Metrics & MoreArticle Recommendations CONSPECTUS: Carbon dioxide (CO 2 ) is not only a greenhouse gas and a common waste product but also an inexpensive, readily available, and renewable carbon resource. It is an important one-carbon (C1) building block in organic synthesis for the construction of valuable compounds. However, its utilization is challenging owing to its thermodynamic stability and kinetic inertness. Although significant progress has been achieved, many limitations remain in this field with regard to the substrate scope, reaction system, and activation strategies. Since 2015, our group has focused on CO 2 utilization in organic synthesis. We are also interested in the vast possibilities of radical chemistry, although the high reactivity of radicals presents challenges in controlling selectivity. We hope to develop highly useful CO 2 transformations involving radicals by achieving a balance of reactivity and selectivity under mild reaction conditions. Over the past 6 years, we along with other experts have disclosed radical-type carboxylative cyclizations and carboxylations using CO 2 .We initiated our research by realizing the Cu-catalyzed radical-type oxytrifluoromethylation of allylamines and heteroaryl methylamines to generate valuable 2-oxazolidones with various radical precursors. Apart from Cu catalysis, visible-light photoredox catalysis is also a powerful method to achieve efficient carboxylative cyclization. In these cases, single-electron-oxidation-promoted C−O bond formation between benzylic radicals and carbamates is the key step. Since carboxylic acids exist widely in natural products and bioactive drugs and serve as important bulk chemicals in industry, we realized further visible-light-promoted carboxylations with CO 2 to construct such chemicals. We have achieved the selective umpolung carboxylations of imines, enamides, tetraalkylammonium salts, and oxime esters by successive single-electron-transfer (SSET) reduction. Using this strategy, we have also realized the dearomative arylcarboxylation of indoles with CO 2 . In addition to the incorporation of 1 equiv of CO 2 per substrate, we have recently developed a visible-light photoredox-catalyzed dicarboxylation of alkenes, allenes, and (hetero)arenes via SSET reduction, which allows the incorporation of two CO 2 molecules into organic compounds to generate valuable diacids as polymer precursors.In addition to the two-electron activation of CO 2 , we sought to develop new strategies to realize efficient and selective transformations via single-electron activation of CO 2 . Inspired by the hypothetical electron-transfer mechanism of iron−sulfur proteins, we have realized the visible-light-driven thiocarboxylation of alkenes with CO 2 using catalytic iron salts as promoters. The in-situ-generated Fe/S complexes are likely able to reduce CO 2 to its radical anion, which could react with alkenes to give a stabilized carbon radical. Moreover, we have also disclosed charge-transfer complex (CTC) formation between thiolate and acrylate/styr...

BackgroundEven though aberrant expression of microRNA (miR)-30d has been reported in prostate cancer (PCa), its associations with cancer progression remain contradictory. The aim of this study was to investigate clinical significance, biological functions and underlying mechanisms of miR-30d deregulation in PCa.MethodsInvolvement of miR-30d deregulation in malignant phenotypes of PCa was demonstrated by clinical sample evaluation, and in vitro and in vivo experiments. The mechanisms underlying its regulatory effect on tumor angiogenesis were determined.ResultsmiR-30d over-expression was observed in both PCa cells and clinical specimens. High-miR-30d was distinctly associated with high pre-operative PSA and Gleason score, advanced clinical and pathological stages, positive metastasis and biochemical recurrence (BCR), and reduced overall survival of PCa patients. Through gain- and loss-of-function experiments, we found that miR-30d promoted PCa cell proliferation, migration, invasion, and capillary tube formation of endothelial cells, as well as in vivo tumor growth and angiogenesis in a mouse model. Simulation of myosin phosphatase targeting subunit 1 (MYPT1), acting as a direct target of miR-30d, antagonized the effects induced by miR-30d up-regulation in PCa cells. Notably, miR-30d/MYPT1 combination was identified as an independent factor to predict BCR of PCa patients. Furthermore, miR-30d exerted its pro-angiogenesis function, at least in part, by inhibiting MYPT1, which in turn, increased phosphorylation levels of c-JUN and activated VEGFA-induced signaling cascade in endothelial cells.ConclusionsmiR-30d and/or its target gene MYPT1 may serve as novel prognostic markers of PCa. miR-30d promotes tumor angiogenesis of PCa through MYPT1/c-JUN/VEGFA pathway.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-017-0615-x) contains supplementary material, which is available to authorized users.