Ferroptosis, a form of regulated cell death caused by lipid peroxidation, was recently identified as a natural tumor suppression mechanism. Here, we show that ionizing radiation (IR) induces ferroptosis in cancer cells. Mechanistically, IR induces not only reactive oxygen species (ROS) but also the expression of ACSL4, a lipid metabolism enzyme required for ferroptosis, resulting in elevated lipid peroxidation and ferroptosis. ACSL4 ablation largely abolishes IR-induced ferroptosis and promotes radioresistance. IR also induces the expression of ferroptosis inhibitors, including SLC7A11 and GPX4, as an adaptive response. IR-or KEAP1 deficiencyinduced SLC7A11 expression promotes radioresistance through inhibiting ferroptosis. Inactivating SLC7A11 or GPX4 with ferroptosis inducers (FINs) sensitizes radioresistant cancer cells and xenograft tumors to IR. Furthermore, radiotherapy induces ferroptosis in cancer patients, and increased ferroptosis correlates with better response and longer survival to radiotherapy in cancer patients. Our study reveals a previously unrecognized link between IR and ferroptosis and indicates that further exploration of the combination of radiotherapy and FINs in cancer treatment is warranted.

Cation deficient transition metal sulfides have attracted increased attention due to their unique properties that arise from degenerate p-doping, particularly their localized surface plasmon resonance (LSPR) and related optical properties. Here, we present the first study of their electrocatalytic activity. We developed a facile one-pot method to prepare p-doped copper sulfide nanoplates with tunable LSPR at moderate temperature (below 100 °C) without any hot injection or rapid mixing step. The doping level was controlled by varying the concentration of cation precursor (Cu 2+ ) to finely tune the LSPR wavelength without changing the nanoplate size or morphology. Cu 2−x S nanoplates with three different doping levels were tested for their electrocatalytic activity for the oxygen reduction reaction (ORR) in alkaline solution. Importantly, increasing the concentration of free holes in Cu 2−x S significantly enhanced the ORR catalytic activity. Furthermore, to improve the electrical conductivity, the most heavily doped Cu 2−x S nanoplates were deposited on carbon black (Vulcan XC-72) and reduced graphene oxide (rGO), thereby leading to substantial enhancement of ORR steadystate current in both electrochemical and mass-transfer controlled potential regions. A calculation of average electron transfer number along with the measured peroxide yield indicated that both carbon black and rGO supported Cu 2−x S catalysts can provide a four-electron reduction pathway. The ORR catalytic activity of the Cu 2−x S nanoplates does not yet match that of stateof-the-art Pt/C catalysts. However, this work opens up new opportunities to apply p-doped copper chalcogenides as electrocatalysts for the ORR beyond conventional nonprecious metal catalysts based upon Fe, Co, N, and C.

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Colorectal cancer (CRC) is one of the most common digestive tract malignancies and inflammation and gut microbiota are well-known key factors to influence CRC development. Akkermansia mucinipila is an important gram-negative anaerobic bacterium that can degrade mucin in gut. Previous studies suggested that A. muciniphila may affect inflammation and cell proliferation, but the relationship between A. muciniphila and CRC is not clarified. Here C57BL/6 mice were administrated with A. muciniphila or PBS and then treated with azoxymethane (AOM)/dextran sodium sulphate (DSS) to induce CRC. The mice receiving A. muciniphila administration had more serious weight loss, shorter colon length and more intestinal tumors than those receiving PBS administration after AOM/DSS treatment. More colon damage and less goblet cells were also observed in A. muciniphila treated mice. Furthermore, A. muciniphila administration induced more Ki67 + proliferating cells, higher PCNA expression and elevated gene expression of proliferation-associated molecules including Snrpd1, Dbf4 or S100A9. At early stage of CRC development, in comparison with controls, the mice receiving A. muciniphila administration also had more body weight loss and shorter colon length, as well as higher gene expression of inflammatory cytokines. Furthermore, the in vitro experimental results showed that the co-culture of colon epithelial cells with A. muciniphila enhanced the cell proliferation and gene expression of proliferation-associated molecules. Therefore, A. mucinipila may promote the formation of CRC in mice through increasing the early level of inflammation and the proliferation of intestinal epithelial cells.