Bis(phosphino)carbazole, HL (HL = 3, 2 -1,8-(PPh 2 ) 2 -carbazole), reacted with rare-earthmetal tris(aminobenzyl) complexes (Ln(CH 2 C 6 H 4 N(Me) 2 -o) 3 ) to afford the first PNP-carbazolide rare-earth-metal bis(alkyl) complexes, LLn(C 6 H 4 CH 2 N(Me) 2 ) 2 (Ln=Y (1), Sc (2), Er (3)). The yttrium complex 1 was characterized by X-ray diffraction analysis as a solvent-free monomer, in which the carbazolide ligand coordinates to the Y 3þ ion in a κP:κN:κP 0 -tridentate mode and the two aminobenzyl groups coordinate to the Y 3þ ion in η 1 C:κN-bidentate modes. Complexes 1-3 combined with [Ph 3 C][B(C 6 F 5 ) 4 ] gave cationic catalyst systems that initiated cis-1,4-polymerizations of 1,3-conjugated dienes with high activities. Especially, the system 1/[Ph 3 C][B(C 6 F 5 ) 4 ] displayed excellent cis-1,4-selectivity ( >99%) and living mode at a broad range of polymerization temperatures (0-80 °C). Remarkably, the living yttrium-polydiene active species could further initiate the ring-opening polymerization of ε-caprolactone to give selectively poly(cis-1,4-diene)b-polycaprolactone block copolymer with controllable molecular weight (M n = (10-70) Â 10 4 ) and narrow polydispersity (PDI = 1.15-1.47).

BackgroundNonalcoholic fatty liver disease is one of the most common liver diseases in the world and is a typical hepatic manifestation of metabolic syndrome which is characterized with lipid accumulation in liver. Nicotinamide phosphoribosyltransferase (NAMPT) has been recently identified as an enzyme involved in nicotinamide adenine dinucleotide (NAD+) biosynthesis and plays an important role in cellular metabolism in variety of organs in mammals. The aim of this study was to investigate the effects of NAMPT on high fat diet-induced hepatic steatosis.MethodsHepatic steatosis model was induced by high fat diet (HFD) in C57BL/6 mice in vivo. HepG2 and Hep1-6 hepatocytes were transfected with NAMPT vector plasmid or treated with NAMPT inhibitor FK866 and then incubated with oleic acid. Lipids accumulation was examined by HE staining or oil red staining. Quantitative RT-PCR and Western blot were used to measure expressions of the genes involved in lipogenic synthesis.ResultsFK866 significantly promoted liver steatosis in the mice fed with HFD and hepatic lipid accumulation in vitro, accompanied by the increases of the expressions of lipogenic genes such as sterol regulatory element-binding protein 1 (SREBP1) and fatty acid synthase (FASN). Nicotinamide mononucleotide (NMN) and NAD+ significantly rescued the actions of FK866 in vitro. In contrast, overexpression of NAMPT in HepG2 and Hep1-6 hepatocytes ameliorated hepatic lipid accumulation. In addition, FK866 decreased the protein levels of Sirt1 and phospho-AMPKα in liver of the HFD fed mice. Furthermore, Resveratrol, a Sirt1 activator, significantly reduced lipogenic gene expressions, while EX-527, a Sirt1 specific inhibitor, had the opposite effects.ConclusionOur results demonstrated that inhibition of NAMPT aggravated the HFD- or oleic acid-induced hepatic steatosis through suppressing Sirt1-mediated signaling pathway. On the one hand, the inhibition of NAMPT reduced the production of NAD+ through inhibiting the NAD+ salvage pathway, resulting in the decrease of Sirt1 activity, and then attenuated the deacetylation of SREBP1 in which the inhibition of SREBP1 activity promoted the expressions of FASN and ACC. On the other hand, the reduced Sirt1 activity alleviated the activation of AMPKα to further enhance SREBP1 activities.Electronic supplementary materialThe online version of this article (doi:10.1186/s12944-017-0464-z) contains supplementary material, which is available to authorized users.

Microbiota-host interactions play critical roles in colorectal cancer (CRC) progression, however, the underlying mechanisms remain elusive. Here, we uncover that Fusobacterium nucleatum (F. nucleatum) induces a dramatic decline of m6A modifications in CRC cells and patient-derived xenograft (PDX) tissues by downregulation of an m6A methyltransferase METTL3, contributing to inducation of CRC aggressiveness. Mechanistically, we characterized forkhead box D3 (FOXD3) as a transcription factor for METTL3. F. nucleatum activates YAP signaling, inhibits FOXD3 expression, and subsequently reduces METTL3 transcription. Downregulation of METTL3 promotes its target kinesin family member 26B (KIF26B) expression by reducing its m6A levels and diminishing YTHDF2-dependent mRNA degradation, which contributes to F. nucleatum-induced CRC metastasis. Moreover, METTL3 expression is negatively correlated with F. nucleatum and KIF26B levels in CRC tissues. A high expression of KIF26B is also significantly correlated with a shorter survival time of CRC patients. Together, our findings provide insights into modulating human m6A epitranscriptome by gut microbiota, and its significance in CRC progression.