Anti-inflammatory mechanisms of neutrophil membrane-coated nanoparticles without drug loading.

Neutrophil membrane-coated nanoparticles (NM-NPs) are nanomedicines with traits of mimicking the surface properties and functions of neutrophils, which are the most abundant type of white blood cells in the human body. NM-NPs have been widely used as targeted drug delivery systems for various inflammatory diseases, but their intrinsic effects on inflammation are not fully characterized yet. This study found that NM-NPs could modulate inflammation by multiple mechanisms without drug loading. NM-NPs could inhibit the recruitment of neutrophils and macrophages to the inflamed site by capturing chemokines and blocking their adhesion to inflamed endothelial cells. After internalized by macrophages and other phagocytic cells, NM-NPs could alter their phenotype by phosphatidylserine and simultaneously degrade the sequestered and neutralized cytokines and chemokines by lysosomal degradation. Under these effects, NM-NPs exhibited significant anti-inflammatory effects on LPS-induced inflammatory liver injury in vivo without drug loading. Our study unveiled the anti-inflammatory effects and mechanisms of NM-NPs without drug loading, and provided new insights and evidence for understanding their biological effects and safety, as well as developing more effective and safe targeted drug delivery systems.

Neutrophil Nanodecoys Inhibit Tumor Metastasis by Blocking the Interaction between Tumor Cells and Neutrophils.

Cancer metastasis is the main cause of cancer-related deaths and involves the interaction between tumor cells and neutrophils. In this study, we developed activated neutrophil membrane-coated nanoparticles (aNEM NPs) as nanodecoys to block neutrophil-mediated cancer metastasis. The aNEM NPs were fabricated by cloaking poly(lactic acid) nanoparticles with membranes derived from activated neutrophils and inherited the functional proteins of activated neutrophils. We demonstrated that aNEM NPs could interfere with the recruitment of neutrophils to the primary tumor and premetastatic niches, inhibit the adhesion of neutrophils to tumor vascular endothelium and circulating tumor cells (CTCs), and disrupt the formation of CTC-neutrophil clusters in vitro and in vivo. In 4T1-bearing mice, aNEM NPs could effectively reduce breast cancer metastasis to various organs in mice. Our results suggest that aNEM NPs are a promising nanomedicine for preventing or treating cancer metastasis by acting as neutrophil nanodecoys.

Enhancing Wettability of Cu3P/Cu Systems through Doping with Si, Sn, and Zr Elements: Insights from First Principles Analysis.

Explaining the wetting mechanism of Cu-P brazing materials and Cu remains challenging. This fundamental research aims to reveal the wettability mechanism of Si, Sn, and Zr doping on the interfacial bond strength of the Cu3P/Cu system through the first principles study. We carried out several sets of calculations to test the validity of the result; included in the work are those used to establish the interfacial structure and to analyze the effect of doping on the wettability. Specific analysis was carried out in terms of three aspects: the work of adhesion (Wad), the charge density difference, and the density of states (DOS). The calculated results show that doping with Si, Sn, and Zr elements can effectively improve the wettability within the CuP/Cu interface with very high accuracy, and is particularly effective when doped with Zr. These results provide an insightful theoretical guide for enhancing the CuP/Cu system's wettability by adding active elements.

PLK4 Is a Potential Biomarker for Abnormal Tumor Proliferation, Immune Infiltration, and Prognosis in ccRCC.

Background: PLK4 is highly expressed and associated with poor prognosis in various malignancies. However, the role of PLK4 in clear cell renal cell carcinoma (ccRCC) is still unclear. This study is aimed at analyzing the expression, the potential regulating mechanism, and the role of PLK4 in the ccRCC by bioinformatics. Methods: PLK4 mRNA expression data and methylation levels in ccRCC were examined using TIMER, UALCAN, MethSurv, NCBI-GEO, and UCSC databases. Quantitative real-time PCR verifies the regulatory relationship between PLK4 and has-miR-214-3p. The GEPIA2 and STRING databases were used to find similar genes of PLK4 and then enriched with R language to analyze their similar genes. Correlations between PLK4 and tumor-infiltrating immune cells and cytokines exerting immunosuppression were analyzed using the TIMER database and the TISIDB databases. Results: PLK4 mRNA expression levels were significantly higher in ccRCC tissues than in paracancerous tissues. ccRCC tissues had lower DNA methylation levels of PLK4 than normal tissues. Importantly, the high PLK4 expression was associated with poor prognosis in ccRCC patients. The has-miR-214-3p negatively regulates the expression of PLK4. GO and KEGG pathway analysis showed that PLK4 coexpressed genes were mainly associated with multiple immune-related pathways, including cytokinesis, sister chromatid adhesions, and mitotic nuclear division. Our data suggest that the PLK4 expression is closely related to the level of immune infiltration and the cytokines that exert immune suppression, and IPS was significantly higher in the PLK4 low expression group. Conclusion: The PLK4 expression is associated with the prognosis of ccRCC patients and affects the immune microenvironment of ccRCC, and PLK4 is expected to be a new target for the diagnosis and treatment of ccRCC.