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BackgroundWith the use of broad-spectrum antibiotics, immunosuppressive drugs, and glucocorticoids, multidrug-resistant Acinetobacter baumannii (MDR-AB) has become a major nosocomial pathogen species. The recent renaissance of bacteriophage therapy may provide new treatment strategies for combatting drug-resistant bacterial infections. In this study, we isolated a lytic bacteriophage vB_AbaM-IME-AB2 has a short latent period and a small burst size, which clear its host’s suspension quickly, was selected for characterization and a complete genomic comparative study.ResultsThe isolated bacteriophage vB_AbaM-IME-AB2 has an icosahedral head and displays morphology resembling Myoviridae family. Gel separation assays showed that the phage particle contains at least nine protein bands with molecular weights ranging 15–100 kDa. vB_AbaM-IME-AB2 could adsorb its host cells in 9 min with an adsorption rate more than 99% and showed a short latent period (20 min) and a small burst size (62 pfu/cell). It could form clear plaques in the double-layer assay and clear its host’s suspension in just 4 hours. Whole genome of vB_AbaM-IME-AB2 was sequenced and annotated and the results showed that its genome is a double-stranded DNA molecule consisting of 43,665 nucleotides. The genome has a G + C content of 37.5% and 82 putative coding sequences (CDSs). We compared the characteristics and complete genome sequence of all known Acinetobacter baumannii bacteriophages. There are only three that have been sequenced Acinetobacter baumannii phages AB1, AP22, and phiAC-1, which have a relatively high similarity and own a coverage of 65%, 50%, 8% respectively when compared with our phage vB_AbaM-IME-AB2. A nucleotide alignment of the four Acinetobacter baumannii phages showed that some CDSs are similar, with no significant rearrangements observed. Yet some sections of these strains of phage are nonhomologous.ConclusionvB_AbaM-IME-AB2 was a novel and unique A. baumannii bacteriophage. These findings suggest a common ancestry and microbial diversity and evolution. A clear understanding of its characteristics and genes is conducive to the treatment of multidrug-resistant A. baumannii in the future.

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Immune checkpoint blockade (ICB) has shown long‐term survival benefits, but only in a small fraction of cancer patients. Recent studies suggest that improved vessel perfusion by ICB positively correlates with its therapeutic outcomes. However, the underlying mechanism of such a process remains unclear. Here, we show that anti‐cytotoxic T‐lymphocyte‐associated protein 4 (CTLA4) treatment‐induced tumor vessel normalization was accompanied by an increased infiltration of eosinophils into breast tumors. Eosinophil accumulation was positively correlated with the responsiveness of a breast tumor to anti‐CTLA4 therapy. Depletion of eosinophils subsequently negated vessel normalization, reduced antitumor immunity and attenuated tumor growth inhibition by anti‐CTLA4 therapy. Moreover, intratumoral accumulation of eosinophils relied on T lymphocytes and interferon γ production. Together, these results suggest that eosinophils partially mediate the antitumor effects of CTLA4 blockade through vascular remodeling. Our findings uncover an unidentified role of eosinophils in anti‐CTLA4 therapy, providing a potential new target to improve ICB therapy and to predict its efficacy.

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Increasing evidence has demonstrated that hypoxia was an aggressive feature in endometrial cancer (EC), which is significantly associated with the tumor grade, lymph node metastasis, and tumor resistance to chemotherapy. However, the relationship between hypoxia and the immune microenvironment in EC is not very clear. Exosomes are small membrane vesicles secreted from a variety of cell types which mediate cell-to-cell communication through transported biomolecules. Here, we investigated whether exosomes can play an immunomodulatory role in intercellular communication between EC cells and macrophages. EC KEL cells were cultured under hypoxia or normoxic condition to collect exosomes. After identification, the exosomes derived from hypoxic or normoxic KEL cells were cultured with the monocyte cell line THP-1 to study the immunoregulation function of KEL cells. The results showed that the total number of exosomes produced by hypoxic KEL cells was significantly higher than that in normoxic condition. In addition, hypoxia markedly stimulated the increase in miRNA-21 expression in the exosomes. After coculture, we found that exosomal miRNA-21 could be horizontally transferred into THP-1 cells. And then, the notably enhanced mRNA expression levels of IL-10 and CD206 in THP-1 cells were observed, suggestive of M2 polarization. To further study the effect of miRNA-21-containing exosomes, we transfected miRNA-21 mimics or inhibitor into THP-1 cells. The results showed that miRNA-21 mimics promoted IL-10 and CD206 mRNA expression levels, and the miRNA-21 inhibitor significantly prevented the alteration induced by intake of hypoxic KEL cell-derived exosomes. In summary, we found that endometrial cancer KEL cells in hypoxic condition promoted monocyte THP-1 cell transformation to M2-like polarization macrophages through delivering exosomal miRNA-21, which may be a potential mechanism of the formation of the immune microenvironment in EC progression.

Every year, billions of dollars are spent on rail track maintenance to keep the serviceability of the railroad network. These maintenance projects (of different types) must be performed by suitable maintenance teams within a planning horizon. This article presents a time-space network model to solve the track maintenance scheduling problem (TMSP). The objective is to minimize the total travel costs of the maintenance teams as well as the impact of maintenance projects on railroad operation, which are formulated by three types of side constraints: mutually exclusive, time window, and precedence constraints. An iterative heuristic solution approach is proposed to solve the large-scale TMSP model with a large number of side constraints. The proposed model and solution approach are applied to a large-scale real-world problem. Compared to the current industry practice the model outcome eliminated all hard sideconstraint violations and reduced the total objective value (travel costs and soft side-constraint violation penalties) by 66.8%.

BackgroundAntiangiogenic agents are commonly used in lung and colon cancer treatments, however, rapid development of drug resistance limits their efficacy.MethodsLentinan (LNT) is a biologically active compound extracted from Lentinus edodes. The effects of LNT on tumor angiogenesis were evaluated by immunohistochemistry in murine LAP0297 lung and CT26 colorectal tumor models. The impacts of LNT on immune cells and gene expression in tumor tissues were determined by flow cytometry, qPCR, and ELISA. Nude mice and IFNγ blockade were used to investigate the mechanism of LNT affecting on tumor angiogenesis. The data sets were compared using two-tailed student’s t tests or ANOVA.ResultsWe found that LNT inhibited tumor angiogenesis and the growth of lung and colon cancers. LNT treatments elevated the expression of angiostatic factors such as IFNγ and also increased tumor infiltration of IFNγ-expressing T cells and myeloid cells. Interestingly, IFNγ blockade, but not T cell deficiency, reversed the effects of LNT treatments on tumor blood vessels. Moreover, long-lasting LNT administration persistently suppressed tumor angiogenesis and inhibited tumor growth.ConclusionsLNT inhibits tumor angiogenesis by increasing IFNγ production and in a T cell-independent manner. Our findings suggest that LNT could be developed as a new antiangiogenic agent for long-term treatment of lung and colon cancers.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0932-y) contains supplementary material, which is available to authorized users.