Background Immunosuppressive microenvironment is a major cause of immunotherapeutic resistance in glioma. In addition to secreting compounds, tumor cells under programmed cell death (PCD) processes release abundant mediators to modify the neighboring microenvironment. However, the complex relationship among PCD status, immunosuppressive microenvironment and immunotherapy is still poorly understood. Methods Four independent glioma cohorts comprising 1,750 patients were enrolled for analysis. The relationships among PCD status, microenvironment cellular components and biological phenotypes were fully explored. Tissues from our hospital and experiments in vitro and in vivo were used to confirm the role of ferroptosis in glioma. Results Analyses to determine enriched PCD processes showed that ferroptosis was the main type of PCD in glioma. Enriched ferroptosis correlated with progressive malignancy, poor outcomes and aggravated immunosuppression in glioblastoma (GBM) patients. Enhanced ferroptosis was shown to induce activation and infiltration of immune cells but attenuated antitumor cytotoxic killing. Tumor-associated macrophages (TAMs) were found to participate in ferroptosis-mediated immunosuppression. Preclinically, ferroptosis inhibition combined with PD-1/L1 blockade generated a synergistic therapeutic outcome in GBM murine models. Conclusions This work provides a molecular, clinical and biological landscape of ferroptosis, suggesting a role of ferroptosis in glioma malignancy and a novel synergic immunotherapeutic strategy that combines immune checkpoint blockade (ICB) treatment with ferroptosis inhibition.

These experimental results expand the scope of the protein database, generating targets for further investigation of the pathogenic mechanism of idiopathic asthenozoospermia.

The high levels of secondary metabolites in rapeseed play important roles in determining the oil quality and feeding value. Here, we characterized the metabolic profiles in seeds of various yellow-and black-seeded rapeseed accessions. Two hundred and forty-eight features were characterized, including 31 phenolic acids, 54 flavonoids, 24 glucosinolates, 65 lipid compounds, and 74 other polar compounds. The most abundant phenolic acids and various flavonoids (epicatechin, isorhamnetin, kaempferol, quercetin, and their derivatives) were widely detected and showed significant differences in distribution between the yellow-and black-seeded rapeseed. Furthermore, the related genes (e.g., BnTT3, BnTT18, BnTT10, BnTT12, and BnBAN) involved in the proanthocyanidin pathway had lower expression levels in yellow-seeded rapeseed, strongly suggesting that the seed coat color could be mainly determined by the levels of epicatechin and their derivatives. These results improve our understanding of the primary constituents of rapeseed and lay the foundation for breeding novel varieties with a high nutritional value.

OBJECTIVE To evaluate the effect of hypoxia‐inducible factor‐1α (HIF‐1α) over‐expression on the invasion‐associated proteins in human prostate cancer cells, as HIF‐1α is a transcriptional factor that could activate genes involved in the response to hypoxia, but might also enhance the invasive potency of prostate cancer cells. MATERIALS AND METHODS Prostate cancer (LNCaP) cells were transfected with recombinant plasmid pcDNA3.1(–)/HIF‐1α and pcDNA3.1(–) control vector using a commercial system, designated as LNCaP/HIF‐1α and LNCaP/pcDNA3.1, respectively. The positive clones were selected with G418 and confirmed by Western blot and indirect immunofluorescence labelling. A polycarbonate filter, coated with a matrix gel, was used to analyse the invasive potency. The expression of E‐cadherin, vimentin, cathepsin D, matrix metalloproteinase (MMP2) and urokinase plasminogen activator receptor (uPAR) was detected by Western blot. RESULTS The expression level of HIF‐1α in LNCaP/HIF‐1α was distinctly higher than that in LNCaP/pcDNA3.1 and LNCaP. Many more cells of LNCaP/HIF‐1α penetrated through the polycarbonate filter than those of LNCaP/pcDNA3.1 and LNCaP. Compared with the LNCaP/pcDNA3.1 and LNCaP cells, the expression of vimentin, cathepsin D, MMP‐2 and uPAR were up‐regulated in LNCaP/HIF‐1α, whereas the expression of E‐cadherin was down‐regulated. CONCLUSION These results show that over‐expression of HIF‐1α directly stimulates the invasive potency of human prostate carcinoma LNCaP cells through the matrix gel. The expression of E‐cadherin, vimentin, cathepsin D, MMP‐2 and uPAR, which are proteins with established roles in the pathophysiology of invasion, could be regulated by HIF‐1α in human prostate cancer cells.