchers. The ratio between substitutions, small indels, and chromosome deletions in the 11p13 locus was within the interval previously published for 20 disease associated genomic loci, but corresponded to a higher end due to very high frequencies of small indels and chromosome deletions. The ratio between substitutions, small indels, and chromosome deletions for disease associated genes, including the PAX6 gene as well as the share of PAX6 missense mutations, differed considerably from those typical for the whole genome. 相似文献
114.
115.
Ravichandran Ramasamy Alexander Shekhtman Ann Marie Schmidt 《International journal of molecular sciences》2022,23(9)
Increasing evidence links the RAGE (receptor for advanced glycation end products)/DIAPH1 (Diaphanous 1) signaling axis to the pathogenesis of diabetic complications. RAGE is a multi-ligand receptor and through these ligand–receptor interactions, extensive maladaptive effects are exerted on cell types and tissues targeted for dysfunction in hyperglycemia observed in both type 1 and type 2 diabetes. Recent evidence indicates that RAGE ligands, acting as damage-associated molecular patterns molecules, or DAMPs, through RAGE may impact interferon signaling pathways, specifically through upregulation of IRF7 (interferon regulatory factor 7), thereby heralding and evoking pro-inflammatory effects on vulnerable tissues. Although successful targeting of RAGE in the clinical milieu has, to date, not been met with success, recent approaches to target RAGE intracellular signaling may hold promise to fill this critical gap. This review focuses on recent examples of highlights and updates to the pathobiology of RAGE and DIAPH1 in diabetic complications. 相似文献
116.
此种小径深井救捞装置运用凸轮轨迹控制原理实现托爪(托捞部件)的顺利转起、放下与固定,操作简便,功能可靠,节能环保,是理想的小径深井救捞装置.该装置也可用于矿井、峡谷、墙(楼)缝、冰窟等条件下的救捞. 相似文献
117.
针对标签印刷生产过程中存在的多品种、小批量、客户定制化程度高、部分生产工序存在不确定性等问题建立了以最小化最大完工时间为目标的柔性作业车间调度模型,提出了一种改进遗传算法(GA).首先,在标准遗传算法的基础上采用整数编码;然后,在选择操作阶段采用轮盘赌法,并通过引入精英解保留策略以确保算法收敛性;最后,提出动态自适应交... 相似文献
118.
戴孟良 《有色冶金设计与研究》2011,32(6):17-19
以韶关冶炼厂为例,详细分析了提高小矿山矿处理量对烧结工艺的影响,探讨了相关的设备技术改造和相应的稳定工艺措施,研究结果和生产实践表明其在降低生产成本方面具有明显效果和推广应用价值. 相似文献
119.
120.
《中国工程学刊》2012,35(5):601-616
The nonlinearity and small strain characteristics of clay are predominant factors to affect the analysis accuracy of surface settlement induced by deep excavation in soft clay. In this study, we use a newly developed constitutive model, namely the undrained soft clay model, to simulate the nonlinearity of soft clay and to describe the degradation of elastic Young's modulus with the increasing stress level, ranging from small strain to near failure. The parameters of the formula can be obtained from conventional soil tests. One well-documented case history is then used to show the parameter determination procedure and validate the proposed model. The states of strain and stress paths for the soil in the excavation are also studied to validate the rationality of the model. Besides, two additional case studies are conducted to verify the model further. 相似文献