OBJECTIVE: ASPP1 (apoptosis stimulating of p53 protein 1) is critical in regulating cell apoptosis as a cofactor of p53 to promote its transcriptional activity in the nucleus. However, whether cytoplasmic ASPP1 affects p53 nuclear trafficking and its role in cardiac diseases remains unknown. This study aims to explore the mechanism by which ASPP1 modulates p53 nuclear trafficking and the subsequent contribution to cardiac ischemia/reperfusion (I/R) injury. METHODS AND RESULTS: The immunofluorescent staining showed that under normal condition ASPP1 and p53 colocalized in the cytoplasm of neonatal mouse ventricular cardiomyocytes, while they were both upregulated and translocated to the nuclei upon hypoxia/reoxygenation treatment. The nuclear translocation of ASPP1 and p53 was interdependent, as knockdown of either ASPP1 or p53 attenuated nuclear translocation of the other one. Inhibition of importin-β1 resulted in the cytoplasmic sequestration of both p53 and ASPP1 in neonatal mouse ventricular cardiomyocytes with hypoxia/reoxygenation stimulation. Overexpression of ASPP1 potentiated, whereas knockdown of ASPP1 inhibited the expression of Bax (Bcl2-associated X), PUMA (p53 upregulated modulator of apoptosis), and Noxa, direct apoptosis-associated targets of p53. ASPP1 was also increased in the I/R myocardium. Cardiomyocyte-specific transgenic overexpression of ASPP1 aggravated I/R injury as indicated by increased infarct size and impaired cardiac function. Conversely, knockout of ASPP1 mitigated cardiac I/R injury. The same qualitative data were observed in neonatal mouse ventricular cardiomyocytes exposed to hypoxia/reoxygenation injury. Furthermore, inhibition of p53 significantly blunted the proapoptotic activity and detrimental effects of ASPP1 both in vitro and in vivo. CONCLUSIONS: Binding of ASPP1 to p53 triggers their nuclear cotranslocation via importin-β1 that eventually exacerbates cardiac I/R injury. The findings imply that interfering the expression of ASPP1 or the interaction between ASPP1 and p53 to block their nuclear trafficking represents an important therapeutic strategy for cardiac I/R injury.

This study focuses on a safety evaluation method for underground gas storage. Gas storage is usually constructed underground in complex environments, and the service life of such facilities is limited. To ensure the secure and long-term operation of gas storage facilities, safety evaluation has become the focus of management. The present paper provides an effective method for safety evaluation. An index system was established as the foundation of the analysis for this evaluation, and the matter-element extension method was applied to obtain a quantitative evaluation result. For the weight values of each index in the matter-element extension method, this paper presents a comprehensive weight computation method based on vague sets and entropy. By application of this method, the safety level of a gas storage facility in the Jintan salt mines (in Jiangsu, China) was calculated, and the evaluation result was 4.6433, which meant the safety level was V and the underground gas storage was slightly at risk. It indicated that the influence on the overall safety and tightness of this gas storage could be ignored in the operation process, but the frequency of regular monitoring should be increased. The defective indexes were also obtained, such as salt rock cohesion, the roof thickness, the volume contraction ratio, the interlayer content, the height of the casing shoe and the adjacent cavity pressure difference, which need to be monitored and modified. This paper evaluated the safety of the underground gas storage from a unique perspective. It is expected that the results of this research will contribute to the maintenance and operational decisions, and provide a reference for management in the energy industry.

Using a difference‐in‐differences (DID) approach, this paper evaluates the effects of China's accelerated depreciation policy on corporate leverage. We find that the policy significantly increases corporate total leverage, which is mainly driven by the increase in long‐term leverage. Moreover, raising investment in fixed assets serves as the primary mediating channel through which the policy affects long‐term leverage and thus, total leverage. Finally, the positive effects of the policy on leverage are primarily significant in firms that are not close to tax exhaustion, and firms that invest in long‐lived assets.

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