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131.
《Bioorganic & medicinal chemistry letters》2020,30(17):127400
Glucose transporter 2 (GLUT2) is involved in glucose uptake by hepatocytes, pancreatic beta cells, and absorptive cells in the intestine and proximal tubules in the kidney. Pancreatic GLUT2 also plays an important role in the mechanism of glucose-stimulated insulin secretion. In this study, novel Fluorine-18-labeled streptozotocin (STZ) derivatives were synthesized to serve as glycoside analogs for in-vivo GLUT2 imaging. Fluorine was introduced to hexyl groups at the 3′-positions of the compounds, and we aimed to synthesize compounds that were more stable than STZ. The nitroso derivatives exhibited relatively good stability during purification and purity analysis after radiosynthesis. We then evaluated the compounds in PET imaging and ex-vivo biodistribution studies. We observed high levels of radioactivity in the liver and kidney, which indicated accumulation in these organs within 5 min of administration. In contrast, the denitroso derivatives accumulated only in the kidney and bladder shortly after administration. Compounds with nitroso groups are thus expected to accumulate in GLUT2-expressing organs, and the presence of a nitroso group is essential for in-vivo GLUT2 imaging. 相似文献
132.
《Bioorganic & medicinal chemistry letters》2020,30(16):127293
LRH-1 is a nuclear receptor that regulates lipid metabolism and homeostasis, making it an attractive target for the treatment of diabetes and non-alcoholic fatty liver disease. Building on recent structural information about ligand binding from our labs, we have designed a series of new LRH-1 agonists that further engage LRH-1 through added polar interactions. While the current synthetic approach to this scaffold has, in large part, allowed for decoration of the agonist core, significant variation of the bridgehead substituent is mechanistically precluded. We have developed a new synthetic approach to overcome this limitation, identified that bridgehead substitution is necessary for LRH-1 activation, and described an alternative class of bridgehead substituents for effective LRH-1 agonist development. We determined the crystal structure of LRH-1 bound to a bridgehead-modified compound, revealing a promising opportunity to target novel regions of the ligand binding pocket to alter LRH-1 target gene expression. 相似文献
133.
Model‐assisted identification of metabolic engineering strategies for Jatropha curcas lipid pathways
Sandra M. Correa Saleh Alseekh Lucía Atehortúa Yariv Brotman Rigoberto Ríos‐Estepa Alisdair R. Fernie Zoran Nikoloski 《The Plant journal : for cell and molecular biology》2020,104(1):76-95
Efficient approaches to increase plant lipid production are necessary to meet current industrial demands for this important resource. While Jatropha curcas cell culture can be used for in vitro lipid production, scaling up the system for industrial applications requires an understanding of how growth conditions affect lipid metabolism and yield. Here we present a bottom‐up metabolic reconstruction of J. curcas supported with labeling experiments and biomass characterization under three growth conditions. We show that the metabolic model can accurately predict growth and distribution of fluxes in cell cultures and use these findings to pinpoint energy expenditures that affect lipid biosynthesis and metabolism. In addition, by using constraint‐based modeling approaches we identify network reactions whose joint manipulation optimizes lipid production. The proposed model and computational analyses provide a stepping stone for future rational optimization of other agronomically relevant traits in J. curcas. 相似文献
134.
黄土区土质与土石质塿土堆积体水力侵蚀过程差异 总被引:2,自引:0,他引:2
利用室内模拟降雨试验,研究了不同雨强及坡度条件下黄土区土质(不含砾石)与土石质(砾石质量分数30%)塿土堆积体的水动力学特征、侵蚀特征及侵蚀动力机制的差异。结果表明: 砾石存在改变了堆积体坡面的水动力学特性,与土质坡面相比,土石质坡面的流速、弗汝德数、单位径流功率和过水断面单位能分别减少1.7%~49.7%、6.7%~60.6%、2.0%~44.6%和1.0%~26.7%;曼宁糙率系数、径流剪切力分别增加6.2%~169.4%、5.7%~79.3%。2.0、2.5 mm·min-1雨强下,土石质坡面侵蚀速率较土质坡面降低26.2%~89.9%,砾石的减沙效益显著。2种堆积体的侵蚀速率与水动力学参数间均可用线性函数拟合,与土质坡面相比,土石质坡面的可蚀性参数均降低,降幅为56.1%~73.3%;而临界水动力学参数中径流剪切力增加11.1%,径流功率、单位径流功率和过水断面单位能分别减少25.4%、64.0%和5.0%。砾石的存在一定程度上控制了工程堆积体坡面降雨侵蚀过程。 相似文献
135.
《Bioorganic & medicinal chemistry》2020,28(5):115307
Adenosine monophosphate (AMP)-activated protein kinase (AMPK) plays a key role in maintaining cellular metabolism. AMP or adenosine diphosphate (ADP) levels rise during metabolic stress, such as during nutrient starvation, hypoxia and muscle contraction, and bind to AMPK to induce activity. Recently, activation of AMPK has been considered an attractive therapeutic strategy in the field of human oncology. Structural optimization of lead compound 2, a new type of AMPK activator with potent AMPK activation activity and attractive selective growth inhibition against human cancer cells, improved aqueous solubility, metabolic stability and animal pharmacokinetics (PK) and culminated in the identification of (5-{1-[(6-methoxypyridin-3-yl)methyl]piperidin-4-yl}-1H-benzimidazol-2-yl)(4-{[4-(trifluoromethyl)phenyl]methyl}piperazin-1-yl)methanone ditosylate, ASP4132 (28). Studies on ASP4132 had advanced to clinical trials for the treatment of cancer. 相似文献
136.
Anaerobic cultivation methods of bacteria are indispensable in microbiology. One methodology is to cultivate the microbes in anaerobic enclosure with oxygen-adosrbing chemicals. Here, we report an electronic extension of such strategy for facultative anaerobic bacteria. The technique is based a bioreactor with entire operation including turbidity measurement, fluidic mixing, and gas delivery in an anaerobic enclosure. Wireless data transmission is employed and the anaerobic condition is achieved with gas pack. Although the technique is not meant to completely replace the anaerobic chamber for strict anaerobic bacteria, it provides a convenient way to bypass the cumbersome operation in anaerobic chamber for facultative anaerobic bacteria. Such a cultivation strategy is demonstrated with Escherichia coli with different carbon sources and hydrogen as energy source. 相似文献
137.
Andjela Bajic Roberto Tarantino Loraine L. Y. Chiu Thomas Duever Stephen D. Waldman 《Biotechnology progress》2020,36(5):e3017
Tissue engineering is a promising option for cartilage repair. However, several hurdles still need to be overcome to develop functional tissue constructs suitable for implantation. One of the most common challenges is the general low capacity of chondrocytes to synthesize cartilage-specific extracellular matrix (ECM). While different approaches have been explored to improve the biosynthetic response of chondrocytes, several studies have demonstrated that the nutritional environment (e.g., glucose concentration and media volume) can have a profound effect on ECM synthesis. Thus, the purpose of this study was to optimize the formulation of cell culture media to upregulate the accumulation of cartilaginous ECM constituents (i.e., proteoglycans and collagen) by chondrocytes in 3D culture. Using response surface methodology, four different media factors (basal media, media volume, glucose, and glutamine) were first screened to determine optimal media formulations. Constructs were then cultured under candidate optimal media formulations for 4 weeks and analyzed for their biochemical and structural properties. Interestingly, the maximal accumulation of proteoglycans and collagen appeared to be elicited by different media formulations. Most notably, proteoglycan accumulation was favored by high volume, low glucose-containing DMEM/F12 (1:1) media whereas collagen accumulation was favored by high volume, high glucose-containing F12 media. While high glutamine-containing media elicited increased DNA content, glutamine concentration had no apparent effect on ECM accumulation. Therefore, optimizing the nutritional environment during chondrocyte culture appears to be a promising, straight-forward approach to improve cartilaginous tissue formation. Future work will investigate the combined effects of the nutritional environment and external stimuli. 相似文献
138.
Lavandula stoechas L. (Lamiaceae) is an attractive shrub native to the Mediterranean regions used for ornamental, melliferous, aromatic and medicinal purposes. Furthermore, this species presents an increasing interest in cosmetics, perfumery and pharmaceutical industries. The variability of qualitative and quantitative metabolic traits among nine wild germplasms representing the distribution area of this species in Tunisia was undertaken. A total of 45 essential oil components were identified in the aerial parts of the studied germplasms. The main essential oil components were camphor (15.32–50.63%), fenchone (6.57–34.70%), 1,8-cineole (0.05–13.45%) and γ-gurjunene (1.10–12.15%). In addition to the well known chemotypes camphor/fenchone and camphor/1.8-cineole, a new chemotype camphor/γ-gurjunene was detected in Tunisian L. stoechas L. Six phenolic acids (quinic acid, gallic acid, p-coumaric acid, 4,5-di-O-caffeoyquinic acid, salviolinic acid and trans cinnamic acid) and five flavonoids (luteolin-7-o-glucoside, naringin, apegenin-7-o-glucoside, quercetin and kampherol) were identified in the ethanolic extracts. Salviolinic acid (46.30–615.18 μg/g) and luteolin-7-o-glucoside (5.98–38.54 μg/g) were the most abundant phenolic compounds. A high significant phytochemical variability (p ˂ 0.01) in the accumulation of volatile and phenolic secondary metabolites among the studied germplasms was recorded. The conducted multivariate (PCA) and clustering (HCA) analyses revealed different classification pattern for essential oil and phenolic compounds. The detected phytochemical polymorphism among the investigated lavender ecotypes didn't show accordance with bioclimatic and geographical areas which suggests genetic background as the main explaining factor. The detected secondary metabolites polymorphism valorises Tunisian L. stoechas L. genetic resources as valuable plant material in further breeding programs. Moreover, an urgent in situ and ex situ conservation measures are required for these wild germplasms threatened by human over-harvesting practices and the occurring dramatic changes in climatic conditions. 相似文献
139.
Daisylyn Senna Tan Yanpu Chen Ya Gao Anastasia Bednarz Yuanjie Wei Vikas Malik Derek Hoi-Hang Ho Mingxi Weng Sik Yin Ho Yogesh Srivastava Sergiy Velychko Xiaoxiao Yang Ligang Fan Johnny Kim Johannes Graumann Gary D. Stormo Thomas Braun Jian Yan Hans R. Schler Ralf Jauch 《Molecular biology and evolution》2021,38(7):2854
140.
Cytotechnology - Low back pain caused by intervertebral disc degeneration has become a global problem that seriously affects public health. The application of nucleus pulposus tissue engineering to... 相似文献