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Endothelial dysfunction is a critical and initiating factor of the vascular complications of diabetes. Inflammation plays an important role in endothelial dysfunction regulated by epigenetic modifications. N6-methyladenosine ([m.sup.6]A) is one of the most prevalent epigenetic modifications in eukaryotic cells. In this research, we identified an [m.sup.6]A demethylase, fat mass and obesity-associated protein (FTO), as an essential epitranscriptomic regulator in diabetes-induced vascular endothelial dysfunction. We showed that enhanced FTO reduced the global level of [m.sup.6]A in hyperglycemia. FTO knockdown in endothelial cells (ECs) resulted in less inflammation and compromised ability of migration and tube formation. Compared with EC [Fto.sup.fl/fl] diabetic mice, EC-specific Fto-deficient (EC [Fto.sup.[DELTA]/[DELTA]]) diabetic mice displayed less retinal vascular leakage and acellular capillary formation. Furthermore, methylated RNA immunoprecipitation sequencing (MeRIPSeq) combined with RNA-Seq indicated that TNIP1 served as a downstream target of FTO. Luciferase activity assays and RNA pull-down demonstrated that FTO repressed TNIP1 mRNA expression by erasing its [m.sup.6]A methylation. In addition, TNIP1 depletion activated NF- [kappa]B and other inflammatory factors, which aggravated retinal vascular leakage and acellular capillary formation, while sustained expression of TNIP1 by intravitreal injection of adeno-associated virus alleviated endothelial impairments. These findings suggest that the FTO-TNIP1-NF-[kappa]B network provides potential targets to treat diabetic vascular complications., Introduction Diabetes mellitus is a global epidemic affecting approximately 10% of the world population (1). Despite advances in normalizing glucose homeostasis, the prevention and treatment of diabetic vascular complications remain [...]

Purpose: To construct a free and accurate breast cancer mortality prediction tool by incorporating lifestyle factors, aiming to assist healthcare professionals in making informed decisions. Patients and Methods: In this retrospective study, we utilized a ten-year follow-up dataset of female breast cancer patients from a major Chinese hospital and included 1,390 female breast cancer patients with a 7% (96) mortality rate. We employed six machine learning algorithms (ridge regression, k-nearest neighbors, neural network, random forest, support vector machine, and extreme gradient boosting) to construct a mortality prediction model for breast cancer. Results: This model incorporated significant lifestyle factors, such as postsurgery sexual activity, use of totally implantable venous access ports, and prosthetic breast wear, which were identified as independent protective factors. Meanwhile, ten-fold cross-validation demonstrated the superiority of the random forest model (average AUC = 0.918; 1-year AUC = 0.914, 2-year AUC = 0.867, 3-year AUC = 0.883). External validation further supported the model's robustness (average AUC = 0.782; 1-year AUC = 0.809, 2-year AUC = 0.785, 3-year AUC = 0.893). Additionally, a free and user-friendly web tool was developed using the Shiny framework to facilitate easy access to the model. Conclusion: Our breast cancer mortality prediction model is free and accurate, providing healthcare professionals with valuable information to support their clinical decisions and potentially promoting healthier lifestyles for breast cancer patients. [ABSTRACT FROM AUTHOR]

Two-dimensional (2D) intrinsic ferromagnetic (FM) semiconductors with high Curie temperature are promising candidates for applications in spintronics. Here, we predict a new class of materials, XCrY3 (X = Al, Ga, In; Y = S, Se, Te) monolayers, by using density functional theory. We systematically study their stability, electronic structures and magnetism. Phonon spectra and MD simulations verify that the XCrY3 monolayers are thermodynamically stable in an ambient environment. They all have a FM ground state and some of them have large perpendicular magnetocrystalline anisotropy energies, up to 1763 μeV per cell for monolayer InCrTe3. Monte Carlo simulations show that the Curie temperatures are between 284 and 351 K for these monolayers, which are near or even exceed room temperature. In addition, GaCrSe3 and InCrTe3 monolayers have desirable direct band gaps. The findings in this work suggest that 2D-XCrY3 may be promising candidates for applications in spintronic devices and will promote further theoretical and experimental studies. [ABSTRACT FROM AUTHOR]

Introduction: Walking pace is associated with various health‐related outcomes. The aim of this study was to investigate the association between self‐reported walking pace and the incidences of diabetic microvascular complications among participants with type 2 diabetes (T2D). Methods: Self‐reported walking pace was classified as brisk, average, or slow. The outcomes were the incidences of diabetic retinopathy, diabetic neuropathy, and diabetic nephropathy. COX proportional hazards models adjusted for sociodemographic, lifestyle, and health‐related factors were used to estimate hazard ratios (HRs) and 95% CIs. Results: A total of 14 518 participants with T2D in the UK Biobank (mean age 59.7 ± 7.0 years, 5028 [34.6%] women) were included. During a median follow‐up of 12.5 (interquartile range: 11.6–13.4) years, 2980 participants developed diabetic microvascular complications. After adjusting for confounding factors, and compared with brisk walkers, slow walkers had a multivariable‐adjusted HR of 1.98 (95% CI 1.58, 2.47) for composite diabetic microvascular complications, 1.54 (95% CI 1.11, 2.14) for diabetic retinopathy, 3.26 (95% CI 2.08, 5.11) for diabetic neuropathy, and 2.32 (95% CI 1.91, 2.82) for diabetic nephropathy. Average walking pace was associated with a higher risk for diabetic nephropathy (HR 1.51, 95 CI% 1.27–1.79) compared with brisk walking. Additionally, ≥1 diabetic microvascular complication occurred in 447 (14.7%) of participants with brisk walking pace, 1702 (19.5%) with average walking pace, and 831 (30.4%) with slow walking pace. Time from study recruitment to first diagnosis was shorter in participants who reported a slow walking pace, compared with brisk or average walkers. Among participants who had diabetic nephropathy as their first diagnosis, slow walking pace was associated with subsequent risk of a second diabetic microvascular complication (HR 3.88, 95 CI% 2.27–6.60). Conclusions: Self‐reported slow walking pace is associated with a higher risk of diabetic microvascular complications among participants with T2D in this population‐based cohort study. [ABSTRACT FROM AUTHOR]