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This is close to the region where intracellular toxic metals are present in the superficial cortex adjacent to leptomeningeal venules (Figure 4E)

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This microenvironment-driven conversion is supported by the transcriptional upregulation of key stemness regulators such as OCT4, NANOG, and SOX2 and is further reinforced by epigenetic modifications such as promoter methylation or histone acetylation, which stabilize the reprogrammed state

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Ishigami, "Senescence Marker Protein-30 Protects Mice Lungs from Oxidative Stress, Aging, and Smoking", Am