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Screening of nanomaterials We prepared different nanomaterials conjugated with NGF siRNA as described in Supplementary Methods

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What the trials measured and when The METAOD005 oral trial measured weight at 12 weeks

The gut microbiota plays a pivotal role, producing metabolites and neurotransmitters that influence brain function via the vagus nerve and enteric nervous system, while the hypothalamicpituitaryadrenal (HPA) axis modulates stress responses, impacting both gut and brain functions (Yang et al., 2018