The hierarchical stratum response system of organism to microgravity during spaceflight.

With the advancement of manned spaceflight technology, significant progress has been made in the fields of aerospace medicine and space biology to address the needs of astronauts in terms of health, safety, and mission performance. The physiological and pathological changes during microgravity exposure, including perception, response, and adaptation mechanisms, are gradually being unraveled. This study aimed to systematically summarize the common features of various molecules and structures within the cell membrane, cytoplasm, and nucleus responsible for sensing microgravity. It further examined the heterogeneous responses across different tissues, organs, and cells, as well as systemic-level interactions and synergies, and proposed a novel multilevel gravity-sensing theory. Additionally, the study highlighted cutting-edge in-orbit health monitoring technologies, including rapid fluid analysis using sensitive biomarkers and non-invasive evaluation using two-photon fluorescence microscopy. Furthermore, it explored the promising applications of emerging therapeutic approaches for microgravity adaptation, including small nucleic acid drugs targeting gene regulation, exosome-based drug delivery systems, and natural small-molecule drugs aimed at combating microgravity effects.