The genomic and immunogenomic landscape of mechanics pathway informs clinical prognosis and response to mechanotherapy

Mechanics shape cell and tissue plasticity and maintain their homeostasis.In cancers,mechanical signals regulate cancer hallmarks via mechanotransduction pathways,such as proliferation,metastasis and metabolic reprogramming.However,comprehensive characterization of mechanotransduction pathway genes and their clinical relevance across different cancer types remains untouched.Herein,we systematically portrayed the alterations of mechanotransduction pathway genes across 31 cancer types using The Cancer Genome Atlas(TCGA)databases.All the cancer types could be categorized into 6 subtypes based upon the transcriptional pattern of mechanics pathway genes.Each subtype has its own unique molecular expression pattern,mutation landscapes,immune infiltrates,and patient clinical outcome.We further found that the responses of two subtypes of cancers,one with the optimal outcome and the other with the worst prognosis,to a classical mechanotherapeutic agent(Fasudil,RhoA/ROCK inhibitor)were totally different,indicating that our cancer stratification system based upon mechanotransduction pathway genes could inform clinical responses of patients to mechanotherapeutic agents.Collectively,our study provides a novel pan-cancer landscape of the mechanotransduction pathways and underscores its potential clinical significance in the prediction of clinical prognosis and therapeutic responses to mechanotherapy among cancer patients.

Linkages Between Tropical Cyclones and Extreme Precipitation over China and the Role of ENSO

This research investigated the linkages between tropical cyclones(TCs)and extreme precipitation,and their associations with El Nino-Southern Oscillation(ENSO)over China.The contribution of TC-induced to total extreme precipitation events along the southeast coast of China was higher than 50%,and the values gradually decreased as TCs moved inland.However,the precipitation extremes(magnitude and frequency)related to TCs did not show statistically significant changes over the most recent 57 years.The impacts of TCs on precipitation extremes are evidently modulated by the ENSO phases.We found less extreme precipitation linked with TCs in southeastern China during El Nino phase,because of the fewer TC tracks over this region and less TC genesis in the western North Pacific(WNP).The small TC track density over southeastern China is due to the prevalent westerly steering flow and abnormal integrated vapor transport from northern to southern China during El Nino years.Additionally,warmer sea surface temperature,more vigorous westerlies,larger vorticity in 250 hPa,and higher divergence in 850 hPa in an El Nino phase jointly displaced the mean genesis of the WNP TCs eastward and this led to fewer TCs passing through southeastern China.