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In cardiomyocytes, Ca2+ entry through voltage-dependent Ca2+ channels (VDCCs) binds to and activates RyR2 channels, resulting in subsequent Ca2+ release from the sarcoplasmic reticulum (SR) and cardiac contraction. Previous research has documented the molecular coupling of small-conductance Ca2+-activated K+ channels (SK channels) to VDCCs in mouse cardiac muscle. Little is known regarding the role of RyRs-sensitive Ca2+ release in the SK channels in cardiac muscle. In this study, using whole-cell patch clamp techniques, we observed that a Ca2+-activated K+ current (IK,Ca) recorded from isolated adult C57B/L mouse atrial myocytes was significantly decreased by ryanodine, an inhibitor of ryanodine receptor type 2 (RyR2), or by the co-application of ryanodine and thapsigargin, an inhibitor of the sarcoplasmic reticulum calcium ATPase (SERCA) (p<0.05, p<0.01, respectively). The activation of RyR2 by caffeine increased the IK,Ca in the cardiac cells (p<0.05, p<0.01, respectively). We further analyzed the effect of RyR2 knockdown on IK,Ca and Ca2+ in isolated adult mouse cardiomyocytes using a whole-cell patch clamp technique and confocal imaging. RyR2 knockdown in mouse atrial cells transduced with lentivirus-mediated small hairpin interference RNA (shRNA) exhibited a significant decrease in IK,Ca (p<0.05) and [Ca2+]i fluorescence intensity (p<0.01). An immunoprecipitated complex of SK2 and RyR2 was identified in native cardiac tissue by co-immunoprecipitation assays. Our findings indicate that RyR2-mediated Ca2+ release is responsible for the activation and modulation of SK channels in cardiac myocytes.

A rolling bearing is an important connecting part between rotating machines. It is susceptible to mechanical stress and wear, which affect the running state of bearings. In order to effectively identify the fault types and analyze the fault severity of rolling bearings, a rolling bearing fault diagnosis method based on multiscale amplitude-aware permutation entropy (MAAPE) and random forest is proposed in this paper. The vibration signals of rolling bearings to be analyzed are decomposed into different coarse-grained time series by using the coarse-graining procedure in multiscale entropy, highlighting the fault dynamic characteristics of vibration signals at different scales. The fault features contained in the coarse-grained time series at different time scales are extracted by using amplitude-aware permutation entropy’s sensitive characteristics to signal amplitude and frequency changes to form fault feature vectors. The fault feature vector set is used to establish the random forest multi-classifier, and the fault type identification and fault severity analysis of rolling bearings is realized through random forest. In order to demonstrate the feasibility and effectiveness of the proposed method, experiments were fully conducted in this paper. The experimental results show that multiscale amplitude-aware permutation entropy can effectively extract fault features of rolling bearings from vibration signals, and the extracted feature vectors have high separability. Compared with other rolling bearing fault diagnosis methods, the proposed method not only has higher fault type identification accuracy, but also can analyze the fault severity of rolling bearings to some extent. The identification accuracy of four fault types is up to 96.0% and the fault recognition accuracy under different fault severity reached 92.8%.

Creativity plays an irreplaceable role in economic and technological development. It seems that religion has a negative association with creativity. If it is true, how can we interpret the rapid development of human society with religious believers comprising 81% of global population? Based on the datasets of the World Values Survey and the Global Creativity Index, this study examined the effects of different religions/denominations on national creativity, and the moderation effect of gross domestic product per capita (GDPpc) in 87 countries. The results showed that: (1) religiosity was negatively associated with creativity at national level; (2) Proportions of Protestant and Catholic adherents in a country were both positively associated with national creativity, while proportion of Islam adherents was negatively associated with national creativity; (3) GDPpc moderated the relationships of creativity with overall religiosity, proportion of Protestant adherents, and proportion of Catholic adherents. In countries with high GDPpc, national religiosity and proportion of Islam could negatively predict national creativity, and proportion of Protestants could positively predict national creativity; in countries with low GDPpc, these relationships became insignificant. These findings suggest that national religiosity hinders creativity to a certain extent. However, some denominations (i.e., Protestant and Catholic) may exert positive influences on creativity due to their religious traditions and values. The religion–creativity relationship at national level only emerges in affluent countries.

Abstract.Although Beclin 1 has been demonstrated to exert an important role in cell autophagy during carcinogenesis, its biological function in lung cancer has yet to be fully elucidated. A previous study by our laboratory identified that knockdown of Beclin 1 promoted cell growth and inhibited apoptosis in the A549 lung cancer cell line. In the present study, a Beclin 1 lentiviral expression vector was constructed, and an A549 cell line was established with a steady expression of Beclin 1. Furthermore, the effect of Beclin 1 overexpression on cell invasion and apoptosis, changes in the activities of the apoptosis-associated caspases-3 and -9, and the overexpression of esophageal cancer-related gene 4 (ECRG4) were examined. The results demonstrated that the overexpression of Beclin 1 in A549 cells reduced cell invasion by Matrigel invasion assay and promoted apoptosis by flow cytometric analysis (P<0.01) compared with Lenex-packaged lentiviral particles and non-transfected control groups. Furthermore, the overexpression of Beclin 1 in A549 cells increased the activities of caspases-3 and -9 and the expression of ECRG4 (P<0.01) compared with Lenex-packaged lentiviral particles and non-transfected control groups. In conclusion, the overexpression of Beclin 1 promoted apoptosis and decreased invasion by upregulating the expression of ECRG4 in A549 lung adenocarcinoma cells. Therefore, the selection of Beclin l as a target for gene therapy represents a more effective method for the treatment of lung cancer. IntroductionBeclin l (the mammalian counterpart of the yeast Atg6 gene) is an essential player in autophagy. Allelic loss or deficiency of the Beclin 1 gene has been demonstrated in human breast cancer, ovarian cancer and prostate cancer; in lung cancer, hepatocellular carcinoma, cervical cancer and lymphoma, the expression of Beclin 1 is very low/almost undetectable (1-4). A previous study identified that Beclin 1 -/-mice died early in embryonic development (5). Although Beclin 1 +/-mice were able to survive, the incidence of cancer was much higher in these animals. In addition, the measured in vivo cell autophagy activity was markedly decreased, and cells reproduced faster in Beclin 1-deficient animals. These findings clearly suggested that there is a close correlation between the inhibition of autophagy activity and the occurrence of cancer.Although Beclin 1 has been demonstrated to exert an important role in cell autophagy during carcinogenesis, its biological function in lung cancer has yet to be fully elucidated. A previous study by our laboratory identified that knockdown of Beclin 1 promoted cell growth and inhibited apoptosis in the A549 lung cancer cell line (6). In the present study, a Beclin 1 lentiviral expression vector was constructed, and an A549 cell line was established with a steady expression of Beclin 1. The effects of Beclin 1 overexpression on cell invasion and apoptosis, changes in the activities of the apoptosis-associated caspases-3 and -9, and the expression of esophageal cancer-related...