Current Research in Toxicology最新文献

{"title":"Effects of mineral fibres in an in vitro placental syncytiotrophoblast model","authors":"Giovanni Tossetta ,&nbsp;Sonia Fantone ,&nbsp;Antonio Domenico Procopio ,&nbsp;Armanda Pugnaloni ,&nbsp;Alessandro Francesco Gualtieri ,&nbsp;Daniela Marzioni","doi":"10.1016/j.crtox.2025.100231","DOIUrl":"10.1016/j.crtox.2025.100231","url":null,"abstract":"<div><div>It is known that mineral fibres can be found in placental tissues, but their effect is not known on these tissues. BeWo in vitro model of syncytiotrophoblast, the outer layer of maternal-foetal barrier, is necessary to understand if mineral fibres can alter placental cell turnover and consequently to influence the outcome of pregnancy. We performed in vitro experiments using chrysotile UICC (UICC), chrysotile Valmalenco (VM) and erionite (ERI) to investigate the potential cytotoxic effects of these mineral fibres on BeWo cells. We demonstrated that all fibres are toxic while only UICC fibres caused a DNA damage that the cells were not able to repair through RAD51 activity. In addition, we demonstrated that DNA replication is not altered while cyclin D1 showed a significant decrease in VM and UICC suggesting that the cell cycle is altered in G1 phase. Moreover, UICC increased active form of caspase 3 demonstrating that apoptosis can be induced in BeWo cells. We suggest that although morphological changes are not visible in BeWo cells treated with these mineral fibres, DNA damage can lead to altered placenta physiology that can be seen late when the damage at the foetal tissues has already occurred.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"8 ","pages":"Article 100231"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143747765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioinformatics study and cytotoxicity of several curcumin analogues in ovarian cancer","authors":"Retno Murwanti ,&nbsp;Ritmaleni ,&nbsp;Navista Sri Octa Ujiantari ,&nbsp;I Made Rhamandana Putra ,&nbsp;Aliffian Farhan Wahyudi ,&nbsp;Vigha Ilmanafi Arifka","doi":"10.1016/j.crtox.2025.100230","DOIUrl":"10.1016/j.crtox.2025.100230","url":null,"abstract":"<div><div>Ovarian cancer ranks as Indonesia’s third-leading cause of cancer-related death, emphasising the need for innovative treatments. This study combined bioinformatics, molecular docking, and experimental assays to tackle this challenge. We identified 166 ovarian cancer-related genes, with MYC standing out as a key target. Analysis of MYC mutations revealed prevalent alterations, though no significant survival differences were observed in patients with or without the mutations. Molecular docking pinpointed compound B155 as a promising MYC inhibitor. A preliminary cytotoxicity assay revealed compound B155′s notable activity, with an 87.19 % inhibition of cell viability at 50 μM. Most of the other curcumin analogues only caused more than 50 % inhibition at the same concentration. This result suggests alternative mechanisms of action, possibly antioxidant effects, warranting further exploration. In summary, this study unveiled MYC as a prime target for ovarian cancer treatment, with curcumin analogues like B155 showing potential. Nonetheless, the complex factors affecting cytotoxicity underscore the need for deeper investigation into these compounds’ mechanisms in ovarian cancer cells.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"8 ","pages":"Article 100230"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143747764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genotoxicity testing of the anthraquinone dye Alizarin Red S","authors":"Benedikt Bauer,&nbsp;Helena Rossi,&nbsp;Henning Hintzsche","doi":"10.1016/j.crtox.2024.100208","DOIUrl":"10.1016/j.crtox.2024.100208","url":null,"abstract":"<div><div>The anthraquinone dye Alizarin Red S (ARS) is used for marking live animals, specifically as a tool for monitoring the stock of the endangered European eel by marking caught fish with ARS before releasing the eels back into the wild. As ARS can be found in recaptured eels even years later, knowledge of potential health hazards of ARS is essential for assessing the food safety of eels marked with ARS. As the compound class of anthraquinones is known for their genotoxic and carcinogenic properties, concerns were raised regarding the food safety of marked eels. Up to now, no data for characterizing the hazard potential of ARS is available. In this study, we aimed at closing this data gap. We tested ARS in liver (HepG2), cervix (HeLa) and lymphoblast (TK-6) cells and identified HepG2 cells as the cell line most sensitive to ARS-induced cytotoxicity. We then investigated oxidative stress, DNA strand breaks, and micronucleus formation in these cells and did not observe effects at sub-cytotoxic concentrations.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"8 ","pages":"Article 100208"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of the gut microbiota and the nicotinate/nicotinamide pathway in rotenone-induced neurotoxicity","authors":"Yan Sai,&nbsp;Wei Ge,&nbsp;Li Zhong,&nbsp;Qifu Zhang,&nbsp;Jingsong Xiao,&nbsp;Yaohui Shan,&nbsp;Wenqi Ye,&nbsp;Haoyin Liu,&nbsp;Shulin Liu,&nbsp;Feng Ye,&nbsp;Xiaogang Wang,&nbsp;He Tang,&nbsp;Yuanpeng Zhao,&nbsp;Guorong Dan","doi":"10.1016/j.crtox.2024.100212","DOIUrl":"10.1016/j.crtox.2024.100212","url":null,"abstract":"<div><div>Rotenone is a natural compound from plants. It is widely used in pesticides because of highly toxic to insects and fish. However, lots of research has reported that rotenone has neurotoxic effects in humans. It is confirmed there is a correlation between rotenone exposure and Parkinson’s disease (PD). Therefore, the role of gut microbiota and related metabolic pathways was investigated in rotenone-induced neurotoxicity. The results showed that the abundance of gut microbiota changed significantly. The differential metabolites were enriched in the nicotinate and nicotinamide metabolism pathways, which had the greatest impact on the entire metabolic system. The contents of acetic acid and butyric acid in intestinal tissues decreased significantly. Additionally, Interleukin-6 (IL-6), Tumor necrosis factor alpha (TNF-α) and vasoactive intestinal peptide (VIP) were significantly up-regulated, while gastrin (GAS) and Ghrelin were significantly down-regulated. Expression of intestinal tight junction protein was significantly reduced. Moreover, nicotinamide adenine dinucleotide (NAD⁺), a the product of the nicotinate/nicotinamide pathways, decreased significantly. And the expression levels of nicotinamide phosphoribosyl transferase (NAMPT) and Solute Carrier Family 25 Member 51 (SLC25A51) also reduced significantly. Therefore, gut microbiota was influenced obviously in rats exposed to rotenone, leading to a decrease of acetic acid and butyric acid contents, which might in turn affect the change of intestinal barrier permeability and induce inflammatory reactions. Meanwhile, the nicotinate/nicotinamide metabolic pathways might play an important role in rats exposed to rotenone.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"8 ","pages":"Article 100212"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11743872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolomic profiling reveals systemic metabolic disruptions induced by combined exposure to particulate matter and ozone","authors":"Yue Ge ,&nbsp;Maliha S. Nash ,&nbsp;Aimen K. Farraj","doi":"10.1016/j.crtox.2025.100216","DOIUrl":"10.1016/j.crtox.2025.100216","url":null,"abstract":"<div><div>Air pollution exposure, especially particulate matter (PM) and ozone (O₃), poses significant health risks, but the systemic metabolic consequences of combined exposures to PM and O₃, remain poorly understood. This study investigated systemic metabolic changes in male spontaneously hypertensive (SH) rats following inhalation exposure to concentrated ambient particles (CAPs) (PM2.5, 150 μg/m³), ozone (O₃) (0.2 ppm), and their combination. Rats were exposed for 4 h, and serum samples were collected 1-hour post-exposure. Using targeted metabolomics, we identified significant alterations in metabolites involved in lipid metabolism (phosphatidylcholines), energy metabolism (acylcarnitine C3), and oxidative stress (glutamine). Notably, the combination exposure induced distinct metabolic changes, including increased acylcarnitine C3 levels, suggesting heightened mitochondrial dysfunction. Principal component analysis revealed overlapping profiles between CAPs and controls, indicating a subtler impact of CAPs compared to ozone or combined exposure. These systemic metabolic alterations are aligned with our previously published proteomics findings in cardiac tissues from the same rats, which showed elevated inflammatory markers (e.g., IL-6, TNF-α) and mitochondrial dysfunction. In conclusion, this study provides new insights into the systemic metabolic effects of air pollutant exposure, identifies novel metabolic targets of pollutant-induced toxicity, highlights the complex interactions resulting from combined exposure to multiple pollutants, and underscores the importance of assessing the combined effects of multiple pollutants in air pollution risk assessments.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"8 ","pages":"Article 100216"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143161099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exacerbation of polyethylene microplastics in animal models of DSS-induced colitis through damage to intestinal epithelial cell conjunctions","authors":"Minkyoung Sung ,&nbsp;Yeon-Ji Lee ,&nbsp;Soo-Eun Sung ,&nbsp;Kyung-Ku Kang ,&nbsp;Jae Woo Park ,&nbsp;Yujeong Lee ,&nbsp;Dongmin Kim ,&nbsp;Sunjong Lee ,&nbsp;Joo-Hee Choi ,&nbsp;Sijoon Lee","doi":"10.1016/j.crtox.2025.100217","DOIUrl":"10.1016/j.crtox.2025.100217","url":null,"abstract":"<div><div>Microplastics are pollutants that occur in various environments and habitats. Inflammatory bowel disease (IBD) is a chronic inflammatory disease accompanied with diarrhea, and the number of patients has increased worldwide. In this study, manufactured fragmented polyethylene-microplastics in the size range of 10–30 ㎛, were oxidized by exposure to ultraviolet light, and then administered to a dextran sodium sulfate-induced colitis mouse model to observe the effects of polyethylene-microplastics on IBD. In the microplastics-treated groups, an increase in disease activity index score, histopathological score, and a decrease in the areas of goblet cells were observed. In addition, the tight junction proteins, ZO-1 and Occludin, were significantly decreased, whereas MPO was significantly increased. Interestingly, E-cadherin, which is an adheren junction, was also decreased, presumably because of the physical effects of microplastics. The results suggest that polyethylene-microplastics worsen IBD and microplastics can affect not only tight junctions, but also adheren junctions.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"8 ","pages":"Article 100217"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143161100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New approach methodologies to assess wanted and unwanted drugs-induced immunostimulation","authors":"Valeria Bettinsoli ,&nbsp;Gloria Melzi ,&nbsp;Irene Marchese ,&nbsp;Sofia Pantaleoni ,&nbsp;Francesca Carlotta Passoni ,&nbsp;Emanuela Corsini","doi":"10.1016/j.crtox.2025.100222","DOIUrl":"10.1016/j.crtox.2025.100222","url":null,"abstract":"<div><div>This review examines various classes of drugs, focusing on their therapeutic and adverse effects, particularly in relation to immunostimulation. We emphasize the potential of new approach methodologies (NAMs) to study both expected and unexpected immunostimulatory effects. By evaluating the modes of action of different immunostimulatory drugs, we aim to provide insights into effectively assessing unwanted immunostimulatory responses. The review begins by exploring drugs that stimulate the immune system—including immunostimulants, monoclonal antibodies, chemotherapeutics, and nucleic acid-based drugs—to outline NAMs that could be employed to evaluate immunostimulation.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"8 ","pages":"Article 100222"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143394826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"L-3-n-butylphthalide alleviates intermittent alcohol exposure-induced hypothalamic cell apoptosis via inhibiting the IRE1α-ASK1-JNK pathway in adolescent rats","authors":"Shanyong Yi ,&nbsp;Lai Wei ,&nbsp;Bin Zhao ,&nbsp;Zhijun Yao ,&nbsp;Bin Yang","doi":"10.1016/j.crtox.2024.100211","DOIUrl":"10.1016/j.crtox.2024.100211","url":null,"abstract":"<div><div>Exposure to alcohol can induce different degrees of damage to various tissues and organs, and brain is the most vulnerable part affected by alcohol. However, there is no detailed report on whether intermittent alcohol exposure can result in pathological changes in the hypothalamus of adolescent rats and the detailed mechanism. This study investigated pathological changes in the hypothalamus, probed the levels of inflammatory factors, and detected the expression of proteins related to endoplasmic reticulum stress (ERS) to determine whether ERS is involved in the injury process of the hypothalamus and the protective mechanism of L-3-n-butylphthalide (L-NBP). The results showed that intermittent alcohol exposure induced hypothalamic nerve injury, including cell apoptosis, increased the levels of inflammatory factors, and upregulated the expression of glucose-regulated protein 78 (GRP78), p-Inositol Requiring Enzyme 1α (p-IRE1α), apoptosis signal-regulating kinase 1 (ASK1), and p-c-Jun N-terminal kinase (p-JNK)). Tauroursodeoxycholic acid (TUDCA), an ERS inhibitor, significantly reduced the pathological damage described above. The increases in the levels of inflammatory factors, pathological injury, and increased levels of proteins associated with the IRE1α-ASK1-JNK pathway were alleviated by L-NBP. The present study indicated that intermittent alcohol exposure could lead to hypothalamic cell apoptosis in adolescent rats and L-NBP could alleviate the above injury by inhibiting the IRE1α-ASK1-JNK pathway.</div><div>Abbreviations: Ang-2, Angiopoietin-2; ASK1, Apoptosis signal-regulating kinase 1; ER, Endoplasmic reticulum; ERS, Endoplasmic reticulum stress; ELISA, Enzyme-linked immunosorbent assay; GFAP, Glial fibrillary acidic protein; GRP78, Glucose-regulated protein 78; IBA1, Ionized calcium binding adapter molecule 1; i.p., Intraperitoneal; IRE1α, Inositol Requiring Enzyme 1α; JNK, c-Jun N-terminal kinase; L-NBP, L-3-n-butylphthalide; PND, Postnatal day; PVDF, Polyvinylidene difluoride; SDS-PAGE, Sodium dodecyl sulfate–polyacrylamide gel electrophoresis; TRAF2, TNF-receptor associated factor 2; TUDCA, Tauroursodeoxycholic acid; VEGF, Vascular endothelial growth factor.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"8 ","pages":"Article 100211"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11741027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A long-term mouse testis organ culture system to identify germ cell damage induced by chemotherapy","authors":"Satoshi Yokota ,&nbsp;Kiyoshi Hashimoto ,&nbsp;Takuya Sato ,&nbsp;Koichi Uemura ,&nbsp;Kazuhide Makiyama ,&nbsp;Takuya Nishimura ,&nbsp;Satoshi Kitajima ,&nbsp;Takehiko Ogawa","doi":"10.1016/j.crtox.2025.100228","DOIUrl":"10.1016/j.crtox.2025.100228","url":null,"abstract":"<div><div>We previously developed the acrosin-green fluorescent protein (GFP) transgenic neonatal mouse organ culture system for rapid and accurate assessment of testicular toxicity. This system effectively evaluates drug-induced toxicity in male germ cells before meiotic entry but cannot assess post-meiotic germ cell toxicity. For many chemicals, the specific stage of germ cell differentiation that is susceptible to toxicity remains unclear, highlighting the need for new methods. In this study, we incubated neonatal mouse testis organ cultures for 35 days to allow post-meiotic cells to develop. The tissue was then exposed to cisplatin to determine the cells that are targeted and to assess the reversibility of the toxicity. We monitored changes in tissue volume and GFP fluorescence, which tracks the progression of spermatogenesis, and confirmed findings by histological analysis. Cisplatin inhibited tissue growth and reduced GFP fluorescence in a concentration-dependent manner. Higher concentrations targeted not only spermatogonia, but also spermatocytes and spermatids. Recovery from toxicity was observed at clinically relevant doses. This study demonstrates that long-term mouse testis organ culture can be used to assess testicular toxicity, enabling the identification of specific germ cell stages targeted by chemicals such as cisplatin.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"8 ","pages":"Article 100228"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143610947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The skin allergy risk assessment-integrated chemical environment (SARA-ICE) defined approach to derive points of departure for skin sensitization","authors":"Emily N. Reinke ,&nbsp;Joe Reynolds ,&nbsp;Nicola Gilmour ,&nbsp;Georgia Reynolds ,&nbsp;Judy Strickland ,&nbsp;Dori Germolec ,&nbsp;David G. Allen ,&nbsp;Gavin Maxwell ,&nbsp;Nicole C. Kleinstreuer","doi":"10.1016/j.crtox.2024.100205","DOIUrl":"10.1016/j.crtox.2024.100205","url":null,"abstract":"<div><div>Mechanistically based non-animal methods for assessing skin sensitization hazard have been developed, but are not considered sufficient, individually, to conclusively define the skin sensitization potential or potency of a chemical. This resulted in the development of defined approaches (DAs), as documented in OECD TG 497, for combining information sources in a prescriptive manner to provide a determination of risk or potency. However, there are currently no DAs within OECD TG 497 that can derive a point of departure (POD) for risk assessment. The Skin Allergy Risk Assessment – Integrated Chemical Environment (SARA-ICE) DA for skin sensitization is a Bayesian statistical model that estimates a human-relevant metric of sensitizer potency, the ED₀₁, an estimate of the human predictive patch test dermal dose at which there is 1% chance of inducing sensitization, which can be used in a risk assessment paradigm. The model accounts for variability of input data and explicitly quantifies uncertainty. SARA-ICE derives the ED₀₁ from a variety of <em>in vitro</em> and <em>in vivo</em> test method data and is built upon historical human, murine, and <em>in vitro</em> test data for 434 chemicals. In addition to the ED₀₁ POD SARA-ICE DA also provides a Globally Harmonized System of Classification and Labelling of Chemicals (GHS) classification probability for GHS subcategories 1A, 1B and not classified (NC). Here we describe the SARA-ICE model and its evaluation, including performance versus benchmark PODs. In addition, via a case study with isothiazolinones (ITs), we demonstrate the utility of SARA-ICE for integrating different data inputs and compare the ED₀₁ for six ITs to existing historical data.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"8 ","pages":"Article 100205"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11719337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}