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Abstract Lung cancer remains the leading cause of cancer death. Treatment with immune checkpoint inhibitor (ICI) alone or combination with chemotherapy served as first-line therapy in non-small cell lung cancer (NSCLC). However, only 20–50% of NSCLC patients respond to ICI. Necroptosis, an inflammatory form of cell death plays an important role in the regulation of tumor immune microenvironment which may affect prognosis and ICI response but its clinical significance in NSCLC patients has remained largely unknown. Therefore, we aimed to analyze the correlation between key necroptotic proteins and necroptosis and clinical outcomes, the status of tumor-infiltrating immune cells, and response to ICI in NSCLC patients. The expression of receptor-interacting protein kinase 3 (RIPK3), mixed lineage kinase domain-like protein (MLKL) and phosphorylated MLKL (pMLKL) were immunolocalized in 125 surgically resected NSCLC patients and 23 NSCLC patients administered with ICI therapy. CD8 + and FOXp3 + T cells and CD163 + M2 macrophages were also immunolocalized. High RIPK3 status was positively correlated with survival of the patients and RIPK3 turned out an independent favorable prognostic factor of the patients. RIPK3 was negatively correlated with CD8 + T cells, while MLKL positively correlated with CD163 + M2 macrophages, suggesting the possible involvement of RIPK3 and MLKL in formulating immunosuppressive microenvironment. In addition, high RIPK3 status tended to be associated with clinical resistance to ICI therapy (P-value = 0.057). Furthermore, NSCLC cells-expressing RIPK3 suppressed T cells response to ICI therapy in vitro. Therefore, RIPK3 and MLKL could induce an immunosuppressive microenvironment, resulting in low response to ICI therapy in NSCLC.

Elucidating the mechanisms of action of steroid hormones will contribute to the development of therapeutic strategies for hormone-dependent tumors. Recent advances in genetic engineering have revealed the complex and diverse mechanisms of steroid hormone signaling; however, these techniques are limited to in vitro or animal experiments. It is believed that verifying hormone signals elucidated using human pathological tissue specimens will directly aid in treatment and diagnosis. However, pathological tissue specimens are generally formalin-fixed paraffin-embedded (FFPE), and protein/gene analyses of FFPE tissues are limited. Protein detection using immunohistochemistry with specific antibodies in FFPE tissues is a classical technique essential for diagnosis and treatment decisions in various types of cancer. In steroid hormone signaling, the expression and localization of receptors, hormone-related enzymes, and proteins encoded by response genes can be clarified using immunohistochemistry. Although protein-protein interactions such as receptor dimers and DNA-binding proteins are mainly detected in vitro, they can be examined in FFPE tissues using in situ proximity ligation assays and southwestern histochemistry, respectively. Using these detection methods, including immunohistochemistry, it is possible to analyze each hormone signaling pathway in hormone-related tumors histopathologically. Although FFPE tissues still suffer from gene and protein denaturation, their advantages include the ability to retrospectively study target factors/signals and obtain spatial information through microscopy. This review describes a visualization method for elucidating steroid hormone signaling in hormone-dependent tumors using FFPE tissues.

Fine metal particles produced by gas atomization are recognized as an essential material for additive manufacturing. However, spatio-temporally resolved images for the atomization process are still lacking. In the present study, we apply a high-speed Schlieren optical system synchronized with a pulse light source with flashing period of 30 ns to a simple atomization setup, consisting of a single supersonic Image 1 jet at Mach number of 1.5 and free-falling tin droplets. Covering the tin droplets by Ar gas, we generate spherical droplets by minimizing the initial oxidation from the ambient. Impinging on the large-momentum gas jet, the tin droplet largely deforms to be shaved the bottom end and bounced above the jet with partially penetrating inside the gas core. The spreading ligaments above the jet thins at first along with the capillary timescale. As the surface oxidation proceeds, the neck transitionally shrinks according to the viscous-capillary timescale, which evidences the direct observation of gas atomization process superposed by the molecular diffusion across the interface. Statistics of collected metal particles demonstrate a bimodal distribution for the diameter, originated from the distinct atomization mechanisms of aerodynamic dominant breakup inside the gas jet and of capillary dominant breakup spreading above the jet.

Abstract Background Systemic-to-pulmonary artery shunt (SPAS) is a rare condition that can occur as a result of congenital heart disease or chronic pulmonary inflammation, occasionally leading to life-threatening hemoptysis. Computed tomography (CT) imaging is crucial in the diagnosis of SPAS, and the optimal management approach for SPAS remains uncertain. This case report presents a novel approach to the treatment of SPAS, consisting of transcatheter arterial embolization of the systemic artery followed by lung segmentectomy. Case presentation A 42-year-old man with abnormal chest findings was referred to us and a diagnosis of SPAS was established based on the CT findings showing a blood flow regurgitation from the dilated left 4th intercostal artery to the Lt. A6. The patient was asymptomatic but we decided to treat him to prevent a risk of future hemoptysis. Transcatheter arterial embolization (TAE) of systemic arteries followed by S6 segmentectomy was successfully performed with minimal blood loss and complete removal of the dilated intra-pulmonary blood vessels. Histological analysis confirmed the diagnosis of SPAS. Conclusion We reported a case of SPAS, who was successfully treated with the combination of TAE and subsequent segmentectomy. The blood loss during surgery was minimal and this strategy appeared to minimize future recanalization and hemoptysis. Further studies and long-term follow-up of SPAS patients are required to establish standardized management guidelines for this rare condition.

The collection rate is a difficult and important issue in the management of polyethylene terephthalate (PET) bottle waste, as it is related to the behavior of the community to participate and comply with the system established by the government. One system that has been shown to increase the collection rate of PET bottle waste is the deposit–refund scheme (DRS). We tested residents’ intention to participate in the DRS using the theory of planned behavior and complemented it with several important variables that could influence the model. The method used is partial least square-structural equation modeling. The result of the study is that all the variables studied were positively influenced according to their respective paths. Nevertheless, environmental awareness is the latent variable with the strongest positive effect on attitude, and attitude has the strongest positive effect on intention. Public information is the latent variable that positively influences all variables related to intention. The proposed model can be applied globally to identify factors that influence recycling participation, particularly for DRS, and help achieve sustainable development goals while initiating a circular economy by recycling plastic bottle waste.

Key Clinical Message Extrapulmonary lymphangioleiomyomatosis (LAM) can present as incidental nodal LAM in gynecological surgery specimens, that warrants systemic investigation and follow‐up of concurrent and subsequent development of pulmonary and extrapulmonary LAM.

To achieve net-zero carbon emissions by 2050, aviation sector is urgently and severely required to reduce carbon dioxide (CO2) emissions. Herein, for the first time, on-site direct and selective imaging of CO2 emissions from aircraft was performed at Fukuoka International Airport in Japan, using the latest infrared camera with a remarkably narrow bandpass filter ranging from 4.2 to 4.4 μm, corresponding to the low-transmittance wavelength of CO2. The high resolutions of the time-series images are 100 mm/pixel in space and 50 ms in time, well capturing the dynamics of jet engine plumes containing the core and bypass flows. Throughout a landing and take-off cycle of a wide-body aircraft, including Boeing 787, Boeing 777, and Airbus A350, CO2 emissions are successfully imaged, clearly demonstrating that the dense CO2 flow in the core jet through the embedded high bypass ratio engines strongly mixes with the bypass jet and ambient air, eventually diffusing downstream. As a result, the applicability of the new real-time monitoring technique was evidenced for the dense CO2 distributions in space including emission sources.

Abstract Background Indium lung is characterized by interstitial pneumonia and/or emphysema which occurs in indium-tin oxide (ITO) workers. Indium lung is now known to progress after stopping exposure to ITO, but the long-term influences of ITO remain unclear. Case presentation Forty seven years old, a never-smoker, who had been engaged in an ITO manufacturing process for 8 years. Emphysema was indicated by the medical check-up for ex-ITO workers, and he was diagnosed with indium lung. He underwent partial lung resections for pneumothorax two times, and obstructive pulmonary dysfunction had progressed through the years. He underwent right single lung transplant 20 years after ITO exposure. Pathologically, his lung showed severe distal acinar emphysema and honeycomb change. Fibrosis and destruction of the lung tissue significantly progressed compared to the previous partial resections. Scanning electron microscopy combined with energy dispersive spectroscopy revealed that the deposited particles contained indium and tin. After the transplantation, his respiratory function was improved. Conclusions In this case, ITO resided in the lung tissue for 20 years, and lung tissue destruction kept progressing. Careful medical follow-up is recommended for ITO-workers even if they are asymptomatic.

Arabidopsis halleri ssp. gemmifera is classified as Cd and Zn hyperaccumulator plant, however, the disparity accumulation preferences in organs (root, stem and leaves) between cadmium and zinc seems less understandable. Therefore, this study aimed to portray accumulation behaviour toward the presence of Cd and Zn in the hydroponic method employing A. halleri ssp. gemmifera. The experiment was conducted by applying this plant using 2 and 300 µM of Cd, and 2 and 200 µM Zn, together with 20% Hoagland solution for 7 days, separately. The results showed that Zn in the medium was uptake faster than Cd. Furthermore, increasing Cd/Zn supply at the medium resulted in an increasing accumulation of Cd/Zn in the organs of the plant. In both Cd treatments, the accumulation followed the order of stem>root>leaves, indicating Cd transportation to the upper part has occurred during this period. The same accumulation preference pattern was also reported in the 200 µM Zn supply. However, at 2 µM Zn supply, Zn accumulation was mainly found in the leaves, followed by the root and stem. A. halleri ssp. gemmifera uptake Zn faster from the medium and translocate rapidly to the leaves at low-level Zn supply. Increasing Zn supply concentration might inhibit the translocation of Zn from stem to leaves. Meanwhile, regardless of Cd supply concentrations, this plant could only translocate Cd to the stem mostly within a short-time exposure period. Therefore, this study concluded that A. halleri ssp. gemmifera exhibited different accumulation responses when exposed to different Cd and Zn supply concentrations.

This study focuses on how to solve cadmium (Cd) contamination in soil because this contaminant decreases soil quality. Soil remediation using the hyperaccumulator plants is an optional process to solve soil contamination. Arabidopsis halleri ssp. gemmifera (hereinafter referred to as A. halleri), is one of the candidate plants expected to be used for phytoremediation of Cd contaminated soil. The A. halleri promote solubilization of Cd in the soil directly or indirectly using its secreted root exudate. However, the effect of the metabolites profile of this plant to Cd uptake from contaminated soil is still unclear. The purpose of this study is to examine the contribution of root exudates of A. halleri to extract Cd in the soil. Cd-contaminated soil used in this study was a farmland soil containing 5.8 mg kg-1 of Cd and 648 mg kg-1 of Zn taken from Tome City, Miyagi Prefecture, Japan. Soil leaching tests were conducted using the solution containing the root exudates from A. halleri plant. The accelerating effect of root exudates of A. halleri on solubilization of Cd is fundamental information to construct the benefit of phytoremediation.

Co3O4 was synthesized on carbon paper (CP) using a facile method to improve electrochemical nitrate-to-ammonia conversion efficiency. The resulting Co3O4-CP electrode demonstrated an exceptional Faradaic efficiency of almost 100% across a broad range of application conditions, with a peak NH3 yield of 3.43 mmol h−1 cm−2 (2.25 mol gCo−1 h−1).

Abstract Background Pulmonary carcinoid tumors rarely coexist with non-small cell lung carcinoma, and only nine cases have been reported previously. The pathogenesis and origin of these combined tumors remain unclear because of its rarity. Case presentation We examined two cases of adenocarcinoma coexisting with a typical or atypical carcinoid tumor: Case 1 was a 77-year-old woman and Case 2 was an 83-year-old woman. Both of these cases had no respiratory symptoms, and underwent pulmonary lobectomies due to incidentally detected lung nodules. Recurrence and metastases were not detected after the surgery. Histologically, carcinoid and adenocarcinoma components were present in both cases. The two components coexisted without mixing with each other. Next-generation sequencing was performed on the two components in these cases. In each case, no common genetic variants were detected. Conclusion We considered that our cases could histologically and genetically represent collision tumors that did not share common progenitor cells. Comprehensive analyses such as whole genome sequencing could provide important information for elucidating the pathogenesis of adenocarcinoma and carcinoid components.

Background: A diagnosis with histological classification by pathologists is very important for appropriate treatments to improve the prognosis of patients with breast cancer. However, the number of pathologists is limited, and assisting the pathological diagnosis by artificial intelligence becomes very important. Here, we presented an automatic breast lesions detection model using microscopic histopathological images based on a Single Shot Multibox Detector (SSD) for the first time and evaluated its significance in assisting the diagnosis. Methods: We built the data set and trained the SSD model with 1361 microscopic images and evaluated using 315 images. Pathologists and medical students diagnosed the images with or without the assistance of the model to investigate the significance of our model in assisting the diagnosis. Results: The model achieved 88.3% and 90.5% diagnostic accuracies in 3-class (benign, non-invasive carcinoma, or invasive carcinoma) or 2-class (benign or malignant) classification tasks, respectively, and the mean intersection over union was 0.59. Medical students achieved a remarkably higher diagnostic accuracy score (average 84.7%) with the assistance of the model compared to those without assistance (average 67.4%). Some people diagnosed images in a short time using the assistance of the model (shorten by average 6.4 min) while others required a longer time (extended by 7.2 min). Conclusion: We presented the automatic breast lesions detection method at high speed using histopathological micrographs. The present system may conveniently support the histological diagnosis by pathologists in laboratories.

Cadmium (Cd), which is present in zinc (Zn) ore, is a toxic metal and causes contamination globally. Phytoremediation is a promising technology for the remediation of sites with low and moderate contamination. Temperature is an important factor in phytoremediation because it has an impact on both plant biomass and the accumulation of heavy metals. However, little is known about the influence of temperature on heavy metal accumulation by the Cd and Zn hyperaccumulator Arabidopsis halleri ssp. gemmifera. The effect of temperature on the distribution of Cd and Zn in A. halleri ssp. gemmifera and the mechanism of metal removal from solution were investigated in this study. Our results showed that the temperature dependence of the distribution of Cd and Zn in the plant was different, which may suggest that the mechanisms of xylem loading were different between Cd and Zn. Although Cd and Zn have partially similar transport pathways, the removal kinetics based on the first-order reaction rate constant revealed that the temperature which maximized rate of absorption was different between Cd and Zn. This study suggests a potential for efficient Cd phytoextraction using A. halleri ssp gemmifera in Cd and Zn co-existing environments.

Using plants as bioremediation agents are rising worldwide as an environmentally friendly tool to remove contaminants such as heavy metals. Arabidopsis halleri ssp. gemmifera is able to hyperaccumulate Cd/Zn, however, the commonality between Cd/Zn accumulation pathways are still vague. This study focused on HMA4 and IRT3 as indicators and investigated their transcription in A. halleri ssp. gemmifera under Cd/Zn treatments. In addition to the known Cd/Zn xylem loading functions in roots, HMA4 showed a potential role in Cd/Zn redistribution or metal efflux from the vascular bundle in leaves due to increased transcription by 3-fold after 7 d under all treatments. On the other hand, IRT3 as a Zn homeostasis gene was expressed continuously in both roots and leaves under single Cd or Zn treatment. However, IRT3 transcription in leaves plunged to 50-fold lower under combined Cd and Zn treatment. The result indicated an increase of intracellular free Zn ion, implying a new unreported mechanism of Zn homeostasis in leaves under the presence of both metals. Furthermore, no competition between Cd/Zn uptake and accumulation suggested the existence of independent transport system for Cd and Zn in A. halleri ssp. gemmifera, which is differed from what have been reported until now.

PET bottle waste is easy to recycle because it is easy to separate, abundant, and competitively priced. Technologies for the treatment of PET bottle waste have been evaluated to date by using life cycle assessment (LCA), but this does not take into account all of the aspects that policymakers consider necessary when selecting an acceptable technology. Aspects such as society, economics, policies, and technical applicability need to be considered along with the environment and resource consumption to complement the LCA results for PET bottle waste. These aspects were selected as criteria for the analytical hierarchy process (AHP), and stakeholders were invited to make a comparison evaluation of the criteria and sub-criteria. Academics were involved to compare the technology options. The results show that society is the highest priority because it is the main actor that ensures the application of the technology, and that job creation is the most important indicator for the selection of the technology in society criteria. After comparing open landfills, sanitary landfills, incineration with energy recovery, pelletizing, glycolysis, and hydrolysis for the utilization of PET bottle waste, this study suggests pelletizing as the acceptable technology for Indonesia because pelletizing is dominant in all the criteria and sub-criteria which support sustainability in waste management. This is the first time that a single plastic fraction that is easy to collect and recycle has been studied with the AHP. The results show that this type of plastic could also be reused in developing countries through mechanical recycling.

Over the past century, the demand for petroleum products has increased rapidly, leading to higher oil extraction, processing and transportation, which result in numerous oil spills in coastal-marine environments. As the spilled oil can negatively affect the coastal-marine ecosystems, its transport and fates captured a significant interest of the scientific community and regulatory agencies. Typically, the environment has natural mechanisms (e.g., photooxidation, biodegradation, evaporation) to weather/degrade and remove the spilled oil from the environment. Among various oil weathering mechanisms, biodegradation by naturally occurring bacterial populations removes a majority of spilled oil, thus the focus on bioremediation has increased significantly. Helping in the marginal recognition of this promising technique for oil-spill degradation, this paper reviews recently published articles that will help broaden the understanding of the factors affecting biodegradation of spilled oil in coastal-marine environments. The goal of this review is to examine the effects of various environmental variables that contribute to oil degradation in the coastal-marine environments, as well as the factors that influence these processes. Physico-chemical parameters such as temperature, oxygen level, pressure, shoreline energy, salinity, and pH are taken into account. In general, increase in temperature, exposure to sunlight (photooxidation), dissolved oxygen (DO), nutrients (nitrogen, phosphorous and potassium), shoreline energy (physical advection—waves) and diverse hydrocarbon-degrading microorganisms consortium were found to increase spilled oil degradation in marine environments. In contrast, higher initial oil concentration and seawater pressure can lower oil degradation rates. There is limited information on the influences of seawater pH and salinity on oil degradation, thus warranting additional research. This comprehensive review can be used as a guide for bioremediation modeling and mitigating future oil spill pollution in the marine environment by utilizing the bacteria adapted to certain conditions.

Indium lung is an occupational lung disease caused by exposure to indium-tin-oxide (ITO) dust. Compared to other occupational lung diseases, indium lung has a shorter latency period and the respiratory status continues to worsen even after exposure to the work environment improves. Paraseptal emphysema which affects mainly the subpleural area is seen on chest images obtained via computed tomography (CT), regardless of the smoking history. However, the pathogenesis of emphysema in indium lung is still unclear. Therefore, we re-evaluated the pathology of three previously reported cases of indium lung. Paraseptal emphysema was observed in both smokers and nonsmokers. Obstructive respiratory impairment worsened over time in the cases with paraseptal emphysema. Many alveolar walls were destroyed independent of the presence or absence of emphysetamous changes or fibrosis. Moreover, bronchiolitis was found to be less common in indium lung than in asbestosis (the most common occupational lung disease) or common cases of chronic obstructive pulmonary disease caused by smoking. It has been shown that ITO causes protease anti-protease imbalance, oxidant-antioxidant imbalance, and continuous, abnormal inflammation (the three major causes of emphysema). In addition, nano-sized ITO is less likely to be trapped in the upper airways and may easily reach the subpleural alveoli. Furthermore, ITO may continue to cause sustained tissue injury at the alveolar level potentially resulting in emphysema. Further studies are needed to elucidate the detailed pathogenesis of indium lung by comparing it with other occupational lung diseases. [ABSTRACT FROM AUTHOR]

Co3O4 was synthesized on carbon paper (CP) using a facile method to improve electrochemical nitrate-toammonia conversion efficiency. The resulting Co3O4-CP electrode demonstrated an exceptional Faradaic efficiency of almost 100% across a broad range of application conditions, with a peak NH3 yield of 3.43 mmol h-1 cm-2 (2.25 mol gCo-1 h-1). [ABSTRACT FROM AUTHOR]

The presence of progesterone receptor (PR) and PR isoform B (PRB) in breast cancer is generally correlated with better clinical outcomes. Additionally, the significance of hormone-independent effects of PR/PRB correlated with better prognosis has been reported in non-small cell lung cancer (NSCLC). However, the detailed mechanism of that still remains unclear. In this study, we examined how microRNAs (miRNAs) could contribute to tumor inhibition via PR/PRB expression, in order to find miRNAs that have tumoragnostic effects between breast cancer and NSCLC. We obtained miRNA data using human tissues of breast cancer and NSCLC from The Cancer Genome Atlas (TCGA) database and PCR array from NSCLC patients of our cohort. Subsequently, we examined the function of the miRNA through in vitro study using breast cancer cell lines. As a result, only let-7b expression was significantly correlated with PR expression in both cancers. Additionally, the expression of let-7b significantly inhibited cell proliferation by inducing PR and PRB expression in breast cancer cell lines. However, the positive correlation of let-7b and PRB required a mediated factor, E2 promoter binding factor 1 (E2F1), obtained from TCGA database analysis. In vitro experiments showed that let-7b significantly inhibited E2F1, and E2F1 significantly inhibited PRB. This study revealed that PRB inhibits the proliferation of breast cancer cells by the let-7b-E2F1 interaction. In addition, the immunohistochemical analysis in NSCLC was also consistent with these in vitro data. Our results could contribute to developing novel therapeutic strategies for patients with PR/PRB-positive cancer by targeting let-7b or PRB expression in breast cancer and possibly NSCLC. [ABSTRACT FROM AUTHOR]

Arabidopsis halleri ssp. gemmifera is classified as Cd and Zn hyperaccumulator plant; however, the disparity accumulation preferences in organs (root, stem and leaves) between cadmium and zinc seems less understandable. Therefore, this study aimed to portray accumulation behaviour toward the presence of Cd and Zn in the hydroponic method employing A. halleri ssp. gemmifera. The experiment was conducted by applying this plant using 2 and 300 µM of Cd, and 2 and 200 µM Zn, together with 20% Hoagland solution for 7 days, separately. The results showed that Zn in the medium was uptake faster than Cd. Furthermore, increasing Cd/Zn supply at the medium resulted in an increasing accumulation of Cd/Zn in the organs of the plant. In both Cd treatments, the accumulation followed the order of stem>root>leaves, indicating Cd transportation to the upper part has occurred during this period. The same accumulation preference pattern was also reported in the 200 µM Zn supply. However, at 2 µM Zn supply, Zn accumulation was mainly found in the leaves, followed by the root and stem. A. halleri ssp. gemmifera uptake Zn faster from the medium and translocate rapidly to the leaves at low-level Zn supply. Increasing Zn supply concentration might inhibit the translocation of Zn from stem to leaves. Meanwhile, regardless of Cd supply concentrations, this plant could only translocate Cd to the stem mostly within a short-time exposure period. Therefore, this study concluded that A. halleri ssp. gemmifera exhibited different accumulation responses when exposed to different Cd and Zn supply concentrations. [ABSTRACT FROM AUTHOR]

This study focuses on how to solve cadmium (Cd) contamination in soil because this contaminant decreases soil quality. Soil remediation using the hyperaccumulator plants is an optional process to solve soil contamination. Arabidopsis halleri ssp. gemmifera (hereinafter referred to as A. halleri), is one of the candidate plants expected to be used for phytoremediation of Cd contaminated soil. The A. halleri promote solubilization of Cd in the soil directly or indirectly using its secreted root exudate. However, the effect of the metabolites profile of this plant to Cd uptake from contaminated soil is still unclear. The purpose of this study was to examine the contribution of root exudates of A. halleri to extract Cd in the soil. Cd-contaminated soil used in this study was a farmland soil containing 5.8 mg kg-1 of Cd and 648 mg kg-1 of Zn taken from Tome City, Miyagi Prefecture, Japan. Soil leaching tests were conducted using the solution containing the root exudates from A. halleri plant. The accelerating effect of root exudates of A. halleri on solubilization of Cd is fundamental information to construct the benefit of phytoremediation. [ABSTRACT FROM AUTHOR]

As shown in our previous studies, the intratrachealadministration of STC1 (stanniocalcin-1) ameliorates pulmonary fibrosis by reducing oxidative and endoplasmic reticulum stress through the uncoupling of respiration in a bleomycin-treated mouse model. However, the overall effect of STC1 on metabolism was not examined. Therefore, we first conducted a comprehensive metabolomics analysis to screen the overall metabolic changes induced by STC1 in an alveolar epithelial cell line using capillary electrophoresis time-of-flight mass spectrometry. The results were subsequently validated in multiple alveolar epithelial and fibroblast cell lines by performing precise analyses of each substance. STC1 stimulated glycolysis, acetyl-CoA synthesis, and the methionine and cysteine-glutathione pathways, which are closely related to the uncoupling of respiration, modulation of epigenetics, and reduction in oxidative stress. These results are consistent with our previous study. Subsequently, we focused on the inhibitory factor SMAD7, which exerts an antifibrotic effect and is susceptible to epigenetic regulation. STC1 upregulates SMAD7 in an uncoupling protein 2-dependent manner, induces demethylation of the SMAD7 promoter region and acetylation of the SMAD7 protein in human alveolar epithelial and fibroblast cell lines and a bleomycin-treated mouse model, and subsequently attenuates fibrosis. The antifibrotic effects of STC1 may partially depend on the regulation of SMAD7. In the evaluation using lung tissue from patients with idiopathic pulmonary fibrosis, SMAD7 expression and acetylation were high in the alveolar structure-preserving region and low in the fibrotic region. The intratracheal administration of STC1 may prevent the development of pulmonary fibrosis by regulating the metabolism-mediated epigenetic modification of SMAD7 in patients. [ABSTRACT FROM AUTHOR]