Simultaneous degradation of glucocorticoids and sterilization using bubbling corona discharge plasma based systems: A promising terminal water treatment facility for hospital wastewater.

Glucocorticoids (GCs) have drawn great concern due to their widespread contamination in the environment and application in treating patients with COVID-19. Due to the lack of data about GC removal using advanced treatment processes, a novel Paralleling and bubbling corona discharge reactor (PBCD) combined with iron-loaded activated-carbon fibre (Fe-ACF) was addressed in this study to degrade GCs represented by Hydrocortisone (HC) and Betamethasone (BT). The results showed that the PBCD-based system can degrade GCs effectively and can achieve effective sterilization. The removal rates of GCs were ranked as PBCD/Fe-ACF > PBCD/ACF > PBCD. The concentration of E. coli was reduced from 109 to 102 CFU/mL after 60 min of PBCD-based system treatment. The abundance of bacteria in actual Hospital wastewater (HWW) was significantly reduced. Plasma changed the physical and chemical properties of ACF and Fe-ACF by etching axial grooves and enhancing stretching vibrations of surface functional groups, thus promoting adsorption and catalytic degradation. For GC degradation, the functional reactive species were identified as •OH, 1O2, and •O2 radicals. Possible degradation pathways for HC and BT were proposed, which mainly included defluorination, keto acid decarboxylation, demethylation, intramolecular cyclization, cleavage and ester hydrolysis, indicating a reduction in GC toxicity. Since GCs are widely used in patients with COVID-19 and their wastewater needs to be sterilized simultaneously, the intensive and electrically driven PBCD-based system is promising in GC pollution control and sterilization in terminal water treatment facilities.

TRIM35 functions as a novel tumor suppressor in breast cancer by inducing cell apoptosis through ubiquitination of PDK1.

Breast cancer is the most common cancer in women. Novel mechanisms and targets are urgently needed to understand and treat this disease due to the complexity of breast cancer. In this study, we evaluated the expression level of tripartite motif-containing (TRIM) 35 in various breast cancer cell lines by qPCR and immunoblot. Cell proliferation assay and flow cytometry were performed upon overexpression and depletion of TRIM35. Xenograft tumor model was applied to validate the findings observed in vitro. The correlation between TRIM35 and outcomes of breast cancer patients was investigated by analyzing The Cancer Genome Atlas database. We observed differential expression of TRIM35 in various breast cancer cell lines. Overexpression of TRIM35 significantly inhibited cell proliferation and promoted cell apoptosis. On the contrary, depletion of TRIM35 exerted the opposite effects on cell proliferation and apoptosis. Mechanistically, TRIM35 reduced PDK1 by ubiquitination, resulting in the degradation of PDK1. Overexpression of TRIM35 significantly suppressed ZR7530 cell line-derived xenograft tumor growth by inducing apoptosis. Finally, a lower level of TRIM35 was associated with a poor prognosis in patients. In conclusion, TRIM35 functions as a tumor suppressor to suppress breast cancer proliferation by inactivating AKT signaling through the increased ubiquitination of PDK1, resulting in the promotion of apoptosis.

CCL11 increases the proportion of CD4+CD25+Foxp3+ Treg cells and the production of IL­2 and TGF­ß by CD4+ T cells via the STAT5 signaling pathway.

CD4+ regulatory T (Treg) cells are associated with immune tolerance and antitumor immunosuppression. The aim of the present study was to investigate the role and molecular mechanism of C­C motif chemokine ligand 11 (CCL11) in the regulation of Treg cells from patients with breast cancer (BC) and healthy individuals in vitro, and from tumor­bearing mice in vivo. CD4+ T cells isolated from patients with BC or healthy individuals were incubated with anti­CCL11 neutralizing antibodies or recombinant human CCL11 protein, in the presence or absence of a STAT5 inhibitor. The serum CCL11 level and proportion of Treg cells characterized as CD4+CD25+forkhead box P3+ (Foxp3) among the CD4+ T cells in patients with BC and healthy individuals were analyzed by ELISA and flow cytometry, respectively. CCL11, C­C motif chemokine receptor 3 (CCR3), Foxp3, phosphorylated­STAT5 and STAT5 expression levels were determined by western blotting. The serum CCL11 level and the proportion of CD4+CD25+Foxp3+ Treg cells were significantly increased in patients with BC compared with healthy individuals. CCL11 blockade reduced the proportion of CD4+CD25+Foxp3+ Treg cells, the expression of CCR3 and Foxp3, and the level of STAT5 activation in tumor­associated CD4+ T cells, in a dose­dependent manner. CCL11 blockade also reduced the proportion of CD4+CD25+Foxp3+ Treg cells and the serum levels of interleukin (IL)­2 and transforming growth factor (TGF)­ß1 in tumor­bearing mice. The recombinant human CCL11 protein increased the proportion of CD4+CD25+Foxp3+ Treg cells, the expression of CCR3 and Foxp3, and the release of IL­2 and TGF­ß1 in non­tumor­associated CD4+ T cells via the STAT5 signaling pathway. The results of the present study may aid in identifying therapeutics that could further modulate the immune system during BC.