Previously, we showed that an oligodeoxynucleotide (ODN) with AAAG repeats (AAAG ODN) rescued mice from fatal acute lung injury (ALI) induced by influenza virus and inhibited production of tumor necrosis factor-α (TNF-α) in the injured lungs. However, its underlying mechanisms remain to be elucidated. Upon the bioinformatic analysis revealing that the sequence of AAAG ODN is in consensus with the interferon regulatory factor 5 (IRF5) binding site in the cis-regulatory elements of proinflammatory cytokines, we tried to explore whether AAAG ODN could attenuate burn injury-induced systemic inflammatory responses by inhibiting the IRF5 pathway. Using a mouse model with sterile systemic inflammation induced by burn injury, we found that AAAG ODN prolonged the lifespan of the mice, decreased the expression of IRF5 in the injured skin, reduced the production of TNF-α and IL-6 in the blood and injured skin, and attenuated the ALI. These effects were correlated with AAAG ODN-mediated inhibition of nuclear translocation of IRF5. The data suggest that AAAG ODN could act as a cytoplasmic decoy capable of interfering the function of IRF5 and be developed as a drug candidate for the treatment of inflammatory diseases.

BackgroundMetagenomics sequencing provides deep insights into microbial communities. To investigate their taxonomic structure, binning assembled contigs into discrete clusters is critical. Many binning algorithms have been developed, but their performance is not always satisfactory, especially for complex microbial communities, calling for further development.ResultsAccording to previous studies, relative sequence compositions are similar across different regions of the same genome, but they differ between distinct genomes. Generally, current tools have used the normalized frequency of k-tuples directly, but this represents an absolute, not relative, sequence composition. Therefore, we attempted to model contigs using relative k-tuple composition, followed by measuring dissimilarity between contigs using d2S\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$$ {d}_2^S $$\end{document}. The d2S\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$$ {d}_2^S $$\end{document} was designed to measure the dissimilarity between two long sequences or Next-Generation Sequencing data with the Markov models of the background genomes. This method was effective in revealing group and gradient relationships between genomes, metagenomes and metatranscriptomes. With many binning tools available, we do not try to bin contigs from scratch. Instead, we developed d2SBin\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$$ {d}_2^S\mathrm{Bin} $$\end{document} to adjust contigs among bins based on the output of existing binning tools for a single metagenomic sample. The tool is taxonomy-free and depends only on k-tuples. To evaluate the performance of d2SBin\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$$ {d}_2^S\mathrm{Bin} $$\end{document}, five widely used binning tools with different strategies of sequence composition or the hybrid of sequence composition and abundance were selected to bin six synthetic and real datasets, after which d2SBin\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$$ {d}_2^S\mathrm{Bin} $$\end{document} was applied to adjust the binning results. Our experiments showed that d2SBin\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$$ {d}_2^S\mathrm{Bin} $$\end{document} consistently achieves the best performance with tuple length k = 6 under the independent identically distributed (i.i.d.) background model. Using the metrics of recall, precision and ARI (Adjusted Rand Index), d2SBin\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$$ {d}_2^S\mathrm{Bin} $$\end{document} improves the binning performance in 28 out of 30 testing experiments (6 datasets with 5 binning tools). The d2SBin\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$$ {d}_2^S\mathrm{Bin} $$\end{document} is available at https://github.com/kunWangkun/d2SBin.ConclusionsExperiments showed that d2S\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$$ {d}_2^S $$\end{document} accurately measures the dissimilarity between contigs of metagenomic reads and that relative sequence composition is more reasonable to bin the contigs. The d2SBin\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$$ {d}_2^S\mathrm{Bin} $$\end{document} can be applied to any existing contig-binning tools for single metagenomic samples to obtain better binning results.

BackgroundPrevious studies have discussed the overlapping and reinforcing effects (defined as a syndemic) of psychosocial problems on high-risk sexual behaviors among men who have sex with men (MSM). The present study aimed to apply the syndemic theory to verify the reinforcing effects of psychosocial problems on unprotected anal intercourse (UAI) among MSM in Shanghai, and determine if other important psychosocial factors fit into the syndemic theory.MethodsData were collected from 547 MSM in Shanghai, China, through face-to-face interviews. The measures for psychosocial problems included the Rosenberg Self-Esteem Scale; the Generalized Anxiety Disorder-7; the Center for Epidemiological Studies Depression Scale; the University of California, Los Angeles Loneliness Scale; and the Sexual Compulsivity Scale. We used multivariate analysis and binary logistic regression to investigate the associations between psychosocial problems and high-risk sexual behaviors.ResultsThe prevalence of UAI among MSM in the past 6 months was 54.5%. Education (graduate from college vs. high school) served as a protective factor against UAI (OR 0.59, 95% CI: 0.38–0.94). There was a high prevalence of psychosocial problems, and at least one-third of participants reported experiencing more than two psychosocial symptoms. Of these psychosocial factors that we investigated, lower self-esteem was associated with UAI in both univariate and multivariate regression model (P = 0.009). Result suggests that overlapping and reinforcing effects of psychosocial problems may increase high risk sexual behaviors among MSM in Shanghai, China (OR 1.65, 95% CI: 1.09–2.50; P = 0.018).ConclusionsWe found further evidence for a syndemic of psychosocial problems among MSM in Shanghai, China. This syndemic may also increase high risk sexual behaviors among MSM. Most HIV prevention interventions are focused on behavior change and only have moderate effects; our findings suggest that a shift from behavior-focused interventions to a more comprehensive strategy that addresses psychosocial factors may be necessary.

BackgroundInterleukin-9 (IL-9) was reported as an active participant in the pathogenesis of allergic asthma. This study aimed to investigate the major source ofIL-9 and its effect on interferon γ (IFN-γ) and immunoglobulin (Ig) secretion by B cells.MethodsWe isolated peripheral blood mononuclear cells from children with allergic asthma and healthy children. IL-9, IL-4 and IFN-γ expression were detected by ELISA, ELISpot and Flowcytometry. Expression of transcription factor PU.1 was measured by Western Blot. We evaluated the effect of IL-9 on B cell activation and Ig production.ResultsResults showed that compared with healthy children, levels of IL-9, IL-4 and PU.1 were elevated and levels of IFN-γ were lower in children with allergic asthma. IL-9-expressing CD4+ T cells did not co-express IL-4. Exogenous IL-9 inhibited IFN-γ production in a dose-dependent manner. Antigen-specific Th9 cells existed in children with house dust mite allergic asthma. IL-9 up-regulated expression of CD69 and CD25 on B cells and combination of IL-9 and IL-4 enhanced IgE production.ConclusionsIn conclusion, our results showed that Th9 cells may be the major source of IL-9 in children with allergic asthma. In these patients, IL-9 impairs IFN-γ production and synergistically promotes IL-4-induced IgE secretion.

BackgroundEpigenetic alterations are strongly associated with the development of cancer. The aim of this study was to identify epigenetic pattern in squamous cell lung cancer (LUSC) on a genome-wide scale.ResultsHere we performed DNA methylation profiling on 24 LUSC and paired non-tumor lung (NTL) tissues by Illumina Human Methylation 450 K BeadArrays, and identified 5214 differentially methylated probes. By integrating DNA methylation and mRNA expression data, 449 aberrantly methylated genes accompanied with altered expression were identified. Ingenuity Pathway analysis highlighted these genes which were closely related to the carcinogenesis of LUSC, such as ERK family, NFKB signaling pathway, Hedgehog signaling pathway, providing new clues for understanding the molecular mechanisms of LUSC pathogenesis. To verify the results of high-throughput screening, we used 56 paired independent tissues for clinical validation by pyrosequencing. Subsequently, another 343 tumor tissues from the Cancer Genome Atlas (TCGA) database were utilized for further validation. Then, we identified a panel of DNA methylation biomarkers (CLDN1, TP63, TBX5, TCF21, ADHFE1 and HNF1B) in LUSC. Furthermore, we performed receiver operating characteristics (ROC) analysis to assess the performance of biomarkers individually, suggesting that they could be suitable as potential diagnostic biomarkers for LUSC. Moreover, hierarchical clustering analysis of the DNA methylation data identified two tumor subgroups, one of which showed increased DNA methylation.ConclusionsCollectively, these results suggest that DNA methylation plays critical roles in lung tumorigenesis and may potentially be proposed as a diagnostic biomarker.Trial registrationChiCTR-RCC-12002830 Date of registration: 2012–12-17.

BackgroundThe incidence of acute erythroid leukemia subtype (AEL) is rare, accounting for 5% of cases of acute myeloid leukemia (AML), and the outcome is dismal. However, in 2016 revision to the WHO classification, the subcategory of AEL has been removed. Myeloblasts are redefined as the percentage of total marrow cells, not non-erythroid cells. Therefore, the previously diagnosed AEL cases are currently diagnosed as AML or myelodyspalstic syndrome (MDS) according to new criteria.MethodsWe respectively reviewed cases of 97 de novo previously diagnosed AEL and all the patients were diagnosed as AML or MDS according to the new classification scheme, and then the clinical characteristics of these two subtypes were compared. Statistical analyses were performed by SPSS software version 18.0.ResultsThe median age was 37 years-old, the two-thirds of previous AEL cases were diagnosed as MDS, and there was no obvious difference between two subtypes except for male/female ratio and age. Cytogenetic, rather than MDS/AML subtypes, can better represent the prognostic factor of previously diagnosed AEL patients. When the cytogenetic risk of patients belonged to MRC intermediate category and age were below 40 years-old in previous AEL cases, the patients who received induction chemotherapy without transplantation had a similar survival compared with the patients who underwent transplantation (3-year OS: 67.2% vs 68.5%).ConclusionsCytogenetic, rather than MDS/AML subtypes, can better represent the prognostic factor of previously diagnosed AEL patients. Transplantation was a better choice for those whose cytogenetic category was unfavorable.