Pseudomonas aeruginosa is a formidable pathogen that causes infections with high mortality rates. Because of its ability to form biofilms and rapidly acquire resistance to many first-line antibiotics, P. aeruginosa-related infections are typically difficult to cure by traditional antibiotic treatment regimes. Thus, new strategies to prevent and treat such infections are urgently required. PA0833 is a newly identified protective antigen of P. aeruginosa that was identified in a screen using a reverse vaccine strategy in our laboratory. In this study, we further confirmed its protective efficacy in murine sepsis and pneumonia models. Immunization with PA0833 induced strong immune responses and resulted in reduced bacterial loads; decreased pathology, inflammatory cytokine expression and inflammatory cell infiltration; and improved survival. Furthermore, PA0833 was identified as an OmpA C-like protein by bioinformatics analysis and biochemical characterization and shown to contribute to bacterial environmental stress resistance and virulence. These results demonstrate that PA0833 is an OmpA C-like protein that induces a protective immune response in mice, indicating that PA0833 is a promising antigen for vaccine development.
Synthetic oligodeoxynucleotides containing unmethylated CpG dinucleotides (CpG ODN) function as potential radiosensitizers for glioma treatment, although the underlying mechanism is unclear. It was observed that CpG ODN107, when combined with irradiation, did not induce apoptosis. Herein, the effect of CpG ODN107 + irradiation on autophagy and the related signaling pathways was investigated. In vitro, CpG ODN107 + irradiation induced autophagosome formation, increased the ratio of LC3 II/LC3 I, beclin 1 and decreased p62 expression in U87 cells. Meanwhile, CpG ODN107 also increased LC3 II/LC3 I expression in U251 and CHG-5 cells. In vivo, CpG ODN107 combined with local radiotherapy induced autophagosome formation in orthotopic transplantation tumor. Investigation of the molecular mechanisms demonstrated that CpG ODN107 + irradiation increased the levels of TLR9 and p-ERK, and decreased the level of p-mTOR in glioma cells. Further, TLR9-specific siRNA could affect the expressions of p-ERK and autophagy-related proteins in glioma cells. Taken together, CpG ODN107 combined with irradiation could induce autophagic cell death, and this effect was closely related to the TLR9-ERK-mTOR signaling pathway in glioma cells, providing new insights into the investigation mechanism of CpG ODN.
Innate immune effectors constitute the first line of host defense against pathogens. However, the roles of these effectors are not clearly defined during Klebsiella pneumoniae (K. pneumoniae) respiratory infection. In the current study, we established an acute pneumonia model of K. pneumoniae respiratory infection in mice and confirmed that the injury was most severe 48 h post infection. Flow cytometric assay demonstrated that alveolar macrophages were the predominant cells in BALF before infection, and neutrophils were quickly recruited after infection, and this was in consistent with the kinetics of chemokine expression. Further, we depleted neutrophils, macrophages, and complement pathways in vivo and challenged these mice with a sublethal dose of K. pneumonia, the result showed that 80%, 60%, and 40% of mice were died in these groups, respectively, while no deaths occurred in the control group. Besides, innate immune effector depleted mice showed higher bacterial burdens in lungs and blood, companied with more severe lung damage and increased levels of cytokine/chemokine expression. These results demonstrated that the innate immune effectors are critical in the early controlling of K. pneumoniae infection, and neutrophils are the most important. Thus, alternative strategies targeting these innate immune effectors may be effective in controlling of K. pneumoniae respiratory infection.
Surface nanobubbles have been presumed to lead to the experimental observation that liquid boiling often occurs at a much lower supersaturation than expected, yet no qualitative theory exists to explain how they participate in the process. Here, we report through a simple theoretical analysis on how the metastable nanobubbles nucleate the liquid-tovapor transition by serving as an intermediate phase. The appearance of metastable nanobubbles inhibits the shrink of the bubble nucleus and changes bubble nucleation into a multistep process. We show three possible mechanisms for heterogeneous nucleation starting from metastable surface nanobubbles: nucleation from pinned nanobubbles, nucleation via nanobubble depinning, and nucleation through nanobubble coalescence, each predicting a significant reduction in a nucleation barrier. The occurrence of a specific nucleation pathway of bubble nucleation depends on the detailed geometry of local substrate roughness. These results give insight into how the appearance of surface nanobubbles changes the nucleation mechanisms of liquid boiling.
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