ARHGAP6 Suppresses Breast Cancer Tumor Growth by Promoting Ferroptosis via RhoA-ROCK1-p38 MAPK Signaling.

BACKGROUND: Ferroptosis, a distinct iron-dependent form of regulated cell death, is induced by severe lipid peroxidation due to reactive oxygen species (ROS) generation. Breast cancer patient survival is correlated with the tumor-suppressing properties of Rho guanosine triphosphatase hydrolase enzyme (GTPase)-activating protein 6 (ARHGAP6). This study investigates the impact and mechanisms of ARHGAP6 on ferroptosis in breast cancer. METHODS: Using quantitative RT-PCR, Western blotting, and immunofluorescence staining, ARHGAP6 expression was detected in a gene expression dataset, cancer tissue samples, and cells. ARHGAP6 was overexpressed or silenced in breast cancer cell lines. Cell proliferation was measured using 5-ethynyl-2-deoxyuridine (EdU) assay, and cell death rate was determined using LDH cytotoxicity assay. As indicators of ferroptosis, Fe2+ ion content, lipid ROS, glutathione peroxidase 4 (GPX4), ChaC glutathione specific gamma-glutamylcyclotransferase 1 (CHAC1), prostaglandin-endoperoxide synthase 2 (PTGS2), solute carrier family 7 member 11 (SLC7A11), and acyl-CoA synthetase long chain family member 4 (ACSL4) levels were evaluated. RESULTS: ARHGAP6 was obviously downregulated in cancer tissues and cells. ARHGAP6 overexpression decreased cell proliferation, elevated cell death and lipid ROS, decreased GPX4 and SLC7A11, increased PTGS2, ACSL4, and CHAC1, and inhibited RhoA/ROCK1 and p38 MAPK signaling in cancer cells. ARHGAP6 knockdown exerted opposite effects to those of ARHGAP6 overexpression. p38 signaling suppression reversed the effect of ARHGAP6 knockdown on ferroptosis, while RhoA/ROCK1 signaling inhibition compromised the effect of ARHGAP6 on p38 MAPK signaling. In mice models, ARHGAP6 together with the ferroptosis inducer RSL3 cooperatively enhanced ferroptosis and inhibited tumor growth of cancer cells. ARHGAP6 mRNA level was positively correlated with that of ferroptosis indicators in tumor tissues. CONCLUSIONS: This study revealed that ARHGAP6 inhibited tumor growth of breast cancer by inducing ferroptosis via RhoA/ROCK1/p38 MAPK signaling. Integrating ARHGAP6 with ferroptosis-inducing agents may be a promising therapeutic strategy for breast cancer treatment.

Plasmonic-Enhanced Bright Single Spin Defects in Silicon Carbide Membranes.

Optically addressable spin defects in silicon carbide (SiC) have emerged as attractable platforms for various quantum technologies. However, the low photon count rate significantly limits their applications. We strongly enhanced the brightness by 7 times and spin-control strength by 14 times of single divacancy defects in 4H-SiC membranes using a surface plasmon generated by gold film coplanar waveguides. The mechanism of the plasmonic-enhanced effect is further studied by tuning the distance between single defects and the surface of the gold film. A three-energy-level model is used to determine the corresponding transition rates consistent with the enhanced brightness of single defects. Lifetime measurements also verified the coupling between defects and surface plasmons. Our scheme is low-cost, without complicated microfabrication and delicate structures, which is applicable for other spin defects in different materials. This work would promote developing spin-defect-based quantum applications in mature SiC materials.

Monitoring of airborne particulates near industrial silica sand mining and processing facilities.

To quantify risk of ambient exposure to airborne particulates around industrial silica sand operations, this study used EPA-certified federal reference method monitors to measure the levels of PM10 and PM2.5 particulate matter. The monitoring sites were chosen based upon EPA siting criteria, dichotomous samplers were calibrated before and after sampling, and pre- and post-weight filter weights were recorded. PM2.5 levels were significantly higher (paired t-tests) at both sites - averages of 7.70 ± 6.15 and 22.7 ± 31.714;µg/m3 - than concurrent background levels of 5.11 and 6.57µg/m3 respectively; and 98th percentile values were 24.9 and 111 µg/m3, respectively. Average PM10 levels were 24.2 and 49.0 µg/m3, and second-highest annual levels were 45.5 and 69.1 µg/m3 (two years) and 62.9 ug/m3 (2015) and 61.5 ug/m3 (2016), respectively for the two sites. Neither precipitation nor wind speed or direction appeared to affect PM2.5 or PM10 concentrations.