BLCAP (bladder cancer-associated protein) gene exhibited tumor suppressor function in different tumors and is regarded as a candidate tumor suppressor gene; however, the mechanism by which BLCAP exerts its function remains elusive. This study investigated the functional association between BLCAP and proliferation or apoptosis in cervical cancer cells, to identify the functional motifs of BLCAP. The BLCAP-shRNA expression vector based on pRNA-U6.1/Hygro plasmid was used to specifically inhibit BLCAP activity in HeLa cells. The optimal shRNA plasmid was selected to knock down BLCAP expression and the biological effects were investigated. The effects on cell cycle and apoptosis were detected by flow cytometric or Annexin V-FITC staining analysis. The gene expression profiles of HeLa cells transfected with blcap-wt and BLCAP-shRNA were analyzed using human signal pathway gene Oligochips. The levels of protein expression and interaction of BLCAP with Rb1 proteins were determined by western blotting and Co-IP assays. The site-specific mutagenesis assay was used to identify amino acid residues important for BLCAP. Significantly differentially expressed genes were found by gene Oligo chips analysis. These genes were all correlated with proliferation, cell cycle and apoptosis. The results of western blotting and Co-IP assays confirmed that overexpression of BLCAP could interact with Rb1 and inhibit Rb1 phosphorylation. Further investigation revealed that SAXX mutation in the key regions of BLCAP suppressed the function of BLCAP and significantly increased the level of phosphorylated Rb1 protein. Here our findings suggested that the functional association of BLCAP and Rb1 might play important roles in proliferation and apoptosis of HeLa cells. It suggested that BLCAP could be a novel therapeutic target for cervical cancer.
High-temperature risk disaster, a common meteorological disaster, seriously affects people’s productivity, life, and health. However, insufficient attention has been paid to this disaster in urban communities. To assess the risk of high-temperature disasters, this study, using remote sensing data and geographic information data, analyzes 973 communities in downtown Wuhan with the geography-weighted regression method. First, the study evaluates the distribution characteristics of high temperatures in communities and explores the spatial differences of risks. Second, a metrics and weight system is constructed, from which the main factors are determined. Third, a risk assessment model of high-temperature disasters is established from disaster-causing danger, disaster-generating sensitivity, and disaster-bearing vulnerability. The results show that: (a) the significance of the impact of the built environment on high-temperature disasters is obviously different from its coefficient space differentiation; (b) the risk in the old city is high, whereas that in the area around the river is low; and (c) different risk areas should design built environment optimization strategies aimed specifically at the area. The significance of this study is that it develops a high-temperature disaster assessment framework for risk identification, impact differentiation, and difference optimization, and provides theoretical support for urban high-temperature disaster prevention and mitigation.
Acyloxy-substituted α,β-unsaturated imines generated in situ from triazoles can act as aza-[4 C] synthons and be trapped by indoles in a stepwise [4 + 2] cycloaddition reaction, thus providing rapid access to valuable pyrido [2,3-b] indoles in high yields. Attractive features of this reaction system include operational simplicity, readily available substrates, construction of sterically demanding quaternary centers, and convenient derivatization using triflate.
A chemoselective tandem reaction of 4acyloxymethylene-1-sulfonyl-1,2,3-triazole and vinyl ether was reported, producing polysubstituted piperidine derivatives in up to 96% yield. The key intermediate N-sulfonyl 1-azadiene generated by migration of the OAc group to the a-imino rhodium carbene was isolated and a plausible mechanism was proposed. Several related ring systems were constructed from the highly functionalized products.
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