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Sepsis-associated encephalopathy is a diffuse brain dysfunction secondary to infection. It has been established that factors such as age and sex can significantly contribute to the development of sepsis-associated encephalopathy. Our recent study implicated a possible link between adenosine-to-inosine RNA editing and sepsis-associated encephalopathy, yet the dynamics of adenosine-to-inosine RNA editing during sepsis-associated encephalopathy and how it could be influenced by factors such as age, sex and antidepressants remain uninvestigated. Our current study analysed and validated transcriptome-wide changes in adenosine-to-inosine RNA editing in the hippocampus of different septic mouse models. Seventy-four sites in 64 genes showed significant differential RNA editing over time in septic mice induced by caecal ligation and perforation. The differential RNA editing might contribute to the RNA expression regulation of the edited genes, with 42.2% differentially expressed. These differentially edited genes, especially those with missense editing, such as glutamate receptor, ionotropic, kainate 2 ( Grik2 , p.M620V), filamin A ( Flna , p.S2331G) and capicua transcriptional repressor ( Cic , p.E2270G), were mainly involved in abnormal social behaviour and neurodevelopmental and psychiatric disorders. Significant effects of age and sex were also observed on sepsis-associated RNA editing. Further comparison highlighted 40 common differential RNA editing sites that caecal ligation and perforation-induced and lipopolysaccharide-induced septic mouse models shared. Interestingly, these findings demonstrate temporal dynamics of adenosine-to-inosine RNA editing in the mouse hippocampus during sepsis, add to the understanding of age and sex differences in the disease and underscore the role of the epigenetic process in sepsis-associated encephalopathy., Competing Interests: The authors report no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Context: The influences of diabetes duration and glycemic control and their potential interplays on the risk of heart failure (HF) remain unclear., Objective: This work aimed to investigate the association of diabetes duration and glycemic control with the risk of HF., Methods: A total of 23 754 individuals with diabetes but without HF during the baseline recruitment of UK Biobank were included in this study. Duration of diabetes was self-reported, and the status of glycemic control was reflected by glycated hemoglobin A1c (HbA1c) levels. Their associations with incident HF were assessed using multivariate Cox models adjusting for traditional risk factors., Results: Duration of diabetes and HbA1c levels both were positively associated with the risk of HF. The hazard ratios (HRs) (95% CI) for diabetes durations of 5 to less than 10, 10 to less than 15, and 15 years or more were 1.09 (0.97-1.23), 1.13 (0.97-1.30), and 1.32 (1.15-1.53), respectively (vs < 5 years); and the HRs for HbA1c of 53.0 to less than 58.5 mmol/mol (7.0% to < 7.5%), 58.5 to less than 63.9 mmol/mol (7.5% to < 8.0%), and 63.9 mmol/mol or greater (8.0%) were 1.15 (1.02-1.31), 1.07 (0.91-1.26), and 1.46 (1.30-1.65), respectively (vs < 53.0 mmol/mol [7.0%]). Individuals with the longest disease duration (≥ 15 years) and poorer glycemic control (HbA1c ≥ 63.9 mmol/mol [8.0%]) had a particularly higher risk of HF (P for interaction = .026)., Conclusion: The risk of HF among individuals with diabetes increases with a longer duration of diabetes and increasing HbA1c levels. This finding may contribute to the individualized prevention of HF in patients with diabetes if being considered in clinical practices and policy-making., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Although radiation resistance is a common challenge in the clinical treatment of esophageal squamous cell carcinoma (ESCC), an effective treatment strategy has yet to be developed. Aberrant expression of microRNAs (miRNAs) is responsible for cancer sensitivity to radiation. In this study, we aimed to identify the miRNAs that are associated with radioresistance in ESCC. We used a miRNA microarray to perform a comparison of miRNA expression in both ESCC parental and acquired radioresistance cell lines. qRT-PCR was used to confirm the alterations. Cell radiosensitivity was determined with a survival fraction assay. Functional analyses of the identified miRNA in ESCC cells with regard to metastasis and apoptosis were performed by transwell assays and flow cytometry. The miRNA targets were identified with pathway analysis and confirmed with a luciferase assay. miR-98 was recognized as the most downregulated miRNA in established radioresistant cell line. AmiR-98 mimic enforced the expression of miRNA-98 and made ESCC cells sensitive to radiotherapy, while anti-miR-98 reversed this process. Optimal results were achieved by decreasing cellular proliferation, decreasing cell migration and inducing apoptosis. The luciferase target gene analysis results showed that the overexpression of miRNA-98 inhibited tumor growth and resistance tolerance by directly binding to the BCL-2 gene. Our study indicated that increasing miRNA-98 expression can be used as a potential radiosensitive therapeutic strategy for treating esophageal cancer cells., (© The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

S-Adenosyl-L-methionine (SAM) is one of the major methyl donors in all living organisms. The exogenous treatment with SAM leads to increased actinorhodin production in Streptomyces coelicolor A3(2). In this study, mutants from different stages of the AfsK-AfsR signal transduction cascade were used to test the possible target of SAM. SAM had no significant effect on actinorhodin production in afsK, afsR, afsS, or actII-open reading frame 4 (ORF4) mutant. This confirms that afsK plays a critical role in delivering the signal generated by exogenous SAM. The afsK-pHJL-KN mutant did not respond to SAM, suggesting the involvement of the C-terminal of AfsK in binding with SAM. SAM increased the in vitro autophosphorylation of kinase AfsK in a dose-dependent manner, and also abolished the effect of decreased actinorhodin production by a Ser/Thr kinase inhibitor, K252a. In sum, our results suggest that SAM activates actinorhodin biosynthesis in S. coelicolor M130 by increasing the phosphorylation of protein kinase AfsK.