Palladium-Catalyzed Asymmetric Hydrogenolysis of Aryl Triflates for Construction of Axially Chiral Biaryls.

Here we report the first palladium-catalyzed asymmetric hydrogenolysis of readily available aryl triflates via desymmetrization and kinetic resolution for facile construction of axially chiral biaryl scaffolds with excellent enantioselectivities and s selectivity factors. The axially chiral monophosphine ligands could be prepared from these chiral biaryl compounds and were further applied to palladium-catalyzed asymmetric allylic alkylation with excellent ee values and high branched and linear ratio, which demonstrated the potential utility of this methodology.

Karyopherin subunit-α 2 expression accelerates cell cycle progression by upregulating CCNB2 and CDK1 in hepatocellular carcinoma.

Different types of cancer exhibit distinct gene expression profiles. The present study aimed to identify a specific gene dysregulated in hepatocellular carcinoma (HCC) that was essential for cancer progression. The whole transcriptomes of primary HCC tissue samples were analyzed with microarrays. The most significantly differentially expressed gene was identified, specifically karyopherin subunit-α 2 (KPNA2), and an analysis using the Oncomine online tool was performed with data from The Cancer Genome Atlas to predict associated genes in HCC. Reverse transcription-quantitative polymerase chain reaction was performed to confirm the gene expression levels of KPNA2, and the RNA interference knockdown of KPNA2 was performed to identify the effect on putative downstream target genes. A proliferation assay and flow cytometry analysis was used to assess the function of KPNA2 in the regulation of the cell cycle. The results demonstrated that KPNA2 expression was significantly upregulated in HCC tumor tissues compared with liver tissues and was associated with cyclin B2 (CCNB2) and cyclin-dependent kinase 1 (CDK1) expression. KPNA2 expression was identified a novel marker to predict the outcome of patients. In addition, KPNA2 knockdown downregulated CCNB2 and CDK1, inhibited cell proliferation and induced cell cycle arrest in the G2/M phase. In conclusion, it was demonstrated that KPNA2 may promote tumor cell proliferation by increasing the expression of CCNB2/CDK1. KPNA2 could be a target for therapeutic intervention in HCC.

Key network approach reveals new insight into Alzheimer's disease.

Alzheimer's disease (AD) is a severe neurodegenerative disorder without curative treatment. Extensive data on pathological molecular processes have been accumulated over the last years. These data combined allows a systems biology approach to identify key regulatory elements of AD and to establish a model descriptive of the disease process which can be used for the development of therapeutic agents. In this study, the authors propose a closed network that uses a set of nodes (amyloid beta, tau, beta-secretase, glutamate, cyclin-dependent kinase 5, phosphoinositide 3-kinase and hypoxia-induced factor 1 alpha) as key elements of importance to the pathogenesis of AD. The proposed network, in total 39 nodes, is able to become a novel tool capable of providing new insights into AD, such as feedback loops. Further, it highlights interconnections between pathways and identifies their combination for therapy of AD.