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Myocardial damage is a critical complication and a significant contributor to mortality in sepsis. MicroRNAs (miRNAs) have emerged as key players in sepsis pathogenesis. In this study, we explore the effect and mechanisms of miR-29b-1-5p on sepsis-induced myocardial damage. Sepsis-associated Gene Expression Omnibus datasets (GSE72380 and GSE29914) are examined for differential miRNAs. The mouse sepsis-induced cardiac injury was established by Lipopolysaccharide (LPS) or cecal ligation and puncture (CLP). LPS-treated HL-1 mouse cardiomyocytes simulate myocardial injury in vitro. miR-29b-1-5p is co-upregulated in both datasets and in cardiac tissue from sepsis mouse and HL-1 cell models. miR-29b-1-5p expression downregulation was achieved by antagomir transduction and confirmed by real-time quantitative reverse transcription PCR. Survival analysis and echocardiography examination show that miR-29b-1-5p inhibition improves mice survival cardiac function in LPS- and CLP-induced sepsis mice. Hematoxylin and eosin and Masson’s trichrome staining and Immunohistochemistry analysis of mouse myocardial α-smooth muscle actin show that miR-29b-1-5p inhibition reduces myocardial tissue injury and fibrosis. The inflammatory cytokines and cardiac troponin I (cTnI) levels in mouse serum and HL-1 cells are also decreased by miR-29b-1-5p inhibition, as revealed by enzyme-linked immunosorbent assay. The expressions of autophagy-lysosomal pathway-related and apoptosis-related proteins in the mouse cardiac tissues and HL-1 cells are evaluated by western blot analysis. The sepsis-induced activation of the autophagy-lysosomal pathway and apoptosis are also reversed by miR-29b-1-5p antagomir. MTT and flow cytometry measurement further confirm the protective role of miR-29b-1-5p antagomir in HL-1 cells by increasing cell viability and suppressing cell apoptosis. Metascape functionally enriches TargetScan-predicted miR-29b-1-5p target genes. TargetScan prediction and dual luciferase assay validate the targeting relationship between miR-29b-1-5p and telomeric repeat-binding factor 2 (TERF2). The expression and function of TERF2 in HL-1 cells and mice are also evaluated. MiR-29b-1-5p negatively regulates the target gene TERF2. TERF2 knockdown partly restores miR-29b-1-5p antagomir function in LPS-stimulated HL-1 cells. In summary, miR-29b-1-5p targetedly inhibits TERF2, thereby enhancing sepsis-induced myocardial injury.

Climate change influences the water cycle and alters the spatiotemporal distribution of hydrological variables, thus complicating the projection of future streamflow and hydrological droughts. Although machine learning is increasingly employed for hydrological simulations, few studies have used it to project hydrological droughts, not to mention bivariate risks (referring to drought duration and severity) as well as their socioeconomic effects under climate change. We developed a cascade modeling chain to project future bivariate hydrological drought characteristics in 179 catchments over China, using five bias-corrected global climate model (GCM) outputs under three shared socioeconomic pathways (SSPs), five hydrological models, and a deep-learning model. We quantified the contribution of various meteorological variables to daily streamflow by using a random forest model, and then we employed terrestrial water storage anomalies and a standardized runoff index to evaluate recent changes in hydrological drought. Subsequently, we constructed a bivariate framework to jointly model drought duration and severity by using copula functions and the most likely realization method. Finally, we used this framework to project future risks of hydrological droughts as well as the associated exposure of gross domestic product (GDP) and population. Results showed that our hybrid hydrological–deep-learning model achieved > 0.8 Kling–Gupta efficiency in 161 out of the 179 catchments. By the late 21st century, bivariate drought risk is projected to double over 60 % of the catchments mainly located in southwestern China under SSP5-85, which shows the increase in drought duration and severity. Our hybrid model also projected substantial GDP and population exposure by increasing bivariate drought risks, suggesting an urgent need to design climate mitigation strategies for a sustainable development pathway. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the predictive validity and reliability of the Waterlow scale in critically adult hospitalised patients. Design: A multi‐centre cohort study. Methods: This study was conducted in 72 intensive care units (ICUs) in 38 tertiary hospitals in Gansu Province, China. All adults admitted to the ICU for greater than or equal to 24 h without pressure injury (PI) on admission were screened by the Waterlow scale on admission, during ICU stay and ICU discharge from April 2021 to February 2023. Receiver operating characteristic (ROC) curves were used to determine a potential cut‐off value for critical adult hospitalised patients. Cut‐off values were then determined using Youden's index, and sensitivity, specificity, positive predictive value, negative predictive value and accuracy were calculated based on these cut‐off values. Test–retest reliability was used to evaluate inter‐rater reliability. Results: A total of 5874 critical patients on admission were included, and 5125 of them were assessed regularly. The area under curve (AUC) was 0.623 (95% CI, 0.574–0.690), with a cut‐off score of 19 showing the best balance among sensitivity of 62.7%, specificity of 57.4%, positive predictive value of 2.07% and negative predictive value of 99.08%. The test–retest reliability between the first assessment and the regular assessment was 0.447. Conclusions: The Waterlow scale shows insufficient predictive validity and reliability in discriminating critical adults at risk of PI development. To further modify the items of the Waterlow scale, exploring specific risk factors for PI in the ICU and clarifying their impact degree was necessary. Risk predictive models or better tools are inevitable in the future. Patient or Public Contribution: Patients or family members supported nurses with PI risk assessment, skin examination and other activities during the inquiry. [ABSTRACT FROM AUTHOR]