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The simplistic and outdated two-hit hypothesis has been replaced by a multi-hit model that integrates various interconnected processes, as shown in Figure 2, where multiple factors act synergistically, encompassing lipotoxicity, gut dysfunction, altered gut-liver axis and innate immune activation, within the context of genetic and environmental factors (68)

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Poudel et al., Redox/photo dual-responsive, self-targeted, and photosensitizer-laden bismuth sulfide nanourchins for combination therapy in cancer

Adult participants, aged between 18 and 70 years, exhibiting HAMD scores ranging from 21 to 31, were allocated to receive either a low-dose of SHR-5 (340 mg/day), a high-dose of SHR-5 (680 mg/day), or a placebo (60)