Facile synthesis of MoS2@red phosphorus heterojunction for synergistically photodynamic and photothermal therapy of renal cell carcinoma.

The therapy of the clear cell renal cell carcinoma (ccRCC) is crucial for the human healthcare due to its easy metastasis and recurrence, as well as resistance to radiotherapy and chemotherapy. In this work, we propose the synthesis of MoS2@red phosphorus (MoS2@RP) heterojunction to induce synergistic photodynamic and photothermal therapy (PDT/PTT) of ccRCC. The MoS2@RP heterojunction exhibits enhanced spectra absorption in the NIR range and produce local heat-increasing under the NIR laser irradiation compared with pure MoS2 and RP. The high photocatalytic activity of the MoS2@RP heterojunction contributes to effective transferring of the photo-excited electrons from the RP to MoS2, which promotes the production of various types of radical oxygen species (ROS) to kill the ccRCC cells. After the NIR irradiation, the MoS2@RP can effectively induce the apoptosis in the ccRCC cells through localized hyperthermia and the generation of ROS, while exhibiting low cytotoxicity towards normal kidney cells. In comparison to MoS2, the MoS2@RP heterojunction shows an approximate increase of 22 % in the lethality rate of the ccRCC cells and no significant change in toxicity towards normal cells. Furthermore, the PDT/PTT treatment using the MoS2@RP heterojunction effectively eradicates a substantial number of deep-tissue ccRCC cells in vivo without causing significant damage to major organs. This study presents promising effect of the MoS2@RP heterojunction-based photo-responsive therapy for effective ccRCC treatment.

Prognostic nomogram to predict cancer-specific survival with small-cell carcinoma of the prostate: a multi-institutional study.

Objective: The aim of this study is to examine the predictive factors for cancer-specific survival (CSS) in patients diagnosed with Small-Cell Carcinoma of the Prostate (SCCP) and to construct a prognostic model. Methods: Cases were selected using the Surveillance, Epidemiology, and End Results (SEER) database. The Kaplan-Meier method was utilized to calculate survival rates, while Lasso and Cox regression were employed to analyze prognostic factors. An independent prognostic factor-based nomogram was created to forecast CSS at 12 and 24 months. The model's predictive efficacy was assessed using the consistency index (C-index), calibration curve, and decision curve analysis (DCA) in separate tests. Results: Following the analysis of Cox and Lasso regression, age, race, Summary stage, and chemotherapy were determined to be significant risk factors (P < 0.05). In the group of participants who received training, the rate of 12-month CSS was 44.6%, the rate of 24-month CSS was 25.5%, and the median time for CSS was 10.5 months. The C-index for the training cohort was 0.7688 ± 0.024. As for the validation cohort, it was 0.661 ± 0.041. According to the nomogram, CSS was accurately predicted and demonstrated consistent and satisfactory predictive performance at both 12 months (87.3% compared to 71.2%) and 24 months (80.4% compared to 71.7%). As shown in the external validation calibration plot, the AUC for 12- and 24-month is 64.6% vs. 56.9% and 87.0% vs. 70.7%, respectively. Based on the calibration plot of the CSS nomogram at both the 12-month and 24-month marks, it can be observed that both the actual values and the nomogram predictions indicate a predominantly stable CSS. When compared to the AJCC staging system, DCA demonstrated a higher level of accuracy in predicting CSS through the use of a nomogram. Conclusion: Clinical prognostic factors can be utilized with nomograms to forecast CSS in Small-Cell Carcinoma of the Prostate (SCCP).

Time trends in surgical provision and cancer-specific outcomes in patients with stage T2-3 kidney cancer: a SEER-based study.

Background and objective: Surgery is the primary therapy that crucially affects the survival of patients with kidney cancer (KC). However, pertinent surgical decision criteria for individuals with stage T2-3 KC are lacking. This study aimed to display the practical choices and evolving trends of surgical procedures and elucidate their implied value. Methods: Through the Surveillance, Epidemiology, and End Results (SEER) dataset, the levels and evolving trends of different surgical methods were examined to determine cancer-specific risk of death (CSRD). Additionally, stratification analysis and survival rate analysis were performed to explore the effectiveness of partial nephrectomy (PN). Results: In this study, 9.27% of patients opted for PN. Interestingly, an upward trend was observed in its decision, with an average annual percentage change (AAPC) of 7.0 (95% CI: 4.8-9.3, P < 0.05). Patients who underwent PN and were in a relatively less severe condition exhibited more favorable CSRD levels (0.17-0.36 vs. 0.50-0.67) and an improvement trend compared with those who underwent radical nephrectomy (RN) (AAPC: -1.9 vs. -0.8). Further analysis showed that the levels of CSRD and survival rates for patients opting for different surgical methods followed a similar pattern. Conclusions: This study showed that RN was still the most common surgical method. Patients with stage T2-3 KC had an increasing preference for PN and exhibited more favorable cancer-related survival outcomes, which underscores the need for further investigation and validation.

Vaporization phosphorization-mediated synthesis of phosphorus-doped TiO2 nanocomposites for combined photodynamic and photothermal therapy of renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is a disease with high incidence and poor prognosis. The conventional treatment involves radiotherapy and chemotherapy, but chemotherapeutic agents are often associated with side effects, i.e., cytotoxicity to nontumor cells. Therefore, there is an urgent need for the development of novel therapeutic strategies for ccRCC. We synthesized spherical P/TiO2 nanoparticles (P/TiO2 NPs) by vaporization phosphorization (VP). X-ray photoelectron spectroscopy (XPS) and ultraviolet-visible diffuse reflectance spectroscopy (UV-Vis DRS) analyses confirmed that the anatase TiO2 surface was successfully doped with phosphorus and produced a large number of oxygen vacancies (OV). Serving as a photosensitizer, P/TiO2 NPs not only extended the photoresponse range to the near-infrared II region (NIR II) but also introduced a donor energy level lower than the TiO2 conduction band, narrowing the band gap, which could facilitate the migration of photogenerated charges and trigger the synergistic treatment of photodynamic therapy (PDT) and photothermal therapy (PTT). During NIR irradiation in vitro, the P/TiO2 NPs generated local heat and various oxygen radicals, including 1O2, ˙O2-, H2O2, and ˙OH, which damaged the ccRCC cells. In vivo, administration of the P/TiO2 NPs + NIR reduced the tumor volume by 80%, and had the potential to inhibit tumor metastasis by suppressing intratumor neoangiogenesis. The P/TiO2 NPs showed superior safety and efficacy relative to the conventional chemotherapeutic agent used in ccRCC treatment. This study introduced an innovative paradigm for renal cancer treatment, highlighting the potential of P/TiO2 NPs as safe and effective nanomaterials and presenting a compelling new option for clinical applications in anticancer therapy.

[Estimation and Critical Source Area Identification of Non-point Source Pollution Based on Improved Export Coefficient Models: A Case Study of the Upper Beiyun River Basin].

Non-point source pollution(NSP) poses a great threat to water ecosystem health. The quantitative estimation of spatial distribution characteristics and accurate identification of critical source areas(CSAs) of NSP are the basis for its efficient and accurate control. The export coefficient model(ECM) has been widely used to assess NSP, but this model should be improved because it ignores pollutant loss in transport processes. In this study, the ECM, which refines the physical transport processes of pollutants through quantifying the loss rate of pollutants in runoff, sediment, and infiltration, was improved to assess NSP and identify CSAs. The simulation accuracy among Johnes ECM, frequent ECM, and improved ECM were analyzed, and the effects of the three models on the simulation results of both spatial distribution characteristics and CSAs were explored. The study showed that:① the simulation error of the improved ECM(-6.79%) was significantly lower than that of the Johnes ECM(50.44%) and the frequent ECM(-84.01%), and this improved ECM increased the simulation accuracy of NSP. ② The spatial distribution characteristics and CSAs of NSP obtained from Johnes, frequent, and improved ECMs were significantly different, and the simulation results of improved ECM were more consistent with the spatial characteristics of NSP in the watershed. The NSP was high in the southeast and low in the northwest of the basin, and the NSP mainly came from urban and cultivated land. ③ Based on the improved ECM, the CSAs of NSP in the basin were mainly distributed in Changping, Shahe, Shigezhuang, the north of Wenquan, and the west of Malianwa Street, accounting for 6.71% of the area. This study can provide an effective tool and scientific reference for the assessment and control of NSP in data-limited regions.

Optimal layout design of groundwater pollution monitoring network using parameter iterative updating strategy-based ant colony optimization algorithm.

The scientific layout design of the groundwater pollution monitoring network (GPMN) can provide high quality groundwater monitoring data, which is essential for the timely detection and remediation of groundwater pollution. The simulation optimization approach was effective in obtaining the optimal design of the GPMN. The ant colony optimization (ACO) algorithm is an effective method for solving optimization models. However, the parameters used in the conventional ACO algorithm are empirically adopted with fixed values, which may affect the global searchability and convergence speed. Therefore, a parameter-iterative updating strategy-based ant colony optimization (PIUSACO) algorithm was proposed to solve this problem. For the GPMN optimal design problem, a simulation-optimization framework using PIUSACO algorithm was applied in a municipal waste landfill in BaiCheng city in China. Moreover, to reduce the computational load of the design process while considering the uncertainty of aquifer parameters and pollution sources, a genetic algorithm-support vector regression (GA-SVR) method was proposed to develop the surrogate model for the numerical model. The results showed that the layout scheme obtained using the PIUSACO algorithm had a significantly higher detection rate than ACO algorithm and random layout schemes, indicating that the designed layout scheme based on the PIUSACO algorithm can detect the groundwater pollution occurrence timely. The comparison of the iteration processes of the PIUSACO and conventional ACO algorithms shows that the global searching ability is improved and the convergence speed is accelerated significantly using the iteration updating strategy of crucial parameters. This study demonstrates the feasibility of the PIUSACO algorithm for the optimal layout design of the GPMN for the timely detection of groundwater pollution.

Review of machine learning-based surrogate models of groundwater contaminant modeling.

Heavy computational load inhibits the application of groundwater contaminant numerical model to groundwater pollution source identification, remediation design, and uncertainty analysis, since a large number of model runs are required for these applications. Machine learning-based surrogate models are an effective approach to enhance the efficiency of the numerical models, and have recently attracted considerable attention in the field of groundwater contaminant modeling. Here, we review 120 research articles on machine learning-based surrogate models for groundwater contaminant modeling that were published between 1994 and 2022. We outline the state of the art method, identify the most significant research challenges, and suggest potential future directions. The six major applications of machine learning-based surrogate models are groundwater pollution source identification, groundwater remediation design, coastal aquifer management, uncertainty analysis of groundwater, groundwater monitoring network design, and groundwater transport parameters inversion. Together, these account for more than 90% of the studies we review. Latin hypercube sampling (LHS) is the most widely used sampling method, and artificial neural networks (ANNs) and Kriging are the two most widely used methods for constructing surrogate model. No method is universally superior, the advantages and disadvantages of different methods, as well as the applicability of these methods for different application purposes of groundwater contaminant modeling were analyzed. Some recommendations on the method selection for various application fields are given based on the reviews and experiences. Based on our review of the state-of-the-art, we suggest several future research directions to enhance the feasibility of the machine learning-based surrogate models of groundwater contaminant modeling: the alleviation of the curse of dimensionality, enhancing transferability, practical applications for real case studies, multi-source dada fusion, and real-time monitoring and prediction.

An immune cell atlas reveals the dynamics of human macrophage specification during prenatal development.

Macrophages are heterogeneous and play critical roles in development and disease, but their diversity, function, and specification remain inadequately understood during human development. We generated a single-cell RNA sequencing map of the dynamics of human macrophage specification from PCW 4-26 across 19 tissues. We identified a microglia-like population and a proangiogenic population in 15 macrophage subtypes. Microglia-like cells, molecularly and morphologically similar to microglia in the CNS, are present in the fetal epidermis, testicle, and heart. They are the major immune population in the early epidermis, exhibit a polarized distribution along the dorsal-lateral-ventral axis, and interact with neural crest cells, modulating their differentiation along the melanocyte lineage. Through spatial and differentiation trajectory analysis, we also showed that proangiogenic macrophages are perivascular across fetal organs and likely yolk-sac-derived as microglia. Our study provides a comprehensive map of the heterogeneity and developmental dynamics of human macrophages and unravels their diverse functions during development.

The PRX-1/TLR4 axis promotes hypoxia-induced radiotherapy resistance in non-small cell lung cancer by targeting the NF-κB/p65 pathway.

Hypoxic lung cancer cells are highly resistant to radiation. Peroxiredoxin-1 (PRX-1), a transcriptional coactivator that enhances the DNA-binding activity of serum reactive factor, has been identified as a target for radiotherapy sensitization, but the underlying molecular mechanism remains unclear. This study aimed to investigate the influence of PRX-1 on radiotherapy sensitivity in hypoxic tumors. Hypoxic lung cancer cells exhibited radiotherapy-resistant phenotypes after irradiation, including increased proliferation, DNA damage repair, cell migration, invasion and stemness. Radio-resistant hypoxic lung cancer cells showed high expression levels of PRX-1. Furthermore, we observed that PRX-1 bound to the promoter region of TRL4 (-300 to -600) and promoted its transcription and expression and that PRX-1/TRL4 activated the NF-κB/p65 signaling pathway. Increased radiotherapy resistance of hypoxic lung cancer cells increased their ability to proliferate, migrate, and maintain stemness in vivo and in vitro. These findings suggest that PRX-1/TRL4 could be used as a target for the treatment of radiotherapy-resistant lung cancer cells and further provide a theoretical basis for the clinical treatment of hypoxic lung cancer cells.

Metronomic capecitabine inhibits liver transplant rejection in rats by triggering recipients' T cell ferroptosis.

BACKGROUND: Capecitabine (CAP) is a classic antimetabolic drug and has shown potential antirejection effects after liver transplantation (LT) in clinical studies. Our previous study showed that metronomic CAP can cause the programmed death of T cells by inducing oxidative stress in healthy mice. Ferroptosis, a newly defined non-apoptotic cell death that occurs in response to iron overload and lethal levels of lipid peroxidation, is an important mechanism by which CAP induces cell death. Therefore, ferroptosis may also play an important role in CAP-induced T cell death and play an immunosuppressive role in acute rejection after trans-plantation. AIM: To investigate the functions and underlying mechanisms of antirejection effects of metronomic CAP. METHODS: A rat LT model of acute rejection was established, and the effect of metronomic CAP on splenic hematopoietic function and acute graft rejection was evaluated 7 d after LT. In vitro, primary CD3+ T cells were sorted from rat spleens and human peripheral blood, and co-cultured with or without 5-fluorouracil (5-FU) (active agent of CAP). The levels of ferroptosis-related proteins, ferrous ion concentration, and oxidative stress-related indicators were observed. The changes in mito-chondrial structure were observed using electron microscopy. RESULTS: With no significant myelotoxicity, metronomic CAP alleviated graft injury (Banff score 9 vs 7.333, P < 0.001), prolonged the survival time of the recipient rats (11.5 d vs 16 d, P < 0.01), and reduced the infiltration rate of CD3+ T cells in peripheral blood (6.859 vs 3.735, P < 0.001), liver graft (7.459 vs 3.432, P < 0.001), and spleen (26.92 vs 12.9, P < 0.001), thereby inhibiting acute rejection after LT. In vitro, 5-FU, an end product of CAP metabolism, induced the degradation of the ferritin heavy chain by upregulating nuclear receptor coactivator 4, which caused the accumulation of ferrous ions. It also inhibited nuclear erythroid 2 p45-related factor 2, heme oxygenase-1, and glutathione peroxidase 4, eventually leading to oxidative damage and ferroptosis of T cells. CONCLUSION: Metronomic CAP can suppress acute allograft rejection in rats by triggering CD3+ T cell ferroptosis, which makes it an effective immunosuppressive agent after LT.

Competing risk models versus traditional Cox models for prognostic factors' prediction and care recommendation in patients with advanced laryngeal squamous carcinoma: a population-based study.

PURPOSE: To explore the prognostic factors and the optimal treatment modalities for patients with stage IVA laryngeal squamous cell carcinoma (LSCC), so as to improve the survival rate of patients. METHODS: Patients with stage IVA LSCC between 2004 and 2019 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. We used competing risk models to build nomograms for predicting cancer-specific survival (CSS). The effectiveness of the model was assessed using the calibration curves and the concordance index (C-index). The above results were compared with the nomogram established by Cox regression analysis. The patients were grouped into low-risk and high-risk groups by competing risk nomogram formula. And the Kaplan-Meier (K-M) method and log-rank test were used to make sure that these groups had a survival difference. RESULTS: Overall, 3612 patients were included. Older age, black race, a higher N stage, a higher pathological grade, and a larger tumor size were independent risk factors for CSS; married marital status, total/radical laryngectomy, and radiotherapy were protective factors. The C-index was 0.663, 0.633, and 0.628 in the train set and 0.674, 0.639, and 0.629 in the test set of the competing risk model, and 0.672, 0.640, and 0.634 in the traditional Cox nomogram for 1, 3, and 5 years. In overall survival and CSS, the prognosis of the high-risk group was poorer than that of the low-risk group. CONCLUSION: For patients with stage IVA LSCC, a competing risk nomogram was created to help screen risk population and guide clinical decision-making.

Directional Torsion Sensor Based on a Two-Core Fiber with a Helical Structure.

A fiber-optic torsion sensor based on a helical two-core fiber (HTCF) is proposed and experimentally demonstrated for simultaneously measuring torsion angle and torsion direction. The sensor consists of a segment of HTCF and two single-mode fibers (SMFs) forming a Mach-Zehnder interferometer (MZI). The helical structure is implemented by pre-twisting a 1 cm long two-core fiber (TCF). The performance of the sensor with pre-twisted angles of 180°, 360°, and 540° is experimentally analyzed. The results show that the sensor can realize the angular measurement and effectively distinguish the torsion direction. It is worth noting that the sensor has maximum sensitivity when the pre-twist angle is 180 degrees. The obtained wavelength sensitivities of torsion and temperature are 0.242 nm/(rad/m) and 32 pm/°C, respectively. The sensor has the advantages of easy fabrication, low cost, compact structure, and high sensitivity, which is expected to yield potential applications in fields where both torsion angle and direction measurements are required.

Development and In Vivo Evaluation of a Novel Vitamin D3 Oral Spray Delivery System.

Developing drugs that are highly selective to host tissues but are the least toxic remains one of the most difficult challenges in cancer treatment. Recent studies have shown that tumor cells from a variety of sources can express vitamin D3 receptors and that the response to vitamin D3 and its analogs is prone to growth arrest and cell death. However, conventional vitamin D3 drug formulations lack dose control and cannot target specific cells or tissues. The aim of this study was to prepare vitamin D3 nanospray for inhalation delivery route. This study evaluated the physical properties of the formulation (particle size distribution and biological stability), the total number of sprays per bottle, the spray volume per spray, and the loading variance of the spray. The optimized vitamin D3 spray formula is easy to spray, has fewer drips, and has a fast drying time. It can be stored for 3 months at 37 ± 2 °C temperature, 75 ± 5% relative humidity, and away from light, and can maintain biological stability. This study showed that compared with traditional nasal sprays, the spray has a larger fan angle (82.1 degrees) and beam width (104.88 mm), more symmetrical spray on both sides of the spray column, a faster coverage of the administration site, and a wider range, which is suitable for inhalation delivery routes.

Risk factors, survival analysis, and nomograms for distant metastasis in patients with primary pulmonary large cell neuroendocrine carcinoma: A population-based study.

Introduction: Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rapidly progressive and easily metastatic high-grade lung cancer, with a poor prognosis when distant metastasis (DM) occurs. The aim of our study was to explore risk factors associated with DM in LCNEC patients and to perform survival analysis and to develop a novel nomogram-based predictive model for screening risk populations in clinical practice. Methods: The study cohort was derived from the Surveillance, Epidemiology, and End Results database, from which we selected patients with LCNEC between 2004 to 2015 and formed a diagnostic cohort (n = 959) and a prognostic cohort (n = 272). The risk and prognostic factors of DM were screened by univariate and multivariate analyses using logistic and Cox regressions, respectively. Then, we established diagnostic and prognostic nomograms using the data in the training group and validated the accuracy of the nomograms in the validation group. The diagnostic nomogram was evaluated using receiver operating characteristic curves, decision curve analysis curves, and the GiViTI calibration belt. The prognostic nomogram was evaluated using receiver operating characteristic curves, the concordance index, the calibration curve, and decision curve analysis curves. In addition, high- and low-risk groups were classified according to the prognostic monogram formula, and Kaplan-Meier survival analysis was performed. Results: In the diagnostic cohort, LCNEC close to bronchus, with higher tumor size, and with higher N stage indicated higher likelihood of DM. In the prognostic cohort (patients with LCNEC and DM), men with higher N stage, no surgery, and no chemotherapy had poorer overall survival. Patients in the high-risk group had significantly lower median overall survival than the low-risk group. Conclusion: Two novel established nomograms performed well in predicting DM in patients with LCNEC and in evaluating their prognosis. These nomograms could be used in clinical practice for screening of risk populations and treatment planning.

Transport stress induces innate immunity responses through TLR and NLR signaling pathways and increases mucus cell number in gills of hybrid yellow catfish (Tachysurus fulvidraco ♀ × Pseudobagrus vachellii ♂).

Transport stress poses a threat to most teleost fish in production, causing mass losses to the aquaculture industry. Fish gills are a mucosa-associated lymphoid tissue in direct contact with water, and they represent an ideal tissue type to study mechanisms of transport stress. In this study, hybrid yellow catfish (Tachysurus fulvidraco ♀ × Pseudobagrus vachellii ♂) were exposed to simulated transport stress for 16 h and then allowed to recover for 96 h. Gill tissues and blood samples were collected at 0 h, 2 h, 4 h, 8 h, and 16 h of transport stress and after 96 h of recovery, as well as from fish in a control group at the same sampling times. The activities of alkaline phosphatase, acid phosphatase, and superoxide dismutase and the total antioxidant capacity first increased and then decreased during the 16 h transport treatment. Exposure to 16 h of transport stress resulted in decreased serum triglyceride and total cholesterol contents, increased serum glucose content, increased activities of alanine aminotransferase and aspartate transaminase, and more mucus cells, compared with the control group. Transcriptome analysis revealed differential expression of 1525 genes (803 down-regulated and 722 up-regulated) between the control and 16 h transportation groups. Functional analyses revealed that the differentially expressed genes were enriched in immune response, signal transduction, and energy metabolism pathways. We found that tlr5, tnfɑ, hsp90ɑ, il-1ß, map2k4, il12ba were clearly up-regulated and arrdc2, syngr1a were clearly down-regulated following 8 h and/or 16 h simulated transport after qRT-PCR validation. These findings suggested that Toll- and NOD-like receptor signaling pathways potentially mediate transport stress. Transport stress altered innate immunity responses and energy use in the gill tissues of hybrid yellow catfish. After 96 h of recovery, only alanine aminotransferase and alkaline phosphatase activities and the number of mucus cells had returned to control levels. We speculate that for juvenile yellow catfish to recover to a normal state, a recovery period of more than 96 h is required after 16 h of transportation. These results provide new perspectives on the immune response of yellow catfish under transport stress and theoretical support for future optimization of their transportation.

COX-2/sEH Dual Inhibitor PTUPB Attenuates Epithelial-Mesenchymal Transformation of Alveolar Epithelial Cells via Nrf2-Mediated Inhibition of TGF-ß1/Smad Signaling.

Background: Arachidonic acid (ARA) metabolites are involved in the pathogenesis of epithelial-mesenchymal transformation (EMT). However, the role of ARA metabolism in the progression of EMT during pulmonary fibrosis (PF) has not been fully elucidated. The purpose of this study was to investigate the role of cytochrome P450 oxidase (CYP)/soluble epoxide hydrolase (sEH) and cyclooxygenase-2 (COX-2) metabolic disorders of ARA in EMT during PF. Methods: A signal intratracheal injection of bleomycin (BLM) was given to induce PF in C57BL/6 J mice. A COX-2/sEH dual inhibitor PTUPB was used to establish the function of CYPs/COX-2 dysregulation to EMT in PF mice. In vitro experiments, murine alveolar epithelial cells (MLE12) and human alveolar epithelial cells (A549) were used to explore the roles and mechanisms of PTUPB on transforming growth factor (TGF)-ß1-induced EMT. Results: PTUPB treatment reversed the increase of mesenchymal marker molecule α-smooth muscle actin (α-SMA) and the loss of epithelial marker molecule E-cadherin in lung tissue of PF mice. In vitro, COX-2 and sEH protein levels were increased in TGF-ß1-treated alveolar epithelial cells (AECs). PTUPB decreased the expression of α-SMA and restored the expression of E-cadherin in TGF-ß1-treated AECs, accompanied by reduced migration and collagen synthesis. Moreover, PTUPB attenuated TGF-ß1-Smad2/3 pathway activation in AECs via Nrf2 antioxidant cascade. Conclusion: PTUPB inhibits EMT in AECs via Nrf2-mediated inhibition of the TGF-ß1-Smad2/3 pathway, which holds great promise for the clinical treatment of PF.