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At the environmental and lifestyle level, dietary patterns [169], environmental pollutants [170, 171], physical activity habits, and smoking/alcohol consumption [172,173,174] have been shown to serve as key external triggers that precipitate or exacerbate disease through modulation of intestinal microbiota homeostasis, disruption of epithelial barrier function, and activation of oxidative stress and inflammatory pathways

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In cell line models of CKD, TMAO-mediated nuclear translocation of Y-box binding protein-1 directly downregulates Gadd45a expression to promote cell cycle progression (Wang L