Archives of Toxicology最新文献

{"title":"Ursolic acid: context-dependent redox activity on oxidative stress and its toxicological implications.","authors":"Ziwei Deng, Ruizhi Hu, Zhangzheng Yin, Shusong Wu, Jianhua He","doi":"10.1007/s00204-026-04569-8","DOIUrl":"https://doi.org/10.1007/s00204-026-04569-8","url":null,"abstract":"<p><p>Oxidative stress is a major contributor to xenobiotic-induced tissue injury, mitochondrial dysfunction, inflammation, ferroptosis, and carcinogenesis. Ursolic acid (UA), a naturally occurring pentacyclic triterpenoid, has emerged as a context-dependent regulator of redox homeostasis. This review summarizes current evidence regarding the dual effects of UA on oxidative stress and its toxicological implications. Under non-malignant conditions, UA generally exerts antioxidant and cytoprotective effects in the majority of experimental models examined. Reduced reactive oxygen species (ROS) accumulation, modulation of nuclear factor erythroid 2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1) signalin, preservation of mitochondrial homeostasis, and attenuation of inflammatory and apoptotic responses appear to underlie these protective activities. Protective effects have been reported in experimental models of hepatic, renal, cardiovascular, neurological, and radiation-associated injury. By contrast, in tumor cells characterized by elevated basal oxidative stress, UA has frequently been shown to exert pro-oxidative actions, though this response is influenced by concentration, exposure duration, and cellular context. In malignant models, UA has been shown to enhance ROS accumulation, disturb redox balance, suppress antioxidant defenses, and promote cell death associated with ferroptosis and apoptosis, thereby increasing sensitivity to chemotherapy and radiotherapy. Despite promising preclinical findings, several limitations continue to restrict clinical translation, including poor oral bioavailability, variable pharmacokinetics, potential herb-drug interactions, and insufficient long-term toxicological evaluation. Overall, current evidence supports UA as a context-dependent redox modulator with dual antioxidant and pro-oxidant activities, although further mechanistic, pharmacokinetic, and translational studies remain necessary.</p>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149103781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic role of fucoidans against oxidative stress: recent developments, translational challenges, and future directions.","authors":"Arduino A Mangoni, Barbara C Wimmer, Joel T Kidgell, Jai Meyers","doi":"10.1007/s00204-026-04572-z","DOIUrl":"https://doi.org/10.1007/s00204-026-04572-z","url":null,"abstract":"<p><p>It is increasingly recognized that redox injury, one of the most extensively studied processes in disease pathophysiology, pharmacology, and toxicology, is rarely explained by an indiscriminate excess of free radicals alone, but rather by a combination of macromolecular injury, maladaptive redox signaling, ferroptosis, and dysregulated inflammation and metabolism. This paradigm shift has revealed several limitations of traditional antioxidants, including a focus on scavenging effects, poor target engagement, unfavorable or uncertain pharmacokinetics, failure to reach specific subcellular compartments, and lack of robust biomarkers of response. Concomitantly, greater attention is currently being paid to natural compounds combining antioxidant, anti-inflammatory, and metabolic effects. Fucoidans, structurally diverse, fucose-rich, sulfated polysaccharides derived mainly from brown seaweeds, are emerging as promising candidates because they target multiple pathways relevant to oxidative injury, including activation of antioxidant systems, preservation of mitochondrial function, attenuation of ferroptosis, and modulation of gut-organ axes that amplify oxidative tissue damage. This review critically appraises studies conducted over the last ten years, with particular emphasis on newly identified mechanisms, quality of fucoidan characterization, disease-model relevance, and translational potential. Current evidence supports an antioxidant effect of fucoidans, particularly in diseases affecting the liver, kidneys, intestines, central nervous system, and skin/wound healing. However, translation is constrained by heterogeneity across source species, extraction, purification, molecular weight, and analytical reporting. Standardized chemistry, robust pharmacokinetic characterization, and comprehensive assessments of biomarkers of response and organ biology are required to validate the role of fucoidans in mitigating oxidative stress.</p>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149103717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glutathione in brain oxidative stress: from redox chemistry to clinical imaging.","authors":"Koji Aoyama","doi":"10.1007/s00204-026-04545-2","DOIUrl":"https://doi.org/10.1007/s00204-026-04545-2","url":null,"abstract":"<p><p>Glutathione (GSH), a tripeptide composed of glutamate, cysteine, and glycine, is the most abundant intracellular low-molecular-weight thiol and serves as a central regulator of cellular redox homeostasis. In addition to its well-established roles in antioxidant defense and detoxification, GSH is essential for maintaining mitochondrial function and cellular viability. Since its discovery more than a century ago, extensive research has progressively revealed the diverse biological functions of GSH. More recently, growing evidence from experimental and clinical studies has demonstrated that disruption of GSH homeostasis is a common feature of multiple neurodegenerative diseases. Because the central nervous system consumes large amounts of oxygen, contains abundant oxidizable lipids, and possesses limited regenerative capacity, maintenance of neuronal GSH homeostasis is indispensable for protecting the brain against oxidative injury. Recent advances have further demonstrated that neuronal GSH synthesis is tightly regulated through specialized mechanisms, including astrocyte-neuron metabolic coupling and excitatory amino acid carrier 1-dependent cysteine transport. This review summarizes the historical development of GSH research, current understanding of the molecular mechanisms regulating brain GSH homeostasis, and how these mechanisms are disrupted in major neurodegenerative diseases. Finally, we discuss promising therapeutic strategies aimed at restoring endogenous neuronal GSH homeostasis and highlight the potential of brain GSH as both a biomarker and therapeutic target for oxidative stress-related neurodegenerative diseases.</p>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149103795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polymyxin antibiotics induce nephrotoxicity through the selective inhibition of Complex I-dependent respiration in mouse and rat mitochondria.","authors":"Edgars Liepinsh, Valerija Meinardte, Kristaps Krims-Davis, Stanislava Korzh, Eduards Sevostjanovs, Helena Cirule, Maija Dambrova, Francesc Rabanal","doi":"10.1007/s00204-026-04566-x","DOIUrl":"https://doi.org/10.1007/s00204-026-04566-x","url":null,"abstract":"<p><p>Colistin and polymyxin B are last-resort antibiotics for the treatment of infections caused by multidrug-resistant Gram-negative bacteria; however, their clinical use is limited by considerable nephrotoxicity. Mitochondrial dysfunction has been proposed as one mechanism that contributes to polymyxin-induced kidney injury, but the precise mitochondrial target remains unclear. In the present study, we investigated the effects of colistin and polymyxin B on mitochondrial respiratory complexes. NMRI mice were treated subcutaneously with colistin or polymyxin B (20 mg/kg) every 8 h for a total of six times, which resulted in the accumulation of colistin and polymyxin B 29 and 40 μg/g kidney tissue, respectively. Both polymyxins increased the expression of markers of tubular damage up to 29-fold and induced mitochondrial dysfunction in the kidney. In in vitro experiments using mitochondria from intact kidneys, low concentrations of colistin inhibited Complex I-dependent respiration in the OXPHOS state, with an IC₅₀ of approximately 5 μg/mL. This effect was Complex I-specific because at 5 μg/mL, colistin and polymyxin B did not impair respiration supported by other respiratory chain complexes or compromise mitochondrial membrane integrity. Similar Complex I inhibition by polymyxins was detected in vitro in rat kidney mitochondria. In conclusion, our findings identify mitochondrial Complex I as a sensitive target of colistin and polymyxin B and suggest that inhibition of Complex I-dependent respiration is a key driver of polymyxin-induced nephrotoxicity. This mechanism provides a toxicological framework for understanding interactions between polycationic peptide antibiotics and mitochondrial respiration and may support the selection and optimisation of safer antimicrobial peptides.</p>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149103763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Applicability of NAMs to support a read-across based hazard assessment workflow for systemic toxicity: a conazole case study.","authors":"Barira Islam, Jenny Irwan, Lukas Wijaya, Bas Ter Braak, Amer Jamalpoor, Tamara Meijer, Clemence Budin, Tjalf de Boer, Shu Liu, Marlene Wedler, Baiba Gukalova, Edgars Liepins, Jaione Telleria, Laura Furlong, Guillame Ollitrault, Sam Davidse, Tessa M S Hagens, Sibel Bahtiri, Olivier Taboureau, Nadine Dreser, Philip Marx-Stoelting, Annika Järvinen, Per Artursson, Patrik Lundquist, Kathrin Bothe, Hennicke Kamp, Marcel Leist, Bob van de Water, Andrew White, Mirjam Luijten, Iain Gardner, Sylvia E Escher","doi":"10.1007/s00204-026-04554-1","DOIUrl":"https://doi.org/10.1007/s00204-026-04554-1","url":null,"abstract":"<p><p>This work explores the applicability of new approach methodologies (NAMs) using a read-across approach to predict systemic toxicity with liver as the critical target organ, and derive a point of departurefor the target compound (TC) difenoconazole. Eight conazoles were used as source compounds (SCs), alongside metabolites hydroxyitraconazole and 1,2,4-triazole. The case study was structured according to the Alternative Safety Profiling Algorithm (ASPA) workflow developed within the RISK-HUNT3R project. Hierarchical clustering using chemical fingerprints identified similarity of different SCs to the TC, supporting their inclusion in the read-across analysis. A broad screening panel of NAMs, including nuclear receptor reporter assays, ToxProfiler, Cell Painting PLUS, transcriptomics in primary human hepatocytes and H295R steroidogenesis assays, was used to characterize biological activity of the TC and SCs and to substantiate the structure-based read-across. In a first prediction round, the nearest neighbour quantitative read-across approach (based on allometrically-scaled human lowest-observed-adverse-effect levels (LOAELs) of the SC) was used to predict 6.57 mg/kg/day as the LOAEL of the TC. This closely aligned with the in vivo-based value of 4.88 mg/kg/day. In a second approach, data from NAMs were used to predict human equivalent dose (HED), and the respective LOAELs of SC and TC, based on physiologically based kinetic modelling with quantitative in vitro to in vivo extrapolation. The HED derived from NAMs was approximately ten-fold lower than the LOAELs from traditional approaches. This case study illustrates suitable (ASPA-guided) approaches as well as the toxicological applicability of a NAM-based read-across assessment to obtain safe/conservative estimates of toxicity.</p>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149103693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interpreting mitochondrial oxidative stress and ion-channel suppression by fentanyl analogues: considerations on experimental units and dose matching.","authors":"Xin Zhang, Yun Zhang","doi":"10.1007/s00204-026-04561-2","DOIUrl":"https://doi.org/10.1007/s00204-026-04561-2","url":null,"abstract":"","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149103769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Scientific perspectives on in vivo developmental neurotoxicity testing: study design, regulatory context, and future directions.","authors":"Pragati S Coder, Richard Lewis, Anika Christoffel, Phil Botham, Richard Bartlett, Megan D'souza, Colin Ehnes, Frank Faulhammer, Susann Fayyaz, Dilshan S Harischandra, Parvinder Kaur, Susanne N Kolle, Abby Li, Jason Manton, Benoît Nihoul, Heidrun Potschka, Emily Richmond, Martijn Rooseboom, Eddie Sloter, Lorna F Tempest, Abigail Toltin, Corina van den Heuvel, Matthew Wolter","doi":"10.1007/s00204-026-04564-z","DOIUrl":"10.1007/s00204-026-04564-z","url":null,"abstract":"<p><p>Developmental neurotoxicity (DNT) potential of (agro)chemicals is assessed in rodents according to OECD Test Guidelines (TG) 426 (DNT) or 443 (Extended One-Generation Reproductive Toxicity; EOGRTS) incorporating a DNT cohort. While the EOGRTS evaluates reproductive and neurotoxicity endpoints across multiple life stages, key differences in study design, dose selection, and exposure duration between OECD 426 and OECD 443 can complicate data interpretation and impact hazard identification and risk assessment. This manuscript evaluates current DNT testing strategies and examines the feasibility of a combined DNT-EOGRTS approach aimed at generating data for regulatory decision making. This combined approach requires substantial modifications to the EOGRTS design, and its implementation should be approached with caution. Given the increased complexity and logistical challenges, additional cognitive assessments such as learning and memory (L&M) should only be included when scientifically justified on a substance specific basis. Retrospective analyses indicate that L&M is among the least sensitive DNT endpoints, and its inclusion in an EOGRTS does not yield a functional equivalent of a standalone DNT. The review also examines regulatory triggers and recent regulatory decisions relevant to inclusion of cognitive assessments. Finally, the status and limitations of alternative approaches, including the in vitro DNT battery and zebrafish embryo models, are discussed. Overall, OECD 426 remains the scientifically preferred approach for DNT assessment. While a combined design may be feasible, it is inherently suboptimal for DNT evaluation. Collectively, this comprehensive review provides recommendations for generating robust DNT data while supporting animal welfare-conscious, future-oriented regulatory testing strategies.</p>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2026-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New approach methodologies for in vitro detection of chemical-induced cholestatic liver injury.","authors":"Amy Maerten, Alexandra-Costina Avîrvarei, Mathieu Vinken","doi":"10.1007/s00204-026-04541-6","DOIUrl":"https://doi.org/10.1007/s00204-026-04541-6","url":null,"abstract":"<p><p>Cholestasis is a pathological impairment of bile acid homeostasis resulting in accumulation of bile acids in the liver and systemic circulation. Cholestasis is of major concern, in particular in pharmaceutical industry, substantiating the need for human-relevant mechanistic screening tools to identify cholestatic liability early in the drug developmental pipeline. New approach methodologies (NAMs) centred around adverse outcome pathway (AOP) networks are promising tools in this respect. Leveraging human-relevant in vitro models integrated in a battery of activity-based in vitro assays allows to target specific key events along the cholestatic pathway. This approach not only enhances human relevance, but also provides deep mechanistic insights essential for human-relevant hazard assessment. The present paper focuses on the practical development of an AOP network-driven in vitro testing platform tailored for cholestatic hazard assessment. In a first part, the mechanistic foundation of cholestasis is discussed based on state-of-the-art toxicological knowledge. In a second part, a standardized workflow for NAM establishment is proposed, detailing the selection of human-relevant in vitro models, and a curated library of activity-based in vitro assays as well as reference chemicals, alongside optimized exposure parameters.</p>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2026-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early metabolic rewiring precedes arsenic-induced carcinogenesis in human lung epithelial cells.","authors":"Richard N Cassidy, Emily Seburn, Andrew Pyman, Wesley N Saintilnord, Shania Mittendorf, Youssef A Hegazy, Ryan D Sheldon, Darrell P Chandler, Yvonne N Fondufe-Mittendorf","doi":"10.1007/s00204-026-04555-0","DOIUrl":"https://doi.org/10.1007/s00204-026-04555-0","url":null,"abstract":"<p><p>Chronic, low-dose inorganic arsenic (iAs) exposure is a major environmental risk factor for lung cancer, yet the early cellular events that link low-dose exposure to carcinogenesis remain poorly understood. Because most people are exposed to iAs at low, chronic doses rather than acutely toxic levels, the metabolic events during this early window are especially relevant to human cancer risk. In this study, we investigated metabolic responses to non-cytotoxic, low-dose iAs exposure (0.5-2.0 µM) in human lung epithelial cells using short (48 h) and long (24-week) exposure models. Integrated transcriptomic and metabolomic analyses revealed that metabolic reprogramming begins within 48 h of exposure, characterized by increased glutathione synthesis, increased glycolysis, and triglyceride accumulation. The early adaptations mirrored the Warburg effect and dynamic lipid remodeling we observed in our chronic model of iAs exposure (0.5 µM). These findings indicate that iAs induces early metabolic rewiring that precedes cell transformation in human lung cells and suggest that low-dose iAs exposure may metabolically prime cells to support later oncogenic events and phenotypes. Metabolic networks underpinning the cellular response to iAs may therefore provide therapeutic targets for preventing or treating iAs-induced lung cancers.</p>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2026-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Linking acute exposure to future risk: an omics-to-AOP new approach method for next-generation risk assessment in a human in vitro lung air-liquid interface model.","authors":"Jack Morikka, Ada Taubert, Hanna-Kaarina Juppi, Giorgia Migliaccio, Zeyad Al-Abdulraheem, Lena Möbus, Sanna Peltola, Noora Perho, Maaret Vaani, Antonio Federico, Dario Greco","doi":"10.1007/s00204-026-04563-0","DOIUrl":"https://doi.org/10.1007/s00204-026-04563-0","url":null,"abstract":"<p><p>New approach methodologies (NAMs) are transforming chemical safety assessment by shifting focus from apical toxicity endpoints toward mechanistic, human-relevant prediction of adverse outcomes. Here, we present a human lung air-liquid interface (ALI) alveolar epithelial model coupled to an omics-to-adverse outcome pathway (AOP) analysis, linking acute sublethal exposure to potential long-term toxicity outcomes. A non-tumorigenic, monoclonal lung alveolar epithelial cell line (Arlo), capable of forming a tight monolayer barrier, was basolaterally exposed to sublethal concentrations (0, 20, 60, 100 µg/mL) of the profibrotic compound bleomycin. Dose-dependent modelling of transcriptomic signatures recapitulated known mechanisms of bleomycin-induced epithelial injury, consistent with early key events in fibrotic AOPs, enabling prediction of downstream adverse outcomes. The transcriptomic signature was overlayed on a network-based representation of human pulmonary fibrosis patient biopsies. When compared to a bleomycin exposed mouse lung model, the in vitro Arlo NAM performed comparably, especially for observing effects on extracellular matrix (ECM) restructuring in an acute exposure setting. Epigenomic profiling identified methylation changes associated with epithelial-mesenchymal transition (EMT), suggesting potential long-term gene expression regulation through epigenetic control. By linking functional endpoints with dose-response transcriptomic and epigenetic signatures, this work provides a reproducible schema for omics-to-AOP next-generation safety assessment and demonstrates that acute exposures can be modelled with a resource and time efficient NAM centred on toxicogenomics, informing on longer-term consequences.</p>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2026-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}