Metabolic inflammatory damage, characterized by Toll-like receptor 4 (TLR4) signaling activation, is a major mechanism underlying lipotoxicity-induced β-cell damage. The present study is aimed at determining whether G protein-coupled receptor 4 (GPR40) agonist can improve β-cell lipotoxicity-induced damage by inhibiting the TLR4-NF-κB pathway. Lipotoxicity, inflammation-damaged β-cells, obese SD, and TLR4KO rat models were used in the study. In vitro, TAK-875 inhibited the lipotoxicity- and LPS-induced β-cell apoptosis in a concentration-dependent manner, improved the insulin secretion, and inhibited the expression of TLR4 and NF-κB subunit P65. Besides, silencing of TLR4 expression enhanced the protective effects of TAK-875, while TLR4 overexpression attenuated this protective effect. Activation of TLR4 or NF-κB attenuated the antagonism of TAK-875 on PA-induced damage. Moreover, the above process of TAK-875 was partially independent of GPR40 expression. TAK-875 reduced the body weight and inflammatory factors, rebalanced the number and distribution of α or β-cells, inhibited the apoptosis of islet cells, and inhibited the expression of TLR4 and NF-κB subunit P65 in obese rats. Further knockout of the rat TLR4 gene delayed the damage induced by the high-fat diet and synergy with the action of TAK-875. These data suggest that GPR40 agonists antagonized the lipotoxicity β-cell damage by inhibiting the TLR4-NF-κB pathway.
The study of maneuverability performance of damaged ship is a major and difficult issue in the study of ship, but the evaluation of damaged ship maneuverability which is one of important damaged ship performance has not been found. In order to predict the damaged ship maneuverability and explore one feasible evaluation method, the assessment factors about damaged ship maneuverability are established innovatively based on its some maneuverability experiments, standards and criteria of intact ship maneuverability, and navigation practice. Then, analytic evaluation process(AHP) and grey relational comprehensive evaluation are combined to evaluate the damaged maneuverability of 29000 ton oil tanker in two kinds of damaged conditions. The values of evaluation factors come from the maneuverability experiments which had been done based on a ship model motion intelligent-controller system. The evaluation example indicates that the assessment factors of damaged maneuverability are feasible, and the synthetic assessment method is effective and concise in evaluating damaged maneuverability. The research can provide some references for ship designers and ship commanders, and is also premise to research an intelligent evaluation system of damaged ship maneuverability.
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