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January 2020 begins a new decade, a chance for the inter-national health community to take a hard look at where we are, where we stand, what we stand for and why we need to stand up. Staring us down are two concurrent global health emergencies the coronavirus epidemic originating in Wu-han, China and climate change. As you read this, the trove of articles and assessments published on both is growing faster than most can absorb.Proton pump inhibitors (PPIs) are used worldwide to treat of acid-related disorders such as peptic ulcer and gastroesophageal reflux disease and to prevent gastroduodenal injuries due to nonsteroidal anti-inflammatory drugs. PPIs are the most potent inhibitors of gastric acid secretion currently available, and they are one of the most commonly prescribed classes of drugs because of their high efficacy and low toxicity. However, long-term PPI use causes histopathological changes such as parietal cell protrusion into the gland lumen, cystic dilation of gastric fundic glands, and foveolar epithelial hyperplasia. These changes can manifest on endoscopic examination as fundic gland polyps, hyperplastic polyps, multiple white and flat elevated lesions, cobblestone-like mucosa, or black spots. Clinicians must be aware of PPI-induced endoscopic features in patients with chronic long-term PPI use. Conversely, identifying patients with long-term PPI use based on their endoscopic findings is important. Recently, potassium-competitive acid blockers (P-CABs), a new class of acid suppressants that inhibit gastric acid secretion more strongly than PPIs, have recently been introduced clinically. Further long-term prospective studies on these gastric mucosal lesions in patients with either PPI or P-CAB use are required to investigate their association with histopathological changes and to establish the clinical significance of these findings.KEAP1 regulates the cytoprotection induced by NRF2 and has been reported to be a candidate tumor suppressor. Recent evidence has shown that mutations in several driver genes cause aberrant DNA methylation patterns, a hallmark of cancer. However, the correlation between KEAP1 mutations and DNA methylation in lung cancer has still not been investigated. In this study, we systematically carried out an integrated multi-omics analysis to explore the correlation between KEAP1 mutations and DNA methylation and its effect on gene expression in lung adenocarcinoma (LUAD). We found that most of the DNA aberrations associated with KEAP1 mutations in LAUD were hypomethylation. Surprisingly, we found several NRF2-regulated genes among the genes that showed differential DNA methylation. selleck compound Moreover, we identified an 8-gene signature with altered DNA methylation pattern and elevated gene expression levels in LUAD patients with mutated KEAP1, and evaluated the prognostic value of this signature in various clinical datasets. These results establish that KEAP1 mutations are associated with DNA methylation changes capable of shaping regulatory network functions. Combining both epigenomic and transcriptomic changes along with KEAP1 mutations may provide a better understanding of the molecular mechanisms associated with the progression of lung cancer and may help to provide better therapeutic approaches.Cardiac fibrosis is a primary phenotype of cardiac remodeling that contributes to cardiac dysfunction and heart failure. The expansion and activation of CD4+ T cells in the heart has been identified to facilitate pathological cardiac remodeling and dysfunction; however, the underlying mechanisms remained not well clarified. Herein, we found that exosomes derived from activated CD4+ T cells (CD4-activated Exos) evoked pro-fibrotic effects of cardiac fibroblasts, and their delivery into the heart aggravated cardiac fibrosis and dysfunction post-infarction. Mechanistically, miR-142-3p that was enriched in CD4-activated Exos recapitulated the pro-fibrotic effects of CD4-activated Exos in cardiac fibroblasts, and vice versa. Furthermore, miR-142-3p directly targeted and inhibited the expression of Adenomatous Polyposis Coli (APC), a negative WNT signaling pathway regulator, contributing to the activation of WNT signaling pathway and cardiac fibroblast activation. Thus, CD4-activated Exos promote post-ischemic cardiac fibrosis through exosomal miR-142-3p-WNT signaling cascade-mediated activation of myofibroblasts. Targeting miR-142-3p in CD4-activated Exos may hold promise for treating cardiac remodeling post-MI.The evolution of insect resistance to pesticides poses a continuing threat to agriculture and human health. While much is known about the proximate molecular and biochemical mechanisms that confer resistance, far less is known about the regulation of the specific genes/gene families involved, particularly by trans-acting factors such as signal-regulated transcription factors. Here we resolve in fine detail the trans-regulation of CYP6CM1, a cytochrome P450 that confers resistance to neonicotinoid insecticides in the whitefly Bemisia tabaci, by the mitogen-activated protein kinase (MAPK)-directed activation of the transcription factor cAMP-response element binding protein (CREB). Reporter gene assays were used to identify the putative promoter of CYP6CM1, but no consistent polymorphisms were observed in the promoter of a resistant strain of B. tabaci (imidacloprid-resistant, IMR), which overexpresses this gene, compared to a susceptible strain (imidacloprid-susceptible, IMS). Investigation of potential trans-acting factors using in vitro and in vivo assays demonstrated that the bZIP transcription factor CREB directly regulates CYP6CM1 expression by binding to a cAMP-response element (CRE)-like site in the promoter of this gene. CREB is overexpressed in the IMR strain, and inhibitor, luciferase, and RNA interference assays revealed that a signaling pathway of MAPKs mediates the activation of CREB, and thus the increased expression of CYP6CM1, by phosphorylation-mediated signal transduction. Collectively, these results provide mechanistic insights into the regulation of xenobiotic responses in insects and implicate both the MAPK-signaling pathway and a transcription factor in the development of pesticide resistance.