The dynamic reliability models of mechanical components with the failure mode of fatigue are mainly based on the linear damage accumulation theory, which is also called the Miner’s rule. But the Miner’s rule has some drawbacks and results in the disagreement between the predicted and experimental value. In this paper, a dynamic reliability model is presented based on a nonlinear fatigue damage accumulation model. First, a modified nonlinear fatigue damage accumulation model based on the Manson–Halford theory is proposed, which considers not only the effect of load sequence but also the influence of load interaction. Some sets of experimental data are used to verify the proposed nonlinear fatigue damage accumulation model under two-stress level loading and multilevel staged loading. The results show that the proposed method has a better agreement between the experimental data and predicted values than the Miner’s rule. Then, based on the modified nonlinear fatigue damage accumulation model, the dynamic reliability model is presented. The data obtained by this dynamic reliability model are compared with Monte Carlo results, and it shows good agreement with Monte Carlo results.
Retinoic acid receptor α (RARα), a member of family of the nuclear retinoic acid receptors (RARs), plays an essential role in various chronic kidney diseases (CKD). Renal tubular epithelial to mesenchymal transition (EMT) is a common mechanism of progression of renal interstitial fibrosis (RIF). Hypoxia has been extensively considered as one of major inducers of renal tubular EMT. However, the effects of RARα on hypoxia-induced EMT have not yet been described so far. The aim of the present study was to explore the roles and potential mechanisms of RARα in hypoxia-induced EMT of renal tubular epithelial cells (RTECs). Our results showed that expression of RARα in RTECs subjected to hypoxia significantly was reduced, accompanied by decreased expression level of the epithelial marker E-cadherin, and increased expression levels of the mesenchymal markers α-smooth muscle actin (α-SMA) and vimentin, in accord with EMT. Meanwhile, hypoxia could cause RTECs to obviously express TGF-β and matrix metalloproteinase-9 (MMP-9). Furthermore, using lentivirus-based delivery vectors to overexpress RARα in RTECs, we demonstrated that RARα alleviated hypoxia-induced EMT of RTECs and downregulated the expression levels of TGF-β and MMP-9. In a word, RARα protects RTECs against EMT induced by hypoxia associated with TGF-β/MMP-9 pathway.
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