BackgroundSirtuin 3 (SIRT3) is one of the seven mammalian sirtuins, which are homologs of the yeast Sir2 gene. SIRT3 is the only sirtuin with a reported association with the human life span. Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) plays important roles in adaptive thermogenesis, gluconeogenesis, mitochondrial biogenesis and respiration. PGC-1α induces several key reactive oxygen species (ROS)-detoxifying enzymes, but the molecular mechanism underlying this is not well understood.ResultsHere we show that PGC-1α strongly stimulated mouse Sirt3 gene expression in muscle cells and hepatocytes. Knockdown of PGC-1α led to decreased Sirt3 gene expression. PGC-1α activated the mouse SIRT3 promoter, which was mediated by an estrogen-related receptor (ERR) binding element (ERRE) (−407/−399) mapped to the promoter region. Chromatin immunoprecipitation and electrophoretic mobility shift assays confirmed that ERRα bound to the identified ERRE and PGC-1α co-localized with ERRα in the mSirt3 promoter. Knockdown of ERRα reduced the induction of Sirt3 by PGC-1α in C2C12 myotubes. Furthermore, Sirt3 was essential for PGC-1α-dependent induction of ROS-detoxifying enzymes and several components of the respiratory chain, including glutathione peroxidase-1, superoxide dismutase 2, ATP synthase 5c, and cytochrome c. Overexpression of SIRT3 or PGC-1α in C2C12 myotubes decreased basal ROS level. In contrast, knockdown of mSIRT3 increased basal ROS level and blocked the inhibitory effect of PGC-1α on cellular ROS production. Finally, SIRT3 stimulated mitochondrial biogenesis, and SIRT3 knockdown decreased the stimulatory effect of PGC-1α on mitochondrial biogenesis in C2C12 myotubes.ConclusionOur results indicate that Sirt3 functions as a downstream target gene of PGC-1α and mediates the PGC-1α effects on cellular ROS production and mitochondrial biogenesis. Thus, SIRT3 integrates cellular energy metabolism and ROS generation. The elucidation of the molecular mechanisms of SIRT3 regulation and its physiological functions may provide a novel target for treating ROS-related disease.

Industry 4.0, Internet of Things, Blockchain, and Business Analytics are the hot research topics and have attracted much attention from scholars and practitioners in recent years. In order to identify the forces driving their development and to promote their development, this paper reviews the extant studies on these topics. The review provides a comprehensive overview of state-of-the-art researches on Industry 4.0, Internet of Things, Blockchain, and Business Analytics. The results assist scholars to figure out the directions of future studies on these topics.

Our results suggest that PQQ can protect rat NP cells against oxidative stress via a mitochondria-mediated pathway. PQQ might be useful as a potential pharmaceutical agent in the prevention of intervertebral disc degeneration.

Objective Clinical data of patients’ measurements and treatment history stored in electronic health record (EHR) systems are starting to be mined for better treatment options and disease associations. A primary challenge associated with utilizing EHR data is the considerable amount of missing data. Failure to address this issue can introduce significant bias in EHR-based research. Currently, imputation methods rely on correlations among the structured phenotype variables in the EHR. However, genetic studies have shown that many EHR-based phenotypes have a heritable component, suggesting that measured genetic variants might be useful for imputing missing data. In this article, we developed a computational model that incorporates patients’ genetic information to perform EHR data imputation. Materials and Methods We used the individual single nucleotide polymorphism’s association with phenotype variables in the EHR as input to construct a genetic risk score that quantifies the genetic contribution to the phenotype. Multiple approaches to constructing the genetic risk score were evaluated for optimal performance. The genetic score, along with phenotype correlation, is then used as a predictor to impute the missing values. Results To demonstrate the method performance, we applied our model to impute missing cardiovascular related measurements including low-density lipoprotein, heart failure, and aortic aneurysm disease in the electronic Medical Records and Genomics data. The integration method improved imputation's area-under-the-curve for binary phenotypes and decreased root-mean-square error for continuous phenotypes. Conclusion Compared with standard imputation approaches, incorporating genetic information offers a novel approach that can utilize more of the EHR data for better performance in missing data imputation.

In this paper, we investigate physical layer security (PLS) in non-orthogonal multiple access-enabled (NOMA-enabled) underlay cognitive radio networks (CRNs) with outdated channel state information (CSI). Considering the influence of outdated CSI on the interference of secondary transmitter (Alice) to primary user (PU), the constraint for the power is adopted to guarantee the quality-of-service (QoS) of PU over Nakagami-m channels. To further analyze the NOMA-enabled underlay CRNs with outdated CSI in PLS perspective, the secrecy performance is evaluated by the closed-form expressions for connection outage probability (COP), the intercept probability (IP) and effective secrecy throughput (EST). In addition, Monte Carlo simulations are provided to verify the derived analytical results. From the analytical results and simulations, it is concluded that a) with the increment of the channel parameter m, the secrecy performance of the considered networks increases in the low SNR region and decreases in the high SNR region, b) the connection performance with the outdated CSI of the interference links only reduce in the high SNR region, because the power margin factor changes significantly in this region, c) considering the impact of the constraint for the power, the secrecy performance and EST performance of the considered networks with the outdated CSI of the interference links increase in the high SNR region, d) the considered networks with NOMA scheme can achieve higher EST than that with orthogonal multiple access (OMA) scheme. INDEX TERMS Physical layer security, cognitive radio, non-orthogonal multiple access (NOMA), outdated channel state information, effective secrecy throughput.