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Can the principles of mechanistic toxicology be leveraged to inform the a prioriSafe-and-Sustainable-by-Design (SSbD) of next-generation ENMs, enabling the decoupling of efficacy from toxicity

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1 Introduction Stroke, which contributes to a growing portion of the global medical burden, can be broadly classified into ischemic stroke and hemorrhagic stroke, with the latter incorporating intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH) ( Ferroptosis, a type of programmed cell death associated with stroke, was initially identified in 2012 and displays distinctive features, such as changes in the structure and density of mitochondria (Figure 1 shows a flowchart summarizing natural products that target ferroptosis after strokes

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