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Acute myeloid leukaemia (AML) is a highly heterogeneous disease, which lead to various findings in transcriptomic research. This study addresses these challenges by integrating 34 datasets, including 26 control groups, 6 prognostic datasets and 2 single‐cell RNA sequencing (scRNA‐seq) datasets to identify 10,000 AML‐related genes (ARGs). We focused on genes with low variability and high consistency and successfully discovered 191 AML signatures (ASs). Leveraging machine learning techniques, specifically the XGBoost model and our custom framework, we classified AML subtypes with both scRNA‐seq and bulk RNA‐seq data, complementing the ELN2022 classification approach. Our research also identified promising treatments for AML through drug repurposing, with solasonine showing potential efficacy for high‐risk AML patients, supported by molecular docking and transcriptomic analyses. To enhance reproducibility and customizability, we developed CSAMLdb, a user‐friendly database platform. It facilitates the reuse and personalized analysis of nearly all results obtained in this research, including single‐gene prognostics, multi‐gene scoring, enrichment analysis, machine learning risk assessment, drug repositioning analysis and literature abstract named entity recognition. CSAMLdb is available at http://www.csamldb.com. [ABSTRACT FROM AUTHOR]

Objective: Observational studies have identified a dual effect of circulating inflammatory proteins and immune cells on cancer progression. However, the specific mechanisms of action have not been clarified in the exacerbation of cutaneous‐origin tumors. Therefore, this study aims to investigate whether the causal relationship between circulating inflammatory factors and basal cell carcinoma (BCC), cutaneous malignant melanoma (SKCM), and cutaneous squamous cell carcinoma (cSCC) is regulated by immune cells. Methods: This study employed the Two‐Sample Mendelian Randomization (TSMR) approach to investigate the causal relationships between 91 circulating inflammatory factors and three prevalent types of skin cancer from a genetic perspective. Bayesian Weighted Mendelian Randomization (BWMR) was also used to validate correlation and reverse MR to assess inverse relationships. Subsequent sensitivity analyses were conducted to limit the impact of heterogeneity and pleiotropy. Finally, the two‐step Mendelian Randomization (two‐step MR) method was utilized to ascertain the mediating effects of specific immune cell traits in the causal pathways linking circulating inflammatory factors with BCC, SKCM, and cSCC. Results: The Inverse Variance Weighted (IVW) method and the Bayesian Weighted Algorithm collectively identified nine inflammatory factors causally associated with BCC, SKCM, and cSCC. The results from Cochran's Q test, mendelian randomization pleiotropy residual sum and outlier (MR‐PRESSO), and MR‐Egger intercept were not statistically significant (p < 0.05). Additionally, the proportions mediated by CD4+ CD8dim T cell %leukocyte, CD4‐CD8‐Natural Killer T %T cell, and CD20 on IgD‐CD38‐B cell for FIt3L, CCL4, and OSM were 9.26%, 8.96%, and 10.16%, respectively. Conclusion: Immune cell levels potentially play a role in the modulation process between circulating inflammatory proteins and cutaneous‐origin exacerbated tumors. This finding offers a new perspective for the in‐depth exploration of cutaneous malignancies. [ABSTRACT FROM AUTHOR]

Thermokarst terrain is developing at an accelerating pace in the ice‐rich permafrost on the Qinghai–Tibet Plateau (QTP), China, and the most dramatic of these terrain‐altering thermokarsts is retrogressive thaw slump (RTS). The freeze–thaw erosion (FTE) impacts are sharply increasing on the Plateau due to RTS, especially as a result of the migration of fine sediments in cold climates, these impacts are still not quantified due to the limitation of hydro‐thermal‐mass transport laws in RTS development. Moreover, it is difficult to assess the impact of RTS on the ecology and environment, especially on soil erosion. This study developed a heat–water‐mass transport coupled model of a RTS in the Beiluhe River Region on the QTP, considering the actual topography, water‐ice phase change, latent heat, and surface heat exchange layer. Based on the observed data of ground temperature, unfrozen water content, and heat flux, the coupled model herein is practicable for presenting the geotemperature regime and groundwater flow in the RTS area, thereby quantifying the ice‐rich permafrost thaw and mass wasting. The results presented indicate that: (1) the seepage velocity of the superficial zone (0–1.5 m depth) is two orders of magnitude higher than that of the permafrost table; (2) the mean ice‐rich permafrost thaw volume was 13.4 m2 from 2016 to 2021; and (3) the cumulative mass transport volume was 22 m2 from July 2020 to September 2021. In addition, the relation between the FTE (shown as the migration of sediments) and the amount of ground ice ablation can be fitted by an exponential equation. This work proposes a reliable method for quantifying the effect of FTE and is helpful to assess the eco‐environmental impacts of RTS. [ABSTRACT FROM AUTHOR]

Cardiac ischemia, hypoxia, arrhythmias, and heart failure share the common electrophysiological changes featured by the elevation of intracellular Ca2+ (Ca2+ overload) and inhibition of the inward rectifier potassium (IK1) channel. IK1 channel agonists have been considered a new type of anti‐arrhythmia and cardioprotective agents. We predicted using a drug repurposing strategy that tetramisole (Tet), a known anthelminthic agent, was a new IK1 channel agonist. The present study aimed to experimentally identify the above prediction and further demonstrate that Tet has cardioprotective effects. Results of the whole‐cell patch clamp technique showed that Tet at 1–100 μmol/L enhanced IK1 current, hyperpolarized resting potential (RP), and shortened action potential duration (APD) in isolated rat cardiomyocytes, while without effects on other ion channels or transporters. In adult Sprague–Dawley (SD) rats in vivo, Tet showed anti‐arrhythmia and anticardiac remodeling effects, respectively, in the coronary ligation‐induced myocardial infarction model and isoproterenol (Iso, i.p., 3 mg/kg/day, 10 days) infusion‐induced cardiac remodeling model. Tet also showed anticardiomyocyte remodeling effect in Iso (1 μmol/L) infused adult rat ventricular myocytes or cultured H9c2 (2‐1) cardiomyocytes. Tet at 0.54 mg/kg in vivo or 30 μmol/L in vitro showed promising protections on acute ischemic arrhythmias, myocardial hypertrophy, and fibrosis. Molecular docking was performed and identified the selective binding of Tet with Kir2.1. The cardioprotection of Tet was associated with the facilitation of IK1 channel forward trafficking, deactivation of PKA signaling, and inhibition of intracellular calcium overload. Enhancing IK1 may play dual roles in anti‐arrhythmia and antiventricular remodeling mediated by restoration of Ca2+ homeostasis. [ABSTRACT FROM AUTHOR]