NOS-like activity of CeO2 nanozymes contributes to diminishing the vascular plaques.

Ceria nanoparticles (CeO2NPs) exhibit great potential in cardiovascular disease and nonalcoholic fatty liver disease due to its excellent antioxidant capacity. However, the profitable effect of CeO2NPs on many diseases is almost all attributed to the regulation of ROS. Apart from the general antioxidant function, there seems to be no more distinct mechanism to reflect its unique multi-disease improvement effect. Here, we for the first time reveal a new discovery of CeO2NPs in mimicking nitric oxide synthase (NOS) by catalyzing L-arginine (L-Arg) to produce nitric oxide (NO) or the derivatives. NOS-like activity of CeO2NPs is original and associated with multiple factors like substrate concentration, pH, temperature and time, etc. where oxygen vacancy ratio plays a more critical role. Meanwhile, NOS-like activity of CeO2NPs successfully elevates NO secretion in endothelial cells and macrophages without expanding eNOS/iNOS expression. Importantly, NOS-like activity of CeO2NPs and the responsive endogenous NO promote the re-distribution of blood lipids and stabilize eNOS expression but suppress iNOS, thus collectively alleviate the accumulation of vascular plaque. Altogether, we provide a new angle of view to survey the outstanding potential of CeO2NPs, apart from the inevitable antioxidant capacity, the covert but possible and more critical NOS-like enzymatic activity is more noteworthy.

Identification of Pyroptosis-Relevant Signature in Tumor Immune Microenvironment and Prognosis in Skin Cutaneous Melanoma Using Network Analysis.

Background: Pyroptosis is closely related to the programmed death of cancer cells as well as the tumor immune microenvironment (TIME) via the host-tumor crosstalk. However, the role of pyroptosis-related genes as prognosis and TIME-related biomarkers in skin cutaneous melanoma (SKCM) patients remains unknown. Methods: We evaluated the expression profiles, copy number variations, and somatic mutations (CNVs) of 27 genes obtained from MSigDB database regulating pyroptosis among TCGA-SKCM patients. Thereafter, we conducted single-sample gene set enrichment analysis (ssGSEA) for evaluating pyroptosis-associated expression patterns among cases and for exploring the associations with clinicopathological factors and prognostic outcome. In addition, a prognostic pyroptosis-related signature (PPRS) model was constructed by performing Cox regression, weighted gene coexpression network analysis (WGCNA), and least absolute shrinkage and selection operator (LASSO) analysis to score SKCM patients. On the other hand, we plotted the ROC and survival curves for model evaluation and verified the robustness of the model through external test sets (GSE22153, GSE54467, and GSE65904). Meanwhile, we examined the relations of clinical characteristics, oncogene mutations, biological processes (BPs), tumor stemness, immune infiltration degrees, immune checkpoints (ICs), and treatment response with PPRS via multiple methods, including immunophenoscore (IPS) analysis, gene set variation analysis (GSVA), ESTIMATE, and CIBERSORT. Finally, we constructed a nomogram incorporating PPRS and clinical characteristics to improve risk evaluation of SKCM. Results: Many pyroptosis-regulated genes showed abnormal expression within SKCM. TP53, TP63, IL1B, IL18, IRF2, CASP5, CHMP4C, CHMP7, CASP1, and GSDME were detected with somatic mutations, among which, a majority displayed CNVs at high frequencies. Pyroptosis-associated profiles established based on pyroptosis-regulated genes showed markedly negative relation to low stage and superior prognostic outcome. Blue module was found to be highly positively correlated with pyroptosis. Later, this study established PPRS based on the expression of 8 PAGs (namely, GBP2, HPDL, FCGR2A, IFITM1, HAPLN3, CCL8, TRIM34, and GRIPAP1), which was highly associated with OS, oncogene mutations, tumor stemness, immune infiltration degrees, IC levels, treatment responses, and multiple biological processes (including cell cycle and immunoinflammatory response) in training and test set samples. Conclusions: Based on our observations, analyzing modification patterns associated with pyroptosis among diverse cancer samples via PPRS is important, which can provide more insights into TIME infiltration features and facilitate immunotherapeutic development as well as prognosis prediction.

Rapid detection of 5 fungal diseases in sunflower (Helianthus annuus) using dual priming oligonucleotide system-based multiplex PCR and capillary electrophoresis.

Rapid and accurate diagnosis of fungal pathogens is essential for disease control in sunflower. In the present study, a multiplex PCR assay was developed based on the dual priming oligonucleotide (DPO) system, which was used to simultaneously detect and identify five major sunflower fungal pathogens. There was no cross-reactivity among the pathogens tested. In each reaction, 0.1 ng genomic DNA templates were sufficient to ensure specificity and accuracy. The system exhibited high adaptability over a wide range of annealing temperatures. No mismatch or nonspecific amplification was observed in the annealing temperatures tested. In combination with capillary electrophoresis, the DPO-primer-based multiplex PCR system provides a rapid, reliable and cost-efficient solution for the diagnosis of fungal pathogens in sunflower.

PIK3CA mutation affects the proliferation of colorectal cancer cells through the PI3K-MEK/PDK1-GPT2 pathway.

The phosphatidylinositol­3­kinase catalytic subunit α (PIK3CA) gene is mutated in numerous human cancers. This mutation promotes the proliferation of tumor cells; however, the underlying mechanism is still not clear. In the present study, it was revealed that the PIK3CA mutation in colorectal cancer (CRC) HCT116 (MUT) rendered the cells more dependent on glutamine by regulating the glutamic­pyruvate transaminase 2 (GPT2). The dependence of glutamine increased the proliferation of cells in a normal environment and resistance to a suboptimal environment. Further study revealed that the mutated PIK3CA could regulate GPT2 expression not only through signal transduction molecule 3­phosphoinositide­dependent kinase (PDK1) but also through mitogen­activated protein kinase (MEK) molecules. In HCT116 cells, MEK inhibitor treatment could reduce the expression of GPT2 signaling molecules, thereby inhibiting the proliferation of CRC cells. A new signal transduction pathway, the PI3K/MEK/GPT2 pathway was identified. Based on these findings, MEK and PDK1 inhibitors were combined to inhibit the aforementioned pathway. It was revealed that the combined application of MEK and PDK1 inhibitors could promisingly inhibit the proliferation of MUT compared with the application of PI3K inhibitors, PDK1 inhibitors, or MEK inhibitors alone. In vivo, MEK inhibitors alone and combined inhibitors had stronger tumor­suppressing effects. There was no significant difference between the PDK1­inhibitor group and normal group in vivo. Thus, these results indicated that mutated PI3K affected GPT2 mediated by the MEK/PDK1 dual pathway, and that the PI3K/MEK/GPT2 pathway was more important in vivo. Inhibiting MEK and PDK1 concurrently could effectively inhibit the proliferation of CRC cells. Targeting the MEK and PDK1 signaling pathway may provide a novel strategy for the treatment of PIK3CA­mutated CRC.