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Acyl-CoA synthetase long-chain family member 4 (ACSL4) activates arachidonic acid (AA) and adrenic acid (AdA) to form PUFA-CoAs, which are subsequently esterified into phospholipids by Lysophosphatidylcholine acyltransferase 3 (LPCAT3), yielding PUFA-PEs such as AdA-PE ( In the setting of IPF, elevated ACSL4 and LOXs expression has been documented in fibrotic lung tissue and alveolar epithelial cell, correlating with enhanced lipid peroxidation and fibrotic progression ( These findings underscore the significance of PUFA metabolism and lipid peroxidation in ferroptosis execution and IPF pathogenesis

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All experiments were performed in triplicate

Interestingly, a decrease in CHAC1 levels enhances cell survival and stress tolerance to As III , with CHAC1 knockdown reducing sensitivity to H 2 O 2