Search

Signal transducer and activator of transcription 3 (STAT3) has a critical role in regulating cell fate, inflammation and immunity.sup.1,2. Cytokines and growth factors activate STAT3 through kinase-mediated tyrosine phosphorylation and dimerization.sup.3,4. It remains unknown whether other factors promote STAT3 activation through different mechanisms. Here we show that STAT3 is post-translationally S-palmitoylated at the SRC homology 2 (SH2) domain, which promotes the dimerization and transcriptional activation of STAT3. Fatty acids can directly activate STAT3 by enhancing its palmitoylation, in synergy with cytokine stimulation. We further identified ZDHHC19 as a palmitoyl acyltransferase that regulates STAT3. Cytokine stimulation increases STAT3 palmitoylation by promoting the association between ZDHHC19 and STAT3, which is mediated by the SH3 domain of GRB2. Silencing ZDHHC19 blocks STAT3 palmitoylation and dimerization, and impairs the cytokine- and fatty-acid-induced activation of STAT3. ZDHHC19 is frequently amplified in multiple human cancers, including in 39% of lung squamous cell carcinomas. High levels of ZDHHC19 correlate with high levels of nuclear STAT3 in patient samples. In addition, knockout of ZDHHC19 in lung squamous cell carcinoma cells significantly blocks STAT3 activity, and inhibits the fatty-acid-induced formation of tumour spheres as well as tumorigenesis induced by high-fat diets in an in vivo mouse model. Our studies reveal that fatty-acid- and ZDHHC19-mediated palmitoylation are signals that regulate STAT3, which provides evidence linking the deregulation of palmitoylation to inflammation and cancer. The palmitoylation of STAT3 is mediated by fatty acids and/or the palmitoyl acyltransferase ZDHHC19, and deregulation of this palmitoylation has a role in inflammation and tumorigenesis., Author(s): Jixiao Niu [sup.1] , Yang Sun [sup.1] , Baoen Chen [sup.1] , Baohui Zheng [sup.1] , Gopala K. Jarugumilli [sup.1] , Sarah R. Walker [sup.2] [sup.3] [sup.6] , Aaron [...]

Unbiased, 'nontargeted' metabolite profiling techniques hold considerable promise for biomarker and pathway discovery, in spite of the lack of successful applications to human disease. By integrating nontargeted metabolomics, genetics, and detailed human phenotyping, we identified dimethylguanidino valeric acid (DMGV) as an independent biomarker of CTdefined nonalcoholic fatty liver disease (NAFLD) in the offspring cohort of the Framingham Heart Study (FHS) participants. We verified the relationship between DMGV and early hepatic pathology. Specifically, plasma DMGV levels were correlated with biopsy-proven nonalcoholic steatohepatitis (NASH) in a hospital cohort of individuals undergoing gastric bypass surgery, and DMGV levels fell in parallel with improvements in post-procedure cardiometabolic parameters. Further, baseline DMGV levels independently predicted future diabetes up to 12 years before disease onset in 3 distinct human cohorts. Finally, we provide all metabolite peak data consisting of known and unidentified peaks, genetics, and key metabolic parameters as a publicly available resource for investigations in cardiometabolic diseases., Introduction Nonalcoholic fatty liver disease (NAFLD) is defined by the presence of hepatic steatosis (via histology or imaging) when there are no causes for secondary hepatic fat accumulation, and it [...]

High viscosity liquids are frequently used in industry and our daily life. So, it is important to develop a lyophobic and low adhesive surface to high viscosity liquids. Here, lyophobic copper surfaces were prepared by a simple solution immersion process. The copper plate with micro-pillar arrays was immersed in a solution containing NaOH and (NH4)2S2O8 to form the hierarchical micro-/nanostructure, and then immersed in a solution of perfluorosilane to reduce the surface energy. Consequently, the lyophobic and low adhesive surface was obtained. The static contact angles of HTPB and HTPB/Al were all higher than 140°, which indicate good lyophobic properties of the surface to the high viscosity liquids. The hierarchical micro-/nanostructure formed in the solution containing 5 mol/L NaOH and 0.3 mol/L (NH4)2S2O8 for 8 h could efficiently decrease the liquid-solid contact area, and then reduce the adhesion forces between the surface and the high viscosity liquids, e. g., 25.5 µN for HTPB and 42.2 µN for HTPB/A1. [ABSTRACT FROM AUTHOR]

ABSTRACT: Polystyrene (PS) microencapsulated paraffin wax (MePW) and PS–SiO2 MePW were used to improve the form‐stability of PW in hydroxyl‐terminated polybutadiene‐derived polyurethane (HTPB) binder. HTPB matrix containing different contents of PS MePW, PS–SiO2 MePW, and PW were prepared. The chemical composition, crystallinity, microstructure, heat capacities, thermal stabilities, thermal reliabilities, leakage, and mechanical properties of the composites were compared using Fourier transforms infrared spectroscope, X‐ray diffractometer, scanning electronic microscope, differential scanning calorimeter, thermo‐gravimetric analyzer, thermal cycling test, leaking test, compression, and tensile tests, respectively. The results showed that the MePW/PW/HTPB composites were prepared without chemical reaction. The thermal stability and mechanical properties of PS–SiO2 MePW/PW/HTPB increased more dramatically than that of PS MePW/PW/HTPB. With the increasing contents of MePWs, the PW leakage of the composites decreased, especially for PS MePW/PW/HTPB. Consequently, the MePW/PW/HTPB composites possess a potential application for PW‐based polymer‐bonded explosive system. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46222. [ABSTRACT FROM AUTHOR]