Epstein-Barr virus-induced gene 3(EBI3) is conventionally viewed as a subunit of IL-27 and IL-35, yet the function of uncomplexed “free” EBI3 is unknown. We show that free EBI3 is an autonomous immunosuppressive cytokine that acts via a gp130/WSX-1/STAT3 axis and epigenetic reprogramming. A free-EBI3-specific sandwich ELISA revealed 23.3 ± 2.2 ng/mL in healthy human sera and equivalent levels in mice; no cross-reactivity with IL-27/IL-35 was observed. Serum free EBI3 was reduced in rheumatoid arthritis(RA; 12.4 ± 1.4 ng/mL) and multiple sclerosis (MS; 14.6 ± 1.4 ng/mL; both p< 0.001) and inversely correlated with disease activity(RA-DAS28-ESR r=-0.67; MS-EDSS r=-0.61). Baseline<15 ng/mL predicted higher flare risk(RA HR = 2.8;MS HR = 3.2;p<0.01). Recombinant free EBI3 activated STAT3 exclusively(EC50≈16 nM), suppressed T-cell proliferation (-40%),IFN-y(-45%) and IL-17(-60%),and drove M2 macrophage polarization (+2.7-fold;p<0.001).Epigenetically,it reduced H3K4me3 at Ifng/Il4 promoters, induced Il10/Tgfb hypomethylation(-35%/-28%), and remodeled 1,021 chromatin-accessible STAT3/NF-kB sites. EBI3-/- mice developed spontaneous colitis and severe EAE; daily free EBI3(1 mg/kg) reversed pathology, whereas IL-27/IL-35 did not. Tissue-targeted delivery(liposomes or nanoparticles) outperformed systemic therapy. Ex-vivo free EBI3 normalized RA/MS patient PBMCs(proliferation-50%; IL-17-52%; p< 0.001). Thus, free EBI3 is a distinct cytokine whose gp130/WSX-1 axis constitutes a biomarker and therapeutic target for inflammatory diseases.

BackgroundAllergic rhinitis (AR) is a common chronic nasal mucosal inflammatory disorder driven by type 2 immunity, but the spatial stromal–immune cell interactions underlying its pathogenesis remain unclear.MethodsWe used 10x Genomics Xenium In Situ spatial transcriptomics to map the nasal mucosa of 10 AR patients and 10 non-allergic controls, combined with unsupervised cell clustering, differential gene expression (DE) analysis of COL1A1+PDGFRA+ fibroblasts, qRT-PCR validation, ligand–receptor modeling (CellPhoneDB/NicheNet), and multimodal integration of spatial, transcriptional, and clinical data.ResultsNine major cell types with tissue-specific localization were identified. The AR samples showed expanded fibroblast-rich regions (34.2 ± 3.1% vs. 15.6 ± 2.4% in controls; p < 0.001) and increased adjacency between CD4+ T cells and fibroblasts (62.3 ± 4.5% vs. 28.7 ± 3.8% in controls; p < 0.001). The fibroblasts in AR had 187 upregulated genes (e.g., TSLP, IL33) that were spatially enriched near CD4+ T cells and validated by qRT-PCR. CD4+ T cells within 20 μm of fibroblasts in AR showed higher Th2 cytokine expression (IL4, IL5, IL13) and Th2/GATA3 signature scores (p < 0.001). Three key ligand–receptor axes (TSLP–IL7R, OX40L–OX40, and ICOSL–ICOS) drove the fibroblast–Th2 crosstalk. A “fibroblast–T cell crosstalk score” was ×4.8 higher in AR (p < 0.001) and correlated with clinical severity (serum IgE: r = 0.71; SPT wheal diameter: r = 0.65; p < 0.001).ConclusionsAR is defined by expanded fibroblast niches, fibroblast-derived type 2 mediators, and ligand–receptor-dependent fibroblast–Th2 crosstalk—a central pathogenic driver and potential therapeutic target.

Background:Probiotics are established candidates for preventing acute otitis media (AOM) in children, yet existing meta-analyses treat all probiotic interventions as a single class, precluding strain-specific clinical guidance. This network meta-analysis (NMA) compared the efficacy and safety of individual probiotic strains for pediatric AOM prevention. Methods:We systematically searched PubMed, Embase, the Cochrane Library, Web of Science, CNKI, WanFang, and CBM from inception to 15 March 2026. Eligible studies were RCTs evaluating probiotic interventions for AOM prevention in children aged 0-18 years. The primary outcome was AOM incidence; secondary outcomes included antibiotic prescription rates, tympanostomy tube placement rates, and adverse events. NMAs were performed using a multivariate random-effects frequentist framework (Stata 17.0). Treatment ranking was estimated using SUCRA values. Results:Eighteen RCTs (reported in 20 publications) enrolling 4,462 children were included, evaluating seven probiotic nodes (SS-K12, SS-24SMB, BB-12, CBA-L74, LGG, Multi-strain, α-Strep) against placebo. For AOM incidence, only CBA-L74 (OR = 0.27, 95% CI: 0.11-0.68; SUCRA = 89.3%) and SS-K12 (OR = 0.44, 95% CI: 0.20-0.94; SUCRA = 71.8%) achieved statistically significant reductions vs. placebo. Sensitivity analyses excluding two high risk-of-bias trials showed that SS-K12's effect was substantially attenuated and lost significance, whereas CBA-L74 remained robustly effective (OR = 0.28, 95% CI: 0.14-0.56). For antibiotic prescription rates, Multi-strain (OR = 0.45; SUCRA = 87.1%) and LGG (OR = 0.69; SUCRA = 65.3%) demonstrated significant reductions; both were superior to SS-K12 in direct pairwise comparisons. No intervention significantly reduced tympanostomy tube placement rates, though Multi-strain showed the most favorable numerical trend (SUCRA = 93.2%). Among exploratory outcomes, SS-K12 and LGG significantly reduced RTI incidence, while CBA-L74 and LGG significantly reduced AGE incidence, with CBA-L74 ranking first for AGE (SUCRA = 95.9%). Conclusions:Probiotic efficacy for AOM prevention is highly strain-specific. CBA-L74 demonstrated the most robust and consistent protection across AOM and gastrointestinal outcomes; Multi-strain combinations and LGG were most effective for antibiotic stewardship. These findings provide the first strain-level evidence base to guide rational probiotic selection in pediatric AOM prevention. Systematic review registration:PROSPERO, https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD420261360351, identifier CRD420261360351.

Current therapies for airway allergy (AA) exhibit limited efficacy in targeting pathogenic Th2-driven inflammation. Probiotics demonstrate immunoregulatory potential, yet the epigenetic mechanisms by which probiotic-derived DNA modulates allergic responses remain unexplored. This study investigates whether Lactobacillus rhamnosus GG DNA (LgDNA) alleviates AA through PD-L1-mediated T cell suppression. A murine AA model was established using house dust mite (Derf2) sensitization and challenge. LgDNA was intranasally administered at 10 μg/mouse/day. Epithelial PD-L1 expression was quantified by flow cytometry and qRT-PCR. KDM5A recruitment and Pd-l1 promoter methylation were analyzed via ChIP-qPCR and bisulfite sequencing. Th2 cell apoptosis was assessed by annexin V/PI staining. LgDNA treatment increased airway epithelial PD-L1 expression by 2.8-fold (P < 0.01) and reduced Derf2-induced Th2 cytokine levels (IL-4: 62 %↓; IL-5: 68 %↓). Mechanistically, LgDNA induced Pd-l1 promoter demethylation (methylation rate: 35 % vs. 78 % in controls) via KDM5A-mediated H3K4me3 modification. KDM5A knockdown abrogated LgDNA-driven PD-L1 upregulation (ΔPD-L1: 1.2-fold vs. 3.1-fold, P < 0.05). PD-L1 overexpression in epithelial cells triggered activated Th2 cell apoptosis (annexin V+PI+: 41 % vs. 12 %), reducing airway hyperresponsiveness by 54 % in AA mice. In summary, LgDNA alleviates AA by epigenetically enhancing epithelial PD-L1 via KDM5A, which induces pathogenic Th2 cell apoptosis. This study identifies a novel probiotic DNA-based epigenetic axis for allergic disease therapy, bridging microbiome biology with immune checkpoint regulation.

BACKGROUND:Th2 polarization is a central driver of allergic airway inflammation, yet the epigenetic mechanisms underlying its dysregulation remain poorly defined. Quercetin is a bioactive flavonoid with immunomodulatory properties. This study investigates whether quercetin alleviates Th2-driven pathology in allergic airway inflammation by targeting IL-10 promoter hypermethylation in airway M2 macrophages. METHODS:Using a murine model of house dust mite (Derf2)-induced allergic airway inflammation, we isolated airway M2 macrophages via flow cytometry and assessed their immunosuppressive capacity using CFSE-based T cell proliferation assays. Epigenetic regulation of Il10 was analyzed by bisulfite sequencing and chromatin immunoprecipitation. Quercetin (intranasal) was administered daily for 7 days. RESULTS:Allergic mice exhibited impaired M2 cell-mediated T cell suppression (proliferation index: 85% vs. 34% in controls, P < 0.01) and IL-10 deficiency in bronchoalveolar lavage fluid (8.5 pg/ml vs. 28.2 pg/ml, P <0.001). Il10 promoter hypermethylation (72% vs. 35% methylation at CpG sites -200 to +100) and reduced KDM5A recruitment were observed in M2 cells from allergic mice. Quercetin treatment reversed these epigenetic defects, restoring KDM5A binding (P < 0.05) and Il10 transcription (2.1-fold increase, P < 0.01), thereby reducing Th2 cytokines and airway hyperresponsiveness. CONCLUSIONS:Our findings identify KDM5A-mediated Il10 promoter demethylation as a critical mechanism for M2 cell immunoregulation in allergic airway inflammation. Quercetin alleviates Th2-driven pathology by restoring Il10 expression via epigenetic reprogramming of M2 macrophages. This study advances the understanding of natural compounds in targeting epigenetic checkpoints and provides a rationale for quercetin-based therapies in allergic diseases.

BackgroundEnvironmental pollutants are known to aggravate allergic diseases, but the molecular mechanisms by which polycyclic aromatic hydrocarbons such as benzo[a]pyrene (BaP) potentiate allergic airway inflammation remain poorly understood.ObjectiveWe investigated how BaP co-exposure modifies house dust mite (HDM)–driven allergic airway responses, focusing on the role of the NLRP3 inflammasome in dendritic cells (DCs).MethodsMice were sensitized and challenged intranasally with HDM with or without BaP. Airway hyperresponsiveness (AHR), bronchoalveolar lavage (BAL) cell counts, lung histopathology, and serum HDM-specific IgE were assessed. Cytokine production and epithelial alarmins were measured by ELISA. The role of NLRP3 was evaluated using Nlrp3−/− mice, in vitro bone marrow–derived DC (BMDC) cultures, and adoptive transfer of lung DCs. T helper cell polarization was analyzed in OT-II co-culture assays.ResultsCo-exposure to BaP and HDM markedly exacerbated airway inflammation, with enhanced AHR, increased eosinophil and neutrophil infiltration, severe goblet cell hyperplasia, and elevated HDM-specific IgE. Cytokine analysis revealed synergistic induction of Th2 (IL-4, IL-5, IL-13) and Th17 (IL-17A) responses, alongside increased epithelial alarmins (TSLP, IL-33). This exacerbated phenotype was abolished in Nlrp3−/− mice, which failed to produce IL-1β/IL-18 and exhibited attenuated inflammation. In vitro, BaP synergized with HDM to activate NLRP3 in BMDCs, leading to caspase-1 cleavage, IL-1β release, and enhanced CD80/CD86 expression. Adoptive transfer of BaP/HDM-exposed WT lung DCs, but not Nlrp3−/− DCs, was sufficient to drive allergic airway inflammation in naïve recipients. Finally, BaP–conditioned WT DCs skewed naïve CD4+ T cells toward Th2 and Th17 lineages, an effect absent in Nlrp3−/− DCs.ConclusionBaP amplifies allergic airway disease by activating the NLRP3 inflammasome in DCs, thereby enhancing DC maturation, cytokine release, and pathogenic Th2/Th17 polarization. These findings identify a critical mechanism linking environmental pollutants to exacerbated allergic asthma and highlight the NLRP3 inflammasome as a potential therapeutic target.

Spatial transcriptomics (ST) technology enables the simultaneous capture of gene expression profile and spatial information within 2D tissue slices. However, conventional analyses that process each individual slice independently often overlook shared features across multiple slices, limiting comprehensive biological insights. To address this, we introduce GRASS, a deep graph representation learning-based framework designed for the integration and alignment of multislice ST data. GRASS consists of two core modules: GRASS_Integration, which employs a heterogeneous graph architecture integrating contrastive learning and a multi-expert collaboration strategy to fully utilize both shared and unique information, enabling multislice integration, clustering, and various downstream analyses; and GRASS_Alignment, which uses a dual-perception similarity metric to guide spot-level alignment, supporting downstream tasks such as imputation and 3D reconstruction. Experimental results on seven ST datasets from five different platforms demonstrate that GRASS consistently outperforms eight state-of-the-art methods in both integration and alignment tasks. By comprehensively addressing multi-level information integration, GRASS emerges as an ideal solution for the joint analysis of multislice ST data.

M2 macrophages (M2 cells) are known to be involved in both Th2 responses and immune regulation. However, the underlying mechanisms remain unclear. Functional abnormalities in macrophages are associated with airway allergy (AA). The objective of this study was to investigate the role of methyltransferase-like 5 (Mettl5) in macrophages and its potential to alleviate AA. In this study, an airway allergy (AA) mouse model was established using dust mite extracts (DME) as the specific antigen. M2 cells were collected from mice with and without AA. The role of Mettl5 in modulating the immune activities of M2 cells was assessed using both epigenetic and immunological approaches. We found that Mettl5 levels were elevated in airway M2 cells from mice with AA. The presence of Mettl5 in airway M2 cells was positively correlated with airway Th2 polarization in these mice. Airway M2 cells from AA mice exhibited impaired immune-suppressive function, which was resolved by ablating the Mettl5 gene in macrophages. Mettl5 was responsible for the hypermethylation of the Il10 promoter in airway M2 cells of AA mice. Exposure to DME induced Mettl5, which in turn recruited USP21 to deubiquitinate GATA3, thereby boosting IL-4 expression in M2 cells. Inhibiting Mettl5 restored the immune-suppressive capacity of airway M2 cells and mitigated experimental AA. In conclusion, Mettl5 plays a critical role in subverting the immune-regulatory capacity and enhancing IL-4 expression in M2 cells. Inhibition of Mettl5 can mitigate experimental AA by restoring the immune-regulatory functions of M2 cells.

With the global rise in preterm birth rates, bronchopulmonary dysplasia (BPD) continues to be a significant problem, affecting morbidity and mortality in surviving preterm infants. Preterm infants are particularly susceptible to oxidative stress induced by sudden increases in oxygen concentration, which plays a crucial role in the pathogenesis of BPD. Herein, we addressed the pathophysiologic mechanisms, clinical treatment, and predictive biomarkers of BPD from an oxidative stress perspective. We first review the importance of oxygen in preterm infants and point out that sustained exposure to hyperoxia exacerbates the susceptibility of the immature lung to free radicals. The antioxidant properties of clinical therapies for BPD in preterm infants are then summarized. Subsequently, based on lipid, protein, and DNA damage mechanisms, we obtained the most comprehensive, accurate, and representative oxidative stress biomarkers. A total of 37 research papers on oxidative stress in BPD were collected. We conclude that 8-OHdG is the most promising biomarker for early prediction of BPD pathogenesis compared to lipid and protein oxidative stress biomarkers.

Spatial transcriptomics (ST) technologies have emerged as an effective tool to identify the spatial architecture of tissues, facilitating a comprehensive understanding of organ function and the tissue microenvironment. Spatial domain identification is the first and most critical step in ST data analysis, which requires thoughtful utilization of tissue microenvironment and morphological priors. Here, we propose a graph contrastive learning framework, GRAS4T, which combines contrastive learning and a subspace analysis model to accurately distinguish different spatial domains by capturing the tissue microenvironment through self-expressiveness of spots within the same domain. To uncover the pertinent features for spatial domain identification, GRAS4T employs a graph augmentation based on histological image priors, preserving structural information crucial for the clustering task. Experimental results on eight ST datasets from five different platforms show that GRAS4T outperforms five state-of-the-art competing methods. Significantly, GRAS4T excels at separating distinct tissue structures and unveiling more detailed spatial domains. GRAS4T combines the advantages of subspace analysis and graph representation learning with extensibility, making it an ideal framework for ST domain identification.

Introduction: The therapeutic efficacy for airway allergies needs to be improved. Th2 polarization is a primary pathological feature of airway allergies. We constructed chimeric antigen-LgDNA (Lactobacillus rhamnosus DNA) nanoparticles (CAP-NPs). The effects of CAP-NPs on reconciling airway Th2 polarization were tested. Methods: In this study, disulfide bond-linked antigen-major histocompatibility complex II (MHC II)-LgDNA nanoparticles (NPs) were constructed and designated CAP-NPs. An airway Th2 polarization mouse model was established to test the effects of CAP-NPs on suppressing the Th2 response. Results: The CAP-NP components of ovalbumin (OVA), major histocompatibility complex II (MHC II), and LgDNA were confirmed in a series of laboratory tests. The CAP-NPs remained stable at pH7.2 for at least 96 h. In in vitro experiments, CAP-NPs bound to the surface of OVA-specific CD4(+) T cells, which resulted in apoptosis of the antigen-specific CD4(+) T cells. Removal of any of the three components from the NPs abolished the induction of apoptosis of antigen specific CD4(+) T cells. CAP-NPs increased the expression of lysine-specific demethylase 5A (KDM5A) in CD4(+) T cells. Histone H3K9 and the gene promoter of caspase 8 were demethylated by KDM5A, which led to transcription and expression of the caspase 8 gene. Administration of CAP-NPs significantly alleviated experimental airway Th2 polarization through activating the caspase 8-apoptosis signaling pathway. Discussion: In this paper, we constructed CAP-NPs that could induce antigen-specific CD4(+) T cell apoptosis. Administration of CAP-NPs efficiently alleviated experimental airway Th2 polarization.

BACKGROUND:It is well-known that Dendritic cells (DCs) are essential in the development of airway Th2 polarization and airway allergy (AA). The underlying mechanism is still not fully understood. The objective of this study is to examine the role of methyltransferase-like protein-5 (Mettl5), a methyltransferase involved in N6-methyladenosine (m6A) methylation, in altering DC's properties to facilitate the development of Th2 polarization and AA. METHODS:Dust mite extracts (DME) were used as a specific antigen to establish an AA mouse model. The epigenetic status of DCs was examined using a Chromatin immunoprecipitation (ChIP) assay. A mouse strain carrying the Mettl5-deficient DCs was used to observe the role of Mettl5 in determining the phenotypes of DCs. RESULTS:The results showed that the expression of Mettl5 was elevated in DCs, which was positively correlated with the AA response. The development of airway Th2 polarization was hindered by Mettl5 depletion in DCs. Mettl5 is involved in the transcription of the Timd4 gene in DCs caused by DME. The degradation of IRF5 by Mettl5 led to an increase in T cell immunoglobulin domain molecule-4 (TIM4) expression in DCs associated with DME. Inhibition of Mettl5 in DCs reconciled the DME-induced airway Th2 polarization and experimental AA. CONCLUSIONS:Airway DCs from AA mice showed elevated amounts of Mettl5, which led to the expression of TIM4. The experimental AA was mitigated by Mettl5 inhibition.

Improvement is needed in the remedies used to control Th2 polarization. Bioengineering approaches have modified immune cells that have immunosuppressive functions. This study aims to generate modified eosinophils (Meos) in vivo and use Meos to balance Th2 polarization and reduce airway allergy. A cell editor was constructed. The editor contained a peptide carrier, an anti-siglec F antibody, MHC II, ovalbumin, and LgDNA (DNA extracted from a probiotic, Lactobacillus rhamnosus GG). Which was designated as Cedit. Meos are eosinophils modified using Cedits. An airway Th2 polarization mouse model was established used to test the effect of Meos on suppressing airway allergy. The Cedits remained physically and chemically stable in solution (pH7.2) for at least 96 h. Cedits specifically bound to eosinophils, which are designated as Meos. Meos produced programmed death ligand-1 (PD-L1); the latter induced antigen specific CD4+ T cell apoptosis. Administration of Cedits through nasal instillations generated Meos in vivo, which significantly reduced the frequency of antigen specific CD4+ T cells in the airways, and mitigated airway Th2 polarization. We constructed Cedit, which could edit eosinophils into Meos in vivo. Meos could induce antigen specific CD4+ T cell apoptosis, and reconcile airway Th2 polarization.

BACKGROUND:Eosinophils have been acknowledged to be involved in the induction of numerous inflammatory disorders. There is still a lack of knowledge about whether eosinophils play a role in immune regulation. The aim of this study is to uncover the immune regulatory functions of eosinophils. METHODS:Blood samples were collected from patients with allergic rhinitis (AR) and healthy control subjects. Peripheral blood mononuclear cells (PBMCs) were isolated from blood samples. Eosinophils were purified from PBMCs using flow cytometry cell sorting and analyzed using immunological approaches. RESULTS:The results showed that eosinophils from healthy subjects had immune regulatory functions on T cell proliferation and cytokine release. Impairment of eosinophil immune regulatory functions was found in AR patients, which was associated with AR responses. Elevated Rab27a expression in eosinophils was associated with their impaired immune regulatory functions and the increased AR responses. Rab27a controlled the release of mediators from eosinophils. Low concentrations of Eosinophil mediators could trigger immune regulatory responses, while high concentrations could trigger inflammatory responses. Regulating Rab27a restored the immune regulatory functions of eosinophils of AR patients. CONCLUSIONS:Eosinophils have immune regulatory functions, which are controlled by the expression of Rab27a. Regulation of Rab27a can improve the immune regulatory functions of eosinophils. The data suggest that inhibition of Rab27a can be a drug candidate for the treatment of eosinophil-related disorders.

Organic dye-based agents with near-infrared (NIR)-II absorption have great potential for cancer theranostics because of the deeper tissue penetration and good biocompatibility. However, proper design is required to develop NIR-II-absorbing dyes with good optical properties. We proposed to construct chalcogen atom-modulated croconaine for NIR-II light-triggered photothermal theranostics. By introducing different chalcogen atoms (O, S, Se, or Te) into the structure of croconaine, the light absorption of croconaine can be precisely regulated from the NIR-I to the NIR-II range due to the heavy-atom effect. Especially, Te-substituted croconaine (CRTe) and its nanoformulations exhibit superior NIR-II responsiveness, a high photothermal conversion efficiency (70.6%), and good photostability. With their favorable tumor accumulation, CRTe-NPs from tumor regions can be visualized by NIR-II optoacoustic systems with high resolution and high contrast; meanwhile, their superior photothermal performance also contributes to efficient cell killing and tumor elimination upon 1064 nm laser irradiation. Therefore, this work provides an efficient strategy for the molecular design of NIR-II organic photothermal agents.

BACKGROUND:The Th2 cell polarization is a crucial factor in the pathogenesis of allergic diseases. The underlying mechanism requires further investigation. Telomerase has an immune-regulating ability. The aim of this study is to elucidate the association between telomerase and Th2 cell polarization in patients with allergic rhinitis (AR). METHODS:CD4+ T cells were isolated from blood samples collected from AR patients and healthy control subjects. RNA sequencing was employed to analyze RNA samples extracted from CD4+ T cells. An AR mouse model was established using the ovalbumin-alum protocol. RESULTS:High telomerase gene activity and high endoplasmic reticulum (ER) stress status were observed in CD4+ T-cells in patients with AR. Positive correlation between the telomerase reverse transcriptase (TERT) gene expression in CD4+ T cells and AR response in patients with AR. TERT facilitated the degradation of Foxp3 proteins in CD4+ T cells, resulting in the polarization of Th2 cells. Sensitization with the ovalbumin-alum protocol enhanced the Tert expression in CD4+ T cells by exacerbating ER stress. Conditional inhibition of the Tert or eukaryotic translation initiation factor 2-α (Eif2a) expression in CD4+ T cells effectively attenuated experimental AR in mice. CONCLUSIONS:Elevated amounts of telomerase in CD4+ T cells were found in CD4+ T cells of subjects with AR. Telomerase promoted Th2 cell polarization by inducing Foxp3 protein degradation and promotes GATA3 activation. Inhibition of TERT or eIF2a alleviated experimental AR.

Background: Allergic rhinitis (AR) is a common hyperreactive nasal disease in otolaryngology, mainly manifested as rhinorrhea, nasal obstruction, nasal itching, and sneezing. Despite medication and immunotherapy, a large proportion of patients do not completely eliminate rhinorrhea. In recent years, the use of nasal anticholinergics in the treatment of AR has gained attention. However, there is currently no consensus on the timing and selection of nasal anticholinergics for AR treatment. Summary: We reviewed previous studies on nasal anticholinergic drugs in AR and summarized the pathogenesis of AR, the role of anticholinergic drugs, cholinergic neural pathways, the mechanisms of nasal anticholinergic drugs, common types and clinical efficacy of nasal anticholinergic drugs, and precautions for their use. We also provided some suggestions for their clinical application. Key Messages: At present, the main drugs of nasal anticholinergics are ipratropium bromide and phencyquine bromide. The cholinergic nervous system is the main neural pathway mediating nasal secretion. Anticholinergic drugs work by blocking the interaction between Ach and the high density of M receptors in the nasal cavity. The clinical effect of nasal anticholinergics is generally good, and there are almost no major or systemic adverse reactions. Nasal anticholinergics provide a more complete treatment for AR patients with poorly controlled rhinorrhea. In the future, nasal anticholinergics will be assessed in high-quality clinical trials and applied clinically.

Breast cancer is a leading cause of cancer mortality among women globally, with over 2.26 million new cases annually, according to GLOBOCAN 2020. This accounts for approximately 25

Mining the scientific literature, combined with data-driven methods, may assist in the identification of optimized catalysts. In this paper, we employed interpretable machine learning to discover ternary metal oxides capable of selective catalytic reduction of nitrogen oxides with ammonia (NH3-SCR). Specifically, we devised a machine learning framework utilizing extreme gradient boosting (XGB), identified for its optimal performance, and SHapley Additive exPlanations (SHAP) to evaluate a curated database of 5654 distinct metal oxide composite catalytic systems containing cerium (Ce) element, with records of catalyst composition and preparation and reaction conditions. By virtual screening, this framework precisely pinpointed a CeO2-MoO3-Fe2O3 catalyst with superior NOx conversion, N2 selectivity, and resistance to H2O and SO2, as confirmed by empirical evaluations. Subsequent characterization affirmed its favorable structural, chemical bulk properties and reaction mechanism. Demonstrating the efficacy of combining knowledge-driven techniques with experimental validation and analysis, our strategy charts a course for analogous catalyst discoveries.