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The raw RNA sequencing data was mapped to human reference genome hg38 using the STAR aligner 63 , and genes annotated in Gencode v36 64 was quantified using featurecounts in the subread package 65

Locally produced IGF-1 also contributes to autocrine and paracrine signallingtissues produce their own IGF-1 in response to GH stimulation, creating local high concentrations even when systemic IGF-1 remains modest

36 Conversely, BMAL1 knockout in chondrocytes ( Col21-CreER, Bmal1 flox/flox ) significantly reduces VEGF and HIF-1 levels while increasing MMP13 and Runx2 expression, ultimately suppressing cell proliferation and promoting apoptosis

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However, this same sensitivity to external stimuli such as sensory deprivation or early life stress can render them vulnerable to dysfunction (155)

Additionally, the CFAX12 system can be adapted to investigate other respiratory diseases and toxic exposures, such as the effects of e-cigarette vapor or heated tobacco products on human lung health