Nutritional supplementation remodels yak cardiac molecular networks through selenoprotein activation and immune quiescence

营养补充通过硒蛋白激活和免疫静止重塑牦牛心脏分子网络

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Abstract

Seasonal nutritional stress during prolonged winters represents a pivotal yet understudied environmental determinant constraining livestock productivity on the Qinghai-Tibet Plateau. While cardiac adaptive mechanisms to chronic hypoxia have been extensively characterized in high-altitude ungulates, the molecular architecture underlying myocardial responses to nutritional perturbation remains largely unexplored. Here, we present the first integrative transcriptomic-proteomic atlas of yak cardiac tissue under differential nutritional regimens. Twelve male Muli yaks were allocated to ad libitum grazing (GRA, n = 18) and winter supplementary feeding (SUP, n = 18) cohorts using a completely randomized design over a 60-day intervention period. Myocardial specimens were interrogated via RNA sequencing and data-independent acquisition mass spectrometry. Differential expression analysis yielded 140 DEGs (48 upregulated, 92 downregulated) and 254 DEPs (79 upregulated, 175 downregulated). Nine-quadrant integration across 4,080 cognate gene-protein pairs unveiled a striking decoupling between transcriptional and translational landscapes: merely 3.4% exhibited concordant directionality, whereas 87.3% manifested protein-exclusive alterations, implicating post-transcriptional governance as the predominant regulatory paradigm. The selenoproteome emerged as a convergent nodal point, with GPX1 (mRNA/protein log₂FC: +0.73/+1.89) and SELENOW (+2.11/+3.00) demonstrating coordinated bi-level induction. Reciprocally, stress-responsive immunosurveillance effectors including ULBP13 (mRNA log₂FC = -10.24) and GZMB (protein log₂FC = -1.50) underwent pronounced attenuation. GPX1 and SELENOW exhibited flawless discriminatory capacity (AUC = 1.00) across both molecular strata. Collectively, these findings delineate a previously unrecognized regulatory axis whereby nutritional rehabilitation orchestrates myocardial molecular homeostasis through selenoprotein-mediated redox fortification coupled with immunoquiescent reprogramming, positioning GPX1 and SELENOW as robust sentinel biomarkers for nutritional status surveillance in high-altitude ruminants.

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