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Ox-LDL-induced endothelial cells injury has been reported to play an important role in the development of atherosclerosis (AS). MicroRNAs have been identified to regulate their target genes post-transcriptionally and they are able to participate in the various diseases, including AS. However, the role of miR-410 in ox-LDL-triggered abnormal function of endothelial cells remains to be elaborated. Hence, our current study was to find out the underlying mechanism of miR-410 in AS. Here, we observed that ox-LDL can inhibit HUVECs growth and lead to a great cell apoptosis both dose-dependently and time-dependently. Meanwhile, it was exhibited that miR-410 expression was remarkably elevated in ox-LDL-indicated HUVECs. miR-410 knockdown was able to induce cell proliferation and alleviate HUVECs apoptosis subjected to ox-LDL. Reversely, signal transducer and activator of transcription 3 (STAT3) expression was greatly decreased in ox-LDL-incubated HUVECs in a time and dose dependent manner. Additionally, these findings exhibited that STAT3 was a target of miR-410, which was validated by a dual-luciferase assay in our study. Additionally, we observed that overexpression of STAT3 rescued ox-LDL induced AS events in vitro. Taken these together, our current study implied that miR-410 silence can inhibit the ox-LDL-induced HUVECs proliferation and rescue cell apoptosis through activating STAT3 in vitro. [ABSTRACT FROM AUTHOR]

[Display omitted] • Nicotine decreases the expression of DHFR and GCH1 to inhibit BH 4 and NO production. • PCB2 prevents nicotine-induced DHFR and GCH1 loss. • PCB2 improves endothelium-dependent vasorelaxation impaired by nicotine. • PCB2 induces vasorelaxation through a PPARδ-BH 4 dependent manner. Smoking is an independent risk factor for the cardiovascular diseases. Nicotine, a major component of tobacco, is responsible for the impaired endothelial-dependent vasorelaxation in smokers. Procyanidin B2 (PCB2), a natural flavonoid, has been reported to possess several potential beneficial effects on the cardiovascular system. However, whether PCB2 prevents nicotine-induced endothelial dysfunction remains unknown. In this study, we demonstrated that PCB2 improved nicotine-impaired endothelium-dependent vasorelaxation in mouse thoracic aortas. Mechanistically, PCB2 increased the expression levels of dihydrofolate reductase (DHFR) and GTP cyclohydrolase 1 (GCH1), two important enzymes in the synthesis of tetrahydrobiopterin (BH 4), in mouse aortas and cultured ECs. GSK0660, a selective antagonist of peroxisome proliferator-activated receptor δ (PPARδ), abolished the PCB2-induced effects on BH 4 synthesis, nitric oxide (NO) production and vasodilation. Collectively, we demonstrated that PCB2 mitigates nicotine-induced endothelial dysfunction through a PPARδ-BH 4 dependent manner, thereby suggesting a novel role of PCB2 in preventing vascular dysfunction caused by nicotine exposure. [ABSTRACT FROM AUTHOR]

• A lifetime extension strategy for power module in wind energy system is proposed. • This strategy is based on the optimal effectiveness of the thermal management. • The effectiveness gives the choice criteria about temperature swing control target. • Each application of temperature control can improve as much lifetime as possible. • Disturbance on the regular operation of wind energy system is greatly reduced. The power module plays a vital role in the renewable energy conversion. But it is one of the most prone to fail components in the wind energy system. The thermal management has been proved to be a cost-effective mean to improve the reliability of wind energy system, but it has a dual nature. To balance the benefit and risk of thermal management, a lifetime extension strategy is proposed. This strategy considers the minimum junction temperature fixed to the lowest ambient temperature and the allowed maximum junction temperature determined by the predefined temperature swing. Then the related wind speeds of predefined temperature swing can be concentrated in a part wind speed area and the effectiveness of thermal management under each predefined temperature swing is calculated. The optimal effectiveness is chosen as a quantitative evaluation criterion to design the working range of thermal management and control target of junction temperature in a long time scale. As a benefit, the economic performance of thermal management is greatly improved in that each application of temperature control can reduce as much consumed lifetime of power module as possible. Case studies and experiments are presented for performance verification of proposed strategy. Results show that the consumed lifetime reduced by each application of temperature control is 6.04 × 10-3%. The expected lifetime of power module is extended from 7.55 years to 22.08 years which meets the target lifetime of wind power generation system (20 years). In addition, this method only needs to be applied in the specified working range where the wind speed is higher than 9.30 m/s. Thus, the disturbance on the system's normal operation is significantly alleviated. [ABSTRACT FROM AUTHOR]