Regional classification of high PM10 concentrations in the Seoul metropolitan and Chungcheongnam-do areas, Republic of Korea.

Since the Seoul metropolitan area is a highly developed megacity, many people are often exposed to high concentrations of particulate matter (PM), with mean aerodynamic diameters equal to or less than 10 µm (PM10), in cold seasons. PM10 concentrations can be influenced by a combination of various factors, including meteorological conditions, anthropogenic emissions, atmospheric chemical reactions, transboundary transport, and geographic characteristics. However, the establishment of an efficient air quality management plan remains challenging due to the limited understanding of the regional PM concentration characteristics. Here, the Seoul metropolitan (Seoul, Gyeonggi-do, and Incheon) and Chungcheongnam-do (Chungcheongnam-do, Daejeon, and Sejong) areas were regionally classified to identify the spatiotemporal air quality in areas where megacities and emission sources are mixed. The four representative regions were determined using the K-means clustering method based on the temporal variations in the observed PM10 concentrations. The first cluster consisted of small cities in the southern and eastern parts of Gyeonggi-do and Chungcheongnam-do, respectively, while the second cluster consisted of Incheon, West Gyeonggi-do, and Seoul. In addition, the third and fourth clusters included West Chungcheongnam-do and East Gyeonggi-do, which are adjacent to the Yellow Sea and downstream area of the westerly wind, respectively. The characteristics of each cluster during the high PM10 concentration events are explainable by wind patterns and the local air pollutant emissions, including nitrogen oxides and sulfur oxides. The obtained regional classification was different from the provincial-level administrative division of South Korea. Therefore, the present study is expected to be a scientific basis for overcoming the limitations of air quality management in administrative districts.

Pulmonary Mycosis Drives Forkhead Box Protein A2 Degradation and Mucus Hypersecretion through Activation of the Spleen Tyrosine Kinase-Epidermal Growth Factor Receptor-AKT/Extracellular Signal-Regulated Kinase 1/2 Signaling.

Pulmonary mycoses are difficult to treat and detrimental to patients. Fungal infections modulate the lung immune response, induce goblet cell hyperplasia and metaplasia, and mucus hypersecretion in the airways. Excessive mucus clogs small airways and reduces pulmonary function by decreasing oxygen exchange, leading to respiratory distress. The forkhead box protein A2 (FOXA2) is a transcription factor that regulates mucus homeostasis in the airways. However, little is known whether pulmonary mycosis modulates FOXA2 function. Herein, we investigated whether Blastomyces dermatitidis and Histoplasma capsulatum-infected canine and feline lungs and airway epithelial cells could serve as higher animal models to examine the relationships between fungal pneumonia and FOXA2-regulated airway mucus homeostasis. The results indicate that fungal infection down-regulated FOXA2 expression in airway epithelial cells, with concomitant overexpression of mucin 5AC (MUC5AC) and mucin 5B (MUC5B) mucins. Mechanistic studies reveal that B. dermatitidis infection, as well as ß-glucan exposure, activated the Dectin-1-SYK-epidermal growth factor receptor-AKT/extracellular signal-regulated kinase 1/2 signaling pathway that inhibits the expression of FOXA2, resulting in overexpression of MUC5AC and MUC5B in canine airway cells. Further understanding of the role of FOXA2 in mucus hypersecretion may lead to novel therapeutics against excessive mucus in both human and veterinary patients with pulmonary mycosis.

Surgical treatment and long-term outcomes of low-grade myofibroblastic sarcoma: a single-center case series of 15 patients.

BACKGROUND: Low-grade myofibroblastic sarcoma (LGMS) is a poorly studied, rare, soft tissue sarcoma. LGMS is characterized by a low malignancy potential, tendency for local recurrence, and low likelihood of distant metastases. However, no studies have reported on the surgical treatment method and its long-term outcomes. METHODS: We included all patients treated for LGMS at our institution between March 2010 and March 2021. Medical charts were retrospectively reviewed to collect demographic information, as well as information about the clinical course, tumor characteristics, and outcomes. Statistical analysis was performed to identify the factors associated with the recurrence rate. RESULTS: Fifteen patients who underwent surgical treatment were enrolled in this study. There were seven cases in the upper extremities, four in the trunk area, three in the lower extremities, and one in the head and neck area. There were no metastatic cases and two cases of local recurrence. CONCLUSIONS: The incidence of LGMS in the extremities or trunk may be higher than expected based on the current literature. Univariate analysis showed that local tissue invasion and surgical method could be associated with local recurrence. Although further large studies are needed to establish risk factors of local recurrence or extent of resection margins, based on our study, wide local excision under the proper diagnosis is the most important treatment.

Optoelectronics of Multijunction Heterostructures of Transition Metal Dichalcogenides.

Among p-n junction devices with multilayered heterostructures with WSe2 and MoSe2, a device with the MoSe2-WSe2-MoSe2 (NPN) structure showed a remarkably high photoresponse, which was 1000 times higher than the MoSe2-WSe2 (NP) structure. The ideality factor of the NPN structure was estimated to be ∼1, lower than that of the NP structure. It is claimed that the NPN structure formed a thinner depletion region than that of the NP structure because of the difference of carrier concentrations of MoSe2 and WSe2. Hence, the built-in electric field was weaker, and the motion of the photocarriers was facilitated. These behaviors were confirmed experimentally from a photocurrent mapping analysis and Kelvin probe force microscopy. The work function depended on the wavelength of the illuminator, and quasi-Fermi level was estimated. The surface photovoltage on the MoSe2 region was higher than that on WSe2 because the lower bandgap of MoSe2 induces more electron-hole pair generation.

FOXA2 depletion leads to mucus hypersecretion in canine airways with respiratory diseases.

Because of exposure to environmental pollutants, infectious agents, and genetic predisposition, companion animals develop respiratory illnesses similar to those in humans. Older dogs of smaller breeds develop canine infectious respiratory disease, chronic bronchitis, and chronic obstructive pulmonary disease, with chronic lung infection, airway goblet cell hyperplasia and metaplasia, and mucus hypersecretion. Excessive mucus clogs airways, reduces gas exchanges, disables the mucociliary clearance, and reduces drug penetration. The Forkhead box protein A2 (FOXA2) is a key transcriptional regulator that maintains airway mucus homeostasis. Prior studies have shown that FOXA2 expression is frequently depleted in diseased human airways. Unfortunately, FOXA2 depletion has not been examined in dogs. Our current study indicated that both single bacterial infection by Pseudomonas aeruginosa and Bordetella bronchiseptica and polymicrobial infection by viral/bacterial pathogens depleted FOXA2 in canine airways, resulting in goblet cell hyperplasia and metaplasia and excessive mucus production. Furthermore, P. aeruginosa virulence factor pyocyanin activated the antagonistic STAT6 and epidermal growth factor receptor signalling pathways to inhibit FOXA2. Unravelling the mechanism of FOXA2 inactivation will hasten the development of non-antibiotic therapeutics to improve mucociliary clearance of pathogens in canine airway.

Temporal pattern classification of PM2.5 chemical compositions in Seoul, Korea using K-means clustering analysis.

Particulate matter with a diameter ≤ 2.5 µm (PM2.5) is a complex mixture of particles with a variety of compositions potentially including sulfate ions (SO42-), nitrate ions (NO3-), ammonium ions (NH4+), organic and inorganic elemental carbon, and metals. Here, the temporal composition evolution of PM2.5 was analyzed to characterize its emission source, origin, and external influences. The concentrations of wintertime PM2.5 chemical compositions in Seoul, Korea during the period of 2012-2021 were classified into four representative clusters using a K-means cluster analysis method. Cluster 1 exhibited high concentrations of NO3- and NH4+ ions mainly due to the prevalence of emissions from domestic manure and fertilizer sources in the northeast. High concentrations of these two ions are conducive to generation of ammonium nitrate (NH4NO3) through atmospheric chemical reactions, resulting in relatively long-lasting high PM2.5 concentrations in Seoul. In cluster 2, high concentrations of SO42-, vanadium, and nickel were observed in frequent south-westerly winds, indicating the domestic influence of industrial facilities. Cluster 3 showed high concentrations of potassium ions and organic carbon, highlighting a pronounced external influence transported from China via prevailing westerly winds. Cluster 4 showed low PM2.5 concentrations accompanied by strong winds in warm environments, which are uncommon in winter. This study revealed that the air quality in Seoul, which was influenced by many factors, could be classified into four representative patterns. Our results provide insights into the emission sources, major influences, and responsible mechanisms of high PM2.5 concentrations in Seoul, which can help with air quality policies.

E3 ubiquitin ligase CBLB regulates innate immune responses and bacterial dissemination during nontuberculous mycobacteria infection.

Nontuberculous mycobacteria (NTM) are emerging opportunistic pathogens causing pulmonary infection to fatal disseminated disease. NTM infections are steadily increasing in children and adults, and immune-compromised individuals are at a greater risk of fatal infections. The NTM disease's adverse pathology and resistance to antibiotics have further worsened the therapeutic measures. Innate immune regulators are potential targets for therapeutics to NTM, especially in a T cell-suppressed population, and many ubiquitin ligases modulate pathogenesis and innate immunity during infections, including mycobacterial infections. Here, we investigated the role of an E3 ubiquitin ligase, Casitas B-lineage lymphoma proto-oncogene B (CBLB), in immunocompromised mouse models of NTM infection. We found that CBLB is essential to prevent bacterial growth and dissemination. Cblb deficiency debilitated natural killer cells, inflammatory monocytes, and macrophages in vivo. However, Cblb deficiency in macrophages did not wane its ability to inhibit bacterial growth or production of reactive oxygen species or interferon γ production by natural killer cells in vitro. CBLB restricted NTM growth and dissemination by promoting early granuloma formation in vivo. Our study shows that CBLB bolsters innate immune responses and helps prevent the dissemination of NTM during compromised T cell immunity.

Loss of cell junctional components and matrix alterations drive cell desquamation and fibrotic changes in Idiopathic Pulmonary Fibrosis.

The distal bronchioles in Idiopathic Pulmonary Fibrosis (IPF) exhibit histopathological abnormalities such as bronchiolization, peribronchiolar fibrosis and honeycomb cysts that contribute to the overall architectural remodeling of lung tissue seen in the disease. Here we describe an additional histopathologic finding of epithelial desquamation in patients with IPF, wherein epithelial cells detach from the basement membrane of the distal bronchioles. To understand the mechanism driving this pathology, we performed spatial transcriptomics of the epithelial cells and spatial proteomics of the basement membrane of the distal bronchioles from IPF patients and patients with no prior history of lung disease. Our findings reveal a downregulation of cell junctional components, upregulation of epithelial-mesenchymal transition signatures and dysregulated basement membrane matrix in IPF distal bronchioles, facilitating epithelial desquamation. Further, functional assays identified regulation between Collagen IV in the matrix, and the junctional genes JUP and PLEC , that is crucial for maintaining distal bronchiolar homeostasis. In IPF, this balanced regulation between matrix and cell-junctions is disrupted, leading to loss of epithelial adhesion, peribronchiolar fibrosis and epithelial desquamation. Overall, our study suggests that in IPF the interplay between the loss of cell junctions and a dysregulated matrix results in desquamation of distal bronchiolar epithelium and lung remodeling, exacerbating the disease. One Sentence Summary: Two-way regulation of cell junctional proteins and matrix proteins drives cellular desquamation and fibrosis in the distal bronchioles of patients with Idiopathic Pulmonary Fibrosis.

Microstructural change of the brain in chronic obstructive pulmonary disease: a voxel-based investigation by MRI.

BACKGROUND: Cognitive deficit is a common problem in patients with chronic obstructive pulmonary disease (COPD). The aim of this study was to prospectively evaluate if MRI can demonstrate microstructural volume loss and the diffusion anisotropic change in subjects with COPD, compared with cognitively normal (CN) subjects. METHODS: Six subjects with severe COPD, 13 with moderate COPD, and 12 CN subjects underwent isotropic volumetric T1-weighted imaging and diffusion tensor imaging (DTI). Voxel-based statistical analyses among groups were performed on brain volumes, fractional anisotropy (FA) and trace. Cognitive function tests were performed in all subjects, and the Cognitive function tests (CFT) scores were compared among the three groups. RESULTS: No significant regional difference in volume was found in both the severe and moderate COPD groups relative to the CN group. Comparing between severe COPD and CN, FA was reduced in both the cerebral cortices, and in frontoparietal periventricular white matter. The trace value of the severe COPD group was significantly higher in the cerebral cortices, and in frontoparietal periventricular white matter, than that of the CN group. The severe COPD group showed significantly lower scores in the language-related, visuospatial, and frontal executive functions compared to those of the CN and moderate COPD group. CONCLUSION: This study demonstrated that COPD could affect the axonal integrity in multiple brain regions, and change in DTI might be related with the severity of the COPD.

Critical contribution of moisture to the air quality deterioration in a warm and humid weather.

The deterioration of air quality that threatens human health is recognized as focal compound hazard. Here, decisive thermodynamic conditions for activation of secondary aerosol formation have been investigated focused on Korea. In a dry environment with relative humidity < 60%, gas phase reaction to form fine particles depended largely on surface temperature. In a wet environment (relative humidity ≥ 60%), however, aqueous phase reaction of secondary inorganic aerosols, which are sulfate, nitrate, and ammonium, accounting for 67% of the total aerosol mass, was more activated. Thus, humidity is as important as temperature in the secondary production of aerosol; air quality often worsened when a low-pressure system was predominant over the Korean Peninsula. It is rather different from the general synoptic conditions of high concentrations of particulate matters characterized by high pressure and atmospheric stagnation. This study suggests additional favorable condition and responsible mechanism of air quality hazards that may be frequent in future.

Next-generation sequencing study on poorly differentiated carcinoma derived from a thirty-year-old epidermoid cyst: A case report.

Although epidermoid cysts are frequently seen as benign lesions, they are highly uncommon to develop into cancerous lesions. A 36-year-old man with a cystic mass present on his left flank since childhood presented to our department. Based on the patient's medical history and abdominal computed tomography scan, we excised the lesion under the suspicion of an epidermoid cyst. Histopathological evaluation revealed the presence of poorly differentiated carcinoma with squamoid and basaloid differentiation, which showed a strong possibility of carcinoma arising from an epidermal cyst. Next-generation sequencing using TruSight oncology 500 assay showed copy number variation of ATM and CHEK1 genes.

Targeting PEA3 transcription factors to mitigate small cell lung cancer progression.

Small cell lung cancer (SCLC) remains a lethal disease with a dismal overall survival rate of 6% despite promising responses to upfront combination chemotherapy. The key drivers of such rapid mortality include early metastatic dissemination in the natural course of the disease and the near guaranteed emergence of chemoresistant disease. Here, we found that we could model the regression and relapse seen in clinical SCLC in vitro. We utilized time-course resolved RNA-sequencing to globally profile transcriptome changes as SCLC cells responded to a combination of cisplatin and etoposide-the standard-of-care in SCLC. Comparisons across time points demonstrated a distinct transient transcriptional state resembling embryonic diapause. Differential gene expression analysis revealed that expression of the PEA3 transcription factors ETV4 and ETV5 were transiently upregulated in the surviving fraction of cells which we determined to be necessary for efficient clonogenic expansion following chemotherapy. The FGFR-PEA3 signaling axis guided the identification of a pan-FGFR inhibitor demonstrating in vitro and in vivo efficacy in delaying progression following combination chemotherapy, observed inhibition of phosphorylation of the FGFR adaptor FRS2 and corresponding downstream MAPK and PI3K-Akt signaling pathways. Taken together, these data nominate PEA3 transcription factors as key mediators of relapse progression in SCLC and identify a clinically actionable small molecule candidate for delaying relapse of SCLC.

The regulatory effect of veratric acid on NO production in LPS-stimulated RAW264.7 macrophage cells.

Veratric acid, a simple benzoic acid derived from plants and fruits, has been reported to have anti-oxidant, anti-inflammation, and blood pressure-lowering effects. This study was designed to evaluate the inhibitory effects of veratric acid on nitric oxide (NO) production in LPS-stimulated RAW264.7 cells. It was found that veratric acid inhibited NO production and inducible nitric oxide synthase (iNOS) expression in LPS-stimulated RAW264.7 cells. The inhibitory effects of veratric acid on the generation of interleukin-6 (IL-6) and interferon-γ (IFN-γ) was determined. Furthermore, veratric acid facilitated the inactivation of glycogen synthase kinase-3ß (GSK-3ß), STAT-1, and STAT-3 in dose-dependent manner. Notably, NF-κB and members of the mitogen activated protein kinase (MAPK) family including p38, ERK, and JNK were dephosphorylated by veratric acid. These findings suggest that the treatment of veratric acid might be effective in neutralizing the over-expression of NO in inflammatory disorders.

Histomorphometric Analysis of Femoral and Sciatic Nerve Regeneration in a Rat Hindlimb Allotransplantation Model.

BACKGROUND: Peripheral nerve regeneration is essential for functional recovery after traumatic limb injury or limb transplantation. With the use of immunosuppression, it has the capacity to provide regeneration and function equal to that of an autograft. The purpose of this study was to determine whether there is any difference in regeneration and rejection response between peripheral femoral and sciatic nerve in rat hindlimb allotransplantation model. METHODS: The hindlimbs of recipient Fischer 344 rats were amputated at the mid-thigh and the donor and recipient femurs were joined by an intramedullary rod. The femoral and sciatic nerves were repaired with 10-O nylon end-to-end suture followed by vessel, muscle, and skin closure. The control group received auto-transplantation and the experimental group received allo-transplantation from Sprague-Dawley donor rats. The recipients were treated with an immunosuppressive agent, FK506 (2 mg/kg), for the observation period. Both sciatic and femoral nerves were harvested 10 weeks after operation and histomorphometric analysis was conducted between these 2 nerves and control group. RESULTS: The sciatic nerve showed better regeneration, with significantly increased percentage nerve, fiber count, and density (P < .05), but demonstrated more immune cell proliferation relative to femoral nerve. CONCLUSIONS: The data showed that there are some differences in axonal regeneration capacity and immune response between large peripheral nerves.

Significant light absorption of brown carbon during the 2020 California wildfires.

In this study, the contribution of brown carbon (BrC) to the absorption aerosol optical depth (AAOD) during the August to October 2020 California wildfires in Fresno, Monterey, and the University of California Santa Barbara (UCSB) was investigated using Aerosol Robotic Network (AERONET) column measurements with Moderate Resolution Imaging Spectroradiometer (MODIS) fire pixel counts. There was an approximate three to five times increase in AAOD and fine-mode aerosols during intensive wildfires in August-October 2020 compared to the wildfires in the previous 18 years (2002-2019). Substantial daily variation in the contribution of BrC to AAOD was correlated with the fire pixel counts (correlation coefficients of 0.63, 0.40, and 0.57 at Fresno, Monterey, and UCSB, respectively). This variation was influenced by regional topography, atmospheric conditions, and distance from the fire. Between August and October 2020, the average contribution of BrC to AAOD at 440 nm due to wildfires was 35.3 ± 5.6, 35.1 ± 6.8, and 40.6 ± 9.5% at Fresno, Monterey, and UCSB, respectively. This was approximately twice as high as for those sites without a direct wildfire influence. The BrC contribution with direct wildfire influence over the period of January-December 2020 at Fresno, Monterey, and UCSB (32.8 ± 7.5, 31.6 ± 7.9, and 40.0 ± 3.5%, respectively) and from 2002 to 2019 (30.7 ± 8.3, 28.5 ± 4.8, and 35.7 ± 14.6%, respectively) was approximately 20% greater than other BrC sources including vehicles, fossil fuel combustion, and residential heating.

Modulation of Inflammatory Pathways and Adipogenesis by the Action of Gentisic Acid in RAW 264.7 and 3T3-L1 Cell Lines.

Gentisic acid (GA), a benzoic acid derivative present in various food ingredients, has been shown to have diverse pharmaceutical activities such as anti-carcinogenic, antioxidant, and hepatoprotective effects. In this study, we used a co-culture system to investigate the mechanisms of the anti-inflammatory and anti-adipogenic effects of GA on macrophages and adipocytes, respectively, as well as its effect on obesity-related chronic inflammation. We found that GA effectively suppressed lipopolysaccharide-stimulated inflammatory responses by controlling the production of nitric oxide and pro-inflammatory cytokines and modulating inflammation-related protein pathways. GA treatment also inhibited lipid accumulation in adipocytes by modulating the expression of major adipogenic transcription factors and their upstream protein pathways. Furthermore, in the macrophage-adipocyte co-culture system, GA decreased the production of obesity-related cytokines. These results indicate that GA possesses effective anti-inflammatory and anti-adipogenic activities and may be used in developing treatments for the management of obesity-related chronic inflammatory diseases.

Differential neurochemical responses of the canine striatum with pentobarbital or ketamine anesthesia: a 3T proton MRS study.

Although anesthetic agents are known to affect cerebral metabolism, pentobarbital and ketamine have been widely used for animal imaging studies. The purpose of this study is to evaluate alterations in striatum metabolites in dogs between anesthetized with pentobarbital and with ketamine in proton magnetic resonance spectroscopy ((1)H-MRS). (1)H-MRS was performed to ten healthy adult beagle dogs (9-11 kg) at a field strength of 3 T in order to identify metabolic changes after pentobarbital or ketamine administration in the striatum in vivo. Ten dogs were divided into 2 groups as follows: 5 as the pentobarbital-administered group (P group) and 5 as the ketamine-administered group (K group). We found that levels of Glx of the P group was significantly lower than that of the K group (6.90 +/- 0.99 (SD) vs 9.77 +/- 1.14 in 5 dogs, p= 0.003). In addition, the P group also has lower levels of Cr (6.29 +/- 0.44 vs 7.89 +/- 0.91 in 5 dogs, p=0.009) and NAA (5.02 +/- 0.65 vs 6.45 +/- 1.13 in 5 dogs, p=0.041) compared to the K group. However, there were no significant difference between the P group and the K group in striatal levels of Cho and Ins (p>0.1). We demonstrated that MRS-measured metabolites in the specific regions of the brain can be influenced by anesthetic agents.

Inactivation of FOXA2 by Respiratory Bacterial Pathogens and Dysregulation of Pulmonary Mucus Homeostasis.

Forkhead box (FOX) proteins are transcriptional factors that regulate various cellular processes. This minireview provides an overview of FOXA2 functions, with a special emphasis on the regulation airway mucus homeostasis in both healthy and diseased lungs. FOXA2 plays crucial roles during lung morphogenesis, surfactant protein production, goblet cell differentiation and mucin expression. In healthy airways, FOXA2 exerts a tight control over goblet cell development and mucin biosynthesis. However, in diseased airways, microbial infections and proinflammatory responses deplete FOXA2 expression, resulting in uncontrolled goblet cell hyperplasia and metaplasia, mucus hypersecretion, and impaired mucociliary clearance of pathogens. Furthermore, accumulated mucus clogs the airways and creates a niche environment for persistent microbial colonization and infection, leading to acute exacerbation and deterioration of pulmonary function in patients with chronic lung diseases. Various studies have shown that FOXA2 inhibition is mediated through induction of antagonistic EGFR and IL-13R-STAT6 signaling pathways as well as through posttranslational modifications induced by microbial infections. An improved understanding of how bacterial pathogens inactivate FOXA2 may pave the way for developing therapeutics that preserve the protein's function, which in turn, will improve the mucus status and mucociliary clearance of pathogens, reduce microbial-mediated acute exacerbation and restore lung function in patients with chronic lung diseases.

Quartz tuning fork based three-dimensional topography imaging for sidewall with blind features.

Atomic force microscopy has a tremendous number of applications in a wide variety of fields, particularly in the semiconductor area for the 3D-stacked device. Imaging three-dimensional (3D) structures with blind features has progressively become a critical technique. Recently, a 3D-atomic force microscopy (AFM) technique has been proposed to image 3D features, especially those having sharp apices, like silicon pillars. However, the scanning strategy has drawbacks, such as long scanning time, and unstable operation, based on the premature algorithm. Herein, an improved 3D-AFM algorithm is reported that overcomes the aforementioned problems by an intelligent 3D scanning algorithm that incorporates sidewall history tracking, troubleshooting for sharp sidewall and sticking, and reactive direction adjustment. The proposed algorithm enables the 3D imagery of ZnO nano-rods and silicon nano-pillars to be achieved by using a high aspect-ratio multiwall carbon nanotube-based AFM probe, without time-consuming disorientation. This study establishes a method to construct a 3D image of arbitrary shape in reduced scanning time.

Exendin-4 restores airway mucus homeostasis through the GLP1R-PKA-PPARγ-FOXA2-phosphatase signaling.

Goblet cell hyperplasia and metaplasia and excessive mucus are prominent pathologies of chronic airway diseases such as chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), and chronic bronchitis. Chronic infection by respiratory pathogens, including Pseudomonas aeruginosa, exacerbates cyclical proinflammatory responses and mucus hypersecretion. P. aeruginosa and its virulence factor pyocyanin contribute to these pathologies by inhibiting FOXA2, a key transcriptional regulator of mucus homeostasis, through activation of antagonistic signaling pathways EGFR-AKT/ERK1/2 and IL-4/IL-13-STAT6-SPDEF. However, FOXA2-targeted therapy has not been previously explored. Here, we examined the feasibility of repurposing the incretin mimetic Exendin-4 to restore FOXA2-mediated airway mucus homeostasis. We have found that Exendin-4 restored FOXA2 expression, attenuated mucin production in COPD and CF-diseased airway cells, and reduced mucin and P. aeruginosa burden in mouse lungs. Mechanistically, Exendin-4 activated the GLP1R-PKA-PPAR-γ-dependent phosphatases PTEN and PTP1B, which inhibited key kinases within both EGFR and STAT6 signaling cascades. Our results may lead to the repurposing of Exendin-4 and other incretin mimetics to restore FOXA2 function and ultimately regulate excessive mucus in diseased airways.