Antibody responses to respiratory syncytial virus: a population-based cross-sectional serological study in Southern China, 2021.

OBJECTIVES: With remarkable progress in the field of respiratory syncytial virus (RSV) prophylaxis, it is critical to understand population immunity against RSV. We aim to describe the RSV pre-F IgG antibodies across all age groups in Southern China and to evaluate the risk factors associated with lower antibody levels. METHODS: We performed a community-based cross-sectional sero-epidemiological study in Anhua County, Hunan Province, Southern China, from July 15, 2021, to November 5, 2021. Serum samples were tested for IgG antibodies against the RSV prefusion F (pre-F) protein using an enzyme-linked immunosorbent assay. We estimated the geometric mean titres (GMTs) and seropositivity rates across all age groups. The generalized linear models were built to identify factors associated with antibody levels. RESULTS: A total of 890 participants aged 4 months to older than 89 years were enrolled. The lowest RSV pre-F IgG GMTs were observed in infants and toddlers aged 4 months to younger than 2 years (3.0; 95% CI, 2.6-3.5). With increasing age, the RSV pre-F IgG GMT increased to 4.3 (95% CI, 4.1-4.4) between the ages of 2 and younger than 5 years and then stabilized at high levels throughout life. All the children had serological evidence of RSV infection by the age of 5 years. Age was associated with RSV pre-F antibody levels in children, with an estimated 1.9-fold (95% CI, 0.8-3.6) increase in titre per year before 5 years of age, although it was not significantly associated with antibody levels in adults aged older than 60 years. DISCUSSION: Our findings could provide a comprehensive understanding of the gaps in RSV immunity at the population level and inform the prioritization of immunization platforms.

Rapid Synthesis of 3-Methyleneisoindolin-1-ones via Metal-Free Tandem Reactions of Ester-Functionalized Aziridines.

We have disclosed a novel metal-free tandem cyclization reaction for the synthesis of 3-methyleneisoindolin-1-ones starting from ester-functionalized aziridines. This strategy can be effectively promoted by DBU and carboxylic acids. Mechanistically, it involves sequential ring opening of aziridines with carboxylic acids, lactamization, and elimination of carboxylic acids.

Decreased TLR7 expression was associated with airway eosinophilic inflammation and lung function in asthma: evidence from machine learning approaches and experimental validation.

BACKGROUND: Asthma is a global public health concern. The underlying pathogenetic mechanisms of asthma were poorly understood. This study aims to explore potential biomarkers associated with asthma and analyze the pathological role of immune cell infiltration in the disease. METHODS: The gene expression profiles of induced sputum were obtained from Gene Expression Omnibus datasets (GSE76262 and GSE137268) and were combined for analysis. Toll-like receptor 7 (TLR7) was identified as the core gene by the intersection of two different machine learning algorithms, namely, least absolute shrinkage and selector operation (LASSO) regression and support vector machine-recursive feature elimination (SVM-RFE), and the top 10 core networks based on Cytohubba. CIBERSORT algorithm was used to analyze the difference of immune cell infiltration between asthma and healthy control groups. Finally, the expression level of TLR7 was validated in induced sputum samples of patients with asthma. RESULTS: A total of 320 differential expression genes between the asthma and healthy control groups were screened, including 184 upregulated genes and 136 downregulated genes. TLR7 was identified as the core gene after combining the results of LASSO regression, SVM-RFE algorithm, and top 10 hub genes. Significant differences were observed in the distribution of 13 out of 22 infiltrating immune cells in asthma. TLR7 was found to be closely related to the level of several infiltrating immune cells. TLR7 mRNA levels were downregulated in asthmatic patients compared with healthy controls (p = 0.0049). The area under the curve of TLR7 for the diagnosis of asthma was 0.7674 (95% CI 0.631-0.904, p = 0.006). Moreover, TLR7 mRNA levels were negatively correlated with exhaled nitric oxide fraction (r = - 0.3268, p = 0.0347) and the percentage of peripheral blood eosinophils (%) (r = - 0.3472, p = 0.041), and positively correlated with forced expiratory volume in the first second (FEV1) (% predicted) (r = 0.3960, p = 0.0071) and FEV1/forced vital capacity (r = 0.3213, p = 0.0314) in asthmatic patients. CONCLUSIONS: Decreased TLR7 in the induced sputum of eosinophilic asthmatic patients was involved in immune cell infiltration and airway inflammation, which may serve as a new biomarker for the diagnosis of eosinophilic asthma.