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Notably, AMPK is widely recognized for its ability to phosphorylate and activate eNOS in diverse pathophysiological contexts [44], and clinical therapeutic agents, such as statins and metformin, also modulate the activation of eNOS mediated by AMPK signaling [45, 46]

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That matters because the FDA drew an administrative line at fifty amino acids, defining anything above it as a biologic subject to an entirely different regulatory framework