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Based on the ICH S2 (R1) guidance document (International Council for Harmonisation, 2011) and White et al.(2020) relevant cytotoxicity was postulated at a minimum of 50% reduction in viability, as compared to the respective vehicle control

However, in local tissues, steroid metabolic reprogramming is driven by pro-inflammatory factors such as TNF-: inflammatory cytokines induce the overexpression of aromatase (Aromatase/CYP19A1), accelerating the conversion of the substrate testosterone into estradiol and leading to an excessive local production of E2 (154, 155)

The nanosensor was constructed by assembling CDs on the surface of AuNPs, forming an impact shell through AuN interactions