Introduction Psoriasis is a chronic inflammatory skin disorder driven by dysregulated immune responses, Th17 cells activation, and keratinocytes hyperproliferation. Despite advances in therapies, high costs and adverse effects limit their utility. Licoisoflavone B (Lico B), bioactive flavonoid derived from licorice, exhibits anti-inflammatory and metabolic modulating properties, yet its mechanisms in psoriasis remain unexplored.Methods We employed integrative bioinformatics, including target prediction, differential expression analysis, and weighted gene co-expression network analysis to identify psoriasis-associated hub genes linked to Lico B. Functional enrichment was analyzed via GO and KEGG pathway. Molecular docking evaluated Lico B's binding affinity to candidate target. The effects of Lico B on Stearoyl-CoA Desaturase 1 (SCD1) expression, lipid metabolism, IL-17-induced keratinocyte proliferation, and Th17 differentiation.Results Bioinformatics revealed Lico B's targets were enriched in lipid metabolism and cell cycle pathways. SCD1 emerged as a key target, supported by strong binding affinity in docking studies. Experimentally, Lico B attenuated IL-17-induced SCD1 upregulation and lipid droplet accumulation in keratinocytes. It suppressed hyperproliferation markers (KRT17/Ki67) in cells and imiquimod-induced psoriatic mice. Furthermore, Lico B reduced Th17 differentiation and IL-17 production in murine models, demonstrating dual antiproliferative and immunomodulatory effects.Conclusion Lico B alleviates psoriasis by targeting SCD1 to modulate lipid metabolism, inhibit keratinocyte hyperproliferation, and dampen Th17/IL-17-driven inflammation. This multimodal mechanism positions Lico B as a novel therapeutic candidate for psoriasis and related inflammatory-metabolic dermatoses.

BackgroundExposure to fine particulate matter (PM2.5) is a well-established risk factor for lung inflammation and injury. Macrophages are key innate immune cells in the lung and play critical roles in maintaining pulmonary immune homeostasis and orchestrating inflammatory responses following environmental insults. However, the precise mechanisms by which PM2.5 modulates macrophage function and contributes to lung injury remain incompletely understood. This study aimed to investigate the role of macrophage phenotypic polarization in PM2.5-induced lung injury and the underlying molecular mechanisms.MethodsA subacute exposure (21-day) PM2.5 mouse model and bone marrow-derived macrophages (BMDMs) were used in vivo and in vitro to evaluate the effects of PM2.5 on pulmonary inflammation, macrophage polarization, mitochondrial injury, and cGAS-STING signaling activation. Pharmacological inhibition of cGAS was performed using RU.521 to assess the functional role of the cGAS-STING pathway in PM2.5-induced macrophage activation and lung injury. Statistical analyses were conducted to compare differences between experimental groups.ResultsPM2.5 exposure triggered pulmonary inflammation and tissue injury, accompanied by increased pulmonary macrophage accumulation and polarization toward the pro-inflammatory M1 phenotype. Mechanistically, PM2.5 induced mitochondrial damage in macrophages, leading to mtDNA release and subsequent activation of cGAS-STING signaling. Pharmacological inhibition of cGAS with RU.521 attenuated STING pathway activation, macrophage M1 polarization, and PM2.5-induced pulmonary inflammation and lung injury in mice.ConclusionsOur study indicates that PM2.5 promotes lung injury by driving macrophage M1 polarization through an mtDNA-cGAS-STING axis, highlighting cGAS-STING signaling as a potential therapeutic target for PM2.5-related lung injury.

Objective:To evaluate the diagnostic and predictive value of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) for frequent exacerbations of chronic obstructive pulmonary disease (AECOPD), and to develop a risk stratification scoring system to optimize clinical management in resource-limited healthcare settings. Patients and Methods:This retrospective observational study enrolled 16,849 AECOPD patients, categorized into frequent exacerbators (≥2 exacerbations/year, n=3,488) and non-frequent exacerbators (<2 exacerbations/year, n=13,361). Comparative analyses of clinical characteristics and inflammatory biomarkers (NLR, PLR, SII, CRP, PCT) were conducted. Spearman correlation, receiver operating characteristic (ROC) curve analysis, and binary logistic regression were employed to assess biomarker performance. A risk scoring system was developed using odds ratios (OR) and regression coefficients (β) of NLR and PLR. Results:The frequent exacerbators group exhibited significantly higher median NLR (6.71 vs 5.10, P < 0.001), mean PLR (239 ± 204 vs 218 ± 195, P < 0.001), and median SII (1,137.48 vs 847.54, P < 0.001). NLR, PLR and SII showed strong positive correlations with CRP and PCT (P < 0.001). ROC analysis identified NLR (specificity = 84.1%) and PLR (sensitivity = 55%) as optimal diagnostic indicators. Regression analysis confirmed NLR and PLR as independent risk factors for frequent exacerbations. The risk stratification system categorized patients into low-risk (<290 points; annual exacerbation rate 17%), intermediate-risk (290-768 points; 19.1%), and high-risk (>768 points; 23.4%) groups. Conclusion:NLR and PLR serve as cost-effective biomarkers for identifying high-risk frequent exacerbators patients with COPD in primary care settings. The percentile-based scoring system enables management strategies to address clinical needs in resource-constrained healthcare environments.

Adhesive arachnoiditis (AA) is a rare form of chronic degenerative pathology associated with persistent inflammation in the arachnoid matter of the spinal cord. Despite the existing knowledge, the detailed pathological mechanisms underlying AA are not fully understood. This study aimed to elucidate through comprehensive single nuclei RNA sequencing (snRNA-seq) to delineate the transcriptomic landscape of AA. From six arachnoid membrane samples, a total of 52,886 cells met the quality control standards for analysis. The main cell populations identified with specific gene markers were as follows: fibroblasts, glial cells, microglial cells, endothelial cells, mural cells, plasma cells, and T cells. Downstream analysis of fibroblasts, glial cells, and microglial cells was performed. Notably, fibroblast subsets 1 and 3 demonstrated a strong association with AA. Among them, subcluster 3 demonstrated elevated expression of genes COL1A1, COL3A1, and FN1, indicative of enhanced Wnt/β-catenin and extracellular matrix (ECM) synthesis pathways. Subcluster 3 was predicted to progressively transform into subcluster 1. In subcluster 1, there was a significant upregulation of genes such as BMP and ALPL, signaling enhanced activation of calcification-related pathways. This was highly relevant to end-stage arachnoid ossification formation. After being activated, microglial cells transformed into inflammatory disease-associated microglial cells and continued to express high levels of chemokines CCL2, CCL4, IL-1β, and other inflammatory factors NAMPT, INPP5D and NLRP3. This might be the main reason why AA recurrence is frequently observed in patients. These insights enhance our understanding of the pathological progression of AA and may contribute to the identification of novel therapeutic targets.

OBJECTIVES:Chronic obstructive pulmonary disease (COPD) frequently coexists with metabolic syndrome (MS), compounding its impact on patients' health and quality of life. This study aimed to elucidate the immune and metabolic response characteristics in COPD patients with and without MS. METHODS:A total of 11,315 COPD patients admitted to the Department of Respiratory and Critical Care Medicine at the Third People's Hospital of Chengdu between January 1, 2013, and May 1, 2023, were selected. Multivariate logistic regression was conducted to identify the risk factors for acute exacerbation of chronic obstructive pulmonary disease. Moreover, from this cohort, 30 patients (18 with COPD and 12 with COPD-MS) were recruited for a further study to investigate the underlying mechanisms of COPD and COPD-MS. Blood samples were collected from these participants to perform transcriptomic and metabolomic analyses, aiming to explore the differences in immune responses and metabolic alterations between the two groups. RESULTS:Our findings indicate a significant enhancement of neutrophil-mediated immune responses in COPD-MS patients. Transcriptomic analysis revealed 327 differentially expressed genes (DEGs) significantly involved in neutrophil-mediated immunity. Key metabolic pathways were disrupted, with 39 differential metabolites identified. Notably, metabolites, such as L-homoarginine and diethanolamine, which were elevated in COPD-MS patients, showed strong correlations with DEGs involved in neutrophil pathways and immune checkpoint regulation. The study also found decreased levels of IL4 and IL5RA in COPD-MS patients, suggesting a shift from Th2 to Th1 inflammatory responses, potentially contributing to glucocorticoid resistance. CONCLUSIONS:COPD patients with metabolic syndrome exhibit a heightened neutrophil-mediated inflammatory response and significant metabolic disturbances, which underscores the need for precise therapeutic strategies targeting both metabolic and inflammatory pathways to improve patient outcomes and manage COPD-MS complexities effectively.

Lung adenocarcinoma (LUAD) progression involves dynamic remodeling of the tumor microenvironment (TME). However, the stage‐specific dynamics of immune and stromal cell remodeling throughout LUAD progression remain incompletely understood. Here, the study systematically profiles the cellular composition and transcriptional states across multiple LUAD stages, integrating early‐stage patient specimens with publicly available datasets encompassing advanced‐stage disease. The analysis reveals a marked stage‐dependent shift from a proliferative and immune‐activated microenvironment in early LUAD to a hypoxia‐enriched and immunosuppressive landscape in advanced disease. A distinct hypoxia‐adapted epithelial tumor cell subpopulation (C5), exhibiting transcriptional features of metastasis, invasion, and hypoxia, and poor prognosis, is identified. Advanced LUAD featured immunosuppressive LGMN⁺ macrophages and STAT1‐driven exhausted CD8⁺ T cells. FKBP11⁺ plasma B cells exhibited exhaustion‐linked metabolic changes. POSTN⁺ CAFs emerged as central mediators of extracellular matrix (ECM) remodeling and immune exclusion. Collectively, the findings reveal a model of hypoxia‐driven functional convergence, in which distinct TME components co‐evolve toward phenotypes that collectively promote immune evasion, matrix remodeling, and tumor progression. These findings may provide insights into stage‐specific cellular dynamics and highlight promising therapeutic targets for precision immunotherapy strategies.

Type 2 Diabetes Mellitus (T2DM) is a growing global health concern that is associated with severe complications including diabetic tendinopathy. In this study, we found that T2DM patients had a significantly higher prevalence of tendon surgery compared to non-T2DM patients, which were alongside impaired ECM and cell adhesion. Notably, metformin-treated T2DM patients had a lower prevalence of tendon surgery compared to other medications, along with improved tendon fiber structure, downregulation of tendon damage marker MMP3, and upregulation of HES1, a Notch signaling effector gene. Metformin also activates Notch signaling in cultured tenocytes, and tendons from diabetic mice and aged monkey. These findings highlight metformin's potential to protect tendons by activating Notch signaling, offering novel insights into its therapeutic benefits beyond glucose regulation.

Air pollution poses a significant threat to respiratory health globally, contributing to the development and worsening of diseases, such as asthma, chronic obstructive pulmonary disease, pulmonary fibrosis, and lung cancer. A key mechanism behind this involves epigenetic reprogramming, where environmental exposures alter gene activity without changing the underlying DNA sequence itself. This review deciphers the multilayered epigenetic mechanisms linking pollutants (e.g., PM 2.5 , cigarette smoke, and ozone) to respiratory pathology, emphasizing reversible modifications that bridge environmental exposure and disease phenotypes. Air pollution-induced epigenetic reprogramming regulates critical biological processes, such as immune imbalance, chronic inflammation, oxidative stress, cellular dysfunction (senescence, apoptosis, and ferroptosis), tissue remodeling (epithelial–mesenchymal transition and fibrosis), and genomic instability. Specifically, aberrant DNA methylation, dysregulated RNA methylation, perturbed noncoding RNA networks, and histone modification abnormalities collectively drive disease pathogenesis. Furthermore, emerging epigenetic therapies targeting these modifications, such as DNA methyltransferase inhibitors (5-AZADC), histone deacetylase inhibitors, and RNA methylation regulators (methyltransferase-like 3 inhibitor STM2457), show promising therapeutic potential. This review highlights the reversibility of epigenetic changes as a strategic basis for intervention, emphasizing the need for future research on mixed exposures, tissue-specific mechanisms, and clinical translation to mitigate the global burden of pollution-related respiratory diseases.

Pseudomonas aeruginosa ( P. aeruginosa ) infections pose a significant threat to public health, underscoring the need for deeper insights into host cellular defenses. This study explores the critical role of autophagy‐related protein 5 (ATG5) in lung epithelial cells during P. aeruginosa infection. Single‐cell RNA transcriptomics revealed a pronounced enrichment of autophagy pathways in type II alveolar epithelial cells (AEC2). Using a conditional Atg5 knockout murine model, we demonstrated that ATG5 deficiency in AEC2 compromises survival, hampers bacterial clearance, and increases pathogen dissemination. Additionally, the loss of ATG5 exacerbated inflammatory responses, notably through the activation of the AKT/PI3K/NF‐κB axis and pyroptosis, which culminated in severe lung injury and epithelial barrier disruption. Mechanistically, the absence of ATG5 disrupted mitophagy, leading to intensified mitochondrial damage. This exacerbated condition coupled with the activation of gasdermin D (GSDMD) by the noncanonical caspase‐11, enhancing the release of mitochondrial DNA (mtDNA), which in turn activated cGAS–STING–NLRP3 signaling in macrophages. These findings highlight the essential role of ATG5 in modulating immune responses and suggest potential therapeutic targets for managing P. aeruginosa ‐induced pulmonary infections.

Objectives:To quantify sex and sociodemographic-specific burdens of cardiometabolic and respiratory diseases attributable to secondhand smoke (SHS) using GBD 2021 data. Study design:Global Burden of Disease (GBD)-based secondary data analysis. Methods:We used sex-disaggregated GBD 2021 estimates (1990-2021) to calculate population attributable fractions (PAFs), cause-specific death rates, and cause-specific DALY rates, and to examine exposure-burden relationships across Socio-demographic Index (SDI) strata. Results:PAFs and exposure declined overall, but heterogeneity persisted by sex and SDI. Females had higher PAFs for COPD and diabetes. Diabetes PAF in females rose slightly from 3.9 % (95 % UI: 1.4-6.4) to 4.0 % (95 % UI: 1.4-6.6). Absolute burdens support these patterns: in 2021 female COPD cause-specific DALY rate was 874.96 (95 % UI: 697.60-1092.43) versus male 606.07 (95 % UI: 490.75-755.31); male IHD death rate was 235.12 (95 % UI: 187.74-296.26) versus female 153.61 (95 % UI: 125.33-192.42). Low- and middle-SDI regions retained the largest burden per unit exposure. Conclusions:Sex differences in SHS-attributable burden persist and vary by SDI; policy responses should be sex- and context-specific.

Objectives:Metastatic spread to the lung is one of the leading causes of fatal outcomes in thyroid cancer, but the underlying molecular mechanisms remain unclear. To investigate how exosomal microRNA-17-5p (miR-17-5p) promotes lung metastasis in thyroid cancer within the framework of the "seed and soil" hypothesis. Methods:Serum exosomes from thyroid cancer lung metastasis patients and controls were analyzed for miR-17, which was elevated in metastatic cases. miR-17 was transfected into embryonic lung fibroblasts (MRC-5), and their supernatants were co-cultured with thyroid cancer cells (Cal62). Cell proliferation and migration were evaluated using colony formation, Ki67 staining, and Transwell assays. Interleukin-6 (IL-6)/interleukin-8 (IL-8) levels and nuclear factor kappa-B (NF-κB)/nuclear factor kappa-B repressing factor (NKRF) expression were analysed by enzyme-linked immunosorbent assays (ELISA) and western blot. In vivo models verified the metastatic-promoting effect of miR-17. Results:miR-17-5p was significantly enriched in serum exosomes of metastatic patients. In MRC-5 cells, it suppressed NKRF, NF-κB signaling, and increased secretion of IL-6 and IL-8, enhancing Cal62 proliferation and migration. Animal experiments confirmed its role in promoting tumor growth and lung metastasis. Conclusions:Exosomal miR-17-5p remodels the pulmonary microenvironment into a pro-inflammatory niche, facilitating thyroid cancer colonization and offering a potential therapeutic target.

The impact of fine particulate matter (PM2.5) on respiratory health, especially in the context of asthma exacerbation, is a critical environmental concern. Our study delved into the molecular mechanisms by which PM2.5 intensified asthma in mice, with a particular focus on N6-methyladenosine (m6A) methylation, mitophagy, and the regulatory roles of STC2 and SQSTM1. Utilizing single-cell RNA sequencing (scRNA-seq), we identified significant changes in immune cell distribution and a notable decrease in epithelial cell numbers in asthmatic mice exposed to PM2.5. We further uncovered that PM2.5 exposure significantly increased m6A methylation in STC2 mRNA, leading to up-regulation of STC2 expression and activation of mitophagy. Mechanistic investigations revealed that METTL3, a key methyltransferase, up-regulated STC2 through m6A-dependent mRNA stability and YTHDF2 binding. STC2, in turn, increased SQSTM1 levels by inhibiting proteasomal degradation, thereby enhancing mitochondrial autophagy and asthma severity. Additionally, we collected peripheral blood samples from asthma patients across different seasons and found that serum concentrations of METTL3 and STC2 were significantly higher during winter, a period of high PM2.5 levels, compared to summer when PM2.5 levels are typically lower. Our findings underscore the potential of targeting m6A methylation and mitophagy as therapeutic strategies for asthma exacerbated by environmental pollution.

Air pollution, particularly from fine particulate matter (PM2.5), poses a significant threat to respiratory health, yet the molecular mechanisms underlying PM2.5-induced lung injury remain incompletely understood. This study investigated the role of N 6-methyladenosine (m6A) methyltransferase METTL3 in regulating mitophagy-dependent ferroptosis in bronchial epithelial cells exposed to PM2.5. Using in vitro and in vivo models, we demonstrated that PM2.5 exposure induced histological alterations in mouse lung tissues, including inflammatory cell infiltration, goblet cell hyperplasia, and mucus hypersecretion, concurrent with enhanced ferroptosis and mitophagy in bronchial epithelial cells. Gain-of-function and loss-of-function experiments showed that METTL3 overexpression exacerbated mitophagy and ferroptosis, while METTL3 silencing attenuated these processes, rescuing cell viability and reducing pulmonary inflammation. In vivo, intratracheal administration of METTL3 recombinant protein recapitulated these effects, confirming its role in amplifying PM2.5-induced lung injury. Mechanistically, PM2.5 upregulated METTL3 expression, which promoted PINK1 mRNA stability through m6A modification, activating the PINK1-dependent mitophagy pathway. This led to the excessive clearance of damaged mitochondria, culminating in iron-dependent lipid peroxidation, dysregulation of ferroptosis-related proteins (ACSL4 and xCT), and ferroptotic cell death. Critically, the inhibition of mitophagy with Mdivi-1 protected against histological damage and ferroptosis in mice, underscoring the therapeutic potential of targeting this pathway. Collectively, our findings established a hierarchical regulatory axis where m6A-mitophagy-ferroptosis drove lung injury. This study uncovered a novel link between epigenetic modification, mitophagy, and ferroptosis, identifying METTL3-mediated m6A modification and mitophagy as potential targets for preventing PM2.5-related respiratory diseases.

SET domain-containing 2 (SETD2) is a histone methyltransferase. It regulates the activity of H3K36me3 to enhance gene transcription. Macrophages (Mϕs) are one of the cell types involved in immune response. The purpose of this study is to clarify the role of SETD2 in regulating the immune property of Mϕ. The Mφs were isolated from the bronchoalveolar lavage fluid (BALF) and analysed through flow cytometry and RNA sequencing. A mouse strain carrying Mφs deficient in SETD2 was used. A mouse model of airway allergy was established with the ovalbumin/alum protocol. Less expression of SETD2 was observed in airway Mϕs in patients with allergic asthma. SETD2 of M2 cells was associated with the asthmatic clinical response. Sensitization reduced the expression of SETD2 in mouse respiratory tract M2 cells, which is associated with the allergic reaction. Depletion of SETD2 in Mφs resulted in Th2 pattern inflammation in the lungs. SETD2 maintained the immune regulatory ability in airway M2 cells. SETD2 plays an important role in the maintenance of immune regulatory property of airway Mφs.

Background Exposure to PM2.5 has been implicated in a range of detrimental health effects, particularly affecting the respiratory system. However, the precise underlying mechanisms remain elusive. Methods To address this objective, we collected ambient PM2.5 and administered intranasal challenges to mice, followed by single-cell RNA sequencing (scRNA-seq) to unravel the heterogeneity of neutrophils and unveil their gene expression profiles. Flow cytometry and immunofluorescence staining were subsequently conducted to validate the obtained results. Furthermore, we assessed the phagocytic potential of neutrophils upon PM2.5 exposure using gene analysis of phagocytosis signatures and bacterial uptake assays. Additionally, we utilized a mouse pneumonia model to evaluate the susceptibility of PM2.5-exposed mice to Pseudomonas aeruginosa infection. Results Our study revealed a significant increase in neutrophil recruitment within the lungs of PM2.5-exposed mice, with subclustering of neutrophils uncovering subsets with distinct gene expression profiles. Notably, exposure to PM2.5 was associated with an expansion of PD-L1 high neutrophils, which exhibited impaired phagocytic function dependent upon PD-L1 expression. Furthermore, PM2.5 exposure was found to increase the susceptibility of mice to Pseudomonas aeruginosa , due in part to increased PD-L1 expression on neutrophils. Importantly, monoclonal antibody targeting of PD-L1 significantly reduced bacterial burden, dissemination, and lung inflammation in PM2.5-exposed mice upon Pseudomonas aeruginosa infection. Conclusions Our study suggests that PM2.5 exposure promotes expansion of PD-L1 high neutrophils with impaired phagocytic function in mouse lungs, contributing to increased vulnerability to bacterial infection, and therefore targeting PD-L1 may be a therapeutic strategy for reducing the harmful effects of PM2.5 exposure on the immune system.

Introduction:Tumor-associated macrophages (TAMs) play a crucial role in the tumor microenvironment (TME), and their polarization state significantly influences patient outcomes. This study investigates the inhibitory effects of β-glucan extracted from Candida albicans on lung cancer progression, focusing on its impact on TAM polarization and the induction of ferroptosis, a form of regulated cell death. Methods:Utilizing both in vivo animal models and in vitro cellular assays, we assessed the impact of β-glucan on tumor growth, cellular proliferation, and migration. We evaluated TAM polarization by analyzing the expression of M1 and M2 markers and identified differentially expressed genes (DEGs) related to ferroptosis. The role of ferroptosis in TAM polarization was further confirmed by assessing the protein levels of ACSL4 and GPX4, intracellular ferrous ion levels, and lipid peroxides. Results:β-glucan treatment significantly reduced tumor size and weight, along with cellular proliferation and migration, suggesting a potent suppressive effect on lung cancer cell growth. β-glucan promoted an M1-like phenotype in TAMs, as evidenced by increased CD86 expression and decreased CD206 expression, and modulated cytokine mRNA levels. RNA sequencing analysis post β-glucan treatment identified a substantial number of DEGs enriched in the ferroptosis pathway. The induction of ferroptosis by β-glucan was further confirmed through the significant upregulation of ACSL4 and downregulation of GPX4, alongside increased intracellular ferrous ion levels and lipid peroxides. The ferroptosis inhibitor Fer-1 abrogated these effects, highlighting the specificity of β-glucan-mediated polarization. Conclusion:These results collectively provide novel insights into the immunotherapeutic potential of β-glucan from Candida albicans and its role in modulating TAM polarization and lung cancer growth, offering a promising avenue for cancer treatment strategies.

BackgroundLower respiratory tract infections represent prevalent ailments. Nonetheless, current comprehension of the microbial ecosystems within the lower respiratory tract remains incomplete and necessitates further comprehensive assessment. Leveraging the advancements in metagenomic next-generation sequencing (mNGS) technology alongside the emergence of machine learning, it is now viable to compare the attributes of lower respiratory tract microbial communities among patients across diverse age groups, diseases, and infection types.MethodWe collected bronchoalveolar lavage fluid samples from 138 patients diagnosed with lower respiratory tract infections and conducted mNGS to characterize the lung microbiota. Employing various machine learning algorithms, we investigated the correlation of key bacteria in patients with concurrent bronchiectasis and developed a predictive model for hospitalization duration based on these identified key bacteria.ResultWe observed variations in microbial communities across different age groups, diseases, and infection types. In the elderly group, Pseudomonas aeruginosa exhibited the highest relative abundance, followed by Corynebacterium striatum and Acinetobacter baumannii. Methylobacterium and Prevotella emerged as the dominant genera at the genus level in the younger group, while Mycobacterium tuberculosis and Haemophilus influenzae were prevalent species. Within the bronchiectasis group, dominant bacteria included Pseudomonas aeruginosa, Haemophilus influenzae, and Klebsiella pneumoniae. Significant differences in the presence of Pseudomonas phage JBD93 were noted between the bronchiectasis group and the control group. In the group with concomitant fungal infections, the most abundant genera were Acinetobacter and Pseudomonas, with Acinetobacter baumannii and Pseudomonas aeruginosa as the predominant species. Notable differences were observed in the presence of Human gammaherpesvirus 4, Human betaherpesvirus 5, Candida albicans, Aspergillus oryzae, and Aspergillus fumigatus between the group with concomitant fungal infections and the bacterial group. Machine learning algorithms were utilized to select bacteria and clinical indicators associated with hospitalization duration, confirming the excellent performance of bacteria in predicting hospitalization time.ConclusionOur study provided a comprehensive description of the microbial characteristics among patients with lower respiratory tract infections, offering insights from various perspectives. Additionally, we investigated the advanced predictive capability of microbial community features in determining the hospitalization duration of these patients.

Eosinophils account for a significant portion of immune cells in the body. It is well known that eosinophils play a role in the pathogenesis of many diseases. In which the interaction between eosinophils and other immune cells is incompletely understood. The aim of this study is to characterize the immune suppressive functions of eosinophils. In this study, an irway allergy mouse model was established. Eosinophils were isolated from the airway tissues using flow cytometry cell sorting. The RAW264.7 cell line was used to test the immune suppressive functions of eosinophils. We observed that eosinophils had immune suppressive functions manifesting inhibiting immune cell proliferation and cytokine release from other immune cells. The eosinophil's immune suppressive functions were mediated by eosinophil-derived molecules, such as eosinophil peroxidase (EPX) and major basic protein (MBP). The expression of Ras-like protein in the brain 27a (Rab27a) was detected in eosinophils, which controlled the release of MBP and EPX by eosinophils. Eosinophil mediators had two contrast effects on inducing inflammatory responses or rendering immune suppressive effects, depending on the released amounts. Administration of an inhibitor of Rab27a at proper dosage could alleviate experimental airway allergy. To sum up, eosinophils have immune suppressive functions and are also inflammation inducers. Rab27a governs the release of EPX and MBP from eosinophils, which leads to immune suppression or inflammation. Modulation of Rab27a can alleviate airway allergy responses by modulating eosinophil’s immune suppressive functions, which has the translational potential for the management of eosinophil-related diseases.

Objective To investigate the impact of Pseudomonas aeruginosa(PA)infection on the function of pulmonary vascular endothelial cells,and explore the mechanism of this bacterium in exacerbating lung inflammation in mice.Methods Two hours after human lung microvascular endothelial cell(HULEC-5a)were infected with the PA strain PAO1,the mRNA levels of autophagy-related gene 5(ATG5),6-phosphofruc-to-2-kinase/fructose-2,6-bisphosphatase 3(PFKFB3),and calcium adhesion protein 5(CDH5)were deter-mined by reverse transcription real-time fluorescent quantitative PCR(RT-qPCR).The protein levels of ATG5,PFKFB3,and vascular endothelial calcium adhesion protein(VE-cadherin)were detected by immunofluores-cence.After the expression of ATG5 and PFKFB3 was respectively knocked down by small interfering RNA(siRNA),RT-qPCR was employed to measure the mRNA levels of ATG5,PFKFB3,and CDH5,and immunofluorescence to detect the protein levels of PFKFB3 and VE-cadherin.In addition,the lactate assay kit was used to determine the level of lactate in the cells.After mice were infected with PAO1,lung inflammation was assessed through his-topathological section staining.Confocal microscopy was employed to capture and analyze fluorescence-labeled PFKFB3 and VE-cadherin in endothelial cells.Results Compared with the control group,the HULEC-5a cells infected with PAO1 showed up-regulated mRNA and protein levels of PFKFB3(all P<0.05),down-regulated mRNA level of CDH5(P =0.023),disrupted continuity and down-regulated protein level of VE-cadherin(P<0.001),and elevated lactate level(P =0.017).Compared with PAO1-infected HULEC-5a cells,knocking down PFKFB3 led to the up-regulated mRNA level of CDH5(P =0.043),lowered lactate level(P =0.047),and restored continuity of VE-cadherin;knocking down ATG5 led to up-regulated mRNA and protein levels of PFKFB3(P =0.013 and P =0.003),elevated lactate level(P =0.015),and down-regulated mRNA level of CDH5(P =0.020)and protein level of VE-cadherin(P =0.001).The HE staining results showed obvious red blood cell leakage,inflammatory cell infiltration,alveolar septal widening,and partial detachment of vascu-lar endothelial cells in the alveoli of PA-infected mice.Immunofluorescence staining showed up-regulated expres-sion of PFKFB3 and decreased fluorescence signal of VE-cadherin in endothelial cells of infected mice compared with normal mice.Conclusion PA may regulate the PFKFB3 pathway via AGT5 to disrupt the function of pulmo-nary vascular endothelial cells,thereby exacerbating the inflammation in the lungs of mice.