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For example, high levels of GSH in the TME not only serve as a key defense line for tumor cells against oxidative stress and ferroptosis but can also directly chelate and inactivate specific metal ions (such as Cu 2 ), thereby weakening the effectiveness of therapeutic strategies based on metal-catalyzed reactions [161]

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On the other hand, various factors, including mitochondrial activation of enzymes, the respiratory chain, complex and decoupling proteins, affect the stability and activity of HIF-1