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The escalation can deepen physiological dependence and make discontinuation more challenging, even when withdrawal symptoms are relatively mild compared to other substances

A recent study demonstrated that nuclear p53 decreases the specialized autophagy-related mitophagy response by transcriptionally downregulating PINK1 (51)

Relative to short-term smokers, long-term smokers are both more likely to be nicotine dependent and report that they are smokers in a survey, since they are more likely to smoke at a given point in time

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