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Natranaerobius thermophilus is a unique extremophilic microorganism that exhibits remarkable adaptability and selectivity to the complex extreme environment characterized by high salt, high alkalinity, high temperature, and anaerobic conditions. However, the regulatory mechanisms of genes and proteins involved in the adaptation strategies of N. thermophilus to saline-alkaline-hot extreme environments remain poorly understood. In this project, we aim to study the adaptive strategies of N. thermophilus under different salt, alkaline, and thermal conditions using the TMT/iTRAQ-based quantitative proteomics approach. This includes investigating long-term adaptations and short-term regulatory responses to varying levels of salinity, alkalinity, and temperature. Additionally, we will explore the comprehensive adaptation mechanisms of N. thermophilus under multiple extreme conditions. This research will enhance our understanding of the intricate regulatory systems employed by extremophilic microorganisms and provide new insights into pushing the boundaries of life. The outcomes of this project will contribute significantly to our understanding of the fundamental principles underlying biological adaptability in extreme environments. By uncovering the adaptation strategies of N. thermophilus, this research will serve as a valuable reference for studying other extremophilic microorganisms and provide a theoretical basis for the development of biotechnological applications to cope with extreme environments. The results of this project will make important contributions to the deeper understanding of the adaptive mechanisms of extremophilic microorganisms and the diversity of life.