Integrated Biomarker Response Emphasizing Neuronal Oxidative Stress and Genotoxicity Induced by Oxamyl in Sprague Dawley Rats: Ameliorative Effect of Ginseng as a Neuroprotective Agent.

Climate change has led to increased and varying pest infestation patterns, triggering a rise in pesticide usage and exposure. The effects of oxamyl, a widely used nematicide in Egypt, encompasses typical signs of carbamate intoxication; nevertheless, long-term effects of oxamyl exposure, particularly on the nervous system, require further elucidation. This study systematically investigated the mechanism and manifestations of repeated subacute exposure to sublethal doses of oxamyl in male SD rats. Data showed a dose-dependent genotoxic effect, manifested as increased bone marrow micronuclei and decreased brain expression of key genes involved in neurogenesis and neuronal development. Coincidently, brain histopathology showed dose-dependent neurodegeneration in various regions, associated with a significant increase in GFAP immunoreactivity, indicative of neuroinflammation. Biochemical examination revealed a typical pattern of cholinesterase inhibition by carbamates in serum and brain tissue, as well as increased oxidative stress markers in the brain such as SOD activity reduction, alongside an increase in NO and MDA. The ability of Ginseng at a 100 mg/Kg dose to ameliorate the effects of oxamyl exposure was investigated. Ginseng use, either as a protective or therapeutic regimen, attenuated the observed genotoxic, neuroinflammatory, and biochemical alterations. Our results indicate that repeated exposure to oxamyl triggers an integrative neurotoxic response, driven by genotoxicity, oxidative stress, and neuroinflammation, that could trigger an increase in neurological and cognitive disorders. These findings emphasize the urgent need for confirmatory translational studies in human subjects to assess these changes and inform policy decisions regarding safe levels of usage and appropriate agricultural and public health practices.

Enhancing drought tolerance in Malva parviflora plants through metabolic and genetic modulation using Beauveria bassiana inoculation.

BACKGROUND: Enhancing crops' drought resilience is necessary to maintain productivity levels. Plants interact synergistically with microorganisms like Beauveria bassiana to improve drought tolerance. Therefore, the current study investigates the effects of biopriming with B. bassiana on drought tolerance in Malva parviflora plants grown under regular irrigation (90% water holding capacity (WHC)), mild (60% WHC), and severe drought stress (30% WHC). RESULTS: The results showed that drought stress reduced the growth and physiological attributes of M. parviflora. However, those bioprimed with B. bassiana showed higher drought tolerance and enhanced growth, physiological, and biochemical parameters: drought stress enriched malondialdehyde and H2O2 contents. Conversely, exposure to B. bassiana reduced stress markers and significantly increased proline and ascorbic acid content under severe drought stress; it enhanced gibberellic acid and reduced ethylene. Bioprimed M. parviflora, under drought conditions, improved antioxidant enzymatic activity and the plant's nutritional status. Besides, ten Inter-Simple Sequence Repeat primers detected a 25% genetic variation between treatments. Genomic DNA template stability (GTS) decreased slightly and was more noticeable in response to drought stress; however, for drought-stressed plants, biopriming with B. bassiana retained the GTS. CONCLUSION: Under drought conditions, biopriming with B. bassiana enhanced Malva's growth and nutritional value. This could attenuate photosynthetic alterations, up-regulate secondary metabolites, activate the antioxidant system, and maintain genome integrity.

Impact of adding zeolite to broilers' diet and litter on growth, blood parameters, immunity, and ammonia emission.

This work was designed to assess the impact of varying zeolite concentrations in diet and litter to enhance broiler's growth performance, immunity, and litter quality. A complete random arrangement was used for distributing 525 unsexed "Cobb 500" broiler chicks into seven treatments (75 chick / treatment), each treatment divided into 3 replicates (25 chicks / replicate). The 1st group (control one) received the recommended basal diet. Zeolite has been introduced to the basal diet (ZD) of the second, third, and fourth groups at concentrations of 5, 10, and 15 g/kg, respectively. The 5th, 6th and 7th groups used zeolite mixed with litter (ZL) at 0.5, 1, and 1.5 kg/m2 of litter, respectively. Due to the obtained results, adding zeolite with levels 15 g/kg of diet and 1.5 kg/1 m2 of litter, a significant improvement occurred in live body weight (LBW), body weight gain (BWG), feed intake (FI), feed conversion ratio (FCR) and European production efficiency factor (EPEF). Also, transaminase enzymes (ALT and AST), creatinine, white blood cells (WBCs) and different Immunoglobulins were significantly increased with different zeolite levels, except urea concentrations which showed reduced due to different zeolite treatments. In addition, spleen relative weight hasn't been affected by zeolite treatments, even though thymus and bursa relative weights had been affected significantly. Moreover, the antibodies' production to Newcastle disease virus (NDV) and Avian influenza virus (AIV) had increased significantly with adding zeolite with levels 10 g/kg of diet and 1.5 kg/1m2 of litter. Litter quality traits (NH3 concentration, pH values, and Moisture content) were improved with zeolite addition. So, zeolite could be employed in both feed and litter of broilers to maximize their production, immunity and improve farm's climate.

Trichuris Globulosa Von Linstow, 1901 from one-humped camel (Camelus dromedarius) in Egypt: prevalence, morphological and molecular study.

BACKGROUND: Trichuris spp. (whipworms) are soil-transmitted helminths distributed worldwide, parasitizing several mammalian hosts such as ruminants, primates, and rodents. Trichuris spp. is one of the most common intestinal parasites affecting both humans and animals, and it can spread directly through the fecal-oral route, resulting in severe illness and financial loss. So, this work aims to detect the frequency of Trichuris spp. in camels in Beheira Governorate, Egypt, and to identify Trichuris spp. through morphometrical studies, molecular analysis, and phylogenetic analysis. RESULTS: A total of 35 dromedaries out of 127 investigated had Trichuris spp. infection, meaning that the overall prevalence was 27.56%. The age of the camel affected the infection rate, older animals (> 5 years) having a higher prevalence of infection (24%) than animals of ages (< 3 years) (20%) than animals of ages (3-5 years) (19.14%). According to season: Trichuris spp. showed a unique pattern in camels in different seasons: summer (31.25%) > autumn (28.13%) > spring (25.8%) > winter (25%) indicating year-round infection. T. globulosa was identified morphometrically from camels in Beheira Governorate, Egypt. The BLAST analysis revealed the presence of T. globulosa isolate from camels using the Genbank database depending on nuclear small subunit ribosomal RNA (18s) and cytochrome b (Cytb) genes. CONCLUSION: A high prevalence of T. globulosa was found in camels in Beheira Governorate, Egypt. This is the first report to confirm the identification of T. globulosa from camel based on morphometrical studies and molecular and phylogenetic analysis in Egypt. More thorough studies on the incidence, molecular, and genetic analysis of Trichuris spp. in Egypt are required in addition to camel control programs.

Offsetting pb induced oxidative stress in Vicia faba plants by foliar spray of chitosan through adjustment of morpho-biochemical and molecular indices.

In the course of their life, plants face a multitude of environmental anomaly that affects their growth and production. In recent decades, lead (Pb) gained an increasing attention as it is among the most significant contaminants in the environment. Therefore, in this study the effects of Pb concentrations (0, 50 and 100 ppm) on Vicia faba plants and attempts to alleviate this stress using chitosan (Chs; 0 and 0.1%) were performed. The results validated that with increasing Pb concentrations, a decline in growth, pigments and protein contents was observed. In the same time, a significant upsurge in the stress markers, both malondialdehyde (MDA) and H2O2, was observed under Pb stress. Nonetheless, foliar spraying with Chs improves the faba bean growth, pigment fractions, protein, carbohydrates, reduces MDA and H2O2 contents and decreases Pb concentrations under Pb stress. Pb mitigation effects by Chs are probably related with the activity of antioxidant enzymes, phenylalanine ammonia lyase (PAL) and proline. The application of Chs enhanced the activities of peroxidase, catalase and PAL by 25.77, 17.71 and 20.07%, respectively at 100 ppm Pb compared to their control. Plant genomic material exhibits significant molecular polymorphism, with an average polymorphism of 91.66% across all primers. To assess the genetic distance created among treatments, the dendrogram was constructed and the results of the similarity index ranged from 0.75 to 0.95, indicating genetic divergence. Our research offers a thorough comprehension of the role of Chs in lessening the oxidative stress, which will encourage the use of Chs in agricultural plant protection.

Performance and economic efficiency of laying hens in response to adding zeolite to feed and litter.

This study investigated the effect of different levels of zeolite in laying hen (Silver Montazah) diet and litter on productive performance, egg quality criteria, and economics during the second stage of production (40-56 wk of age). An experiment with a 3 × 4 factorial design was performed to study the effects of four levels of zeolite (0, 10, 15, and 20 g/kg feed) in the diet and three levels of zeolite (0, 1.5, and 2 kg/m2) in the litter. Adding zeolite to diet and litter significantly improved final BW and BW change, egg number, egg weight, egg mass, laying rate, feed consumption (FC), and feed conversion ratio (FCR), as well as egg quality criteria when compared to the unsupplemented group. Additionally, adding zeolite at a level of 2 kg /m2 litter and 20 g/kg diet achieved the greatest enhancement in productive performance features. Therefore, it can be suggested that the greatest results were obtained in laying farms when zeolite was added as a litter addition and as a supplement to feed.

Efficacy of dietary supplements of Glycyrrhiza glabra (Licorice) and maduramicin alone or in combination with Eimeria tenella infected chicks: A clinical study and molecular docking.

Background: Coccidiosis is one of the most economically significant poultry diseases worldwide, caused by the pathogenic Eimeria species, and is characterized by decreased weight gain (WG) and failure to grow due to malabsorption, low feed conversion rate, bloody diarrhea, and dehydration. Aim: This study investigated the effectiveness of licorice root extract (LRE) in controlling cecal coccidiosis to determine whether its combination with maduramicin could help alleviate the pathological, biochemical, and histopathological effects of cecal coccidiosis in Sasso broiler chicks. Methods: A total of 125 one-day-old Sasso broiler chicks were categorized into five equal groups (n = 25), each consisting of five replicates (n = 5 per replicate). G1-LE received a basal diet supplemented with LRE (3 g/kg); G2-ME received a basal diet containing maduramycin (0.5 g/kg); and G3-LME received a basal diet containing LRE and maduramicin together with the same rates. G4-E (positive control) and G5-N (negative control) received no additives in their feed. Birds in groups (G1-4) were challenged on day 14 of the experiment by orally intercropping a 1 ml suspension of Eimeria tenella sporulated oocysts. Results: Groups of birds fed on LRE and maduramicin separately or together appeared to be in good condition where no deaths or clinical abnormalities were observed, based on the analysis of clinicopathological examination. Compared with the G4-E positive control, the dropping scoring and oocyst shedding of groups G1-LE, G2-ME, and G3-LME along the 10th-day post-challenge (dpc), as well as macroscopic and microscopic lesions scoring at the 7th dpc, was considerably lower. The dual supplementation use of LRE and maduramicin in G3-LME's reduced the harmful effects of coccidian, which appeared only as a mononuclear cellular infiltration and a small number of oocysts invading the intestinal glands. Molecular docking revealed that LRE and maduramicin interacted with E. tenella DNA polymerase, E. tenella apical membrane antigen 1, and microneme protein binding sites resulting in reduced E. tenella replication and invasion. Conclusion: The inclusion of LRE and maduramicin, individually or in combination, in the diet might effectively mitigate the detrimental effects of coccidiosis.

Predictors of early mortality after lung transplantation for idiopathic pulmonary arterial hypertension.

Lung transplantation remains an important therapeutic option for idiopathic pulmonary arterial hypertension (IPAH), yet short-term survival is the poorest among the major diagnostic categories. We sought to develop a prediction model for 90-day mortality using the United Network for Organ Sharing database for adults with IPAH transplanted between 2005 and 2021. Variables with a p value ≤ 0.1 on univariate testing were included in multivariable analysis to derive the best subset model. The cohort comprised 693 subjects, of whom 71 died (10.2%) within 90 days of transplant. Significant independent predictors of early mortality were: extracorporeal circulatory support and/or mechanical ventilation at transplant (OR: 3; CI: 1.4-5), pulmonary artery diastolic pressure (OR: 1.3 per 10 mmHg; CI: 1.07-1.56), forced expiratory volume in the first second percent predicted (OR: 0.8 per 10%; CI: 0.7-0.94), recipient total bilirubin >2 mg/dL (OR: 3; CI: 1.4-7.2) and ischemic time >6 h (OR: 1.7, CI: 1.01-2.86). The predictive model was able to distinguish 25% of the cohort with a mortality of ≥20% from 49% with a mortality of ≤5%. We conclude that recipient variables associated with increasing severity of pulmonary vascular disease, including pretransplant advanced life support, and prolonged ischemic time are important risk factors for 90-day mortality after lung transplant for IPAH.

Attenuation of Zucchini mosaic virus disease in cucumber plants by mycorrhizal symbiosis.

KEY MESSAGE: Arbuscular mycorrhizal fungi generated systemic acquired resistance in cucumber to Zucchini yellow mosaic virus, indicating their prospective application in the soil as a sustainable, environmentally friendly approach to inhibit the spread of pathogens. The wide spread of plant pathogens affects the whole world, causing several plant diseases and threatening national food security as it disrupts the quantity and quality of economically important crops. Recently, environmentally acceptable mitigating practices have been required for sustainable agriculture, restricting the use of chemical fertilizers in agricultural areas. Herein, the biological control of Zucchini yellow mosaic virus (ZYMV) in cucumber (Cucumis sativus L.) plants using arbuscular mycorrhizal (AM) fungi was investigated. Compared to control plants, ZYMV-infected plants displayed high disease incidence (DI) and severity (DS) with various symptoms, including severe yellow mosaic, mottling and green blisters of leaves. However, AM fungal inoculation exhibited 50% inhibition for these symptoms and limited DS to 26% as compared to non-colonized ones. The detection of ZYMV by the Enzyme-Linked Immunosorbent Assay technique exhibited a significant reduction in AM-inoculated plants (5.23-fold) compared with non-colonized ones. Besides, mycorrhizal root colonization (F%) was slightly reduced by ZYMV infection. ZYMV infection decreased all growth parameters and pigment fractions and increased the malondialdehyde (MDA) content, however, these parameters were significantly enhanced and the MDA content was decreased by AM fungal colonization. Also, the protein, proline and antioxidant enzymes (POX and CAT) were increased with ZYMV infection with more enhancements due to AM root colonization. Remarkably, defence pathogenesis-related (PR) genes such as PR-a, PR-b, and PR-10 were quickly expressed in response to AM treatment. Our findings demonstrated the beneficial function of AM fungi in triggering the plant defence against ZYMV as they caused systemic acquired resistance in cucumber plants and supported their potential use in the soil as an environment-friendly method of hindering the spread of pathogenic microorganisms sustainably.

Trichoderma cf. asperellum and plant-based titanium dioxide nanoparticles initiate morphological and biochemical modifications in Hordeum vulgare L. against Bipolaris sorokiniana.

BACKGROUND: Spot blotch is a serious foliar disease of barley (Hordeum vulgare L.) plants caused by Bipolaris sorokiniana, which is a hemibiotrophic ascomycete that has a global impact on productivity. Some Trichoderma spp. is a promising candidate as a biocontrol agent as well as a plant growth stimulant. Also, the application of nanomaterials in agriculture limits the use of harmful agrochemicals and helps improve the yield of different crops. The current study was carried out to evaluate the effectiveness of Trichoderma. cf. asperellum and the biosynthesized titanium dioxide nanoparticles (TiO2 NPs) to manage the spot blotch disease of barley caused by B. sorokiniana and to assess the plant's innate defense response. RESULTS: Aloe vera L. aqueous leaf extract was used to biosynthesize TiO2 NPs by reducing TiCl4 salt into TiO2 NPs and the biosynthesized NPs were detected using SEM and TEM. It was confirmed that the NPs are anatase-crystalline phases and exist in sizes ranging from 10 to 25 nm. The T. cf. asperellum fungus was detected using morphological traits and rDNA ITS analysis. This fungus showed strong antagonistic activity against B. sorokiniana (57.07%). Additionally, T. cf. asperellum cultures that were 5 days old demonstrated the best antagonistic activity against the pathogen in cell-free culture filtrate. Also, B. sorokiniana was unable to grow on PDA supplemented with 25 and 50 mg/L of TiO2 NPs, and the diameter of the inhibitory zone increased with increasing TiO2 NPs concentration. In an in vivo assay, barley plants treated with T. cf. asperellum or TiO2 NPs were used to evaluate their biocontrol efficiency against B. sorokiniana, in which T. cf. asperellum and TiO2 NPs enhanced the growth of the plant without displaying disease symptoms. Furthermore, the physiological and biochemical parameters of barley plants treated with T. cf. asperellum or TiO2 NPs in response to B. sorokiniana treatment were quantitively estimated. Hence, T. cf. asperellum and TiO2 NPs improve the plant's tolerance and reduce the growth inhibitory effect of B. sorokiniana. CONCLUSION: Subsequently, T. cf. asperellum and TiO2 NPs were able to protect barley plants against B. sorokiniana via enhancement of chlorophyll content, improvement of plant health, and induction of the barley innate defense system. The present work emphasizes the major contribution of T. cf. asperellum and the biosynthesized TiO2 NPs to the management of spot blotch disease in barley plants, and ultimately to the enhancement of barley plant quality and productivity.

Unique properties of titanium dioxide quantum dots assisted regulation of growth and biochemical parameters of Hibiscus sabdariffa plants.

Owing to the uniqueness of quantum dots (QDs) as a potential nanomaterial for agricultural application, hence in the present study, titanium dioxide quantum dots (TiO2 QDs) were successfully synthesized via sol-gel technique and the physico-chemical properties of the prepared TiO2 QDs were analyzed. Based on the results, the TiO2 QDs showed the presence of anatase phase of TiO2. TEM examination revealed spherical QDs morphology with an average size of 7.69 ± 1.22 nm. The large zeta potential value (-20.9 ± 2.3 mV) indicate greater stability of the prepared TiO2 QDs in aqueous solutions. Moreover, in this work, the application of TiO2 QDs on Hibiscus sabdariffa plants was conducted, where H. sabdariffa plants were foliar sprayed twice a week in the early morning with different concentrations of TiO2 QDs (0, 2, 5, 10, 15 and 30 ppm) to evaluate their influence on these plants in terms of morphological indexes and biochemical parameters. The results exhibited an increasing impact of the different used concentrations of TiO2 QDs on morphological indexes, such as fresh weight, dry weight, shoot length, root length, and leaf number, and physio-biochemical parameters like chlorophyll a, chlorophyll b, carotenoid contents, total pigments and total phenolic contents. Remarkably, the most prominent result was recorded at 15 ppm TiO2 QDs where plant height, total protein and enzymatic antioxidants like catalase and peroxidase were noted to increase by 47.6, 20.5, 29.5 and 38.3%, respectively compared to control. Therefore, foliar spraying with TiO2 QDs positively serves as an effective strategy for inducing optimistic effects in H. sabdariffa plants.

Differential Transcriptomic Signatures of Small Airway Cell Cultures Derived from IPF and COVID-19-Induced Exacerbation of Interstitial Lung Disease.

Idiopathic pulmonary fibrosis (IPF) is a pathological condition wherein lung injury precipitates the deposition of scar tissue, ultimately leading to a decline in pulmonary function. Existing research indicates a notable exacerbation in the clinical prognosis of IPF patients following infection with COVID-19. This investigation employed bulk RNA-sequencing methodologies to describe the transcriptomic profiles of small airway cell cultures derived from IPF and post-COVID fibrosis patients. Differential gene expression analysis unveiled heightened activation of pathways associated with microtubule assembly and interferon signaling in IPF cell cultures. Conversely, post-COVID fibrosis cell cultures exhibited distinctive characteristics, including the upregulation of pathways linked to extracellular matrix remodeling, immune system response, and TGF-ß1 signaling. Notably, BMP signaling levels were elevated in cell cultures derived from IPF patients compared to non-IPF control and post-COVID fibrosis samples. These findings underscore the molecular distinctions between IPF and post-COVID fibrosis, particularly in the context of signaling pathways associated with each condition. A better understanding of the underlying molecular mechanisms holds the promise of identifying potential therapeutic targets for future interventions in these diseases.

Pulmonary, circulatory and renal considerations in the early postoperative management of the lung transplant recipient.

Lung transplantation volumes and survival rates continue to increase worldwide. Primary graft dysfunction (PGD) and acute kidney injury (AKI) are common early postoperative complications that significantly affect short-term mortality and long-term outcomes. These conditions share overlapping risk factors and are driven, in part, by circulatory derangements. The prevalence of severe PGD is up to 20% and is the leading cause of early death. Patients with pulmonary hypertension are at a higher risk. Prevention and management are based on principles learned from acute lung injury of other causes. Targeting the lowest effective cardiac filling pressure will reduce alveolar edema formation in the setting of increased pulmonary capillary permeability. AKI is reported in up to one-half of lung transplant recipients and is strongly associated with one-year mortality as well as long-term chronic kidney disease. Optimization of renal perfusion is critical to reduce the incidence and severity of AKI. In this review, we highlight key early post-transplant pulmonary, circulatory, and renal perturbations and our center's management approach.

Evaluation of synergistic approach of spinel cadmium-copper nanoferrites as magnetic catalysts for promoting wastewater decontamination: Impact of Ag ions doping.

Metal substitution is an efficient strategy to improve the catalytic activity of ferrite-based catalysts. In this study, Cd0.5Cu0.5-xAgxFe2O4 (where 0 ≤ x ≤ 0.5) ferrites were fabricated via a simple co-precipitation method. The influence of the silver ions on the structural, magnetic, and catalytic characteristics of the spinel nanoparticles, as well as on their morphology, was examined. X-ray diffractograms revealed a crystalline cubic spinel structure with crystallite sizes in the nanoregime (7-15 nm). The saturation magnetization reduced from 29.8 to 2.80 emu as the Ag+ doping increased. Two prominent absorption bands were visible in Fourier-transform infrared spectra at 600 cm-1 and 400 cm-1, respectively, and they belonged to the tetrahedral (A) and octahedral (B) sites. The samples were then used as catalysts for the oxidative breakdown of the typical organic contaminant indigo carmine dye (IC). The catalytic process followed the first-order kinetic model, and the rate constant increased from 0.007 to 0.023 min-1 with increasing of Ag+ doping. Cd0.5Cu0.5-xAgxFe2O4 exhibited excellent catalytic performance in the pH range of 2-11, which means that they are promising efficient and stable materials for Fenton-based alkaline wastewater treatment. Finally, the pathway includes, HO•, HO2-•, and O2-• as oxidants resulted from the synergistic effects of Fe3+, Cu2+, and Ag+, with H2O2 and surface hydroxyl groups have been proposed.

In vivo and In vitro evaluation of the antifungal activity of the PGPR Bacillus amyloliquefaciens RaSh1 (MZ945930) against Alternaria alternata with growth promotion influences on Capsicum annuum L. plants.

Alternaria alternata that threatens pepper production and causes major economic harm is responsible for the leaf spot/blight disease. Chemical fungicides have been widely employed; unfortunately, fungicidal resistance is a current concern. Therefore, finding new environmentally friendly biocontrol agents is a future challenge. One of these friendly solutions is the use of bacterial endophytes that have been identified as a source of bioactive compounds. The current study investigates the in vivo and in vitro fungicidal potential of Bacillus amyloliquefaciens RaSh1 (MZ945930) against pathogenic A. alternata. In vitro, the results revealed that RaSh1 exhibited strong antagonistic activity against A. alternata. In addition to this, we inoculated pepper (Capsicum annuum L.) plants with B. amyloliquefaciens RaSh1 and infected them with A. alternata. As a result of A. alternata infection, which generated the highest leaf spot disease incidence (DI), the plant's growth indices and physio-biochemical characteristics significantly decreased, according to our findings. Our results also showed the abnormal and deformed cell structure using light and electron microscopy of A. alternata-infected leaves compared with other treatments. However, DI was greatly reduced with B. amyloliquefaciens RaSh1 application (40%) compared to pepper plants infected with A. alternata (80%), and this led to the largest increases in all identified physio-biochemical parameters, including the activity of the defense-related enzymes. Moreover, inoculation of pepper plants with B. amyloliquefaciens RaSh1 decreased electrolyte leakage by 19.53% and MDA content by 38.60% as compared to A. alternata infected ones. Our results show that the endophyte B. amyloliquefaciens RaSh1 has excellent potential as a biocontrol agent and positively affects pepper plant growth.

Targeting ATP12A, a Nongastric Proton Pump α Subunit, for Idiopathic Pulmonary Fibrosis Treatment.

Idiopathic pulmonary fibrosis (IPF) is a pathological condition of unknown etiology that results from injury to the lung and an ensuing fibrotic response that leads to the thickening of the alveolar walls and obliteration of the alveolar space. The pathogenesis is not clear, and there are currently no effective therapies for IPF. Small airway disease and mucus accumulation are prominent features in IPF lungs, similar to cystic fibrosis lung disease. The ATP12A gene encodes the α-subunit of the nongastric H+, K+-ATPase, which functions to acidify the airway surface fluid and impairs mucociliary transport function in patients with cystic fibrosis. It is hypothesized that the ATP12A protein may play a role in the pathogenesis of IPF. The authors' studies demonstrate that ATP12A protein is overexpressed in distal small airways from the lungs of patients with IPF compared with normal human lungs. In addition, overexpression of the ATP12A protein in mouse lungs worsened bleomycin induced experimental pulmonary fibrosis. This was prevented by a potassium competitive proton pump blocker, vonoprazan. These data support the concept that the ATP12A protein plays an important role in the pathogenesis of lung fibrosis. Inhibition of the ATP12A protein has potential as a novel therapeutic strategy in IPF treatment.