CHD4 R975H mutant activates tumorigenic pathways and promotes stemness and M2-like macrophage polarization in endometrial cancer.

Endometrial cancer (EC), one of the most prevalent carcinomas in females, is associated with increasing mortality. We identified the CHD4 R975H mutation as a high-frequency occurrence in EC patients through a comprehensive survey of EC databases. Computational predictions suggest that this mutation profoundly impacts the structural and functional integrity of CHD4. Functional assays revealed that the CHD4 R975H mutation enhances EC cell invasion, proliferation, and colony formation, promoting a cancer stem cell (CSC)-like phenotype. RNA-seq analysis of cells expressing CHD4 R975H mutant revealed a transcriptomic landscape marked by the activation of several cancer-promoting signaling pathways, including TNF-α signaling via NF-κB, KRAS, P53, mTOR, TGF-ß, EGFR, Myc and growth factor signaling. Validation assays confirmed the activation of these pathways, further demonstrating that CHD4 R975H mutation induces stemness in EC cells and M2-like polarization of tumor-associated macrophages (TAMs). Our study elucidated the oncogenic role of CHD4 R975H mutation, highlighting its dual impact on facilitating cancer stemness and transforming TAMs into an immunosuppressive subtype. These findings contribute valuable insights into the molecular mechanisms driving EC progression and open avenues for targeted therapeutic interventions.

Indoor airborne particle sources and outdoor haze days effect in urban office areas in Guangzhou.

To identify the sources of PM2.5 pollutants in work environments and determine whether the air quality inside an office was affected by a change in outdoor pollution status, concurrent indoor and outdoor measurements of PM2.5 were conducted at five different office spaces in the urban center of Guangzhou on low pollution days (non-episode days, NEDs), and high pollution days (haze episode days, EDs). Indoor-outdoor relationships between the PM2.5 mass and its chemical constituents, which included water-soluble ions, carbonaceous species, and metal elements, were investigated. A principle component analysis (PCA) was performed to further confirm the relationship between the indoor and outdoor PM2.5 pollution. The results reveal that (1) Printing and ETS (Environmental tobacco smoking) were found to be important office PM2.5 sources and associated with the enrichment of SO42-, OC, EC and some toxic metals indoors; (2) On EDs, serious outdoor pollution and higher air exchange rate greatly affected all studied office environments, masking the original differences of the indoor characteristics (3) Fresh air system could efficiently filter out most of the outside pollutants on both NEDs and EDs. Overall, the results of our study suggest that improper human behavior is associated with the day-to-day generation of indoor PM2.5 levels and sporadic outdoor pollution events can lead to poor indoor air quality in urban office environments. Moreover, fresh air system has been experimentally proved with data as an effective way to improve the air quality in office.