Fig 1: Putative protein cascades involved in rapid acclimatization in 25 K (A) group. Figure represents protein networks and processes involved in redox homeostasis, energy homeostasis, inflammatory signaling, protein misfolding and cytoskeletal (alveolar) integrity for 25 K (A). Dotted black lines represent events derived from literature. Bold black lines represent experimental findings. Central signaling molecules like STAT-3, Nrf and RXR begin cascade. STAT-3 levels fall back to normoxic levels in 25 K (A) group plasma causing lowered inflammatory signaling, increased VDR/RXR signaling and increased anti-oxidant response. Lowered inflammatory signaling is observed via MCP-1 levels as well as increased Calpain-2 levels. Increased VDR/RXR signaling helps restore energy homeostasis in 25 K (A) group as compared to 15 K group which is observed via NAD/NADH ratio and increased levels of glycolytic enzymes. VDR also plays a small role in calcium homeostasis. Free Ca2+ levels are reduced significantly in 25 K (A) group. This helps restore levels of cytoskeletal proteins with housekeeping functions. This, in part, causes alveolar structural integrity to endure extreme hypobaric conditions. Reduction in free Ca2+ levels also improves Calpain-2 levels. Actin is required for Nrf2 translocation into nucleus. When levels of actin are restored, Nrf2 mediated oxidative stress response is activated. Inflammatory signaling is further reduced due to it. Also, antioxidant protein levels increase to strengthen redox homeostasis. This entire process occurs within lung and plasma. Thus, proteins like GPX3, SOD1, HPX, CAT, MDH-1, STAT-3, TR2, RXR, Tubulin, Sult 1A1 and MCP-1 can provide important clues regarding the acclimatization status when their levels at normoxia and extreme hypobaric hypoxia (as in 25 K (A) group) are compared on following the stated acclimatization strategy of 10 h at 59 kPa followed by 1 h of normobaric normoxia exposure (99 kPa).