Frontiers in toxicology最新文献

{"title":"Potential mammary carcinogens used in food contact articles: implications for policy, enforcement, and prevention.","authors":"Lindsey V Parkinson, Birgit Geueke, Jane Muncke","doi":"10.3389/ftox.2024.1440331","DOIUrl":"https://doi.org/10.3389/ftox.2024.1440331","url":null,"abstract":"<p><p>Many nations have food contact material (FCM) legislation purporting to protect citizens from hazardous chemicals, often specifically by regulating genotoxic carcinogens. Despite such regulations, cancers that are associated with harmful chemical exposures are highly prevalent, especially breast cancer. Using the novel Key Characteristics of Toxicants framework, Kay et al. found 921 substances that are potential mammary carcinogens. By comparing Kay et al.'s chemicals list with our own Database on migrating and extractable food contact chemicals (FCCmigex), we found that 189 (21%) of the potential mammary carcinogens have been measured in FCMs. When limiting these results to migration studies published in 2020-2022, 76 potential mammary carcinogens have been detected to migrate from FCMs sold in markets across the globe, under realistic conditions of use. This implies that chronic exposure of the entire population to potential mammary carcinogens from FCMs is the norm and highlights an important, but currently underappreciated opportunity for prevention. Reducing population-wide exposure to potential mammary carcinogens can be achieved by science-based policy amendments addressing the assessment and management of food contact chemicals.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"6 ","pages":"1440331"},"PeriodicalIF":3.6,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11458522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395689","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":"Cocktail effects of clothianidin and imidacloprid in zebrafish embryonic development, with high and low concentrations of mixtures.","authors":"Seonggeun Zee, Moonjung Hyun, Hee-Jung Sim, Kanghee Kim, Ju-Chan Kang, Chang-Beom Park","doi":"10.3389/ftox.2024.1464069","DOIUrl":"10.3389/ftox.2024.1464069","url":null,"abstract":"<p><p>There is growing concern that sprayed neonicotinoid pesticides (<i>neonics</i>) persist in mixed forms in the environmental soil and water systems, and these concerns stem from reports of increase in both the detection frequency and concentration of these pollutants. To confirm the toxic effects of <i>neonics</i>, we conducted toxicity tests on two <i>neonics</i>, clothianidin (CLO) and imidacloprid (IMD), in embryos of zebrafish. Toxicity tests were performed with two different types of mixtures: potential mixture compounds and realistic mixture compounds. Potential mixtures of CLO and IMD exhibited synergistic effects, in a dose-dependent manner, in zebrafish embryonic toxicity. Realistic mixture toxicity tests that are reflecting the toxic effects of mixture in the aquatic environment were conducted with zebrafish embryos. The toxicity of the CLO and IMD mixture at environmentally-relevant concentrations was confirmed by the alteration of the transcriptional levels of target genes, such as cell damage linked to oxidative stress response and thyroid hormone synthesis related to zebrafish embryonic development. Consequently, the findings of this study can be considered a strategy for examining mixture toxicity in the range of detected environmental concentrations. In particular, our results will be useful in explaining the mode of toxic action of chemical mixtures following short-term exposure. Finally, the toxicity information of CLO and IMD mixtures will be applied for the agricultural environment, as a part of chemical regulation guideline for the use and production of pesticides.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"6 ","pages":"1464069"},"PeriodicalIF":3.6,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11445189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367701","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":"Overview of human health effects related to glyphosate exposure.","authors":"Flavia Silvia Galli, Marta Mollari, Valentina Tassinari, Cristian Alimonti, Alessandro Ubaldi, Camilla Cuva, Daniele Marcoccia","doi":"10.3389/ftox.2024.1474792","DOIUrl":"10.3389/ftox.2024.1474792","url":null,"abstract":"<p><p>Glyphosate is a chemical compound derived from glycine, marketed as a broad-spectrum herbicide, and represents one of the most widely used pesticides in the world. For a long time, it was assumed that glyphosate was harmless, either due to its selective enzymatic acting method on plants, and because commercial formulations were believed to contain only inert chemicals. Glyphosate is widely spread in the environment, the general population is daily exposed to it via different routes, including the consumption of both plant, and non-plant based foods. Glyphosate has been detected in high amounts in workers' urine, but has been detected likewise in bodily fluids, such as blood and maternal milk, and also in 60%-80% of general population, including children. Considering its massive presence, daily exposure to glyphosate could be considered a health risk for humans. Indeed, in 2015, the IARC (International Agency for Research on Cancer) classified glyphosate and its derivatives in Group 2A, as probable human carcinogens. In 2022, nevertheless, EFSA (European Food Safety Authority) stated that the available data did not provide sufficient evidence to prove the mutagenic/carcinogenic effects of glyphosate. Therefore, the European Commission (EC) decided to renew the approval of glyphosate for another 10 years. The purpose of this review is to examine the scientific literature, focusing on potential risks to human health arising from exposure to glyphosate, its metabolites and its commercial products (e.g., Roundup^®), with particular regard to its mutagenic and carcinogenic potential and its effects as endocrine disrupter (ED) especially in the human reproductive system.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"6 ","pages":"1474792"},"PeriodicalIF":3.6,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11445186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367702","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":"Twenty years of <i>in vitro</i> nanotoxicology: how AI could make the difference.","authors":"Luisa Campagnolo, Valentina Lacconi, Joanna Filippi, Eugenio Martinelli","doi":"10.3389/ftox.2024.1470439","DOIUrl":"https://doi.org/10.3389/ftox.2024.1470439","url":null,"abstract":"<p><p>More than two decades ago, the advent of Nanotechnology has marked the onset of a new and critical field in science and technology, highlighting the importance of multidisciplinary approaches to assess and model the potential human hazard of newly developed advanced materials in the nanoscale, the nanomaterials (NMs). Nanotechnology is, by definition, a multidisciplinary field, that integrates knowledge and techniques from physics, chemistry, biology, materials science, and engineering to manipulate matter at the nanoscale, defined as anything comprised between 1 and 100 nm. The emergence of nanotechnology has undoubtedly led to significant innovations in many fields, from medical diagnostics and targeted drug delivery systems to advanced materials and energy solutions. However, the unique properties of nanomaterials, such as the increased surface to volume ratio, which provides increased reactivity and hence the ability to penetrate biological barriers, have been also considered as potential risk factors for unforeseen toxicological effects, stimulating the scientific community to investigate to which extent this new field of applications could pose a risk to human health and the environment.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"6 ","pages":"1470439"},"PeriodicalIF":3.6,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11457712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395690","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 new database contains 520 studies investigating the carcinogenicity data of 238 pharmaceuticals across 14 ATC classifications.","authors":"Panagiotis G Karamertzanis, Martina Evangelisti, Marco Daniele Parenti, Jochen Vom Brocke, Alberto Del Rio, Ingo Bichlmaier","doi":"10.3389/ftox.2024.1450612","DOIUrl":"10.3389/ftox.2024.1450612","url":null,"abstract":"","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"6 ","pages":"1450612"},"PeriodicalIF":3.6,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11442431/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142360729","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":"Light pollution: time to consider testicular effects.","authors":"Peter Y Liu","doi":"10.3389/ftox.2024.1481385","DOIUrl":"10.3389/ftox.2024.1481385","url":null,"abstract":"<p><p>Technological advances have led to a modern-day lighting and smartphone revolution, with artificial light exposure at night increasing to levels never before seen in the evolutionary history of living systems on Earth. Light as a pollutant, however, remains largely unrecognized, and the reproductive effects of light pollution are mostly if not entirely unconsidered. This is despite the reproductive system being intricately linked to metabolism and the circadian system, both of which can be disturbed even by low levels of light. Here, we aim to change this perspective by reviewing the physiological and pathophysiological mechanisms by which light exposure alters the intricate hormonal, metabolic and reproductive networks that are relevant to reproductive toxicology. Nascent human studies have recently identified the photoreceptors responsible for the light dose relationship with melatonin suppression and circadian re-entrainment, directly shown the association between the alignment of light-dark cycles with activity-rest cycles on metabolic health and provided proof-of-principle that properly timed blue light-enriched and blue light-depleted delivery can accelerate circadian re-entrainment. With these advances, there is now a need to consider testicular effects of light pollution.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"6 ","pages":"1481385"},"PeriodicalIF":3.6,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11439877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333857","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 use of <i>in vitro</i> bioassays and chemical screening to assess the impact of a minimally processed vegetable facility on wastewater quality.","authors":"N H Aneck-Hahn, M C Van Zijl, L Quinn, C Swiegelaar, N Nhlapo, W de Bruin, L Korsten","doi":"10.3389/ftox.2024.1439126","DOIUrl":"10.3389/ftox.2024.1439126","url":null,"abstract":"<p><p>Fruit- and vegetable-processing facilities may contaminate wastewater via contaminants found in the produce and disinfecting chemicals used. These contaminants may include agrochemicals, pesticides, and disinfectants such as chlorine and quaternary ammonium compounds (QACs). Some compounds may exhibit harmful endocrine-disrupting activity. This study investigated the impact of a minimally processed vegetable facility on wastewater quality via <i>in vitro</i> bioassays and chemical screening. Estrogen activity was assessed via a yeast estrogen screen (YES), and (anti-)androgenic and glucocorticoid activities were evaluated via an MDA-kb2 reporter gene assay. The samples were screened via gas and liquid chromatography-tandem mass spectrometry (GC-MS/MS and LC-MS/MS) to identify target compounds, and GC coupled with time-of-flight mass spectrometry (GC-TOFMS) was used for non-targeted screening. Sample complexity and chemical profiles were assessed using GC-TOFMS. Estrogenic activity was detected in 16 samples (n = 24) with an upper limit of 595 ± 37 ng/L estradiol equivalents (EEqs). The final wastewater before discharge had an EEq of 0.23 ng/L, which is within the ecological effect-based trigger value range for the estrogenic activity of wastewater (0.2-0.4 ng/L EEq). Androgenic activity was detected in one sample with a dihydrotestosterone equivalent (DHTEq) value of 10 ± 2.7 ng/L. No antiandrogenic activity was detected. The GC-MS/MS and LC-MS/MS results indicated the presence of multiple pesticides, nonylphenols, triclocarban, and triclosan. Many of these compounds exhibit estrogenic activity, which may explain the positive YES assay findings. These findings showed that wastewater from the facility contained detergents, disinfectants, and pesticides and displayed hormonal activity. Food-processing facilities release large volumes of wastewater, which may affect the quality of the water eventually being discharged into the environment. We recommend expanding conventional water quality monitoring efforts to include additional factors like endocrine activity and disinfectant byproducts.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"6 ","pages":"1439126"},"PeriodicalIF":3.6,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11439871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333858","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":"Glyphosate and a glyphosate-based herbicide dysregulate the epigenetic landscape of Homeobox A10 (<i>Hoxa10</i>) gene during the endometrial receptivity in <i>Wistar</i> rats.","authors":"Virginia Lorenz, Florencia Doná, Dalma B Cadaviz, María M Milesi, Jorgelina Varayoud","doi":"10.3389/ftox.2024.1438826","DOIUrl":"https://doi.org/10.3389/ftox.2024.1438826","url":null,"abstract":"<p><p>We observed that gestational plus lactational exposure to glyphosate (Gly), as active ingredient, or a glyphosate-based herbicide (GBH) lead to preimplantation losses in F1 female <i>Wistar</i> rats. Here, we investigated whether GBH and/or Gly exposure could impair <i>Hoxa10</i> gene transcription by inducing epigenetic changes during the receptive stage in rats, as a possible herbicide mechanism implicated in implantation failures. F0 dams were treated with Gly or a GBH through a food dose of 2 mg Gly/kg bw/day from gestational day (GD) 9 up to lactational day 21. F1 female rats were bred, and uterine tissues were analyzed on GD5 (preimplantation period). Transcripts levels of <i>Hoxa10</i>, DNA methyltransferases (<i>Dnmt1, Dnmt3a</i> and <i>Dnmt3b</i>), histone deacetylases (<i>Hdac-1</i> and <i>Hdac-3</i>) and histone methyltransferase (<i>EZH2)</i> were assessed by quantitative polymerase chain reaction (qPCR). Four CpG islands containing sites targeted by B<i>stU</i>I methylation-sensitive restriction enzyme and predicted transcription factors (TFs) were identified in <i>Hoxa10</i> gene. qPCR-based methods were used to evaluate DNA methylation and histone post-translational modifications (hPTMs) in four regulatory regions (RRs) along the gene by performing methylation-sensitive restriction enzymes and chromatin immunoprecipitation assays, respectively. GBH and Gly downregulated <i>Hoxa10</i> mRNA. GBH and Gly increased DNA methylation levels and Gly also induced higher levels than GBH in all the RRs analyzed. Both GBH and Gly enriched histone H3 and H4 acetylation in most of the RRs. While GBH caused higher H3 acetylation, Gly caused higher H4 acetylation in all RRs. Finally, GBH and Gly enhanced histone H3 lysine 27 trimethylation (H3K27me3) marker at 3 out of 4 RRs studied which was correlated with increased <i>EZH2</i> levels. In conclusion, exposure to GBH and Gly during both gestational plus lactational phases induces epigenetic modifications in regulatory regions of uterine <i>Hoxa10</i> gene. We show for the first time that Gly and a GBH cause comparable gene expression and epigenetic changes. Our results might contribute to delineate the mechanisms involved in the implantation failures previously reported. Finally, we propose that epigenetic information might be a valuable tool for risk assessment in the near future, although more research is needed to establish a cause-effect relationship.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"6 ","pages":"1438826"},"PeriodicalIF":3.6,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11427440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333856","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":"Inhibitory effects of NaF on mitochondrial energy generation in human platelets <i>in vitro</i>.","authors":"Tetsuhiro Tsujino, Tomoni Kasahara, Hideo Kawabata, Taisuke Watanabe, Koji Nishiyama, Yutaka Kitamura, Takao Watanabe, Hajime Okudera, Tomoharu Mochizuki, Takashi Ushiki, Tomoyuki Kawase","doi":"10.3389/ftox.2024.1421184","DOIUrl":"https://doi.org/10.3389/ftox.2024.1421184","url":null,"abstract":"<p><strong>Background: </strong>fluoride is a beneficial ion that has been used in various fields, from industrial products to therapeutics. However, due to its narrow therapeutic index, fluoride sometimes acts as a toxic agent at relatively higher concentrations in the human body. Based on the interest in genetic stability, its cytotoxic effects have been investigated mainly in nucleated, adherent cells, such as fibroblasts. However, the sensitivity of blood cells, especially anucleate platelets, to fluoride is poorly understood. To fill this gap in the literature, we investigated the effects of relatively low levels of fluoride on platelet energy metabolism, function, and viability.</p><p><strong>Methods: </strong>Platelet-rich plasma (PRP) was prepared from 15 non-smoking healthy male adults (age: 28-63) and treated with NaF (0.5 or 1.0 mM) in microtubes for up to 3 days. Platelet function was evaluated based on aggregation and adhesion activities. Platelet energy metabolism was evaluated based on intracellular ATP levels, extracellular lactate levels, and respiration activities. The mitochondrial membrane potential (Em) and localization of reactive oxygen species (ROS) were visualized using cytochemical methods. Platelet viability was evaluated by cell counting and tetrazolium reduction.</p><p><strong>Result: </strong>NaF (1 mM) significantly reduced platelet viability and inhibited functions. Behind these phenomena, NaF substantially decreased mitochondrial Em and increased ROS production along with significant decreases in oxygen consumption and ATP levels. Simultaneously, NaF increased the lactate levels. Although not statistically significant, similar effects were observed at 0.5 mM NaF.</p><p><strong>Conclusion: </strong>At relatively low levels, NaF has the potential to attenuate platelet function probably primarily through the inhibition of mitochondrial energy generation. Cytotoxicity may be directly related to ROS production. These findings suggest that when used topically, for example, for caries prevention in the oral cavity, NaF could interfere with wound healing and tissue regeneration by endogenous and exogenously added platelets in the form of PRP.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"6 ","pages":"1421184"},"PeriodicalIF":3.6,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11410780/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142302562","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 rare case of early onset lewy body dementia with parkinsonism associated with chronic exposure to copper contaminated drinking water.","authors":"Marcia H Ratner, Jonathan S Rutchik","doi":"10.3389/ftox.2024.1451235","DOIUrl":"https://doi.org/10.3389/ftox.2024.1451235","url":null,"abstract":"<p><p>There is a well-recognized relationship between a person's body burden of essential trace elements such as copper and their neurological function in which both deficiencies and exposures to excessive concentrations are associated with adverse clinical outcomes. Preclinical studies indicate chronic excess copper exposure is associated with altered motor function, dopaminergic neuronal loss, astrocytosis, and microgliosis. Copper also promotes oligomerization and fibrilization of α-synuclein suggesting it may hasten the course of an α-synucleinopathy. Here we report a rare case of early onset Lewy Body Dementia with Parkinsonism in a 53-year-old Caucasian woman exposed to copper contaminated drinking water for more than 10 years. Her hair and that of her daughter had streaks of blue-green discoloration as did the porcelain sinks in their home. Testing confirmed copper contamination of the drinking water. A neurologist diagnosed her with Lewy Body Dementia with Parkinsonism. Skin biopsy for phosphorylated α was consistent with a diagnosis of an α-synucleinopathy. These findings suggest chronic exposure to excessive copper may act as disease modifying factor in Lewy Body Dementia with Parkinsonism. It has previously been recommended that individuals at risk of Alzheimer's disease (AD) avoid excessive intake of copper. Genetic studies indicate that Lewy Body Dementia shares risk factors and pathways with AD. Based on the observations in this patient we recommend that individuals at risk for an α-synucleinopathy based on a positive family history, genetic testing, and/or positive results on a skin biopsy for phosphorylated α-synuclein avoid exposure to excess copper.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"6 ","pages":"1451235"},"PeriodicalIF":3.6,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11402898/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142302545","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}