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Chronic exposure to pesticide mixtures through diet is common, yet their combined metabolic effects and interactions with dietary factors remain unclear. We identified four pesticides prevalent in human exposure (imazalil, thiabendazole, boscalid, lambda-cyhalothrin) and assessed their combined impacts on hepatic metabolism and metabolic homeostasis using human liver cells and male mice fed standard chow or western diets. We found that the pesticide mixture induced metabolic perturbations in human hepatocytes. In addition, the pesticide mixture altered hepatic gene expression in chow-fed mice and exacerbated western diet-induced glucose intolerance, fasting hyperglycemia, and insulin resistance without affecting body weight or liver steatosis. These findings reveal that dietary context influences the metabolic consequences of pesticide mixtures, highlighting the need to consider nutritional status when evaluating environmental contaminant risks. Our results suggest that pesticide mixtures at reference doses m

Scenarios serve as a critical tool in climate change analysis, enabling the exploration of future evolution of the climate system, climate impacts, and the human system (including mitigation and adaptation actions). This paper describes the scenario framework for ScenarioMIP as part of CMIP7. The design process has involved various rounds of interaction with the research community and user groups at large. The proposal covers a set of scenarios exploring high levels of climate change (to explore high-end climate risks), medium levels of climate change (anchored to current policy), and low levels of climate change (aligned with current international agreements). These scenarios follow very different trajectories in terms of emissions, with some likely to experience peaks and subsequent declines in greenhouse gas concentrations in this century. An important innovation is that most scenarios are intended to be run, if possible, in emission-driven mode, providing a better representation of the Earth system uncert