Objective:To investigate the expression changes at the transcriptional level in normal lung tissues of mice after exposure to heavy ion radiation for different durations at different doses, aiming to provide evidence for exploring sensitive genes of heavy ion radiation, heavy ion radiation effect and the damage mechanism.Methods:Experiments on the temporal kinetics: the whole thorax of mice was irradiated with 14.5Gy carbon-ions and the total RNA of lung tissue was extracted at 3days, 7days, 3 weeks and 24 weeks. In dose-dependent experiment, the total RNA of lung tissue was extracted at 1 week after irradiated with a growing thoracic dose of 0, 7.5, 10.5, 12.5, 14.5, 17.5 and 20Gy. Protein-to-protein interaction (PPI) analysis and gene-ontology biological process enrichment analysis were performed on significant differentially expressed genes (DEGs).Results:A clearly differential expression patterns were observed at 3-day (acute stage), 1-week (subacute stage), 3-week (inflammatory stage) and 24-week (fibrosis stage) following 14.5Gy carbon-ions irradiation. Among those, the 3-day time point was found to be the mostly different from the other time points, whereas the 7-day time point had the highest uniformity with the other time points. Cellular apoptosis was the main type of cell death in normal lung tissues following carbon-ions exposure. The interactive genes of Phlda3, GDF15, Mgmt and Bax were identified as the radiosensitive genes, and Phlda3 was the center ( R=0.76, P<0.001). Conclusion:The findings in this study provide transcriptional insights into the biological mechanism underlying normal lung tissue toxicity induced by carbon-ions.

The nucleocapsid (N) protein of SARS-CoV-2 has been reported to have a high ability of liquid-liquid phase separation, which enables its incorporation into stress granules (SGs) of host cells. However, whether SG invasion by N protein occurs in the scenario of SARS-CoV-2 infection is unknow, neither do we know its consequence. Here, we used SARS-CoV-2 to infect mammalian cells and observed the incorporation of N protein into SGs, which resulted in markedly impaired self-disassembly but stimulated cell cellular clearance of SGs. NMR experiments further showed that N protein binds to the SG-related amyloid proteins via non-specific transient interactions, which not only expedites the phase transition of these proteins to aberrant amyloid aggregation in vitro, but also promotes the aggregation of FUS with ALS-associated P525L mutation in cells. In addition, we found that ACE2 is not necessary for the infection of SARS-CoV-2 to mammalian cells. Our work indicates that SARS-CoV-2 infection can impair the disassembly of host SGs and promote the aggregation of SG-related amyloid proteins, which may lead to an increased risk of neurodegeneration.
Amyloidogenic Proteins/metabolism* ; Amyotrophic Lateral Sclerosis/genetics* ; Animals ; COVID-19 ; Cytoplasmic Granules/metabolism* ; Mammals ; SARS-CoV-2 ; Stress Granules