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Because bulk cytosolic readouts obscure compartmental signals, measurement should rely on ER-targeted genetically encoded H 2 O 2 probes (e.g., roGFP-Orp1 or HyPer-ER), which report local peroxidatic events without cytosolic averaging and allow discrimination of ER-confined redox dynamics from extra-ER sources (Rashdan and Pattillo 2020

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Furthermore, integration of advanced manufacturing (GMP-compatible processes, scalable encapsulation techniques), quantitative multi-omics and mechanistic studies (metagenomics, metabolomics, host transcriptomics), and standardized safety assessments will be essential for clinical translation