Increasing evidence suggests that long noncoding RNAs (lncRNAs) play crucial roles in various biological processes. However, little is known about the effects of lncRNAs on autophagy. Here we report ...that a lncRNA, termed cardiac autophagy inhibitory factor (CAIF), suppresses cardiac autophagy and attenuates myocardial infarction by targeting p53-mediated myocardin transcription. Myocardin expression is upregulated upon H
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and ischemia/reperfusion, and knockdown of myocardin inhibits autophagy and attenuates myocardial infarction. p53 regulates cardiomyocytes autophagy and myocardial ischemia/reperfusion injury by regulating myocardin expression. CAIF directly binds to p53 protein and blocks p53-mediated myocardin transcription, which results in the decrease of myocardin expression. Collectively, our data reveal a novel CAIF-p53-myocardin axis as a critical regulator in cardiomyocyte autophagy, which will be potential therapeutic targets in treatment of defective autophagy-associated cardiovascular diseases.
This research delves into the application effects of Fuzzy Comprehensive Evaluation (FCE) and quantitative weight analysis in the structure management of human resources (SMHR) to optimize the ...structure management. The research begins by analyzing the existing problems in SMHR, such as incomplete performance feedback and error-prone outsourcing decisions. By leveraging human resource management (HRM) characteristics, the researchers construct the SMHR evaluation index system. The Analytical Hierarchy Process (AHP) is employed to establish a hierarchical human resource structure model to determine the relative weight of each HRM indicator. Subsequently, the FCE method is utilized to build an SMHR optimization model, which is then scrutinized and assessed by means of an example. The findings indicate that the consistency ratio (C.R.) values of the first and second-level evaluation factors of the constructed model are less than 0.1, thus passing the consistency test and demonstrating credibility. Ultimately, the research effectively grades SMHR in the enterprise through the analysis of HRM optimization. Accordingly, this research presents a set of optimization suggestions and measures, including the establishment of a professional HRM operation team, acceleration of the construction of a professional talent team, enhancement of the intelligent level of the HRM center, and transition towards digital sharing. These proposed measures can serve as valuable experimental references for the optimization and improvement of HRM structures in future enterprises.
Virtual reality（VR） training technology in the mining industry is a new field of research and utilization.The successful application of VR training system is critical to mine safety and production. ...Through the statistics of the current research and applications of VR training systems in mining industry, all the input/output devices are classified. Based on the classifications of the input/output devices that are used in the VR system, the current VR training systems for the mining industry could be divided into three types： screen-based general type, projector-based customized type, and head-mounted display（HMD）-based intuitive type. By employing a VR headset, a smartphone and a leap motion device, an HMDbased intuitive type VR training system prototype for drilling in underground mines has been developed.Ten trainees tried both the HMD-based intuitive system and the screen-based general control system to compare the experiences and training effects. The results show that the HMD-based system can give a much better user experience and is easy to use. Three of the five components of a VR training system,namely, the user, the tasks, and software and database should be given more attention in future research.With more available technologies of input and output devices, VR engines, and system software, the VR training system will eventually yield much better training results, and will play a more important role in as a training tool for mine safety.
The inflammatory response plays an important role in carcinogenesis. However, the functional role and mechanism of the UCHL3-associated inflammatory response in ovarian cancer remain to be ...characterized. Here, we report that increased expression of UCHL3 facilitates tumourigenesis by targeting TRAF2 protein, thereby enhancing the inflammatory response. The expression of UCHL3 is elevated in ovarian cancer patients and is associated with an unfavourable prognosis. Genetic ablation of UCHL3 was found to markedly block ovarian cancer cell proliferation, viability and migration both in vitro and in vivo. Mechanistically, luciferase pathway screening results show that NF-κB signalling is clearly activated compared with other pathways. UCHL3 was found to activate NF-κB signalling by deubiquitinating and stabilizing TRAF2, leading to tumourigenesis. Our results indicate that highly expressed UCHL3 enhances inflammation by stabilizing TRAF2, which in turn facilitates tumourigenesis in ovarian cancer, and that UCHL3 is a potential target for ovarian cancer patients with increased inflammation.
In eukaryotic cells, DNA replication licensing is precisely regulated to ensure that the initiation of genomic DNA replication in S phase occurs once and only once for each mitotic cell division. A ...key regulatory mechanism by which DNA re-replication is suppressed is the S phase-dependent proteolysis of Cdt1, an essential replication protein for licensing DNA replication origins by loading the Mcm2-7 replication helicase for DNA duplication in S phase. Cdt1 degradation is mediated by CRL4Cdt2 ubiquitin E3 ligase, which further requires Cdt1 binding to proliferating cell nuclear antigen (PCNA) through a PIP box domain in Cdt1 during DNA synthesis. Recent studies found that Cdt2, the specific subunit of CRL4Cdt2 ubiquitin E3 ligase that targets Cdt1 for degradation, also contains an evolutionarily conserved PIP box-like domain that mediates the interaction with PCNA. These findings suggest that the initiation and elongation of DNA replication or DNA damage-induced repair synthesis provide a novel mechanism by which Cdt1 and CRL4Cdt2 are both recruited onto the trimeric PCNA clamp encircling the replicating DNA strands to promote the interaction between Cdt1 and CRL4Cdt2. The proximity of PCNA-bound Cdt1 to CRL4Cdt2 facilitates the destruction of Cdt1 in response to DNA damage or after DNA replication initiation to prevent DNA re-replication in the cell cycle. CRL4Cdt2 ubiquitin E3 ligase may also regulate the degradation of other PIP box-containing proteins, such as CDK inhibitor p21 and histone methylase Set8, to regulate DNA replication licensing, cell cycle progression, DNA repair, and genome stability by directly interacting with PCNA during DNA replication and repair synthesis.
The purpose of this paper is to propose methodologies for statistical inference of low dimensional parameters with high dimensional data. We focus on constructing confidence intervals for individual ...coefficients and linear combinations of several of them in a linear regression model, although our ideas are applicable in a much broader context. The theoretical results that are presented provide sufficient conditions for the asymptotic normality of the proposed estimators along with a consistent estimator for their finite dimensional covariance matrices. These sufficient conditions allow the number of variables to exceed the sample size and the presence of many small non‐zero coefficients. Our methods and theory apply to interval estimation of a preconceived regression coefficient or contrast as well as simultaneous interval estimation of many regression coefficients. Moreover, the method proposed turns the regression data into an approximate Gaussian sequence of point estimators of individual regression coefficients, which can be used to select variables after proper thresholding. The simulation results that are presented demonstrate the accuracy of the coverage probability of the confidence intervals proposed as well as other desirable properties, strongly supporting the theoretical results.
Characterizing the long-term nanometer-scale interactions between lysosomes and mitochondria in live cells is essential for understanding their functions but remains challenging due to limitations of ...the existing fluorescent probes. Here, we develop cell-permeable organic fluorescent probes for lysosomes with excellent specificity and high photostability. We also use an existing Atto 647N dye with high brightness and excellent photostability to achieve specific labeling of mitochondria in live cells. Using these probes, we obtain dual-color structured illumination microscopy (SIM) images of dynamic physical lysosome-mitochondrion interactions in live cells at an ~90-nm resolution over a long time course of ~13 min. We successfully record the consecutive dynamic processes of lysosomal fusion and fission, as well as four types of physical lysosome-mitochondrion interactions by super-resolution imaging. Our probes provide an avenue for understanding the functions and the dynamic interplay of lysosomes and mitochondria in live cells.
In pigs, three circovirus species within the genus Circovirus have been identified so far, including the non‐pathogenic Porcine circovirus 1 (PCV1), the pathogenic Porcine circovirus 2 (PCV2) and the ...recently identified Porcine circovirus 3 (PCV3). In April 2019, a new circovirus with a distinct relationship to other circoviruses was identified in several pigs with severe clinical disease in Hunan province, China. The size of the viral genome, tentatively designated as porcine circovirus type 4 (PCV4), is 1,770 nucleotides (nt). PCV4 shows the highest genomic identity to mink circovirus (66.9%) and has identities of 43.2%–51.5% to the other PCV genomes. Two major genes, a replicase (Rep) gene spanning 891 nt and a capsid (Cap) gene spanning 687 nt, were predicted. Furthermore, a TaqMan® real‐time polymerase chain reaction (PCR) targeting the replicase gene was developed to investigate the prevalence of PCV4 in 187 clinical samples from Hunan province, China. The results revealed an overall PCV4 prevalence of 12.8%, with the highest positive rates in nasal swabs (28.5%, 6/21) followed by serum samples (13.4%, 11/82). The clinical significance and pathogenesis of this virus needs further investigation.
The aim of this study was to analyze the clinical data, discharge rate, and fatality rate of COVID‐19 patients for clinical help. The clinical data of COVID‐19 patients from December 2019 to February ...2020 were retrieved from four databases. We statistically analyzed the clinical symptoms and laboratory results of COVID‐19 patients and explained the discharge rate and fatality rate with a single‐arm meta‐analysis. The available data of 1994 patients in 10 literatures were included in our study. The main clinical symptoms of COVID‐19 patients were fever (88.5%), cough (68.6%), myalgia or fatigue (35.8%), expectoration (28.2%), and dyspnea (21.9%). Minor symptoms include headache or dizziness (12.1%), diarrhea (4.8%), nausea and vomiting (3.9%). The results of the laboratory showed that the lymphocytopenia (64.5%), increase of C‐reactive protein (44.3%), increase of lactic dehydrogenase (28.3%), and leukocytopenia (29.4%) were more common. The results of single‐arm meta‐analysis showed that the male took a larger percentage in the gender distribution of COVID‐19 patients 60% (95% CI 0.54, 0.65), the discharge rate of COVID‐19 patients was 52% (95% CI 0.34,0.70), and the fatality rate was 5% (95% CI 0.01,0.11).
Research Highlights
Our study explored the clinical and epidemiological characteristics of COVID‐19 patients, and proposed the need to focus on other systemic symptoms such as the gastrointestinal tract firstly, which could be of use for clinical work.
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