Co-expression network analysis reveals the pivotal role of mitochondrial dysfunction and interferon signature in juvenile dermatomyositis

Background Juvenile dermatomyositis (JDM) is an immune-mediated disease characterized by chronic organ inflammation. The pathogenic mechanisms remain ill-defined. Methods Raw microarray data of JDM were obtained from the gene expression omnibus (GEO) database. Based on the GSE3307 dataset with 39 samples, weighted correlation network analysis (WGCNA) was performed to identify key modules associated with pathological state. Functional enrichment analyses were conducted to identify potential mechanisms. Based on the criteria of high connectivity and module membership, candidate hub genes were selected. A protein-protein interaction network was constructed to identify hub genes. Another dataset (GSE11971) was used for the validation of real hub genes. Finally, the real hub genes were used to screen out small-molecule compounds via the Connectivity map database. Results Three modules were considered as key modules for the pathological state of JDM. Functional enrichment analysis indicated that responses to interferon and metabolism were dysregulated. A total of 45 candidate hub genes were selected according to the pre-established criteria, and 20 genes could differentiate JDM from normal controls by validation of another external dataset (GSE11971). These real hub genes suggested the pivotal role of mitochondrial dysfunction and interferon signature in JDM. Furthermore, drug repositioning highlighted the importance of acacetin, helveticoside, lanatoside C, deferoxamine, LY-294002, tanespimycin and L01AD from downregulated genes with the potential to perturb the development of JDM, while betonicine, felodipine, valproic acid, trichostatin A and sirolimus from upregulated genes provided potentially therapeutic goals for JDM. Conclusions There are 20 real hub genes associated with the pathological state of JDM, suggesting the pivotal role of mitochondrial dysfunction and interferon signature in JDM. This analysis predicted several kinds of small-molecule compounds to treat JDM

The Genomic Evolution and the Transmission Dynamics of H6N2 Avian Influenza A Viruses in Southern China

In China, the broad prevalence of H6 subtype influenza viruses, increasingly detected in aquatic birds, promotes their exchange materials with other highly pathogenic human-infecting H5N1, H5N6, and H7N9 influenza viruses. Strikingly, some H6 subtype viruses can infect pigs, dogs, and humans, posing risks to public health. In this study, 9 H6N2 viruses recovered from waterfowl species in the Guangdong province of China in 2018 were isolated and sequenced. Phylogenetic analysis revealed that the genome sequences of these H6N2 viruses belonged to Group I, except for the NP gene in Group III. Coalescent analyses demonstrated that the reassortment of NA and NS genes have occurred in two independent clusters, suggesting H6 subtype viruses had been undergoing a complex reassortant. To examine the evolutionary dynamics and the dissemination of the H6 subtype viruses, a Bayesian stochastic search variable selection was performed for results showing higher viral migration rates between closer provinces, including Guangdong, Jiangxi, Guangxi, and Fujian. Notably, the transmission routes of the H6 subtype viruses were concentrated in Jiangxi Province, the most frequent location for input and output transmission and a region containing Poyang Lake, a well-known wintering site for migration birds. We also found that the aquatic birds, especially ducks, were the most common input source of the viral transmission. In addition, we also found that eight positively selected amino acid sites were identified in HA protein. Given their continuous dissemination and the broad prevalence of the H6 subtype influenza viruses, continued surveillance is warranted in the future

A Bioinspired Immunostimulatory System for Inducing Powerful Antitumor Immune Function by Directly Causing Plasma Membrane Rupture

Abstract The Gasdermin protein is a membrane disruptor that can mediate immunogenic pyroptosis and elicit anti‐tumor immune function. However, cancer cells downregulate Gasdermin and develop membrane repair mechanisms to resist pyroptosis. Therefore, an artificial membrane disruptor (AMD) that can directly mediate membrane rupture in pyroptosis‐deficient cells and induce antitumor immune responses in a controllable manner will be valuable in preclinical and clinical research. A micron‐scale Ce6‐based AMD that can directly induce plasma membrane rupture (PMR) in gasdermin‐deficient tumor cells is established. Micron‐scale AMDs localize Ce6 specifically to the plasma membrane without labeling other organelles. Compared to free Ce6 molecules, the use of AMDs results in a higher degree of specificity for the plasma membrane. Due to this specificity, AMDs mediate fast and irreversible PMR under 660 nm red light. Furthermore, the AMDs are capable of inducing programmed cell death and lytic cell death in a catalytic manner, demonstrating that the amount of Ce6 used by AMDs is only one‐fifth of that used by Ce6 alone when inducing 80% of cancer cell death. In vivo, the AMDs show specificity for tumor targeting and penetration, suggesting that light‐driven programmed cell death is specific to tumors. AMDs are applied to antitumor therapy in gasdermin‐deficient tumors, resulting in efficient tumor elimination with minimal damage to major organs when combined with anti‐PD‐1 therapy. Tumor regression is correlated with PMR‐mediated inflammation and T‐cell‐based immune responses. This study provides new insights for designing bioinspired membrane disruptors for PMR and mediating anti‐tumor immunotherapy. Additionally, AMD is a dependable tool for examining the immunogenicity of PMR both in vitro and in vivo

The extent and nature of television food advertising to children in Xi’an, China

Abstract Background To explore the extent and nature of television food advertising especially unhealthy food advertising to primary school children in Xi’an, China. Methods Television data were recorded for 2 weekdays and 2 weekend days between 6:00 and 22:00 during May and June in 2012 from a total of five television channels most popular with children in Xi’an. Pearson χ2 tests and logistic regression were applied to determine differences in the proportion of healthy food, unhealthy food and miscellaneous food advertisements for different channels, programs, dates, viewing periods and the use of persuasive marketing tactics. Results Of the 5527 advertisements transcribed, 25.5 % were for food, among which 48.1 % were considered to be unhealthy. The frequency of food advertisements was 6 per hour per channel, including 3 unhealthy food advertisements. Compared with healthy and miscellaneous food advertisements, more unhealthy food advertisements were shown during afternoon, weekends and children’s non-peak viewing times as well as on children’s television channels, central television channels and non-children’s programmes. Unhealthy foods contributed the highest proportion of all food advertisements containing promotional characters (51.7 %) and premium offers (59.1 %). Both promotional characters and premium offers appeared more on non-children’s television channels. Conclusions The majority of food advertisements were for unhealthy food. More unhealthy food ads were shown in children’s non-peak time and afternoon as well as non-children’s channels. More children-oriented persuasive marketing tactics were used in unhealthy food ads especially in non-children’s channels. Therefore, intervening in the entrance of unhealthy foods into the market and establishing regulations related to food advertising especially unhealthy food advertisements are important strategies to prevent children’s exposure to unhealthy food and childhood obesity

Who Should Be Targeted for the Prevention of Birth Defects? A Latent Class Analysis Based on a Large, Population-Based, Cross-Sectional Study in Shaanxi Province, Western China.

BACKGROUND:The wide range and complex combinations of factors that cause birth defects impede the development of primary prevention strategies targeted at high-risk subpopulations. METHODS:Latent class analysis (LCA) was conducted to identify mutually exclusive profiles of factors associated with birth defects among women between 15 and 49 years of age using data from a large, population-based, cross-sectional study conducted in Shaanxi Province, western China, between August and October, 2013. The odds ratios (ORs) and 95% confidence intervals (CIs) of associated factors and the latent profiles of indicators of birth defects and congenital heart defects were computed using a logistic regression model. RESULTS:Five discrete subpopulations of participants were identified as follows: No folic acid supplementation in the periconceptional period (reference class, 21.37%); low maternal education level + unhealthy lifestyle (class 2, 39.75%); low maternal education level + unhealthy lifestyle + disease (class 3, 23.71%); unhealthy maternal lifestyle + advanced age (class 4, 4.71%); and multi-risk factor exposure (class 5, 10.45%). Compared with the reference subgroup, the other subgroups consistently had a significantly increased risk of birth defects (ORs and 95% CIs: class 2, 1.75 and 1.21-2.54; class 3, 3.13 and 2.17-4.52; class 4, 5.02 and 3.20-7.88; and class 5, 12.25 and 8.61-17.42, respectively). For congenital heart defects, the ORs and 95% CIs were all higher, and the magnitude of OR differences ranged from 1.59 to 16.15. CONCLUSIONS:A comprehensive intervention strategy targeting maternal exposure to multiple risk factors is expected to show the strongest results in preventing birth defects

Summary of factors associated with birth defects in Shaanxi Province, 2011–2013 (N = 29,547).

<p>Summary of factors associated with birth defects in Shaanxi Province, 2011–2013 (N = 29,547).</p

Additional file 1: Table S1. of The extent and nature of television food advertising to children in Xi’an, China

Programme types for TV advertising spots. Table S2. Product types in TV advertising. Table S3. Food types in TV food advertising. (DOCX 23 kb

Fit statistics for LCA models with 2 to 6 classes.

<p>Fit statistics for LCA models with 2 to 6 classes.</p