Archives of Toxicology最新文献

{"title":"PFC/PFAS concentrations in human milk and infant exposure through lactation: a comprehensive review of the scientific literature.","authors":"Neus González, Jose L Domingo","doi":"10.1007/s00204-025-03980-x","DOIUrl":"https://doi.org/10.1007/s00204-025-03980-x","url":null,"abstract":"<p><p>Per- and polyfluoroalkyl substances (PFAS), previously known as perfluorinated compounds (PFC), are a group of synthetic chemicals widely used over the past decades. Their extensive application, combined with their environmental persistence, has contributed to their ubiquitous presence in the environment and the associated toxicological risks. Regarding humans, blood serum testing remains the primary method for biomonitoring PFAS exposure, while breast milk has also been used due to the transfer of these substances from mothers to infants during lactation. This paper aims to review the scientific literature (using PubMed and Scopus databases) on PFAS concentrations in the breast milk of non-occupationally exposed women. Where available, the estimated daily intake of these compounds by breastfeeding infants is also examined. The reviewed studies are categorized by continent and country/region, revealing a significant lack of data for many countries, including both developed and developing nations. The findings indicate substantial variability in PFAS concentrations, influenced by factors such as geographic location, sampling year, and the specific PFAS analyzed. Among the identified compounds, perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are most commonly detected, along with perfluorohexanesulfonic acid (PFHxS) and perfluorononanoic acid (PFNA), being the only PFAS with regulated maximum levels in certain foodstuffs. Most studies were conducted before the implementation of the current (updated) tolerable weekly intake (TWI) values for these substances. Consequently, the majority reported a low health risk for breastfeeding infants, even in high-intake scenarios. Nevertheless, biomonitoring studies are urgently needed in countries with limited or no data, and new investigations should assess whether current estimated intakes exceed the updated TWI. Special focus should be given to rural and industrial areas where exposure levels remain poorly understood.</p>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476093","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":"Development of human growth hormone-treated chimeric mice with humanized livers for an evaluation model of drug-induced fatty liver disease.","authors":"Sho Morioka, Seigo Sanoh, Yuji Ishida, Suzue Furukawa, Yuko Ogawa, Yaichiro Kotake, Chise Tateno","doi":"10.1007/s00204-025-03986-5","DOIUrl":"https://doi.org/10.1007/s00204-025-03986-5","url":null,"abstract":"<p><p>Chimeric mice with humanized livers were used to evaluate drug-induced liver injury (DILI). However, lipid accumulation is observed in the human hepatocytes of chimeric mice because of human growth hormone deficiency (GHD), which is an obstacle in the evaluation of drug-induced fatty liver disease (DIFLD), a common type of DILI. Previously, we showed that lipid droplets were reduced by the administration of human growth hormone (h-GH) to chimeric mice. Although h-GH administration reduces the lipid droplets, an optimal h-GH treatment method for assessing DIFLD has not yet been developed. This study investigated the appropriate h-GH dosage required to reduce lipid droplets and reproduce physiological conditions in humans. Moreover, the LXR agonist TO901317 was administered to h-GH-treated chimeric mice to evaluate the new h-GH treatment's effectiveness for DIFLD assessment. The results in blood h-GH levels, oil-red O liver sections, and gene expression levels in the liver suggested that 0.25 mg/kg/day would be an appropriate h-GH dosage to reduce lipid droplets and reproduce human physiological condition. At this dose, TO901317-induced lipid accumulation and lipid synthesis-related gene expression in humanized livers in a dose-dependent manner, suggesting that this new mouse model could be useful for evaluating human DIFLD. In summary, the administration of h-GH at an appropriate dosage regulated lipid homeostasis in the humanized livers of chimeric mice and h-GH-administered chimeric mice may represent a highly sensitive evaluation model for human DIFLD. The study also suggests a correlation between GH levels and lipid metabolism, potentially related to conditions like GHD and aging.</p>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466723","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":"Octamethylcyclotetrasiloxane (D4) lacks endocrine disruptive potential via estrogen pathways.","authors":"Christopher J Borgert, Lyle D Burgoon","doi":"10.1007/s00204-024-03896-y","DOIUrl":"https://doi.org/10.1007/s00204-024-03896-y","url":null,"abstract":"<p><p>Octamethylcyclotetrasiloxane (D4) is a volatile, highly lipophilic monomer used to produce silicone polymers found in many consumer products and used widely in industrial applications and processes. Many reviews of the toxicology of D4 conclude that its adverse effects on endocrine-sensitive endpoints occur by a MoA dependent on systemic toxicity rather than one mediated via endocrine activity, but others identify D4 as an estrogenic endocrine disruptive chemical (EDC) based on results of screening-level assays indicating that D4 interacts with ERα and at high doses, affects estrogen-sensitive endpoints in rodents. To resolve these divergent interpretations, we tested two specific hypotheses related to the interaction of D4 with estrogen receptor-alpha subtype (ERα) at the biochemical and molecular levels of biological organization and a third specific hypothesis related to estrogenic and anti-estrogenic pathways at the physiological level. At the physiological level, we used an established WoE methodology to evaluate all data relevant to estrogen agonist and antagonist activity of D4 by examining its effects on ERα-relevant endpoints in rodent toxicology studies. At the biochemical level, we calculated whether D4 could produce a functionally significant change in the ERα occupancy by 17β-estradiol (E2) using equations well-established in pharmacology. For these calculations, we used data on the potency and kinetics of D4 from studies in rats as well as published potency and affinity data on endogenous estrogens and their circulating concentrations in humans. At the molecular level, we used established molecular docking techniques to evaluate the potential for D4 and related chemicals to fit within and to activate or block the binding pocket of ERα. Our analyses indicate that the estrogenic effect of D4 is molecularly, biochemically, and physiologically implausible, which corroborates previous evaluations of D4 that concluded it is not an estrogenic endocrine disruptor. The claim that D4 exhibits estrogenic endocrine disruptive properties based on a presumed link between the results of screening-level assays (RUA and ERTA) and adverse effects is not supported by the data and relies on deficient evaluative and interpretative methods. Instead, a plausible mechanistic explanation for the various adverse effects of D4 observed in rodent studies, including its effects in reproduction studies, is that these are secondary to high-dose-dependent, physico-chemical effects that perturb cell membrane function and produce rodent-specific sensory irritation.</p>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456527","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":"Targeting MLKL ameliorates T-2 toxin-induced cartilage damage by inhibiting chondrocyte death and matrix degradation in mice.","authors":"Meng Zhang, Xiaoru Zhao, Yue Liu, Yinan Liu, Yawen Shi, Ying Zhang, Jinghong Chen","doi":"10.1007/s00204-025-03966-9","DOIUrl":"https://doi.org/10.1007/s00204-025-03966-9","url":null,"abstract":"<p><p>T-2 toxin is the most toxic mycotoxin found in contaminated food and animal feed that threatens health. Exposure to T-2 toxin causes cartilage damage and leads to joint disorders, but the mechanisms underlying T-2 toxin-induced cartilage damage remain unclear. The results showed that T-2 toxin-induced chondrocyte death in articular cartilage from rats fed T-2 toxin (200 ng/g b.w./day) caused a significant increase in phosphorylated receptor-interacting protein 3 (p-RIPK3) and phosphorylated mixed lineage kinase-like protein (p-MLKL). In vitro studies showed that T-2 toxin (48 ng/mL) reduced the viability of C-28/I2 chondrocytes, increased cell apoptosis, and significantly upregulated the expression of p-MLKL. The results suggest that chondrocyte necroptosis is involved in T-2 toxin-induced cartilage damage. Furthermore, necrostatin-1 (Nec-1), a necroptosis inhibitor, significantly attenuated T-2 toxin-induced cell death and the increase of p-MLKL. Further studies showed that mlkl^-/- mice suppressed T-2 toxin-induced chondrocyte death, and mlkl^-/- mice upregulated T-2 toxin-induced proteoglycan content and type II collagen reduction in mouse articular cartilage, and reduced increased matrix metalloproteinase-13 expression. Besides, the p-RIPK3 and p-MLKL were significantly increased in the articular cartilage of KBD patients. This study highlights the role of RIPK3/MLKL-mediated necroptosis in T-2 toxin-induced articular cartilage damage. Inhibition of MLKL alleviates T-2 toxin-induced cartilage damage by reducing chondrocyte death and matrix degradation in mice. These results suggest a potential therapeutic target for mitigating T-2 toxin-induced cartilage damage.</p>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447745","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":"The role of NLRP3 inflammasome activation in proinflammatory and cytotoxic effects of metal nanoparticles.","authors":"Michael Aschner, Anatoly V Skalny, Airton C Martins, Yousef Tizabi, Irina P Zaitseva, Abel Santamaria, Rongzhu Lu, Yordanka Y Gluhcheva, Alexey A Tinkov","doi":"10.1007/s00204-025-03972-x","DOIUrl":"https://doi.org/10.1007/s00204-025-03972-x","url":null,"abstract":"<p><p>Exposure to metal nanoparticles (NPs) is known to induce inflammatory responses in various tissues, thus limiting their therapeutic potential. NOD-like receptor protein 3 (NLRP3) inflammasome activation is an essential component of innate immunity playing a significant role in inflammation and development of inflammatory diseases. Therefore, the objective of the present review was to summarize data on the role of NLRP3 inflammasome in proinflammatory effects induced by metal NPs, and to discuss the underlying molecular mechanisms, including its dependence on the physical and chemical properties of metal NPs. Titanium, zinc, silver, aluminum, iron, cobalt, nickel, vanadium, and tungsten nanoparticles, as well as metal-based quantum dots have all been shown to induce NLRP3 inflammasome activation in vitro in macrophages and monocytes, dendritic cells, keratinocytes, hepatocytes, enterocytes, microglia, astrocytes, lung epithelial cells, endotheliocytes, as well as certain types of cancer cells. In vivo studies confirmed the role of NLRP3 pathway activation in development of colitis, pulmonary inflammation, liver damage, osteolysis, and neuroinflammation induced by various metal nanoparticles. Briefly, particle endocytosis with subsequent lysosomal damage, induction of ROS formation, K⁺ efflux, increased intracellular Ca²⁺ levels, and NF-κB pathway activation results in NLRP3 inflammasome complex assembly, caspase-1 activation, and cleavage of pro-IL-1β and pro-IL-18 to mature proinflammatory cytokines, while gasdermin D cleavage induces pyroptotic cell death. Moreover, small-sized and rod-shaped metal NPs exert a more profound stimulatory effect on NLRP3 inflammasome activation, but contrary findings have also been reported. Taken together, it is concluded that NLRP3 inflammasome may mediate both adverse proinflammatory effects of metal nanoparticles, as well as their beneficial effect when used as antitumor agents.</p>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439754","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":"Unanticipated differences in the rat plasma metabolome of genistein and daidzein.","authors":"Gina Montoya, Bennard van Ravenzwaay, Walburga Seefelder, Volker Haake, Hennicke Kamp","doi":"10.1007/s00204-025-03967-8","DOIUrl":"https://doi.org/10.1007/s00204-025-03967-8","url":null,"abstract":"<p><p>Genistein (GEN) and daidzein (DAI) are soy isoflavones known to bind to estrogen receptors. Overall health effects of GEN and DAI in humans exhibit a dual nature, presenting both health benefits and concerns related to their interaction with the estrogen receptor. The metabolomes of these isoflavones were determined in 28-day oral studies in male and female Wistar rats to elucidate (1) metabolites changes, (2) compare their metabolomes with other compounds and (3) identify toxicological modes of action (MoA). Dose levels for GEN were 1000 and 300 mg/kg bw by gavage and 1000 and 300 ppm (via diet). DAI gavage dose levels were 1000 and 100 mg/kg bw. Results were evaluated using the MetaMap^®Tox data base. Both compounds demonstrated metabolome profiles which were associated with estrogenic profiles and compounds, predominantly in females. However, the metabolomes were compound specific with relatively few common metabolite changes. There were no relevant matches between any GEN and any DAI treatment group indicating that both compounds are substantially different from metabolome perspective. Ranking of the metabolome patters for GEN and DAI with ≥ 1000 compounds in the MetaMap^®Tox database revealed correlations with estrogenic and other hormonally active compounds. GEN-treated females correlated best with Cabergoline, a dopamine D2 receptor agonist, DAI females with tamoxifen and diethylstilbestrol, suggesting that even their estrogenic activity may be different. Beyond estrogenic effects, the high dose (HD) DAI metabolome indicated altered fatty acid metabolism associated with PPAR-alpha activation. For GEN, there was an indication of ethanolamine-like liver effects. Dose levels without estrogenic effects for GEN were 1000 and 100 mg/kg bw for males and females respectively, there were no estrogenic effects in the feeding studies. For DAI males, the no estrogenic effect level was 300 mg/kg bw, for females < 100 mg/kg bw, suggesting that DAI may be a more potent estrogen than GEN in rats.</p>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424912","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":"Obituary: Eugenio Vilanova.","authors":"Carmen Estevan, Jorge Estévez, Miguel A Sogorb","doi":"10.1007/s00204-025-03977-6","DOIUrl":"https://doi.org/10.1007/s00204-025-03977-6","url":null,"abstract":"","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424872","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":"Bridging imaging-based in vitro methods from biomedical research to regulatory toxicology.","authors":"Monica Piergiovanni, Milena Mennecozzi, Erio Barale-Thomas, Davide Danovi, Sebastian Dunst, David Egan, Aurora Fassi, Matthew Hartley, Philipp Kainz, Katharina Koch, Sylvia E Le Dévédec, Iris Mangas, Elena Miranda, Jo Nyffeler, Enrico Pesenti, Fernanda Ricci, Christopher Schmied, Alexander Schreiner, Nadine Stokar-Regenscheit, Jason R Swedlow, Virginie Uhlmann, Fredrik C Wieland, Amy Wilson, Maurice Whelan","doi":"10.1007/s00204-024-03922-z","DOIUrl":"https://doi.org/10.1007/s00204-024-03922-z","url":null,"abstract":"<p><p>Imaging technologies are being increasingly used in biomedical research and experimental toxicology to gather morphological and functional information from cellular models. There is a concrete opportunity of incorporating imaging-based in vitro methods in international guidelines to respond to regulatory requirements with human relevant data. To translate these methods from R&D to international regulatory acceptance, the community needs to implement test methods under quality management systems, assess inter-laboratory transferability, and demonstrate data reliability and robustness. This article summarises current challenges associated with image acquisition, image analysis, including artificial intelligence, and data management of imaging-based methods, with examples from the developmental neurotoxicity in vitro battery and phenotypic profiling assays. The article includes considerations on specific needs and potential solutions to design and implement future validation and transferability studies.</p>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405223","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":"A benchmark concentration-based strategy for evaluating the combined effects of genotoxic compounds in TK6 cells.","authors":"Julie Sanders, Roel Anthonissen, George E Johnson, Tamara Vanhaecke, Birgit Mertens","doi":"10.1007/s00204-025-03971-y","DOIUrl":"https://doi.org/10.1007/s00204-025-03971-y","url":null,"abstract":"<p><p>Chemical risk assessment has historically focused on single compounds, neglecting the implications of combined exposures. To bridge this gap, several methodologies, such as concentration addition (CA) and independent action (IA), have been developed. However, a systematic, consistent, and integrated approach across various legislative frameworks is still lacking. The assessment of combined effects of genotoxicants is even more challenging, as genotoxicity data are typically evaluated qualitatively, without considering the effect size. This study aimed to develop a quantitative approach for evaluating the combined effects of genotoxic compounds with both similar and dissimilar modes of action (MoA), based on the benchmark concentration (BMC) principle. A proof-of-concept study was conducted using the in vitro micronucleus (MNvit) test to examine two types of binary mixtures: ethyl methanesulfonate (EMS) and methyl methanesulfonate (MMS), which share similar MoA, and MMS and etoposide (ETP), which have dissimilar MoA. The methodology involved collecting data for individual compounds, calculating BMC values, composing mixtures with different ratios and inducing various effect levels, testing these mixtures, and comparing the experimental results with the modelled data to verify additivity. The findings indicated that for both mixtures, the experimental responses aligned with the predicted additive effects, supporting the validity of the additivity principle. This study highlights the potential of an optimized BMC-based approach as a robust framework for testing chemical mixtures. It should be adopted in future studies to evaluate a wider range of genotoxic compounds, offering a more comprehensive and quantitative strategy for assessing combined chemical exposures.</p>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405219","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":"SIRT3 regulates PFKFB3-mediated glycolysis to attenuate cisplatin-induced ototoxicity both in vivo and in vitro.","authors":"Wei Tang, Shimin Zong, Peiyu Du, Xuan Yu, Ting Li, Bo Liu, Yu Zhong, Wenyang Lei, Wenting Yu, Hongjun Xiao","doi":"10.1007/s00204-025-03975-8","DOIUrl":"https://doi.org/10.1007/s00204-025-03975-8","url":null,"abstract":"<p><p>Cochlear hair cell death is the primary cause of cisplatin-induced ototoxicity, currently lacking widely applicable clinical methods for effective prevention and treatment. In this study, an in vivo cisplatin-induced ototoxicity model was established by intraperitoneal injection of 12 mg/kg cisplatin. We found that ablation of SIRT3 exacerbates cisplatin-induced hearing loss and cochlear hair cell damage. An in vitro cisplatin-induced ototoxicity model was established using 5 µM cisplatin in cochlear explants and OC-1 cells. We found that the absence of SIRT3 impairs cochlear hair cell glycolytic metabolism, leading to excessive accumulation of ROS and significant reduction in MMP levels, thereby promoting apoptosis. In contrast, overexpression of SIRT3 in OC-1 cells promotes cochlear hair cell survival and reduces cochlear hair cell apoptosis. Inhibition of PFKFB3 reduces glycolytic metabolism in OC-1 cells, and the protective effect conferred by SIRT3 overexpression is lost. In summary, the protective effect of SIRT3 may be mediated by the regulation of PFKFB3-dependent glycolysis and the mitigation of cisplatin-induced excessive ROS accumulation.</p>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405227","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}