Wuhan Union Hospital

Despite advances in anthelmintic therapy, there are currently no effective treatments for schistosomiasis-induced liver fibrosis. Previous studies have reported elevated marginal zone B and B1 cell specific protein (MZB1) expression in fibrotic diseases, but its function remains unclear, and its role in schistosomiasis has not been investigated. This study aimed to explore the function and mechanism of MZB1 in Schistosoma japonicum infection. We evaluated the expression of Mzb1 in the liver and spleen of Schistosoma-infected mice using methods such as Western blot, qPCR, and immunohistochemistry. We also employed adeno-associated virus (AAV) to knock down Mzb1 gene expression, assessing the role of Mzb1 in the progression of schistosomiasis and its downstream pathways. Additionally, in vivo experiments were conducted using downstream endoplasmic reticulum stress agonists and inhibitors to evaluate the role of this pathway in the progression of schistosomiasis. Our findings demonstrated that Mzb1 was significantly upregulated in the liver and spleen tissues of infected mice. Knockdown of Mzb1 markedly reduced liver fibrosis and splenomegaly. Mzb1 was predominantly expressed in CD20-positive B cells and was found to activate endoplasmic reticulum (ER) stress. Inhibition of ER stress alleviated liver fibrosis and splenomegaly, while activation of ER stress exacerbated these pathological conditions and reversed the protective effects of Mzb1 knockdown. We identified Mzb1 as a key factor that promotes liver fibrosis and splenomegaly in schistosomiasis through the activation of ER stress. This novel pathogenic mechanism may provide a potential therapeutic target for the treatment of schistosomiasis-induced liver fibrosis.

Accurate detection of neutrophil activity is critical for assessing the severity of bacterial inflammation. Herein, we report an activatable dye-sensitized lanthanide nanoprobe (LnNP@ZW800-SC@PEG) with enhanced second near-infrared fluorescence for the real-time imaging of neutrophil-secreted hypochlorite in vivo. By screening of four cyanine derivatives, LnNP@ZW800-SC is identified with the brightest fluorescence at 1523nm and the high absolute quantum yield (0.85%) compared to other derivatives. Mechanistic studies reveal that the high conjugation efficiency and enhanced absorption of the ZW800-SC dyes facilitate efficient energy transfer to Yb3+ and Er3+, leading to boosted NIR-IIb emission. Leveraging the bright emission, LnNP@ZW800-SC enables high-resolution, sensitive, and specific imaging of hypochlorite, both in vitro and in a murine model of LPS-induced lymphatic inflammation. This work provides a rational design strategy for coordinating dye moieties to enhance dye sensitization, thereby boosting the second near-infrared fluorescence of lanthanides and optimizing their imaging performance for biological applications.

Allergen immunotherapy (AIT) is the only etiological treatment for allergic rhinitis (AR) patients, yet the impact of allergen sensitization patterns on AIT efficacy remains unclear. This study aimed to assess the effectiveness of subcutaneous immunotherapy (SCIT) using a native house dust mite (HDM) allergen extract in Chinese AR patients with diverse HDM sensitization patterns. This prospective multicenter study across three allergy centers in China enrolled patients aged 5-65 diagnosed with HDM-induced AR. Serum-specific IgE testing for nine HDM components (Der p1, Der p2, Der p23, Der f1, Der f2, Der p5, Der p7, Der p10, Der p21) categorized patients into two groups: Group A with sensitization limited to major allergen components and Group B with sensitization to minor components with or without major components. Both groups underwent 1 year of HDM SCIT (Allergopharma, Germany), whose efficacy was assessed using the visual analogue scale (VAS) and combined symptom medication scores (CSMS). Serum IgE and IgG4 levels against the nine HDM components were measured pre- and post-treatment, and SCIT-related adverse reactions were recorded. The study enrolled 168 patients, with 75 in Group A and 93 in Group B. Group B patients had higher asthma prevalence and elevated baseline HDM sIgE and total IgE levels. After 1 year, Group B showed significantly greater CSMS reduction (67.70% vs. 59.09%, p = 0.03) and VAS improvement (66.67% vs. 50.00%, p = 0.01) compared to Group A. Group A had increased new sensitization risk to minor allergens (Der p5, Der p7, Der p21). No significant difference in SCIT efficacy was observed between patients with and without new sensitization. Both groups exhibited increased sIgG4 levels against all nine HDM allergens, with a more pronounced elevation of sIgG4 levels to Der p21 observed in Group B compared to Group A (p = 0.02). SCIT-related adverse reactions were comparable (p > 0.05). The native HDM allergen extract demonstrates efficacy in Chinese AR patients with varying sensitization patterns. It offers enhanced benefits for patients sensitized to minor allergens with or without major allergens of HDM, positioning it as the preferred option for individuals with AR. Chinese Clinical Trial Registry identifier: ChiCTR2300078642.

The genome-wide association study (GWAS) summary data utilized in this study are publicly available from the IEU OpenGWAS project, UK Biobank (UKB), FinnGen and Blood Cell Consortium. We acknowledge all the consortiums, investigators, and participants for making these resources available. Table S1: The IVs for downregulated IL-13 signaling proxied by decreased circulating eosinophil counts. Table S2: Overview of outcome GWAS datasets and sample overlap bias estimates. Table S3: Results of Mendelian randomization. Table S4: Heterogeneity test of Mendelian randomization. Table S5: Pleiotropy test of Mendelian randomization. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.