Exploring Ribosomal Genes as Potential Biomarkers of the Immune Microenvironment in Respiratory Syncytial Virus Infection.

Respiratory syncytial virus (RSV) is the most common pathogen causing acute lower respiratory tract infection in infants and children. Due to limited knowledge of the pathological and molecular mechanisms of immunodeficiency underlying RSV disease, there is currently a lack of an approved and effective RSV vaccine to combat RSV infections. This study aimed to identify genes associated with immune dysfunction using bioinformatics methods to gain insights into the role of dysregulated immune genes in RSV disease progression, and to predict potential therapeutic drugs by targeting dysregulated immune-related genes. 423 immune-related differential genes (DEIRGs) were filtered from the blood samples of 87 healthy individuals and 170 RSV patients. According to CIBERSORT analysis, the blood of RSV patients showed increased infiltration of various immune cells. Subsequently, ten immune-related hub genes were screened via Protein-Protein Interaction Networks. Six signature immune-related genes (RPS2, RPS5, RPS13, RPS14, RPS18, and RPS4X) as candidate characteristic genes for the diagnostic model were identified by Lasso regression. The AUC value of the ROC curve of the six signature genes was 0.884. This result, intriguingly, suggested that all six immune-related genes with a good internal validation effect were ribosome family genes. Finally, through molecular docking analyses targeting these differential immune genes, ADO and fluperlapine were found to have high stable binding to major proteins of important immune-related genes in nine drug-protein interactions. Overall, the present study screened immune-related genes that are dysregulated in the development of RSV disease to investigate the pathogenesis of RSV infection from the standpoint of immune disorders. Unexpectedly, bioinformatics analysis revealed that ribosome family genes may be involved in the immune dysregulation of RSV disease, and these genes as targets formed the basis for potential drug modification candidates in RSV disease.

Insight into the role of mitochondrion-related gene anchor signature in mitochondrial dysfunction of neutrophilic asthma.

OBJECTIVE: At present, targeting molecular-pharmacological therapy is still difficult in neutrophilic asthma. The investigation aims to identify and validate mitochondrion-related gene signatures for diagnosis and specific targeting therapeutics in neutrophilic asthma. METHODS: Bronchial biopsy samples of neutrophilic asthma and healthy people were identified from the GSE143303 dataset and then matched with human mitochondrial gene data to obtain mitochondria-related differential genes (MitoDEGs). Signature mitochondria-related diagnostic markers were jointly screened by support vector machine (SVM) analysis, least absolute shrinkage, and selection operator (LASSO) regression. The expression of marker MitoDEGs was evaluated by validation datasets GSE147878 and GSE43696. The diagnostic value was evaluated by receiver operating characteristic (ROC) curve analysis. Meanwhile, the infiltrating immune cells were analyzed by the CIBERSORT. Finally, oxidative stress level and mitochondrial functional morphology for asthmatic mice and BEAS-2B cells were evaluated. The expression of signature MitoDEGs was verified by qPCR. RESULTS: 67 MitoDEGs were identified. Five signature MitoDEGs (SOD2, MTHFD2, PPTC7, NME6, and SLC25A18) were further screened out. The area under the curve (AUC) of signature MitoDEGs presented a good diagnostic performance (more than 0.9). There were significant differences in the expression of signature MitoDEGs between neutrophilic asthma and non-neutrophilic asthma. In addition, the basic features of mitochondrial dysfunction were demonstrated by in vitro and in vivo experiments. The expression of signature MitoDEGs in the neutrophilic asthma mice presented a significant difference from the control group. CONCLUSIONS: These MitoDEGs signatures in neutrophilic asthma may hold potential as anchor diagnostic and therapeutic targets in neutrophilic asthma.

Multi-Model Fusion-Based Hierarchical Extraction for Chinese Epidemic Event.

In recent years, Coronavirus disease 2019 (COVID-19) has become a global epidemic, and some efforts have been devoted to tracking and controlling its spread. Extracting structured knowledge from involved epidemic case reports can inform the surveillance system, which is important for controlling the spread of outbreaks. Therefore, in this paper, we focus on the task of Chinese epidemic event extraction (EE), which is defined as the detection of epidemic-related events and corresponding arguments in the texts of epidemic case reports. To facilitate the research of this task, we first define the epidemic-related event types and argument roles. Then we manually annotate a Chinese COVID-19 epidemic dataset, named COVID-19 Case Report (CCR). We also propose a novel hierarchical EE architecture, named multi-model fusion-based hierarchical event extraction (MFHEE). In MFHEE, we introduce a multi-model fusion strategy to tackle the issue of recognition bias of previous EE models. The experimental results on CCR dataset show that our method can effectively extract epidemic events and outperforms other baselines on this dataset. The comparative experiments results on other generic datasets show that our method has good scalability and portability. The ablation studies also show that the proposed hierarchical structure and multi-model fusion strategy contribute to the precision of our model. Supplementary Information: The online version contains supplementary material available at 10.1007/s41019-022-00203-6.

Selective effect of mercury on Th2-type cytokine production in humans.

UNLABELLED: Mercury induces autoimmune disease and increases IL-4 production and IgE levels in certain rodent strains. The object of this study was to determine if mercury was capable of inducing Th2 cytokine production in human leucocytes. Human peripheral blood mononuclear cells (PBMC) were incubated with PMA/ionomycin or Con A in the presence or absence of methyl mercury (CH(3)Hg) or mercuric chloride (HgCl(2)). IL-4 and gamma-IFN were measured by ELISA. RESULTS: IL-4 production significantly increased at low concentrations of CH(3)Hg (0.5 uM, p < 0.01), while gamma-IFN production was suppressed starting at CH(3)Hg 2 uM (p = 0.004). Inorganic mercury (HgCl(2)) increased IL-4 only at concentrations 10-20 times higher than CH(3)Hg. These findings suggest a mechanism by which mercury could trigger or potentiate TH2 cytokine production in humans.