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Abstract Developing high‐performance and reusable adhesives from renewable feedstocks is of significance to sustainable development, yet it still remains a formidable task. Herein, castor oil, melevodopa, and iron ions are used as building blocks to construct a novel bio‐based supramolecular adhesive (BSA) with outstanding adhesion performances. It is prepared through partial coordination between melevodopa functionalized castor oil and Fe3+ ions. Noncovalent interactions between adherends and the catechol unit from melevodopa contribute to reinforcing adhesion, and the metal‐ligand coordination between catechol and Fe3+ ions is utilized to strengthen cohesion. By combining strong adhesion and tough cohesion, the prepared BSA achieves an adhesion strength of 14.6 MPa at ambient temperature, a record‐high value among reported bio‐based adhesives as well as supramolecular adhesives to the best of knowledge. It also outperforms those adhesives at cryogenic temperature, realizing another record‐high adhesion strength of 9.5 MPa at −196 °C. In addition, the BSA displays excellent multi‐reusability with more than 87% of the original adhesion strength remaining even after reuse for ten times. It is highly anticipated that this line of research will provide a new insight into designing bio‐based adhesives with outstanding adhesion performances and excellent multi‐reusability.

Abstract Aims/Introduction To compare the effects of gliclazide, liraglutide and metformin on body composition in patients with type 2 diabetes mellitus with non‐alcoholic fatty liver disease. Materials and Methods A total of 85 patients were randomly allocated to receive gliclazide (n = 27), liraglutide (n = 29) or metformin (n = 29) monotherapy for 24 weeks. Body composition was measured using dual‐energy X‐ray absorptiometry. Results Liraglutide and metformin reduced total, trunk, limb, android and gynoid fat mass; this also led to weight reduction. However, gliclazide treatment produced no significant changes in weight or fat mass, likely because reductions in fat mass were concomitant with increases in lean tissue mass. Blood glucose concentrations and glycated hemoglobin levels improved in all treatment arms; levels of the latter were lower in patients treated with liraglutide and metformin. Serum alanine aminotransferase concentrations decreased in all treatment arms, whereas serum aspartate aminotransferase concentrations were reduced only by liraglutide and metformin. In all patients, weight loss and total, trunk, limb, and android fat mass reductions were positively correlated with decreases in serum alanine aminotransferase and aspartate aminotransferase levels, whereas reductions in waist circumference were positively correlated with lower serum alanine aminotransferase levels. Conclusions Compared with gliclazide, liraglutide and metformin monotherapies result in greater weight loss, reductions in body fat mass, and better blood glucose control among type 2 diabetes mellitus patients with non‐alcoholic fatty liver disease. Reductions in weight, fat mass and waist circumference favorably affect hepatic function.

Development of nitrate tolerance is a major drawback to nitrate therapy. Prostacyclin (PGI2) is a powerful vasodilator produced from prostaglandin (PGH2) by prostacyclin synthase (PGIS) in endothelial cells. This study aimed to determine the role of PGIS S-nitrosylation in nitrate tolerance induced by nitroglycerin (GTN). In endothelial cells, GTN increased PGIS S-nitrosylation and disturbed PGH2 metabolism, which were normalized by mutants of PGIS cysteine 231/441 to alanine (C231/441A). Clearance of nitric oxide by carboxy-PTIO or inhibition of S-nitrosylation by N-acetyl-cysteine decreased GTN-induced PGIS S-nitrosylation. Enforced expression of mutated PGIS with C231/441A markedly abolished GTN-induced PGIS S-nitrosylation and nitrate cross-tolerance in Apoe -/- mice. Inhibition of cyclooxygenase 1 by aspirin, supplementation of PGI2 by beraprost, and inhibition of PGIS S-nitrosylation by N-acetyl-cysteine improved GTN-induced nitrate cross-tolerance in rats. In patients, increased PGIS S-nitrosylation was associated with nitrate tolerance. In conclusion, GTN induces nitrate cross-tolerance through PGIS S-nitrosylation at cysteine 231/441., (© 2018 American Society for Clinical Pharmacology and Therapeutics.)

Several transcription factors function in the specification and differentiation of the endoderm, including the zinc finger transcription factor GATA4. Despite its essential role in endoderm development, the transcriptional control of the Gata4 gene in the developing endoderm and its derivatives remains incompletely understood. Here, we identify a distal enhancer from the Gata4 gene, which directs expression exclusively to the visceral and definitive endoderm of transgenic mouse embryos. The activity of this enhancer is initially broad within the definitive endoderm but later restricts to developing endoderm-derived tissues, including pancreas, glandular stomach, and duodenum. The activity of this enhancer in vivo is dependent on evolutionarily-conserved HOX- and GATA-binding sites, which are bound by PDX-1 and GATA4, respectively. These studies establish Gata4 as a direct transcriptional target of homeodomain and GATA transcription factors in the endoderm and support a model in which GATA4 functions in the transcriptional network for pancreas formation.