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Diabetic cardiac fibrosis increases ventricular stiffness and facilitates the occurrence of diastolic dysfunction. Retinoid X receptor (RXR) plays an important role in cardiac development and has been implicated in cardiovascular diseases. In the present study, we investigated the effects of RXR agonist treatment on streptozotocin (STZ)-induced diabetic cardiomyopathy (DCM) and the underlying mechanism. Sprague-Dawley (SD) rats induced by STZ injection were treated with either RXR agonist bexarotene (Bex) or vehicle alone. Echocardiography was performed to determine cardiac structure and function. Cardiac fibroblasts (CFs) were treated with high glucose (HG) with or without the indicated concentration of Bex or the RXR ligand 9-cis-retinoic acid (9-cis-RA). The protein abundance levels were measured along with collagen, body weight (BW), blood biochemical indexes and transforming growth factor-β (TGF-β) levels. The effects of RXRα down-regulation by RXRα small interfering RNA (siRNA) were examined. The results showed that bexarotene treatment resulted in amelioration of left ventricular dysfunction by inhibiting cardiomyocyte apoptosis and myocardial fibrosis. Immunoblot with heart tissue homogenates from diabetic rats revealed that bexarotene activated liver kinase B1 (LKB1) signaling and inhibited p70 ribosomal protein S6 kinase (p70S6K). The increased collagen levels in the heart tissues of DCM rats were reduced by bexarotene treatment. Treatment of CFs with HG resulted in significantly reduced LKB1 activity and increased p70S6K activity. RXRα mediated the antagonism of 9-cis-RA on HG-induced LKB1/p70S6K activation changes in vitro. Our findings suggest that RXR agonist ameliorates STZ-induced DCM by inhibiting myocardial fibrosis via modulation of the LKB1/p70S6K signaling pathway. RXR agonists may serve as novel therapeutic agents for the treatment of DCM. [ABSTRACT FROM AUTHOR]

In this paper, 30 beam tests, 48 Losberg pullout tests and 6 standard pullout tests were conducted to investigate bond-slip response of sand-coated deformed glass fibre-reinforced polymer (GFRP) rebars in concrete. The specimen parameters varied were concrete strength, embedment length, bar diameter and test method. Two failure modes including pullout failure and splitting failure were observed. The experimental bond stress-slip (τ-s) curves of sand-coated deformed GFRP rebars in concrete in pullout failure included a micro-slippage branch, a slippage branch, a descending branch and a residual branch, while the τ-s curves in splitting failure included a micro-slippage branch and a slippage branch. Based on the tests, a new bond-slip constitutive model for sand-coated deformed GFRP rebars in concrete was presented. Compared with other available models, the model proposed in this paper can provide more reliable simulations of the test results. [ABSTRACT FROM AUTHOR]