A mendelian randomisation study of the causal effect of exercise intensity on the development of type 2 diabetes

ObjectiveThis study examines the causal effects of varying exercise intensities on type 2 diabetes mellitus (T2D) through Mendelian randomization (MR) analysis, using genetic variants as instrumental variables.MethodsA two-sample MR analysis was performed, employing Inverse Variance Weighted (IVW) as the primary method, supported by weighted median, MR-Egger regression, MR-PRESSO, and MR robustness-adjusted contour scores. Data were obtained from the International Exercise Genetics Database (IEGD) and the Global Diabetes Research Consortium (GRC), encompassing over 150,000 individuals for exercise intensity and around 200,000 T2D patients and controls. SNPs linked to exercise intensity were selected based on genome-wide significance (P < 5 × 10^-8) and linkage disequilibrium criteria (distance >10,000 kb, r^2 < 0.001).ResultsThe IVW analysis suggested that high-intensity exercise might reduce T2D risk, but the association was not statistically significant (OR = 0.667, 95% CI = 0.104–4.255, P = 0.667). The wide confidence interval indicates uncertainty in the effect estimate. Low-intensity exercise showed no significant effect on T2D risk (OR ∼ 1.0). Sensitivity analyses, including weighted median and MR-Egger regression, confirmed no significant association between high-intensity exercise and T2D risk. The MR-PRESSO analysis found no significant outliers, and the global test for pleiotropy was non-significant (P = 0.455). Cochran’s Q test for heterogeneity in the IVW analysis was non-significant (Q = 12.45, P = 0.234), indicating consistency among SNP-derived estimates.ConclusionHigh-intensity exercise potentially reduces T2D risk, but the association is not statistically significant. Further research is needed to understand the complex relationship between exercise intensity and T2D

Local and Global Linear Convergence of General Low-Rank Matrix Recovery Problems

We study the convergence rate of gradient-based local search methods for solving low-rank matrix recovery problems with general objectives in both symmetric and asymmetric cases, under the assumption of the restricted isometry property. First, we develop a new technique to verify the Polyak-Lojasiewicz inequality in a neighborhood of the global minimizers, which leads to a local linear convergence region for the gradient descent method. Second, based on the local convergence result and a sharp strict saddle property proven in this paper, we present two new conditions that guarantee the global linear convergence of the perturbed gradient descent method. The developed local and global convergence results provide much stronger theoretical guarantees than the existing results. As a by-product, this work significantly improves the existing bounds on the RIP constant required to guarantee the non-existence of spurious solutions.</jats:p

Local and Global Linear Convergence of General Low-Rank Matrix Recovery Problems

We study the convergence rate of gradient-based local search methods for solving low-rank matrix recovery problems with general objectives in both symmetric and asymmetric cases, under the assumption of the restricted isometry property. First, we develop a new technique to verify the Polyak-Lojasiewicz inequality in a neighborhood of the global minimizers, which leads to a local linear convergence region for the gradient descent method. Second, based on the local convergence result and a sharp strict saddle property proven in this paper, we present two new conditions that guarantee the global linear convergence of the perturbed gradient descent method. The developed local and global convergence results provide much stronger theoretical guarantees than the existing results. As a by-product, this work significantly improves the existing bounds on the RIP constant required to guarantee the non-existence of spurious solutions

Coupling effect of ultrasonic vibration and beam oscillation on FQZ soften inhibition of laser welded Al-Mg alloy joints

A novel ultrasonic vibration assisted laser beam oscillation welding (UV-LBOW) method was developed and applied on the butt-welding of Al-Mg alloy sheets. Due to the synergistic enhancement of the molten pool flow by ultrasound vibration and laser beam oscillation, the microstructure morphology of fusion zone (FZ) was comprised of equiaxed grains. Additionly, a uniform element distribution was generated from the boundary to the center of the FZ. An enhanced tensile strength of 347 MPa and a fraction elongation of 19.0 % were obtained due to the grain refinement and solid solution strengthening effects

Peripheral Administration of NMU Promotes White Adipose Tissue Beiging and Improves Glucose Tolerance

Purpose. Targeting white adipose tissue (WAT) beiging has been proposed as an effective way to increase thermogenesis and improve glucose metabolism. Neuromedin U (NMU) is a neuropeptide that could increase energy expenditure, while its effects on WAT beiging and glucose homeostasis remain to be investigated. Methods. Male C57BL/6 mice were fed with high fat diet (HFD) to induce obesity and hyperglycemia and then treated with chronic subcutaneous injection of NMU. Body weight and food intake were recorded daily. After 14 days of injection, intraperitoneal glucose tolerance tests and 18F-fluorodeoxyglucose micro-positron emission tomography/computed tomography (18F-FDG micro-PET/CT) scans were conducted. Subcutaneous WAT (sWAT) and interscapular brown adipose tissue were collected for the evaluation of adipocyte size, expression of uncoupling protein 1 (Ucp1), and other thermogenic-related genes. Stromal vascular fraction of subcutaneous WAT was extracted for the measurement of type 2 innate lymphocytes (ILC2s) proportions. Results. Glucose tolerance was markedly improved by peripherally administered NMU. Micro-PET/CT suggested that NMU promoted WAT beiging, which was further confirmed by haematoxylin and eosin (H&amp;E) staining and immunohistochemistry. In diet-induced-obese (DIO) mice, NMU activated thermogenic-related genes in WAT. In addition, NMU stimulated ILC2s in the stromal vascular fraction of WAT. Conclusion. Taken together, our study indicates that peripheral administration of NMU is a potential therapeutic strategy for the promotion of WAT beiging and the improvement of impaired glucose tolerance.</jats:p

Peripheral Administration of NMU Promotes White Adipose Tissue Beiging and Improves Glucose Tolerance

Purpose. Targeting white adipose tissue (WAT) beiging has been proposed as an effective way to increase thermogenesis and improve glucose metabolism. Neuromedin U (NMU) is a neuropeptide that could increase energy expenditure, while its effects on WAT beiging and glucose homeostasis remain to be investigated. Methods. Male C57BL/6 mice were fed with high fat diet (HFD) to induce obesity and hyperglycemia and then treated with chronic subcutaneous injection of NMU. Body weight and food intake were recorded daily. After 14 days of injection, intraperitoneal glucose tolerance tests and 18F-fluorodeoxyglucose micro-positron emission tomography/computed tomography (18F-FDG micro-PET/CT) scans were conducted. Subcutaneous WAT (sWAT) and interscapular brown adipose tissue were collected for the evaluation of adipocyte size, expression of uncoupling protein 1 (Ucp1), and other thermogenic-related genes. Stromal vascular fraction of subcutaneous WAT was extracted for the measurement of type 2 innate lymphocytes (ILC2s) proportions. Results. Glucose tolerance was markedly improved by peripherally administered NMU. Micro-PET/CT suggested that NMU promoted WAT beiging, which was further confirmed by haematoxylin and eosin (H&E) staining and immunohistochemistry. In diet-induced-obese (DIO) mice, NMU activated thermogenic-related genes in WAT. In addition, NMU stimulated ILC2s in the stromal vascular fraction of WAT. Conclusion. Taken together, our study indicates that peripheral administration of NMU is a potential therapeutic strategy for the promotion of WAT beiging and the improvement of impaired glucose tolerance

Landslide Susceptibility Evaluation Based on Potential Disaster Identification and Ensemble Learning

Catastrophic landslides have much more frequently occurred worldwide due to increasing extreme rainfall events and intensified human engineering activity. Landslide susceptibility evaluation (LSE) is a vital and effective technique for the prevention and control of disastrous landslides. Moreover, about 80% of disastrous landslides had not been discovered ahead and significantly impeded social and economic sustainability development. However, the present studies on LSE mainly focus on the known landslides, neglect the great threat posed by the potential landslides, and thus to some degree constrain the precision and rationality of LSE maps. Moreover, at present, potential landslides are generally identified by the characteristics of surface deformation, terrain, and/or geomorphology. The essential disaster-inducing mechanism is neglected, which has caused relatively low accuracies and relatively high false alarms. Therefore, this work suggests new synthetic criteria of potential landslide identification. The criteria involve surface deformation, disaster-controlling features, and disaster-triggering characteristics and improve the recognition accuracy and lower the false alarm. Furthermore, this work combines the known landslides and discovered potential landslides to improve the precision and rationality of LSE. This work selects Chaya County, a representative region significantly threatened by landslides, as the study area and employs multisource data (geological, topographical, geographical, hydrological, meteorological, seismic, and remote sensing data) to identify potential landslides and realize LSE based on the time-series InSAR technique and XGBoost algorithm. The LSE precision indices of AUC, Accuracy, TPR, F1-score, and Kappa coefficient reach 0.996, 97.98%, 98.77%, 0.98, and 0.96, respectively, and 16 potential landslides are newly discovered. Moreover, the development characteristics of potential landslides and the cause of high landslide susceptibility are illuminated. The proposed synthetic criteria of potential landslide identification and the LSE idea of combining known and potential landslides can be utilized to other disaster-serious regions in the world

Establishment of human esophageal cancer xenograft model in immunocompetent mice and explorations of related immunological changes

Abstract [Background]To combine the primary cells of human esophageal cancer with a new type of three dimensional (3D) microcarrier 6, and then to inoculate the complex subcutaneously into immunocompetent mice. To establish a new animal xenograft tumor model of human esophageal cancer, and to explore the changes in the immune indicators of mice during tumor formation. [Methods] 1. Isolate and extract the primary cells of human esophageal squamous cell carcinoma (SCC); mix them well with the 3D microcarriers and fully incubate them. Then, inoculate the complex into the armpits of immunocompetent mice, and record the tumor formation rate and the pathological characteristics of xenograft tumors. 2. Isolate cells in the blood, bone marrow, and spleen of the experimental mice and the control mice, and detect changes in CD3+, CD4+, CD8+, myeloid-derived suppressor cells (MDSCs), and dendritic cells (DCs) by flow cytometry. [Results] The microcarrier 6-based model subcutaneously transplanted primary cells of human esophageal cancer, which further successfully grew into xenograft tumors in immunocompetent mice; the tumor formation rate was 80%. The hematoxylin-eosin (HE) staining and immunohistochemistry (IHC) characteristics indicated consistencies with the human esophageal cancer cells. The flow cytometry analysis showed that CD3+ and CD4+ cells in the peripheral blood and bone marrow of the tumor-formed mice were significantly reduced (P &lt; 0.05). The cell counts of MDSCs and DCs in the blood, bone marrow, and spleen were elevated as compared with the control group, and with the MDSCs increased the most dramatically and statistically significant increase (P &lt; 0.05). [Conclusion] The new type of 3D microcarriers were combined with human esophageal SCC cells; this model could be used to successfully construct an immunocompetent mouse xenograft model of human esophageal cancer. We further found that during tumor formation, the tumor cells may inhibit cellular immunity by regulating MDSCs, leading to tumor immunity escape and promoting tumor development.</jats:p