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Hypoglycemic drugs such as metformin increase glucose uptake and utilization by peripheral tissues to maintain glucose homeostasis, and the AMP-activated protein kinase (AMPK) signaling pathway is an important component of this pharmacological activity. Liver kinase B1 (LKB1) acts as a kinase upstream of AMPK and plays an important regulatory role in glucose metabolism. In recent years, as a tumor suppressor, LKB1's antitumor activity has been widely studied, yet its hypoglycemic activity is not clear. Here, using biochemical and cell viability assays, site-directed mutagenesis, immunoblotting, and immunofluorescence staining, we found that a natural product, antroalbol H isolated from the basidiomycete mushroom Antrodiella albocinnamomea, increases cellular glucose uptake in murine L6 myotubes and 3T3-L1 adipocytes. Of note, our results indicated that this effect is related to LKB1-mediated Thr-172 phosphorylation of AMPKα. Furthermore, we observed that antroalbol H induces the phosphorylation of LKB1 specifically at Thr-189 and changes subcellular localization of LKB1. Finally, antroalbol H treatment strikingly promoted glucose transporter type 4 (GLUT4) translocation to the plasma membrane. We conclude that antroalbol H promotes Thr-189 phosphorylation of LKB1, leading to AMPK activation, revealing this residue as a potential target for increasing glucose uptake, and that antroalbol H therefore has potential for managing hyperglycemia. [ABSTRACT FROM AUTHOR]

Graphical abstract A defect structure model has been suggested for Cu2+ in BeO crystal and the calculations of EPR parameters based on the model have been carried out by the use of the CDM and PTM, the calculated EPR parameters from the two methods are in reasonable agreement with the experimental values. The defect structure around Cu2+ impurity centers in BeO crystal have been determined by analyzing the EPR parameters. Highlights • A full ligand-field energy matrix (10 × 10) diagonalization treatment for the EPR parameters of 3d9 ions in trigonally distorted tetrahedral symmetry is presented. • High-order perturbation formulas for the EPR parameters of 3d9 ions in trigonally distorted tetrahedral symmetry are derived. • The calculated EPR parameters based both on CDM and PTM are in reasonable agreement with the experimental values. • A defect structure model for Cu2+ impurity centers in BeO crystal has been suggested and determined by the investigation of the EPR parameters. Abstract The electron paramagnetic resonance(EPR) parameters (g factors g i and hyperfine structure constants A i , where i = x , z) for Cu2+ ions embedded in beryllium oxide (BeO) crystal at Be2+ sites with C 3v local symmetry have been calculated by the complete diagonalization method (CDM) and high-order perturbation theory method (PTM). The calculated results from the two methods are in reasonable agreement with the observed data available. The defect structural data of the trigonal Cu2+ center in beryllium oxide are determined from the calculations and analyses. The calculated results show that the Be2+ ions are replaced by Cu2+ ions in BeO crystal and the ligands undergo outward movement. [ABSTRACT FROM AUTHOR]

RNA polymerase III (Pol III) is responsible for the production of small noncoding RNA species, including tRNAs and 5S rRNA. Pol III--dependent transcription is generally enhanced in trans- formed cells and tumors, but the underlying mechanisms remain not well-understood. It has been demonstrated that the BRF1 subunit of TFIIIB is essential for the accurate initiation of Pol III--dependent transcription. However, it is not known whether BRF1 undergoes ubiquitin modification and whether BRF1 ubiquitination regulates Pol III--dependent transcription. Here, we show that RNF12, a RING domain-containing ubiquitin E3 ligase, physically interacts with BRF1. Via direct interaction, RNF12 catalyzes Lys27 - and Lys33-linked polyubiquitination of BRF1. Furthermore, RNF12 is able to negatively regulate Pol III--dependent transcription and cell proliferation via BRF1. These findings uncover a novel mechanism for the regulation of BRF1 and reveal RNF12 as an important regulator of Pol III--dependent transcription. [ABSTRACT FROM AUTHOR]

• The evaporation characteristic differences of three evaporation models are studied and compared. • Evaporation models have strong influences on simulation results in spray flame. • The A-S evaporation model shows a rapid mixture and evaporation. • The droplet evaporation time is related to the topology structure of flame according to the statistical results of gas-phase parameters. • The NC-TEL evaporation model appears to be better on two-phase ethanol jet flame simulation. High-precision numerical simulation of aero-engine combustors requires a suitable evaporation model. At present, quantitative research on the effects of the evaporation model on two-phase turbulence combustion simulation is insufficient. Ethanol has a higher latent heat of evaporation than other fuels like acetone and aero kerosene, thus it is especially sensitive to the evaporation model. This paper uses LES to simulate turbulence in an aero-engine combustor, and TPDF to describe the interaction between turbulence and chemical reactions. Numerical simulation results of the Abramzon-Sirignano (A-S), Spalding, and thick exchange layer (NC-TEL) evaporation models for high-Reynolds number ethanol combustion in two-phase turbulent jet flames are analyzed and compared with experimental data. Results suggest that per unit time, the A-S evaporation model has the largest evaporation mass, followed by the NC-TEL evaporation model, while the Spalding evaporation model has the smallest evaporation mass. Through quantitative analysis of the different evaporation models' influence on temperature, mixture fraction, and liquid phase distribution, it is found that the A-S evaporation model fits the experimental data better in the central region of jet flame but has worse performance in the other flame regions. The simulation result of the Spalding model is good in the X/D = 10 section, and that of the NC-TEL model shows the best result at X/D > 10 sections and in the outer regions of the jet flame. The maximum difference between the NC-TEL model results and the experimental data was 21.856 % in liquid phase velocity. Hence, the NC-TEL model has the best simulation performance. [ABSTRACT FROM AUTHOR]

Four bipolar materials including of CN-TAZ-1Cz , CN-TAZ-2Cz , CN-TAZ-3Cz and CN-TAZ-4Cz were successfully designed and synthesized by incorporating electron-accepting cyano, 1, 2, 4-triazole and pyridine and electron-donating carbazole. The synthesized materials displayed deep-blue and blue emissions in the range of 404–475 nm in CH 2 Cl 2 solution and thin film. The charge-transfer (CT) excited state in CN-TAZ-1Cz and CN-TAZ-3Cz resulted in a large redshift of 163 and 144 nm with the increasing polarities of solvents. The dominated local-electron (LE) and weak CT excited state were observed in emission of CN-TAZ-2Cz , while CN-TAZ-4Cz exhibited mainly CT excited state with redshift of 23 nm. Their performances in organic light-emitting devices (OLEDs) were characterized by using titled bipolar materials as emitting materials and hosts. The non-doped blue device based CN-TAZ-3Cz exhibits the maximum EQE of 3.9% and the. The device hosted CN-TAZ-3Cz and doped Ir(ppy) 3 achieved the maximum current efficiency of 64.5 l m/W, external quantum efficiency (EQE) of 18.4% and radiative exciton yield of 66%. [ABSTRACT FROM AUTHOR]

For the past decade, cancer genomic studies have focused on mutations leading to splice-site disruption, overlooking those having splice-creating potential. Here, we applied a bioinformatic tool, MiSplice, for the large-scale discovery of splice-site-creating mutations (SCMs) across 8,656 TCGA tumors. We report 1,964 originally mis-annotated mutations having clear evidence of creating alternative splice junctions. TP53 and GATA3 have 26 and 18 SCMs, respectively, and ATRX has 5 from lower-grade gliomas. Mutations in 11 genes, including PARP1, BRCA1, and BAP1, were experimentally validated for splice-site-creating function. Notably, we found that neoantigens induced by SCMs are likely several folds more immunogenic compared to missense mutations, exemplified by the recurrent GATA3 SCM. Further, high expression of PD-1 and PD-L1 was observed in tumors with SCMs, suggesting candidates for immune blockade therapy. Our work highlights the importance of integrating DNA and RNA data for understanding the functional and the clinical implications of mutations in human diseases. [ABSTRACT FROM AUTHOR]

Recognition of the host plant is a prerequisite for infection by pathogenic bacteria. However, how bacterial cells sense plant-derived stimuli, especially chemicals that function in regulating plant development, remains completely unknown. Here, we have identified a membrane-bound histidine kinase of the phytopathogenic bacterium Xanthomonas campestris, PcrK, as a bacterial receptor that specifically detects the plant cytokinin 2-isopentenyladenine (2iP). 2iP binds to the extracytoplasmic region of PcrK to decrease its autokinase activity. Through a four-step phosphorelay, 2iP stimulation decreased the phosphorylation level of PcrR, the cognate response regulator of PcrK, to activate the phosphodiesterase activity of PcrR in degrading the second messenger 3',5'-cyclic diguanylic acid. 2iP perception by the PcrK-PcrR remarkably improves bacterial tolerance to oxidative stress by regulating the transcription of 56 genes, including the virulenceassociated TonB-dependent receptor gene ctrA. Our results reveal an evolutionarily conserved, inter-kingdom signaling by which phytopathogenic bacteria intercept a plant hormone signal to promote adaptation to oxidative stress. [ABSTRACT FROM AUTHOR]

Since its high stability, large specific surface area, honeycomb structure, high recovery and reproducibility, magnetic graphene has become a research hotspot in recent years. Batch equilibrium experiments of methylene blue (MB) were conducted on magnetic graphene nanosheets (Fe 3 O 4 @GNs) and magnetic graphene oxide (Fe 3 O 4 @GO) to probe effect of oxygen-containing functional groups (OFGs) on the potential active centers and adsorption mechanism of the cationic dyes. The microstructure and morphology of the magnetic graphene-based materials were characterized by X-ray diffraction spectra (XRD), Fourier transform infrared spectra (FTIR) and Scanning electron microscopy (SEM) technologies. Owing to the OFGs attenuation, Fe 3 O 4 @GNs presented a very high maximum monolayer MB adsorption capacity of 211.34 mg g −1 at 318 K and can be recycled easily by an external magnet. The kinetic results prove that the adsorption rate of MB mainly controlled by a chemical-sorption involving π–π force through sharing and electrons exchange between Fe 3 O 4 @GNs and MB molecular. It indicates that the enhanced hydrophobic and the strong π–π interaction can be influenced from the disappearing of C O functional groups. This group may be responsible for the attractive performance of Fe 3 O 4 @GNs. In addition, SEM results confirm that the role of Fe 3 O 4 nanoparticles is not only can effectively prevent the aggregation of GNs but also be beneficial to improving the adsorption ability. [ABSTRACT FROM AUTHOR]

Two novel bipolar Ir(III) complexes named (Czppy) 2 Ir(tfmptz) and (Czppy) 2 Ir(pptz) were synthesized and characterized, where the Czppy is 9-(4-(pyridin-2-yl)phenyl)-9H-carbazole, tfmptz refers to 2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)pyridine and Hpptz represents 2-(1H-tetrazol-5-yl)pyridine, respectively. Their molecular structures were confirmed by 1 H NMR and photophysical were investigated. The performances in phosphorescent organic light emitting devices (PhOLEDs) were characterized by a heavy doping concentration of 20 wt% in host as emitting layer. The results suggest that the number of nitrogen atoms in ancillary has no obvious effects on their photophysical properties. Both (Czppy) 2 Ir(tfmptz) and (Czppy) 2 Ir(pptz) display the blue-green emission with the peaks at 492, 526 nm. The performances of complexes (Czppy) 2 Ir(tfmptz) in PhOLEDs superior to that of the (Czppy) 2 Ir(pptz) due to the poor thermal stability. [ABSTRACT FROM AUTHOR]

• Dy 3 Ni 2 ingots and melt-spun ribbons were fabricated. • The ductility and coercive force were enhanced obviously with increasing the melt-spinning rate. • The phase transition temperature was tuned successfully in a range between 40 and 60 K by controlling the solidification rate. • A significant enhancement of refrigerant capacity power and an increase of the full-width-at-half maximum of the temperature dependence of magnetic entropy change curve were obtained in Dy 3 Ni 2 ribbons. Both mechanical and magnetic properties of Dy 3 Ni 2 ingots and melt-spun ribbons were investigated in the present work. The melt spinning rate has an important effect on their performance. The higher the melt spinning rate, the better the ductility, the larger the coercive force of ribbons. With increasing the spinning rate, the intensity of the diffraction peak suggesting the presence of polycrystalline becomes weaker and weaker, and eventually disappeared. The magnetic phase transition temperature is decreased from 66 K to 38 K with increasing the spinning rate. All samples undergo a second order paramagnetic-ferromagnetic phase transition. The full-width-at-half maximum of the temperature dependence of magnetic entropy change curve in Dy 3 Ni 2 ribbons was much larger than that of Dy 3 Ni 2 ingot. So a high refrigerant capacity power about 530 J.kg −1 of Dy 3 Ni 2 ribbons was achieved. [ABSTRACT FROM AUTHOR]

Indoleamine 2,3-dioxygenase 1 (IDO1) is regarded as an attractive target for cancer immunotherapy. To rationalize the detailed interactions between IDO1 and its inhibitors at the atomic level, an integrated computational approach by combining molecular mechanics and quantum mechanics methods was employed in this report. Specifically, the binding modes of 20 inhibitors was initially investigated using the induced fit docking (IFD) protocol, which outperformed other two docking protocols in terms of correctly predicting ligand conformations. Secondly, molecular dynamics (MD) simulations and MM/PBSA free energy calculations were employed to determine the dynamic binding process and crucial residues were confirmed through close contact analysis, hydrogen-bond analysis and binding free energy decomposition calculations. Subsequent quantum mechanics and nonbonding interaction analysis were carried out to provide in-depth explanations on the critical role of those key residues, and Arg231 and 7-propionate of the heme group were major contributors to ligand binding, which lowed a great amount of interaction energy. We anticipate that these findings will be valuable for enzymatic studies and rational drug design. [ABSTRACT FROM AUTHOR]

Transition-metal-free hydrodehalogenation of aryl halides (eg. bromides) can take place efficiently in the presence of green polyethylene glycol (PEG-800) and t-BuOK without adding any extra solvents and additives. A radical mechanism is proposed for this transition-metal-free dehalogenation of aryl halides and the role of polyethylene glycol is both reaction promotor and activated alkyl CH donor. [ABSTRACT FROM AUTHOR]

BACKGROUND & AIMS: The incidence of inflammatory bowel disease (IBD) is increasing in Asia, but little is known about disease progression in this region. The Asia-Pacific Crohn's and Colitis Epidemiology Study was initiated in 2011, enrolling subjects from 8 countries in Asia (China, Hong Kong, Indonesia, Sri Lanka, Macau, Malaysia, Singapore, and Thailand) and Australia. We present data from this ongoing study. METHODS: We collected data on 413 patients diagnosed with IBD (222 with ulcerative colitis [UC], 181 with Crohn's disease [CD], 10 with IBD unclassified; median age, 37 y) from 2011 through 2013. We analyzed the disease course and severity and mortality. Risks for medical and surgical therapies were assessed using Kaplan-Meier analysis. RESULTS: The cumulative probability that CD would change from inflammatory to stricturing or penetrating disease was 19.6%. The cumulative probabilities for use of immunosuppressants or anti-tumor necrosis factor agents were 58.9% and 12.0% for patients with CD, and 12.7% and 0.9% for patients with UC, respectively. Perianal CD was associated with an increased risk of anti-tumor necrosis factor therapy within 1 year of its diagnosis (hazard ratio, 2.97; 95% confidence interval, 1.09-8.09). The cumulative probabilities for surgery 1 year after diagnosis were 9.1% for patients with CD and 0.9% for patients with UC. Patients with CD and penetrating disease had a 7-fold increase for risk of surgery, compared with patients with inflammatory disease (hazard ratio, 7.67; 95% confidence interval, 3.93-14.96). The overall mortality for patients with IBD was 0.7%. CONCLUSIONS: In a prospective population-based study, we found that the early course of disease in patients with IBD in Asia was comparable with that of the West. Patients with CD frequently progress to complicated disease and have accelerated use of immunosuppressants. Few patients with early stage UC undergo surgery in Asia. Increasing our understanding of IBD progression in different populations can help optimize therapy and improve outcomes. [ABSTRACT FROM AUTHOR]

In wild-type phototrophic organisms, carotenoids (Crts) are primarily packed into specific pigment–protein complexes along with (Bacterio)chlorophylls and play important roles in the photosynthesis. Diphenylamine (DPA) inhibits carotenogenesis but not phototrophic growth of anoxygenic phototrophs and eliminates virtually all Crts from photocomplexes. To investigate the effect of Crts on assembly of the reaction center–light-harvesting (RC–LH) complex from the filamentous anoxygenic phototroph Roseiflexus (Rfl.) castenholzii, we generated carotenoidless (Crt-less) RC–LH complexes by growing cells in the presence of DPA. Here, we present cryoEM structures of the Rfl. castenholzii native and Crt-less RC–LH complexes with resolutions of 2.86 Å and 2.85 Å, respectively. From the high-quality map obtained, several important but previously unresolved details in the Rfl. castenholzii RC–LH structure were determined unambiguously including the assignment and likely function of three small polypeptides, and the content and spatial arrangement of Crts with bacteriochlorophyll molecules. The overall structures of Crt-containing and Crt-less complexes are similar. However, structural comparisons showed that only five Crts remain in complexes from DPA-treated cells and that the subunit X (TMx) flanked on the N-terminal helix of the Cyt-subunit is missing. Based on these results, the function of Crts in the assembly of the Rfl. castenholzii RC–LH complex and the molecular mechanism of quinone exchange is discussed. These structural details provide a fresh look at the photosynthetic apparatus of an evolutionary ancient phototroph as well as new insights into the importance of Crts for proper assembly and functioning of the RC–LH complex. [ABSTRACT FROM AUTHOR]