Triaxial Creep Mechanical Behaviors and Creep Damage Model of Dolomitic Limestone Material under Multi-Stage Incremental Loading.

Dolomitic limestone is the main surrounding rock material in Yangzong tunnel engineering; the instantaneous mechanical properties and creep behaviors of limestone are significant for stability evaluation during the stages of tunnel excavation and long-term maintenance. Herein, four conventional triaxial compression tests were carried out to explore its instantaneous mechanical behavior and failure characteristics; subsequently, the creep behaviors of limestone subjected to multi-stage incremental axial loading at the confinements of 9 MPa and 15 MPa were studied by employing an advanced rock mechanics testing system (i.e., MTS815.04). The results reveal the following. (1) comparing the curves of axial strain-, radial strain-, and volumetric strain-stress under different confining pressures shows that these curves present a similar trend, whereas the stress drops during the post-peak stage decelerate with the increase in confining pressure, suggesting that the rock transits from brittleness to ductility. The confining pressure also has a certain role in controlling the cracking deformation during the pre-peak stage. Besides, the proportions of compaction- and dilatancy-dominated phases in the volumetric strain-stress curves differ obviously. Moreover, the failure mode of the dolomitic limestone is a shear-dominated fracture but is also affected by the confining pressure. (2) When the loading stress reaches a creep threshold stress, the primary and steady-state creep stages occur successively, and a higher deviatoric stress corresponds to a greater creep strain. When the deviatoric stress surpasses an accelerated creep threshold stress, a tertiary creep appears and then is followed by creep failure. Furthermore, the two threshold stresses at 15 MPa confinement are greater than that at 9 MPa confinement, suggesting that the confining pressure has an obvious impact on the threshold values and a higher confining pressure corresponds to a greater threshold value. Additionally, the specimen's creep failure mode is one of "abrupt" shear-dominated fracturing and is similar to that under a conventional triaxial compression test at high confining pressure. (3) A multi-element nonlinear creep damage model is developed by bonding a proposed visco-plastic model in series with the Hookean substance and Schiffman body, and can accurately describe the full-stage creep behaviors.

The cardiovascular protective effect and mechanism of calycosin and its derivatives.

Cardiovascular disease is the main cause of mortality and morbidity in the world, especially in developing countries. Drug therapy is one of the main ways to treat cardiovascular diseases. Among them, great progress has been made in the treatment of cardiovascular diseases with traditional Chinese medicine. In terms of experimental research, the mechanism of traditional Chinese medicine in the treatment of cardiovascular diseases has been thoroughly discussed in vitro and in vivo. In terms of clinical treatment, traditional Chinese medicine with flavonoids, saponins and alkaloids as the main effective components has a definite effect on the treatment of cardiovascular diseases such as arrhythmia, myocardial ischemia, angina pectoris and myocardial infarction, with high safety and good application prospects. With the further research on the effective ingredients, mechanism and adverse reactions of traditional Chinese medicine, it will be beneficial to the effectiveness of traditional Chinese medicine, reduce side effects and promote the modernization of traditional Chinese medicine. Calycosin and its derivatives, the main bioactive flavonoids in Astragalus membranaceus have multiple biological effects, such as antioxidant, pro-angiogenesis, anti-tumour, and anti-inflammatory effects. Based on the above biological effects, calycosin has been shown to have good potential for cardiovascular protection. The potent antioxidant effect of calycosin may play an important role in the cardiovascular protective potential. For injured cardiac myocytes, calycosin and its derivatives can alleviate the cell damage mainly marked by the release of myocardial enzymes and reduce the death level of cardiac myocytes mainly characterized by apoptosis through various mechanisms. For vascular endothelial cells, calycosin also has multiple effects and multiple mechanisms, such as promoting vascular endothelial cell proliferation, exerting vasodilating effect and directly affecting the synthesis function of endothelial cells. The present review will address the bioactivity of calycosin in cardiovascular diseases such as protective effects on cardiac myocytes and vascular endothelial cells and elucidate main mechanism of calycosin and its derivatives to exert the above biological effects.

Oleuropein Protects Cardiomyocyte against Apoptosis via Activating the Reperfusion Injury Salvage Kinase Pathway In Vitro.

Oleuropein, the main glycoside present in olives, has been reported to have cardioprotective effect, but the exact mechanism has not been clearly elucidated. This study attempted to clarify the cardioprotective effect of oleuropein against simulated ischemia/reperfusion- (SI/R-) induced cardiomyocyte injury in vitro and further explore the underlying mechanism. Here we confirmed that oleuropein reduced the cell injury in neonatal rat cardiomyocyte induced by SI/R evidenced by decreasing MTT dye reduction and LDH activity in the culture medium. Meanwhile, the compound also inhibited reactive oxygen species excessive generation and stabilized mitochondrial membrane potential after SI/R. The flow cytometry assessment results indicated the inhibition of cellular apoptosis with oleuropein treatment. Furthermore, western blot analysis showed that oleuropein attenuated the expression of Cyt-C, c-caspase-3, and c-caspase-9, increased the Bcl-2/Bax ratio, and enhanced the phosphorylation of ERK1/2 and Akt after SI/R. However, the phosphorylation enhancement was partially abolished in the presence of LY294002 (PI3K inhibitor) and U0126 (ERK inhibitor). All these findings indicate that oleuropein has the protective potential against SI/R-induced injury and its protective effect may be partly due to the attenuation of apoptosis via the activation of the PI3K/Akt and ERK1/2 signaling pathways.

Changed profile of microRNAs in acute lung injury induced by cardio-pulmonary bypass and its mechanism involved with SIRT1.

OBJECTIVE: Acute lung injury (ALI) is a severe complication for patients undergoing cardiac surgery necessitating cardio-pulmonary bypass (CPB), however, the possible relationship between microRNAs change and ALI induced by CPB is still not completely understood. OBJECTIVE: the aim of this study is to determine the microRNAs level changes in patients with ALI induced by CPB and its involved mechanism. METHODS: We collected blood samples from 45 patients and performed microRNA microarray experiments to determine the microRNAs level changes in patients with ALI induced by CPB then the result was verified by quantitative real-time PCR (qRT-PCR). Plasma TNF-α level and respiration parameters including respiration index (RI) and oxygenation index (OI) were measured at five different time points before or after CPB. Meanwhile the correlationship between significantly changed microRNAs and TNF-α level and respiration parameters was analyzed. Further more, we transfected miR-320 mimic and inhibitor into A549 cells and observed the proliferation inhibition and apoptosis change caused by oxygen-glucose deprivation/reperfusion. Finally we using dual-luciferase reporter assay, qRT-PCR and western blot investigated the potential target of miR-320. RESULTS: The level of miR-320 was higher in CPB caused ALI with the most significance. Correlation analysis found that the level of miR-320 was positively associated with TNF-α and RI (r = 0.649 and 0.564, P < 0.05), but negative correlated with OI (r = -0.638, P < 0.05). In A549 cells, up-regulated miR-320 induced proliferation inhibition and more apoptosis. SIRT1 may be a target of miR-320 and higher miR-320 resulted in lower expression of SIRT both in mRNA and protein level. CONCLUSION: miR-320 may mediate the ALI after CPB in which alveolar epithelial cells are injured via down-regulating SIRT1.