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Nevertheless, there are some drawbacks of PHH, such as poor availability, donor variability, high procurement costs, and limited culture duration, as they can rapidly lose their liver-specific metabolic competence in vitro

Complexity increases with additional stack components, requiring careful attention to interactions, timing, and individual response assessment

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For this purpose, we adopted two approaches: (1) a proteomic approach using FLAG-tagged macrocycles and (2) live-cell imaging using fluorescently labelled macrocycles