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UHPLC-QE orbitrap/MS analysis The LC-MS-based metabolic analyses were carried out using a UHPLC system (1290, Agilent Technologies) with a UPLC HSS T3 column (2.1 mm 100 mm, 1.8 m, Waters) coupled to a Q Extractive Orbitrap Mass Spectrometer (Thermo Fisher Scientific, USA) in ESI positive (POS) and negative (NEG) ion modes