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Epigenetics is a biological process that modifies and regulates gene expression, affects neuronal function, and contributes to pain. However, the mechanism by which epigenetics facilitates and maintains chronic pain is poorly understood. We aimed to determine whether [N.sup.6]-methyladenosine (m6A) specifically modified by methyltransferase-like 14 (METTL14) alters neuronal activity and governs pain by sensitizing the GluN2A subunit of the N-methyl-D-aspartate receptor (NMDAR) in the dorsal root ganglion (DRG) neurons in a model of chemotherapy-induced neuropathic pain (CINP). Using dot blotting, immunofluorescence, gain/loss-of-function, and behavioral assays, we found that m6A levels were upregulated in L4-L6 DRG neurons in CINP in a DBP/METTL14-dependent manner, which was also confirmed in human DRGs. Blocking METTL14 reduced m6A methylation and attenuated pain hypersensitivity. Mechanistically, METTL14-mediated m6A modification facilitated the synaptic plasticity of DRG neurons by enhancing the GluN2A subunit of NMDAR, and inhibiting METTL14 blocked this effect. In contrast, overexpression of METTL14 upregulated m6A modifications, enhanced presynaptic NMDAR activity in DRG neurons, and facilitated pain sensation. Our findings reveal a previously unrecognized mechanism of METTL14-mediated m6A modification in DRG neurons to maintain neuropathic pain. Targeting these molecules may provide a new strategy for pain treatment., Introduction Chemotherapy-induced neuropathic pain (CINP) is a debilitating complication caused by damage to the peripheral nervous system by chemotherapeutic agents, including paclitaxel (1). CINP occurs in approximately 50% to 90% [...]

An electrochemical sensing approach for ultrasensitive DNA methyltransferase (MTase) activity assay is proposed. After specific cleavage reaction in the presence of a methylated state, strand displacement polymerization (SDP) is initiated in the solution. The product of upstream SDP further triggers downstream SDP, which enriches abundant electrochemical species at the electrode. The whole process is quite convenient with shared enzymes. Due to the cascade signal amplification, ultrahigh sensitivity is promised. Inhibitor screening results are also demonstrated to be good. Besides, target MTase can be accurately determined in human serum samples, confirming excellent practical utility. This work provides a reliable approach for the analysis of MTase activity, which is of vital importance for related biological studies and clinical applications. [ABSTRACT FROM AUTHOR]

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This correction notice is for an article titled "Digital exclusion and cognitive impairment in older people: findings from five longitudinal studies" published in BMC Geriatrics. The authors have reported that a wrong Supplementary file was initially published with the article, and it has now been replaced with the correct file. The corrected article includes a brief introduction to the five cohorts, tables, figures, and the STROBE Statement. The authors of the article are Yuge Wang, Zhigang Wu, Lanzhi Duan, Sijia Liu, Ruzhao Chen, Tao Sun, Jiang Wang, Jianghua Zhou, Hongxia Wang, and Pan Huang. [Extracted from the article]

Background Subarachnoid haemorrhage (SAH), primarily caused by rupture of intracranial aneurysm, has a high incidence rate in women. We aimed to evaluate the association between female hormonal and reproductive factors and SAH.Methods A prospective cohort of 226,469 participants from the UK Biobank was followed for a median period of 14.75 years. Cox proportional hazards models and restricted cubic splines were used to explore the associations between 13 major factors and SAH, including menarche age, menopausal status, age at menopause, reproductive lifespan, pregnancy history, age at first and last live births, number of live births, adverse fertility outcomes, history of oral contraception or hormone-replacement therapy (HRT) use, and surgical history of hysterectomy or bilateral oophorectomy.Results SAH occurred in 769 of participants during the follow-up period. Both women with a younger age at menarche (<12 years) and post-menopausal women had a higher SAH risk (hazard ratio (HR), 1.28; 95% confidence interval (CI), 1.06-1.54) and HR, 1.48; 95%CI, 1.10-1.99) respectively. A higher risk of SAH was identified in those with an earlier age at menopause (<40 years: HR, 2.09; 95%CI, 1.43-3.06; 40-44 years: HR, 1.68; 95%CI, 1.23-2.29). A shorter reproductive lifespan (<30 years) was associated with increased SAH risk (HR, 1.64; 95%CI, 1.28-2.11), while a longer reproductive lifespan (>42 years) showed a protective effect (HR, 0.65; 95%CI, 0.55-0.77). Younger age at first live birth (<24 years) was associated with SAH (HR, 1.39; 95%CI, 1.13-1.72). Hysterectomy (HR, 2.55; 95%CI, 2.12-3.05) or bilateral oophorectomy (HR, 1.51; 95%CI, 1.14-2.01) also predisposed women to SAH. Age at last live birth, number of live births, pregnancy history, adverse fertility outcomes, and HRT or oral contraceptive use were not associated with SAH.Conclusions Female hormonal and reproductive factors are important for evaluating SAH risk in women. In particular, earlier menopause is associated with an increased risk of SAH.

Background: Previous studies have mostly investigated the risk factors affecting the occurrence of leukoaraiosis and the risk factors affecting the severity of leukoaraiosis in patients with ischemic stroke, but there are relatively few studies on the risk factors and clinical characteristics affecting the severity of leukoaraiosis in the population with the most common type of first-episode ischemic stroke caused by intracranial atherosclerotic stenosis in China. Methods: We retrospectively studied patients with first-ever ischemic stroke due to intracranial atherosclerotic stenosis. All patients underwent diffusion weight magnetic resonance imaging and adjunctive examinations such as magnetic resonance angiography and/or computed tomography angiography and/or digital subtraction angiography. The characteristics and clinical data were also statistically analyzed. Results: Of the 504 patients enrolled, 176 (34.92%), 202 (40.08%), and 126 (25.00%) patients were in the mild, moderate, and severe groups, respectively, and the patients were older in the severe group compared with the moderate and mild groups (p < 0.05). Hypertension was more severe in the severe group compared with the severe and mild groups (p < 0.05). The time to hospital admission was shorter in the severe group compared with the moderate and mild groups (p < 0.05). The admission National Institutes of Health stroke scale was higher in the severe group than in the moderate and mild groups (p < 0.05). homocysteine, glucose, glycohemoglobin A1c, neutrophil-lymphocyte ratio, and ultrasensitive C-reactive protein to albumin ratio levels were significantly different between the three groups (p < 0.05). There was no significant correlation between the distribution of infarct foci in the anterior and posterior circulation in the three groups (p > 0.05). Conclusion: Age and homocysteine were independent risk factors for leukoaraiosis severity in patients with acute ischemic stroke, and all were positively associated with leukoaraiosis severity. Hypertension, glucose, glycohemoglobin A1c, neutrophil-lymphocyte ratio and ultrasensitive C-reactive protein to albumin ratio levels were highly significant in evaluating the prognosis of patients., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)