Toxicology and applied pharmacology最新文献

{"title":"Lung microbiota metabolite L-malic acid attenuates the airway inflammation in asthma by inhibiting ferroptosis","authors":"Lishan Lin ,&nbsp;Danhui Huang ,&nbsp;Haohua Huang ,&nbsp;Lingyan Xie ,&nbsp;Yi Huang ,&nbsp;Cuiping Ye ,&nbsp;Lanhe Chu ,&nbsp;Yujie Qiao ,&nbsp;Xiaojing Meng ,&nbsp;Shaoxi Cai ,&nbsp;Hangming Dong","doi":"10.1016/j.taap.2025.117396","DOIUrl":"10.1016/j.taap.2025.117396","url":null,"abstract":"<div><div>Inhaled environmental allergens, such as house dust mites (HDM), have been shown to induce an inflammatory reaction, tissue injury, and increased airway sensitivity in the lungs, ultimately leading to the development of allergic asthma. The imbalance of respiratory microbiota and metabolites plays a crucial role in the progression of allergic asthma. However, there is limited knowledge available regarding the alterations in respiratory microbiota and metabolites and their impact on the host in the context of asthma. The aim of this study was to investigate the potential pathways involved in the development of asthma through the analysis of lung flora and metabolites. A mouse model of house dust mite (HDM)-induced asthma was established, and alveolar lavage samples were collected for microbiome 16S rRNA sequencing and untargeted metabolic analysis. Microbiological analyses indicated a significant alteration in the microbiota after 4 and 6 weeks of HDM nebulisation stimulation. This was characterized by a decrease in microbial diversity, as well as reductions in the relative proportion of <em>Gallionella</em> and <em>Lactobacillus</em>. Conversely, the abundance of <em>Flavobacterium</em> and <em>Ralstonia</em> increased in the HDM4W and HDM6W groups, respectively. Metabolomic analyses revealed seven distinct metabolites, among them L-malic acid, which were linked to signaling pathways in a mouse model of HDM-induced asthma. The correlation analysis demonstrated a positive association between L-malic acid and <em>Rhodanobacter</em> and <em>Nocardioides</em>. L-malic acid was discovered to be efficacious in reducing airway inflammation in mice with house dust mite-induced asthma. Further analysis revealed that this change was linked to lipid peroxidation and changes in ferroptosis markers, namely GPX4 and FTH. These findings suggest that L-malate inhibits ferroptosis. However, the introduction of ferroptosis inducers, such as Erastin, was observed to negate the beneficial effect of butyrate. In summary, this research implies that the respiratory microbiota metabolite L-malic acid lessens airway inflammation in asthma by inhibiting ferroptosis, offering a potential approach for managing asthma.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"500 ","pages":"Article 117396"},"PeriodicalIF":3.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144089733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “FOXO3a reactivation mediates the synergistic cytotoxic effects of rapamycin and cisplatin in oral squamous cell carcinoma cells” [Toxicology and Applied Pharmacology 251 (2011) 8–15]","authors":"Liang Fang ,&nbsp;Huiming Wang ,&nbsp;Lin Zhou ,&nbsp;Da Yu","doi":"10.1016/j.taap.2025.117397","DOIUrl":"10.1016/j.taap.2025.117397","url":null,"abstract":"","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"501 ","pages":"Article 117397"},"PeriodicalIF":3.3,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic arsenic exposure of ovarian surface and fallopian tube cultures induces giant and/or multinucleated cells with phagocytosis-like properties and an inflammatory phenotype","authors":"Cristina M. Andrade-Feraud ,&nbsp;Arlet M. Acanda de la Rocha ,&nbsp;Noah E. Berlow ,&nbsp;Santiago Duque ,&nbsp;Alexander Velazco ,&nbsp;Diego Castillo ,&nbsp;Baylee Holcomb ,&nbsp;Ebony R. Coats ,&nbsp;Yasmin R. Ghurani ,&nbsp;Catherine M. Lucey ,&nbsp;Brandon Pearson ,&nbsp;Tomás R. Guilarte ,&nbsp;Diana J. Azzam","doi":"10.1016/j.taap.2025.117394","DOIUrl":"10.1016/j.taap.2025.117394","url":null,"abstract":"<div><div>Chronic exposure to arsenic, a toxic metalloid frequently found in groundwater and food, represents a significant environmental health risk and has been implicated in the etiology of several cancers, including ovarian cancer. However, the precise pathways through which arsenic exerts its toxic impact on the ovary are not fully understood. This study investigates the impact of chronic arsenic exposure at environmentally relevant concentrations (75 ppb or μg/L) on primary human ovarian surface (OCE1) and fallopian tube (FNE1) cultures derived from the same donor. These heterogeneous cultures provide a unique, human-relevant platform to investigate how chronic arsenic exposure influences distinct cell types within a shared microenvironment. Prolonged arsenic exposure induced significant cytotoxicity and promoted the formation of giant and/or multinucleated cells in both cultures. These cells exhibited phagocytosis-like properties, actively engulfing apoptotic debris. Transcriptomic analyses and pathway enrichment revealed robust activation of pro-inflammatory signaling, notably the canonical NF-κB pathway. This was marked by nuclear translocation of the NF-κB p65 subunit and elevated expression and secretion of pro-inflammatory cytokines, including TNFα, IL-6, and IL-8, driving a sustained inflammatory response. Moreover, arsenic-exposed cells displayed persistent DNA damage, as indicated by increased γ-H2AX foci, accompanied by nuclear structural alterations and elevated expression of cancer stem cell markers, including OCT2, CD133, and ALDH1. These findings suggest that arsenic-induced inflammation and genomic instability converge to promote a tumor-supportive microenvironment, highlighting the potential role of chronic arsenic exposure in ovarian carcinogenesis, particularly in the context of inflammation-driven carcinogenesis.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"500 ","pages":"Article 117394"},"PeriodicalIF":3.3,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144071873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Screening of oxidative stress components of cigarette smoke based on machine learning model integration","authors":"Yuxin Hong ,&nbsp;Jiayu Lv ,&nbsp;Yuxuan Hong ,&nbsp;Jiahao Wang ,&nbsp;Xuhao Huang ,&nbsp;Chao Chen","doi":"10.1016/j.taap.2025.117387","DOIUrl":"10.1016/j.taap.2025.117387","url":null,"abstract":"<div><div>Cigarette smoke, a complex mixture of more than 7000 chemicals, poses a significant threat to human health, with oxidative stress being an important mechanism in its associated diseases. Traditional methods for assessing the toxicity of cigarette smoke components, such as animal and cell-based assays, are often limited by their high cost and time consumption. This study integrates multiple machine learning algorithms and diverse data sources to construct a robust predictive model for identifying oxidative stress-inducing components in cigarette smoke. Utilizing a multi-dataset, multi-target and multi-algorithm modeling strategy, we developed an integrated model comprising 704 sub-models. These models were trained from 9 datasets related to reactive oxygen species (ROS)-associated pathways. The integrated model demonstrated better performance in external validation compared to individual models, predicting 974 ROS-positive components from 7111 cigarette smoke components. These components were clustered into 10 major classes, providing new insights into the structural diversity of oxidative stress-inducing components in cigarette smoke. Our findings offer a novel approach for enhancing the predictive capability of toxicity models and advancing the understanding of oxidative stress-related toxicity in cigarette smoke components.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"500 ","pages":"Article 117387"},"PeriodicalIF":3.3,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143942420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of tungsten in modulating DNA double-strand break repair and class switch recombination","authors":"Rowa Bakadlag ,&nbsp;Hsiang Chou ,&nbsp;Cynthia Guilbert ,&nbsp;Vincent M. Luo ,&nbsp;Alexandre Orthwein ,&nbsp;Koren K. Mann","doi":"10.1016/j.taap.2025.117392","DOIUrl":"10.1016/j.taap.2025.117392","url":null,"abstract":"<div><div>Tungsten, a transition metal with widespread applications, is increasingly recognized as an environmental contaminant with potential health impacts. While tungsten exposure has been previously associated with increased DNA damage, its specific effects on DNA repair mechanisms remain poorly understood. Here, we found that tungsten alone did not induce DNA damage <em>in vitro</em>, as assessed by γ-H2AX phosphorylation. However, tungsten exacerbated DNA double-strand breaks induced by genotoxic agents, delayed γ-H2AX resolution, and induced cell cycle arrest. Mechanistically, GFP-based reporter assays revealed that tungsten impairs both homologous recombination (HR) and non-homologous end joining (NHEJ), which coincided with reduced recruitment of critical repair proteins, including BRCA1, 53BP1, and ATM at DSB sites. To assess functional consequences of impaired DNA repair due to tungsten exposure, we examined immunoglobulin (Ig) class switch recombination (CSR), a critical antibody diversification process reliant on the repair of DSBs. Using the CH12F3 B cell line, we showed that tungsten significantly impaired cytokine stimulated-CSR from IgM to IgA without affecting cell proliferation or activation-induced cytidine deaminase (<em>Aicda</em>) expression. Furthermore, <em>ex vivo</em> activation of splenic B cells confirmed that tungsten exposure inhibits CSR from IgM to IgG1, independent of cell proliferation. Together, these data indicate that tungsten exposure impairs canonical DSB repair pathways and CSR, highlighting the potential consequences for immune function upon environmental or occupational exposure to tungsten.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"500 ","pages":"Article 117392"},"PeriodicalIF":3.3,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144027970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integration of computational models to predict botanical phytochemical constituent clearance routes by the Extended Clearance Classification System (ECCS)","authors":"Yitong Liu ,&nbsp;Michael Lawless ,&nbsp;Amy L. Roe ,&nbsp;Stephen S. Ferguson","doi":"10.1016/j.taap.2025.117385","DOIUrl":"10.1016/j.taap.2025.117385","url":null,"abstract":"<div><div>The Extended Clearance Classification System (ECCS) is a framework that predicts a chemical's predominant rate-determining clearance route: metabolism, hepatic uptake, or renal clearance. The ECCS prediction is based upon molecular weight, ionization state, and membrane permeability, which could be predicted by quantitative structure-activity relationship (QSAR) models. The ECCS also indicates potential chemical interactions via drug-metabolizing enzymes and transporters. This study used the ECCS to evaluate phytochemical constituents and predicted drug-metabolizing enzyme and transporter pathways to understand botanical clearance in humans. First, 82 phytochemical constituents were classified into six ECCS classes based on QSAR-predicted properties. Next, constituents in classes 1A and 2 were further explored as potential substrates for 18 drug-metabolizing enzymes followed by predictions for hepatic clearance, while constituents in classes 3 and 4 leveraged predictions for glomerular filtration and renal transporters. Finally, potential interactions between phytochemical constituents and drugs were discussed. Results showed that more than half of the phytochemical constituents were in ECCS class 2, whose Phase I metabolism were predicted to be predominantly mediated by CYP3A4, CYP2D6, and CYP1A2. Additionally, over 20 % of the phytochemical constituents fell into ECCS class 4, which were predicted to be predominantly cleared in unchanged forms by glomerular filtration and active renal secretion by OAT1/3 or OCT2. Classes 1A and 2 compounds exhibit high interaction potential via CYPs, while classes 3 and 4 compounds have relatively low potential for renal uptake transporter mediated interactions. This study represents a data-driven framework for exploring and contextualizing botanical constituent information to inform safety evaluations.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"500 ","pages":"Article 117385"},"PeriodicalIF":3.3,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144049976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harnessing FDA-approved dipyridamole to inhibit NLRP3 inflammasome and improve outcomes of acute lung injury in sepsis","authors":"Xiuhui Chen ,&nbsp;Yutong Zheng ,&nbsp;Xiaofeng Zhang ,&nbsp;Anran Zheng ,&nbsp;Junjun Huang ,&nbsp;Guoliang Deng ,&nbsp;Xuna Wu ,&nbsp;Yuying Peng ,&nbsp;Xiaoling Zhang ,&nbsp;Renshan Chen ,&nbsp;Qing Xiao ,&nbsp;Weijun Ye","doi":"10.1016/j.taap.2025.117383","DOIUrl":"10.1016/j.taap.2025.117383","url":null,"abstract":"<div><div>Aberrant activation of the NLRP3 inflammasome is critically involved in sepsis-induced acute lung injury (ALI), with inhibition of this pathway emerging as a promising therapeutic approach. This study identifies Dipyridamole, an FDA-approved drug, as a novel inhibitor of the NLRP3 inflammasome. Mechanistically, Dipyridamole suppresses mitochondrial ROS release and directly interacts with NEK7, thereby preventing its association with NLRP3 and impeding inflammasome complex assembly. In an LPS-induced sepsis model, Dipyridamole significantly ameliorated ALI, reduced inflammatory responses, and improved survival rates in model mice. Additionally, Dipyridamole effectively inhibited NLRP3 inflammasome activation in lung tissue. These findings position Dipyridamole as a potent NLRP3 inflammasome inhibitor with substantial therapeutic potential for managing sepsis-induced ALI.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"500 ","pages":"Article 117383"},"PeriodicalIF":3.3,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143936899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the effects of Tempol on oxidative stress and angiotensin-II induced hypertension in mice exposed to nicotine from electronic and tobacco cigarettes","authors":"Wael A. Alanazi ,&nbsp;Yazeed Alqudayri ,&nbsp;Faleh Alqahtani ,&nbsp;Fawaz Alasmari ,&nbsp;Doaa M. El-Nagar","doi":"10.1016/j.taap.2025.117386","DOIUrl":"10.1016/j.taap.2025.117386","url":null,"abstract":"<div><div>Electronic cigarette (<em>E</em>-Cig) is commonly used as an alternative to tobacco cigarette (T-Cig), as it lacks many of the toxicants present in T-Cigs. However, the toxicological mechanisms underlying <em>E</em>-Cig-induced hypertension are not yet well understood. The goal of this research was to explore the effects of Tempol in reducing hypertension caused by T-Cig and <em>E</em>-Cig exposure by mitigating oxidative stress and regulating angiotensin-II production in mouse models subjected to T-Cig and <em>E</em>-Cig smoke. Male C57BL/6 J mice were assigned to eight distinct groups: Air, Air + Tempol, T-Cig, T-Cig + Tempol, NIC-free <em>E</em>-Cig, NIC-free E-Cig + Tempol, E-Cig, and E-Cig + Tempol. Mice exposed to smoking for 12 min per hour, 6 cycles/day, 7 days/week for 4 weeks. Blood pressure was monitored, and Angiotensin-II and cGMP levels were measured using ELISA. Oxidative stress markers (GPx, GSTA1, SOD, MDA, nitrite) were assessed by RT-PCR and biochemical assays. The collected data showed a weight loss with high blood pressure and vasoconstriction in the T-Cig and <em>E</em>-Cig groups. Results showed an induction of angiotensin-II, GPx, GSTA1, SOD, and MDA. In contrast, cGMP and nitrite levels were reduced in the T-Cig and <em>E</em>-Cig groups. Tempol treatment regulated oxidative stress markers, angiotensin-II and cGMP levels, leading to a significant reduction in blood pressure. The results indicate that Tempol is essential in reducing oxidative stress and the effects of angiotensin-II caused by T-Cig and <em>E</em>-Cig exposure, thereby contributing to the regulation of systemic hemodynamic function.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"500 ","pages":"Article 117386"},"PeriodicalIF":3.3,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143948148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Flavor-induced inflammation and cytotoxicity in human aortic smooth muscle cells: Potential implications for E-cigarette safety","authors":"Mariam Bitar ,&nbsp;Clément Mercier ,&nbsp;Laurent Bertoletti ,&nbsp;Jérémie Pourchez ,&nbsp;Valérie Forest","doi":"10.1016/j.taap.2025.117388","DOIUrl":"10.1016/j.taap.2025.117388","url":null,"abstract":"<div><div>Electronic nicotine delivery systems (ENDS), commonly known as e-cigarettes, are considered safer alternatives to tobacco smoking, yet their long-term health effects, particularly on cardiovascular health, remain unclear. The aim of this study was to investigate the cytotoxic and pro-inflammatory effects of device power, nicotine content and flavor molecules on human aortic smooth muscle cells. AoSMCs cells were exposed to e-liquids and e-cigarette aerosol condensates containing different ratios of propylene glycol (PG) and vegetable glycerin (VG), nicotine (0, 10, 20 mg/mL), and flavors (cinnamon, menthol, tobacco), with the devices operated at different power levels (10 W, 15 W, 25 W). After a 24 h incubation, cytotoxicity was evaluated using lactate dehydrogenase (LDH) release, while pro-inflammatory effects were measured by interleukin-8 (IL-8) production. The results showed no significant cytotoxicity or inflammation in cells exposed to PG/VG base or nicotine-containing e-liquids. However, e-liquids as well as aerosol condensates containing flavors induced significant increases in IL-8 production compared to controls without flavor. Moreover, the pro-inflammatory response was more pronounced in response to aerosol condensates than to the corresponding e-liquids. Cinnamon, in particular, produced the highest inflammatory response, and the effect was enhanced at higher power settings (25 W), which also induced cytotoxicity, particularly at high concentrations. These findings demonstrate that flavors, especially cinnamon, and device power levels are key factors influencing the inflammatory potential and cytotoxicity of e-cigarette aerosols. Further studies are needed to explore the long-term cardiovascular risks associated with ENDS use and the role of flavor molecules and of their thermal degradation products.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"500 ","pages":"Article 117388"},"PeriodicalIF":3.3,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potent and highly selective inhibition of selpercatinib towards UDP-glucuronosyltransferase 1A4 (UGT1A4) isoform","authors":"Yueyi Liu ,&nbsp;Xin Lv ,&nbsp;Hang Yin ,&nbsp;Lili Jiang","doi":"10.1016/j.taap.2025.117393","DOIUrl":"10.1016/j.taap.2025.117393","url":null,"abstract":"<div><div>Selpercatinib is a potent and highly selective Rearranged during Transfection (RET) kinase inhibitor for patients with RET fusion-positive thyroid cancer and non-small-cell lung cancer. The present study aims to investigate the inhibitory effects of selpercatinib towards human UDP-glucuronosyltransferases (UGTs), and assess its risk for drug-drug interactions (DDIs) via UGT inhibition. The inhibition of selpercatinib towards 12 recombinant human UGT isoforms were measured. Our data demonstrated that selpercatinib exhibited highly selective inhibition towards UGT1A4. Enzyme kinetic study indicated that selpercatinib competitively inhibited the activity of UGT1A4, with a <em>K</em>_i value of 1.57 ± 0.14 μM. The quantitative prediction of DDIs risk indicated that the co-administration of selpercatinib with UGT1A4 substrate might trigger clinically significant DDIs. Additional caution should be taken to avoid unexpected DDIs when selpercatinib and other UGT1A4 substrates are combined.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"500 ","pages":"Article 117393"},"PeriodicalIF":3.3,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}