Construction of a predictive model of respiratory endoscopic intervention in children with lobar pneumonia caused by Mycoplasma pneumoniae infection.

Background: This study aimed to analyze the clinical features of children with lobar pneumonia caused by Mycoplasma pneumoniae (MP) infection, to explore the independent risk factors for bronchoscopic intervention in children with lobar pneumonia caused by MP infection. There is a lack of objective assessment tools to guide the use of bronchoscopy in clinical practice. For children with lobar pneumonia caused by MP infection, whether line shall be actively bronchoscope intervention therapy remains to be further defined. We also aimed to construct an early warning model of bronchoscopic intervention to provide an objective evaluation tool for clinicians. Methods: We collected the clinical data of 533 children with lobar pneumonia caused by MP infection. The patients were divided into three groups according to the interventional indications for bronchoscopy and whether they were treated with bronchoscopic intervention, and the clinical features and prognosis of the three groups were compared. A binary logistic regression analysis was performed on the indicators with a significance value of P<0.05, which we retrieved from the comparative analysis between the first two groups to uncover the independent risk factors and regression equations concerning bronchoscopic intervention. The regression coefficient (ß) of our regression model was then used to score related values in the model to construct a predictive scoring model of bronchoscopic intervention for the treatment of children with lobar pneumonia caused by MP infection. Results: Children with lobar pneumonia caused by MP infection who demonstrated absolute indications for bronchoscopy exhibited more severe clinical manifestations, and children without absolute indications for bronchoscopy had a better prognosis even without bronchoscopic intervention. To establish our early warning model of bronchoscopic intervention for children with lobar pneumonia caused by MP infection, we used the following indices: C-reactive protein ≥20.94 mg/L (ß1=2.253) received 3 points, while a fever duration before bronchoscopy ≥6.5 d (ß2=1.424), lactate dehydrogenase ≥461.5 U/L (ß3=1.246), or fever (ß4=1.223) each received 2 points, and the complication of pleural effusion (ß5=0.841) received 1 point, for a total possible score of 10 points. Conclusions: When the score for the children with lobar pneumonia caused by MP infection was ≥6, the possibility of bronchoscopic intervention for treatment was >80%. The higher the score, the greater the possibility of bronchoscopic intervention.

Clinical characteristics of pediatric patients hospitalized with community-acquired pneumonia and cytomegalovirus DNA detected in bronchoalveolar lavage fluid.

Background: This study aimed to investigate the clinical characteristics of pediatric patients hospitalized with community-acquired pneumonia (CAP) and concomitant cytomegalovirus (CMV) infection. Methods: This cross-sectional study enrolled consecutive pediatric patients admitted with CAP who tested positive for CMV DNA in bronchoalveolar lavage fluid (BALF). Flexible fiberoptic bronchoscopy was performed when routine treatment for CAP proved ineffective. The study participants were further stratified into two groups based on CMV serological test results: recent CMV infection group and CMV replication group. Clinical characteristics were compared between these two groups. Results: Among 124 patients aged 1-11 months included in this study, 80 (64.5%) patients were categorized as having recent CMV infection, and 44 (35.5%) tested positive for CMV replication. Co-infection with other pathogens was detected more frequently in the CMV replication group (n = 29, 65.9%) than in the recent CMV infection group (n = 35, 43.7%; P = 0.018). Patients with recent CMV infection were younger and exhibited higher levels of alanine transaminase (ALT) and aspartate aminotransferase compared to those with CMV replication (all P < 0.05). Multivariable regression analysis showed age was independently associated with recent CMV infection (odds ratio [OR], 0.707; 95% confidence interval [CI], 0.586-0.853; P < 0.001). Notably, receiver operating characteristic curve analysis showed that a CMV PCR level of 3,840 copies/ml in blood samples had a sensitivity of 34.7% and specificity of 90.0% for diagnosis of recent CMV infection with an area under the curve (AUC) of 0.625 (95% CI: 0.513-0.736, P = 0.048). A CMV PCR level of 6,375 copies/ml in urine samples had a sensitivity of 77.1% and specificity of 61.5% for diagnosis of recent CMV infection with an AUC of 0.695 (95% CI: 0.531-0.858, P = 0.04). Furthermore, multivariate linear regression analysis revealed that the blood CMV DNA copy number was associated with ALT (B = 0.001; P < 0.001). Conclusions: The CMV DNA copy numbers in blood and urine could serve as discriminatory markers between recent CMV infection and CMV replication. Measuring CMV DNA levels in blood may be an effective method for monitoring liver function impairment in pediatric patients presenting with CAP and concurrent CMV infection.

DDX20 positively regulates the interferon pathway to inhibit viral infection.

The DEAD-box (DDX) family comprises RNA helicases characterized by the conserved sequence D(Asp)-E(Glu)-A(Ala)-D(Asp), participating in various RNA metabolism processes. Some DDX family members have been identified for their crucial roles in viral infections. In this study, RNAi library screening of the DDX family unveiled the antiviral activity of DDX20. Knockdown of DDX20 enhanced the replication of viruses such as vesicular stomatitis virus (VSV) and herpes simplex virus type I (HSV-1), while overexpression of DDX20 significantly diminished the replication level of these viruses. Mechanistically, DDX20 elevated the phosphorylation level of IRF3 induced by external stimuli by facilitating the interaction between TBK1 and IRF3, thereby promoting the expression of IFN-ß. The increased IFN-ß production, in turn, upregulated the expression of interferon-stimulated genes (ISGs), including Cig5 and IFIT1, thereby exerting the antiviral effect. Finally, in an in vivo infection study, Ddx20 gene-deficient mice exhibited increased susceptibility to viral infection. This study provides new evidence that DDX20 positively modulates the interferon pathway and restricts viral infection.

Housekeeping U1 snRNA facilitates antiviral innate immunity by promoting TRIM25-mediated RIG-I activation.

U1 small nuclear RNA (snRNA) is an abundant and evolutionarily conserved 164-nucleotide RNA species that functions in pre-mRNA splicing, and it is considered to be a housekeeping non-coding RNA. However, the role of U1 snRNA in regulating host antiviral immunity remains largely unexplored. Here, we find that RNVU1-18, a U1 pseudogene, is significantly upregulated in the host infected with RNA viruses, including influenza and respiratory syncytial virus. Overexpression of U1 snRNA protects cells against RNA viruses, while knockdown of U1 snRNA leads to more viral burden in vitro and in vivo. Knockout of RNVU1-18 is sufficient to impair the type I interferon-dependent antiviral innate immunity. U1 snRNA is required to fully activate the retinoic acid-inducible gene I (RIG-I)-dependent antiviral signaling, since it interacts with tripartite motif 25 (TRIM25) and enhances the RIG-I-TRIM25 interaction to trigger K63-linked ubiquitination of RIG-I. Our study reveals the important role of housekeeping U1 snRNA in regulating host antiviral innate immunity and restricting RNA virus infection.

Intervention with ICOSL Antibodies Alleviates Inflammatory Infiltrations in Mice with Neutrophilic Asthma.

Background: Neutrophilic asthma is characterized by the predominant infiltration of neutrophils in airway inflammation. Objective: To explore the therapeutic potential of an antibody against the inducible T cell co-stimulator ligand (ICOSL) in a mouse model of neutrophilic asthma. Methods: Female BALB/c mice were randomly assigned to different groups. They were then injected with ovalbumin (OVA)/lipopolysaccharides (LPS) to induce neutrophilic asthma. The mice were then treated with either anti-ICOSL (the I group), control IgG (the G group), or no treatment (the N group). Additionally, a control group of mice received vehicle PBS and was labeled as the C group (n=6 per group). One day after the last allergen exposure, cytokine levels were measured in plasma and bronchoalveolar lavage fluid (BALF) using ELISA. After analyzing and categorizing BALF cells, the lung tissues were examined histologically and immunohistochemically. Results: Administering anti-ICOSL resulted in a significant decrease in the total number of inflammatory infiltrates and neutrophils found in BALF. Moreover, it led to a decrease in the levels of interleukin (IL)-6, IL-13, and IL-17 in both BALF and plasma. Additionally, there was an increase in IFN-γ levels in the BALF of asthmatic mice (p<0.05 for all). Treatment with anti-ICOSL also reduced lung interstitial inflammation, mucus secretion, and ICOSL expression in asthmatic mice. Conclusion: The treatment of anti-ICOSL effectively improved lung interstitial inflammation and mucus secretion in mice with neutrophilic asthma by restoring the balance of Th1/Th2/Th17 responses. These findings indicate that blocking the ICOS/ICOSL signaling could be an effective way to manage neutrophilic asthma.

The predictive values of soluble B7-DC in children with refractory mycoplasma pneumoniae pneumonia.

Background: Refractory mycoplasma pneumoniae pneumonia (RMPP) is a serious mycoplasma pneumoniae infection and is difficult to diagnose early. The levels of serum soluble B7-dendritic cell (sB7-DC) in children with mycoplasma pneumoniae pneumonia (MPP) were assessed to explore the clinical significance of sB7-DC levels in RMPP. Methods: A total of 65 patients with mycoplasma pneumoniae pneumonia (MPP) were enrolled in this study between January 2017 and December 2018. The patients were divided into the general mycoplasma pneumoniae pneumonia (GMPP) (n=30) and RMPP groups (n=35); the data of 20 normal children served as a control group (n=20). An enzyme-linked immunoassay kit was used to detect the expression of soluble B7-dendritic cell (sB7-DC) and other inflammatory factors. Binary logistic regression was performed to identify the independent predictors of RMPP. Receiver operating characteristic (ROC) curves were drawn to evaluate the value of each independent risk factor in the early diagnosis of RMPP. Results: The results showed that compared to the GMPP group, children in the RMPP group had a significantly longer hospital stay and had a significantly longer fever duration (P<0.05). The values of interferon-gamma (IFN-γ), interleukin 17 (IL-17), and sB7-DC in the RMPP group were significantly higher than those in the normal control and GMPP groups (all P<0.05). The results of the correlation analysis showed that sB7-DC was positively correlated with IFN-γ and IL-17 and these indicators could be used in combination to evaluate the severity of the disease. The binary logistic regression analysis identified IL-17 and sB7-DC as independent risk factors for RMPP (P<0.05). The ROC curve analysis showed that the cut-off values of IL-17 and sB7-DC were 309.6 pg/L and 1,109.7 pg/mL, respectively. The areas under the curve (AUCs) of IL-17 and sB7-DC were 0.741 and 0.794, respectively. The sensitivity of IL-17 to RMPP prediction was 83.3%, and the specificity was 62.9%. The sensitivity and specificity of sB7-DC to RMPP were 86.7% and 62.9%, indicating that sB7-DC had the highest predictive power for RMPP. Conclusions: The level of serum sB7-DC may play an important role in the early diagnosis of RMPP. Our research results provide a theoretical basis for the early diagnosis of RMPP.

Epidemiological and clinical characteristics of human rhinovirus caused bronchiolitis in children in Southeast China.

BACKGROUND: Human rhinovirus (hRV) is a critical viral pathogen implicated in bronchiolitis in children. However, there is no study on hRV bronchiolitis in children from Southeast China. The aim of this study was to determine the incidence and clinical features of hRV bronchiolitis in Southeast China. METHODS: The study was carried out in Children's Hospital of Soochow University on children admitted with the diagnosis of bronchiolitis from January 2013 to December 2014. hRV was tested using reverse-transcription polymerase chain reaction. RESULTS: hRV was identified in 140 of 797 specimens (17.6%). hRV was detected with a highest rate in June and August. The hRV positive rate in patients younger than 6 months of age was significantly lower than that in other age groups (P<0.01). The most common radiological finding was hyperinflation (51.4%). Patients with hRV infection were older and more likely to have eczema than those with RSV. CONCLUSIONS: The hRV was an important viral pathogen associated with bronchiolitis in children with an epidemic peak in summer. Most of patients were between 6 to 24 months and with a high presence of eczema.

Antimicrobial susceptibility and serotype distribution of Streptococcus pneumoniae isolates among children in Suzhou, China.

Background: Streptococcus pneumoniae (SP) is responsible for pneumococcal diseases with severe morbidity and mortality. High rates of drug resistance constitute serious public health concerns. Vaccination has proven to be an effective means of reducing disease burden. Epidemiological information of antibiotic susceptibilities and serotype distribution will be of great help to the management of pneumococcal infections. This study reported the serotype distribution and antibiotic resistance pattern of SP in hospitalized children in Suzhou during the years 2017-2018. The aim is to reduce pneumococcal resistance and guide vaccination. Methods: The clinical data of hospitalized children with SP were collected and analyzed. A total of 2,446 strains of SP were isolated from these patients. Serotypes were determined using the Quellung reaction. Antibiotic resistance was tested using the E-test diffusion method. Results: The non-susceptible rates of the isolates to penicillin, amoxicillin, and cefotaxime were 9.5%, 27.7%, and 27.2%, respectively. And 97.6% of SP isolates showed multidrug-resistant (MDR). The most common resistance pattern of non-invasive isolates was macrolides + sulfamethoxazole + clindamycin + tetracycline. The major serotypes of this resistance pattern were 6A, 23F, 6B, 19F, 15B. The most extensive resistance pattern of invasive isolates was macrolides + ß-lactams + sulfamethoxazole + clindamycin + tetracycline. The most common serotypes of the pattern were 19F, 19A, 6B, 23F, 6A. The most common serotypes were 19F (28.6%), 6B (11.9), 23F (11.2%), 6A (10.6%), and 19A (9.1%). In the isolates with MDR, the first five most common serotypes were 19F, non-vaccine serotype (NVT), 6B, 6A and 23F. Strains belonging to different serotypes exhibited distinct antimicrobial resistance patterns and were found to be associated with different diseases. The coverage rates of pneumococcal conjugate vaccine (PCV)7 and PCV13 in all isolates reached 60.4% (310/513) and 80.9% (415/513), respectively. Conclusions: The main serotypes of SP in Suzhou were 19F, 6B, 23F, 6A, and 19A. The use of PCV13 is beneficial to children in Suzhou.

The CARDS toxin of Mycoplasma pneumoniae induces a positive feedback loop of type 1 immune response.

Background: Within the past 3-5 years, Mycoplasma pneumoniae has become a major pathogen of community-acquired pneumonia in children. The pathogenic mechanisms involved in M. pneumoniae infection have not been fully elucidated. Methods: Previous protein microarray studies have shown a differential expression of CXCL9 after M. pneumoniae infection. Here, we conducted a hospital-based study to explore the clinical significance of the type 1 immune response inflammatory factors interferon (IFN)-γ and CXCL9 in patients with M. pneumoniae pneumonia (MPP). Then, through in vitro experiments, we explored whether CARDS toxin stimulated F-DCs (dendritic cells incubated with Flt3L) to promote Th-cell differentiation; we also investigated the IFN-γ-induced CXCL9 secretion pathway in macrophages and the role of CXCL9 in promoting Th1 cell migration. Results: The CXCL9 expression level was upregulated among patients with a higher fever peak, fever duration of greater than 7 days, an imaging manifestation of lobar or segmental, or combined pleural effusion (P<0.05). The peripheral blood levels of IFN-γ and CXCL9, which were higher in patients than in the healthy control group, were positively correlated with each other (r=0.502, P<0.05). In patients, the CXCL9 expression level was significantly higher in the bronchoalveolar lavage fluid (BALF) than in the peripheral blood, and the BALF CXCL9 expression level was higher than that in the healthy control group (all P<0.05). Our flow cytometry analysis revealed that M1-phenotype macrophages (CD16 + CD64 + CD163-) were predominant in the BALF from children with MPP. In in vitro experiments, F-DCs stimulated with CARDS toxin promoted the differentiation of CD4 + IFN-γ + Th (Th1) cells (P<0.05). Moreover, IFN-γ induced high levels of CXCL9 expression in M1-type macrophages in a dose-dependent and time-dependent manner. Additionally, macrophages transfection with STAT1-siRNA-1 downregulated the expression of CXCL9 (P<0.05), and CXCL9 promoted Th1 cell migration (P<0.05). Conclusions: Our findings suggest that CARDS toxin induces a type 1 immune response positive feedback loop during M. pneumoniae infection; this putative mechanism may be useful in future investigations of immune intervention approaches for M. pneumoniae pneumonia.

[Association of Haemophilus influenzae infection with environmental and climatic factors in Suzhou, China]. / è‹å·žåœ°åŒºæµæ„Ÿå—œè¡€æ†èŒæ„ŸæŸ“ä¸ŽçŽ¯å¢ƒæ°”å€™çš„ç›¸å ³å› ç´ åˆ†æž.

OBJECTIVES: To investigate the epidemiological characteristics of respiratory Haemophilus influenzae (HI) infection in children in Suzhou, China and its association with climatic factors and air pollutants. METHODS: The data on air pollutants and climatic factors in Suzhou from January 2016 to December 2019 were collected. Respiratory secretions were collected from 7 940 children with acute respiratory infection who were hospitalized during this period, and bacterial culture results were analyzed for the detection of HI. A stepwise regression analysis was used to investigate the association of HI detection rate with air pollutants (PM2.5, PM10, NO2, SO2, CO, and O3) and climatic factors (monthly mean temperature, monthly mean humidity, monthly total rainfall, monthly total sunshine duration, and monthly mean wind speed). RESULTS: In 2016-2019, the 4-year overall detection rate of HI was 9.26% (735/7 940) among the children in Suzhou. The children aged <1 year and 1-<3 years had a significantly higher HI detection rate than those aged ≥3 years (P<0.01). The detection rate of HI in spring was significantly higher than that in the other three seasons, and the detection rate of HI in autumn was significantly lower than that in the other three seasons (P<0.001). The multiple linear regression analysis showed that PM10 and monthly mean wind speed were independent risk factors for the detection rate of HI: the detection rate of HI was increased by 0.86% for every 10 µg/m3 increase in the concentration of PM10 and was increased by 5.64% for every 1 m/s increase in monthly mean wind speed. Air pollutants and climatic factors had a lag effect on the detection rate of HI. CONCLUSIONS: HI is an important pathogen for acute respiratory infection in children in Suzhou and is prevalent in spring. PM10 and monthly mean wind speed are independent risk factors for the detection rate of HI.

Clinical characteristics and etiology of children with bronchiolitis before and during the COVID-19 pandemic in Suzhou, China.

Objective: We sought to compare the clinical characteristics and etiology of children with bronchiolitis in Suzhou before the pandemic of coronavirus disease 2019 (COVID-19) with those during the pandemic. Methods: Children who were hospitalized with bronchiolitis in the Department of Respiratory Disease, Children's Hospital of Soochow University were retrospectively enrolled over 3 consecutive years (2019, 2020, and 2021) from February 1 to January 31. Medical records were reviewed for etiology, clinical manifestations, and laboratory examination results. Results: The pathogen detection rate and the positive respiratory syncytial virus (RSV) detection rate were lowest in 2020 and highest in 2021. The rate of human rhinovirus detection in 2021 was higher than that in 2019 but similar to that in 2020. The RSV-positive rate differences among the 3 years varied by age group. Regarding the monthly distribution of RSV-positive cases over the 3-year study, all age groups showed a significant increase in the number of cases during the winter of 2021, and this increase started as early as October. With regard to clinical manifestations, the proportion of children presenting with stuffy nose rhinorrhea in 2021 [73.33% (165/225)] was greater than that in 2019 [48.61% (122/251)] and 2020 [57.06% (97/170)], while the proportion of children with gastrointestinal symptoms in 2021 [11.56% (26/225)] was smaller than that in 2019 [25.50% (64/251)] but similar to that in 2020 [17.06% (29/170)]. Conclusions: After the implementation of COVID-19 pandemic-related interventions, significantly lower pathogen detection and RSV-positive rates were observed in children with bronchiolitis in 2020. An upward trend in these rates was observed in 2021, coinciding with the relaxation of COVID-19 prevention measures. Strengthening infection control and surveillance systems is extremely important for future work.

MiR-493-5p inhibits Th9 cell differentiation in allergic asthma by targeting FOXO1.

The role of micro RNAs (miRNAs) in asthma remains unclear. In this study, we examined the role of miRNA in targeting FOXO1 in asthma. Results showed that miR-493-5p was one of the differentially expressed miRNAs in the PBMCs of asthmatic children, and was also associated with Th cell differentiation. The miR-493-5p expression decreased significantly in the OVA-induced asthma mice than the control groups. The miR-493-5p mimic inhibited the expression of the IL-9, IRF4 and FOXO1, while the inhibitor restored these effects. Moreover, the Dual-Luciferase analysis results showed FOXO1 as a novel valid target of miR-493-5p. According to the rescue experiment, miR-493-5p inhibited Th9 cell differentiation by targeting FOXO1. Then the exosomes in association with the pathogenesis of asthma was identified. Various inflammatory cells implicated in asthmatic processes including B and T lymphocytes, DCs, mast cells, and epithelial cells can release exosomes. Our results demonstrated that the DC-derived exosomes can inhibit Th9 cell differentiation through miR-493-5p, thus DC-derived exosomal miR-493-5p/FOXO1/Th9 may serve as a potential therapeutic target in the development of asthma.

Protein Acetylation Going Viral: Implications in Antiviral Immunity and Viral Infection.

During viral infection, both host and viral proteins undergo post-translational modifications (PTMs), including phosphorylation, ubiquitination, methylation, and acetylation, which play critical roles in viral replication, pathogenesis, and host antiviral responses. Protein acetylation is one of the most important PTMs and is catalyzed by a series of acetyltransferases that divert acetyl groups from acetylated molecules to specific amino acid residues of substrates, affecting chromatin structure, transcription, and signal transduction, thereby participating in the cell cycle as well as in metabolic and other cellular processes. Acetylation of host and viral proteins has emerging roles in the processes of virus adsorption, invasion, synthesis, assembly, and release as well as in host antiviral responses. Methods to study protein acetylation have been gradually optimized in recent decades, providing new opportunities to investigate acetylation during viral infection. This review summarizes the classification of protein acetylation and the standard methods used to map this modification, with an emphasis on viral and host protein acetylation during viral infection.

Durability of Nano-Reinforced Recycled Aggregate Concrete under Load and Chloride Ingress.

The improved performance of recycled aggregate has an important impact on its use in engineering. In this study, to improve the weak surface properties, recycled aggregates were treated by nano-silica slurry and applied to concrete beam specimens. Under the action of cracks caused by continuous load and drying-wetting cycles with chloride ingress, the effects of different recycled aggregate additions, nano-silica contents and crack widths on the self-healing performance of cracks and the resistance to chloride ingress of the recycled concrete beams were investigated. It was found that the self-healing rate of cracks increased first and then decreased with increased nano-silica content, reaching a maximum when the content reached 0.4%. Greater amounts of additive in the recycled aggregate increased the concentration of free chloride ions in cracks. However, this concentration was found to be weakened in nano-reinforced aggregate. From a comprehensive perspective, the relative chloride ion concentration can be effectively reduced by controlling the crack width to be smaller than 0.12 mm and using improved recycled aggregates treated with 0.2% nano-silica material. This study provides a reference for the application of recycled aggregate concrete under severe environmental and load conditions.

Matrix metalloproteinase 3 restricts viral infection by enhancing host antiviral immunity.

Viral pandemics pose great threats to human health and the economy. The host evolved a complex immune response against viral infection. Matrix metalloproteinase 3 (MMP3), also known as stromelysin-1, has an emerging role in immune regulation during pathogen infection. Using in vitro and in vivo infection models, we showed that MMP3 exhibits broad-spectrum antiviral activities against vesicular stomatitis virus (VSV), influenza A virus (H1N1) and human herpes virus 1 (HSV-1). MMP3 deficient mice are susceptible to viral infection and display a compromised antiviral immune response. Correspondingly, the mice with MMP3 overexpression are resistant to viral infection. The mechanistic study suggested that MMP3 is translocated from the cytoplasm into the cell nucleus upon virus infection and influence NF-κB activities, thus amplifying antiviral immune responses. This study suggested a novel function of MMP3 in viral infection and provided new ideas for developing antiviral drugs based on modulating MMP activity.

Foxp2 inhibits Th9 cell differentiation and attenuates allergic airway inflammation in a mouse model of ovalbumin-induced asthma.

This study aimed to explore the effects of forkhead box P2 gene (Foxp2) on T-helper 9 (Th9) differentiation in asthmatic mice. An in vivo asthmatic mouse model was induced with ovalbumin (OVA). An in vitro model was established by culturing CD4+ T cells with TGF-ß, IL-4, and anti-IFN-γ. ELISA, flow cytometry, qRT-PCR and Western blot were performed to examine IL-9 secretion, Th9 cell number, and Th9 cell transcription factor expression, respectively. Pathological changes in lung tissues and airway mucus secretion were assessed with HE and PAS glycogen staining. Anti-IL-9 mAb reversed the elevation in Th9 cells and IL-9 expression in lung tissues and bronchoalveolar lavage fluid (BALF) of asthmatic mice. Foxp2 was downregulated in BALF and lung tissue of asthmatic mice and Th9 cells. Overexpression of Foxp2 inhibited Th9 cell differentiation in vitro and improved airway inflammation in vivo. Our study suggests that overexpression of Foxp2 attenuates allergic asthma by inhibiting Th9 cell differentiation.

High Expression of MUC5AC, MUC5B, and Layilin Plays an Essential Role in Prediction in the Development of Plastic Bronchitis Caused by MPP.

Plastic bronchitis (PB) is a rare respiratory condition which can result in severe respiratory complications such as respiratory failure and death. Mycoplasma pneumoniae infection is a main etiology cause of plastic bronchitis. However, the pathogenesis of plastic bronchitis complicated by Mycoplasma pneumoniae pneumonia (MPP) has not yet been fully elucidated. Our article aims to explore biomarkers for early prediction of MPP cases complicated with plastic bronchitis. We utilized a protein chip to screen for significantly different proteins among the groups of healthy, general Mycoplasma pneumoniae pneumonia (GMPP) and refractory Mycoplasma pneumoniae pneumonia (RMPP) patients, where layilin exhibited a potent change across biology information technology. Next, we demonstrated the high expression of MUC5AC, MUC5B, and layilin in bronchoalveolar lavage fluid (BALF) of MPP cases complicated with plastic bronchitis. Further study suggested that the level of layilin had a positive correlation with both MUC5AC and MUC5B. A receiver operating characteristic (ROC) analysis was performed to assess the diagnostic values of MUC5AC, MUC5B, and layilin in MPP cases with PB. Data show that the three indicators have similar diagnostic ability for MPP children with plastic bronchitis. Then, we used different concentrations of community-acquired respiratory distress syndrome (CARDS) toxin or lipid-associated membrane proteins (LAMPs) to simulate an in vitro experiment. The in vitro assay revealed that CARDS toxin or LAMPs induced A549 cells to secrete MUC5AC, MUC5B, layilin, and proinflammatory factors. These findings suggest that MUC5AC, MUC5B, and layilin are correlated with MPP. The high expression of MUC5AC, MUC5B, and layilin play an essential role in prediction in the development of plastic bronchitis caused by MPP. The high expression of MUC5AC, MUC5B, and layilin may be relevant to the severity of illness.

Glycosylation of viral proteins: Implication in virus-host interaction and virulence.

Glycans are among the most important cell molecular components. However, given their structural diversity, their functions have not been fully explored. Glycosylation is a vital post-translational modification for various proteins. Many bacteria and viruses rely on N-linked and O-linked glycosylation to perform critical biological functions. The diverse functions of glycosylation on viral proteins during viral infections, including Dengue, Zika, influenza, and human immunodeficiency viruses as well as coronaviruses have been reported. N-linked glycosylation is the most common form of protein modification, and it modulates folding, transportation and receptor binding. Compared to N-linked glycosylation, the functions of O-linked viral protein glycosylation have not been comprehensively evaluated. In this review, we summarize findings on viral protein glycosylation, with particular attention to studies on N-linked glycosylation in viral life cycles. This review informs the development of virus-specific vaccines or inhibitors.

LincRNA-EPS impairs host antiviral immunity by antagonizing viral RNA-PKR interaction.

LincRNA-EPS is an important regulator in inflammation. However, the role of lincRNA-EPS in the host response against viral infection is unexplored. Here, we show that lincRNA-EPS is downregulated in macrophages infected with different viruses including VSV, SeV, and HSV-1. Overexpression of lincRNA-EPS facilitates viral infection, while deficiency of lincRNA-EPS protects the host against viral infection in vitro and in vivo. LincRNA-EPS-/- macrophages show elevated expression of antiviral interferon-stimulated genes (ISGs) such as Mx1, Oas2, and Ifit2 at both basal and inducible levels. However, IFN-ß, the key upstream inducer of these ISGs, is downregulated in lincRNA-EPS-/- macrophages compared with control cells. RNA pulldown and mass spectrometry results indicate that lincRNA-EPS binds to PKR and antagonizes the viral RNA-PKR interaction. PKR activates STAT1 and induces antiviral ISGs independent of IFN-I induction. LincRNA-EPS inhibits PKR-STAT1-ISGs signaling and thus facilitates viral infection. Our study outlines an alternative antiviral pathway, with downregulation of lincRNA-EPS promoting the induction of PKR-STAT1-dependent ISGs, and reveals a potential therapeutic target for viral infectious diseases.

MiR-29b regulates Th2 cell differentiation in asthma by targeting inducible B7-H3 and STAT3.

BACKGROUND: MicroRNAs play an important role in T cell responses. However, how microRNAs regulate Th cells in asthma remains poorly defined. OBJECTIVE: In this study, we investigated the mechanism and pathways of miR-29b regulating Th cells in asthma, in order to find new targets for asthma. METHODS: We detected miR-29b, B7-H3 and STAT3 in the peripheral blood of children with asthma, explored the relationship between these molecules and their effects on T cells through in vitro cell culture, and verified it by animal model. RESULTS: MiR-29b levels were decreased in the peripheral blood mononuclear cells from children with asthma. Vitro studies found that the expression of miR-29b in macrophages was decreased and the expression of B7-H3 and STAT3 was increased after house dust mite (HDM) stimulation. After down-regulation of miR-29b in macrophages, the expressions of B7-H3 and STAT3 in macrophages were increased and T cells differentiate into Th2 cells. After the addition of B7-H3 or STAT3 antibodies, the differentiation of naive T cells into Th2 cells was reduced. In OVA induced mice asthmatic model, after the up-regulation of miR-29b in lung, the expression of B7-H3 and STAT3 decreased in the lung tissues of mice, and the expression of Th2 cells and type II cytokine decreased simultaneously. The pathological changes of lung tissues were also alleviated. CONCLUSION: The expression of miR-29b is decreased in asthmatic children. MiR-29b can inhibit Th2 cell differentiation by inhibiting B7-H3 and STAT3 pathways at the same time, and reduce asthmatic immune inflammation.