Toxicological Sciences最新文献

{"title":"Suppression of haptoglobin and loss of striatal neurons in mice chronically exposed to chlorpyrifos-contaminated drinking water.","authors":"Emma Fikse, Faith Anderson, Soyeon Cho, Jessica Landry, Elisa Carloni, Karl Biggs, Kathleen Paul, Thomas Daley, T Y Chang, Arminja Kettenbach, Matthew C Havrda","doi":"10.1093/toxsci/kfag012","DOIUrl":"10.1093/toxsci/kfag012","url":null,"abstract":"<p><p>Exposure to agricultural chemicals is a risk factor for neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD). Chlorpyrifos (CPF) is an organophosphate insecticide widely used in agricultural and occupational settings. Epidemiological studies have associated CPF exposure with developmental impairments and an increased risk of AD and PD. Experimental characterization of the impact of chronic, systemic CPF exposure is essential for understanding how organophosphates actually influence disease risk. Multiple studies have assessed the effects of gestational exposure to CPF in preclinical models. To model exposure faced by adults, we administered CPF-contaminated drinking water to mice from 6 to 22 mo of age. This chronic exposure led to systemic effects, including reduced levels of the acute-phase protein haptoglobin (HTP) in both plasma and liver. Notably, the combination of aging and CPF exposure resulted in astrogliosis in the hippocampus and striatum, as well as neuronal loss in the striatum, primarily due to the loss of GAD65/67-immunoreactive interneurons. Having identified CPF-driven suppression of HPT in peripheral tissues, we examined HPT expression in brain tissues. We readily detected HPT expression in brain microglia. We then cultivated primary microglia and found that CPF exposure decreased HPT secretion in vitro. These findings indicate systemic and neurotoxic effects resulting from adult exposure to CPF-contaminated water.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13017363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146158615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute exposure to diethylhexyl phthalate (DEHP) and diisononyl phthalate (DiNP) impacts pituitary hormones and inflammatory markers, suggesting altered reproductive aging in adult female mice.","authors":"Yinka Ojo, Karen Weis, Mary Laws, Catheryne Chiang, Ramses Santacruz-Marquez, Francky Maemble Ntomb, Jodi Flaws, Lori Raetzman","doi":"10.1093/toxsci/kfag020","DOIUrl":"10.1093/toxsci/kfag020","url":null,"abstract":"<p><p>Phthalates are ubiquitous endocrine-disrupting chemicals whose exposure is associated with accelerated reproductive aging in humans. We focused on the pituitary gland, the source of the gonadotropins: Follicle-stimulating hormone (FSH) and luteinizing hormone (LH). We hypothesized that the common phthalates di-(2-ethylhexyl) phthalate (DEHP) and diisononyl phthalate (DiNP) modulate inflammation in the pituitary and impact gonadotropin expression acutely and during aging. To test this, female CD-1 mice were orally dosed with corn oil or varying concentrations of DEHP and DiNP for 10 days. Pituitary tissues were collected immediately after dosing or 15 months post-dosing, processed, and analyzed by quantitative real-time PCR (qPCR) and immunohistochemistry. We found that acute phthalate exposure did not alter Fshb and Lhb mRNA expression compared with controls, but both DEHP and DiNP reduced FSH immunopositive cell number. Phthalate exposure also decreased Il1b, and increased Il18 and Tnf mRNA levels compared with controls, suggesting an inflammatory imbalance. At 15 months post-dosing, DiNP exposure increased Lhb and Il1b mRNA levels, but repressed Fshb and Nlrp3 mRNA levels compared with controls. Next, using dissociated cultures, we investigated the impact of phthalates and the proinflammatory stimulus lipopolysaccharide (LPS) on inflammation and gonadotropin gene expression directly at the pituitary. Both the DEHP metabolite MEHP and LPS decreased Fshb, but not Lhb mRNA relative to control. MEHP also repressed the induction of Il1b by LPS. Together, these findings suggest that acute exposure to phthalate alters mRNA expression of inflammatory markers and gonadotropins in the pituitary, which could alter the process of reproductive aging.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13383081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146228644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safetyome and specialized panels for over 3,000 phenotypes: a systematic and translational approach using human genetics and pharmacology.","authors":"Xin Liu, Yen-Wei Chen, Xiao Xu, David Smith, Fan Fan","doi":"10.1093/toxsci/kfag021","DOIUrl":"10.1093/toxsci/kfag021","url":null,"abstract":"<p><p>Drug candidates are often evaluated for their activities against unexpected targets (off-targets), to either prospectively flag potential hazards or to provide mechanistic insights for a given phenotype. The in vitro to in vivo translatability is critical when selecting which \"phenotypically consequential\" off-targets to screen. To this end, human genetics and indication-based pharmacology offer unraveled insights. Enhanced natural language processing tools were applied to harness the power of large data obtained from 7 genetics and 2 pharmacology databases. Mapping biological roles to organ systems, we curated targets implicated in 22 organ systems of safety concerns, resulting in a safetyome composed of over ∼11,000 proteins. This is a significant expansion from our previously proposed screen, whose scope included phenotypes affecting 5 organ systems. Prioritization of the large panel using expression pattern and gene conservation across species resulted in a core panel of 500 targets. Mapping biological roles obtained from the databases to specific terms allowed us to systematically generate over 3,000 phenotype-based (specialized) panels, which can be used as gene or protein sets for issue resolution. All three components: The full safetyome, the core panel of 500 targets, and the over 3,000+ specialized panels, were systematically and orthogonally tested using independent data source, i.e., gene expression data from the Comparative Toxicogenomics Database. All panels, together with a user-friendly App, are published to aid effective safety assessment and issue resolution with strong \"translational\" focus.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13016935/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146228678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serine hydrolase targets of a sarin surrogate anticholinesterase and oxime-mediated reactivation in rat brain.","authors":"Chiquita Y Price, Edward C Meek, Matthew K Ross, Janice E Chambers","doi":"10.1093/toxsci/kfag024","DOIUrl":"10.1093/toxsci/kfag024","url":null,"abstract":"<p><p>Although acetylcholinesterase (AChE) is the primary inhibitory target for organophosphate (OP) insecticides and chemical warfare nerve agents, research supports the concept that the wide range of systems affected by OPs are not solely dependent on the anticholinesterase activity of OPs but are attributable to the inhibition of other serine hydrolases. Oxime reactivators play an integral role in the treatment of acute OP exposure by returning function to OP-inhibited AChE. Our laboratory has synthesized and patented a platform of oxime reactivators (US Patent 9,227,937) that have provided central neuroprotection through returning function to OP-inhibited AChE in the brain and preservation of neuronal and glial structures from damage in a rat model; the current US-approved oxime, pralidoxime, does not provide central neuroprotection. Thus, returning function to other OP-inhibited serine hydrolases by these novel oximes could provide additional secondary neuroprotection. Rat brain proteins were studied using activity-based protein profiling (ABPP) for serine hydrolase targets of a highly relevant sarin surrogate, nitrophenyl isopropyl methylphosphonate (NIMP), alone or in combination with Oxime 20, our lead novel AChE reactivator. ABPP indicated that NIMP significantly inhibited 6 serine hydrolases, and of these were the well-known serine hydrolases fatty acid amide hydrolase and monoacylglycerol lipase, which are important in endocannabinoid signaling. Oxime 20 administration after NIMP treatment showed only limited remediation of the inhibition experienced by these targets. The impact of this study is the identification of secondary serine esterase targets that could be explored for esterase reactivating therapeutics for the treatment of OP poisoning.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147445351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A human airway-on-a-chip microphysiological system for modeling chlorine gas toxicity.","authors":"Sean V Murphy, Shiny A P Rajan, Kevin Lindert, Tracey Young, Yan Jiao, Yu Zhou, Oula Khoury, Malcolm McSwain, Sivanandane Sittadjody, Zeeshan Hamid, Phillip W Clapp, Timothy S Leach, Timothy C Orr, Douglas Shankle, Emily Whitaker, Khiry Sutton, Steven E Albertson, Kristina Stumpf, Lysette Mutkus, Trang Simon, Gauri Kulkarni, Jeannie Chan, Jingyun Lee, Laura A Cox, Ge Li, Charity Campbell, Michael Olivier, Sobha Puppala, Tony E Reeves, Carl D Langefeld, Hannah C Ainsworth, Julie Ziegler, Amy Zinnia, Mohammad S Khan, Frank C Marini, Stephen J Walker, Thomas D Shupe, Alan Jacobson, Cristina M Furdui, Andrew C Bishop, Adam R Hall, Michael C Seeds, Kimberly D Reeves, Anthony Atala","doi":"10.1093/toxsci/kfaf179","DOIUrl":"10.1093/toxsci/kfaf179","url":null,"abstract":"<p><p>There is a critical need to understand pathophysiological mechanisms involved in injury from acute chlorine gas (Cl2) exposure. Limited information is available regarding the time course and mechanisms of injury after acute Cl2 exposure due to a lack of human clinical data and limited fidelity of pre-clinical animal models. We designed and integrated a Cl2 exposure platform to generate and deliver precise concentrations of Cl2 to a microfluidic human airway-on-a-chip microphysiological system. Chemical, biological, structural, and functional airway-on-a-chip responses to Cl2 exposure were characterized across multiple concentrations, exposure times, and post-exposure timepoints. Transcriptomics and metabolomics analyses delineated key molecular, cellular, and physiological pathways involved in the acute response to Cl2 exposure. This work represents a significant advancement towards high-throughput, human-relevant characterization of pulmonary toxicants and medical countermeasure development, addressing critical gaps in toxicology modeling while reducing reliance on animal studies.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13017778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145821038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ToxPoint: the case study for respiratory sensitization assessment of methyl methacrylate using new approach methodologies.","authors":"Frank Faulhammer, Susanne N Kolle, Karin Wiench","doi":"10.1093/toxsci/kfag008","DOIUrl":"10.1093/toxsci/kfag008","url":null,"abstract":"","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146182340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ovarian hormone deficiency enhances wood smoke-induced immune dysfunction via transcriptomic and metabolic alterations.","authors":"Mijung Oh, Sydnee Yazzie, Eunju Lim, Onamma Edeh, Charlotte McVeigh, Alicia Bolt, Jennifer M Gillette, Katherine E Zychowski","doi":"10.1093/toxsci/kfag023","DOIUrl":"10.1093/toxsci/kfag023","url":null,"abstract":"<p><p>The increasing frequency and severity of wildfires have heightened public exposure to smoke, highlighting the importance of identifying susceptibility factors, including ovarian hormone deficiency. Here, we used single-cell RNA sequencing to profile bone marrow immune cells from ovariectomized (OVX) mice exposed to either filtered air (FA) or wood smoke (WS), followed by functional validation in macrophages from both OVX and Sham-operated mice. Single-cell analyses focused on the OVX context; interactions between surgery and exposure were confirmed at the functional level in assays that included both Sham and OVX groups. In OVX mice, WS broadly suppressed transcriptional programs involved in antigen processing, leukocyte activation, antiviral defense, and bone remodeling. This was associated with altered immune cell composition, including increased memory CD8+ T cells and decreased granulocytes and interferon-responsive populations. Bone marrow-derived macrophages (BMDMs) from WS-exposed OVX mice displayed metabolic reprogramming, characterized by the reversal of OVX-induced suppression of oxidative phosphorylation and glycolytic activity, along with reduced expression of M2-associated genes, without concurrent induction of M1-associated genes. This immune-metabolic decoupling suggests that WS exposure under ovarian hormone deficiency may imprint a lasting program in the bone marrow macrophage axis. Together, these findings show that ovarian hormone deficiency increases vulnerability to WS-induced immune disruption in the bone marrow. WS triggers macrophage reprogramming only under ovarian hormone deficiency, leading to heightened metabolic activity alongside suppression of key immune pathways, identifying a novel mechanism of immunotoxicity. These findings emphasize the need to consider hormonal status in air pollution risk assessment.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":"209 3","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13014470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147514946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering the mechanisms of Cupferron reproductive toxicity: insights from in vitro assays, network toxicology, and molecular docking.","authors":"Mustafa Daşman, Mohammed T Qaoud, Mahmoud Abudayyak","doi":"10.1093/toxsci/kfag014","DOIUrl":"10.1093/toxsci/kfag014","url":null,"abstract":"<p><p>Cupferron, widely used in industrial and analytical contexts, has been proposed as a potential nitric oxide (NO) donor; however, its effects on the male reproductive system remain unclear. We assessed toxicity in TM3 (Leydig) and TM4 (Sertoli) mouse cells. Cytotoxicity (6 to 0.0035 mg/ml) was measured by MTT/NRU; genotoxicity by comet assay; oxidative stress markers (MDA, 8-OHdG, GSH, SOD) and testosterone by ELISA; cell death and ROS by flow cytometry; and gene expression by RT-qPCR. MTT IC50 values were 0.131 mg/ml (TM3) and 0.219 mg/ml (TM4). At 0.125 mg/ml, comet assay revealed markedly increased DNA damage, ≥ 16-fold (P ≤ 0.05) in both TM3 and TM4 cells. In TM4, MDA and 8-OHdG rose ≥ 1.3-fold, while SOD activity increased in both TM3 (1.2-fold) and TM4 (1.5-fold) cells (P ≤ 0.05). Annexin V/PI analysis indicated increased necrosis without significant changes in apoptosis. Testosterone levels were unaffected at all doses. RT-qPCR showed upregulation of SOD1, HMOX1, GSTA1, GPX1 antioxidant genes in both TM3 and TM4 (P ≤ 0.05). Network toxicology highlighted NOS1, NOS3, and PTGS2 as putative targets, supported by docking indicating high affinity and substrate-like poses, implicating modulation of oxidative/inflammatory pathways. ADMETLab 3.0 predicted genotoxic, hepatotoxic, and carcinogenic risks. Overall, Cupferron induces oxidative stress, DNA damage, necrosis, and antioxidant gene activation in Leydig and Sertoli cells, supporting potential male reproductive toxicity and the need for comprehensive in vivo and mechanistic in vitro studies.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146158462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural variation suggests candidate genes underlying Caenorhabditis elegans susceptibility to diverse toxicants.","authors":"Timothy A Crombie, Ryan Mckeown, Samuel J Widmayer, Amanda O Shaver, Nicolas D Moya, J B Collins, Janneke Wit, Robyn E Tanny, Christian Braendle, Lewis Stevens, Lisa Van Sluijs, Matthew V Rockman, Mark G Sterken, Marie-Anne Félix, Erik C Andersen","doi":"10.1093/toxsci/kfag019","DOIUrl":"10.1093/toxsci/kfag019","url":null,"abstract":"<p><p>Genetic differences among individuals shape how they respond to environmental toxicants, but the identification and validation of the genes responsible for this variation is difficult, particularly in humans. Consequently, our limited knowledge of the genes that influence susceptibility constrains our ability to accurately predict the risks posed by environmental toxicants. To identify genes underlying natural differences in toxicant susceptibilities, we measured the effects of 23 environmental toxicants on larval development across 195 genetically diverse Caenorhabditis elegans strains using a high-throughput imaging platform. We then combined these response data with whole-genome sequences to perform genome-wide association mappings, identifying 40 genomic regions where genetic variants are correlated with susceptibility differences. Many of these regions are enriched for genes involved in biological processes previously linked with toxicant responses, supporting the potential contributions of these genes to natural variation in susceptibility. Using biologically informed heuristics based on genomic context and functional annotation, we prioritized genes for follow-up experimentation and identified 94 candidate susceptibility genes, offering feasible targets for experimental validation that could ultimately inform toxicant risk prediction and regulatory assessment by linking genetic variation to differences in susceptibility. Analysis of natural genetic variation among 195 wild C. elegans strains identified 94 candidate genes putatively linked to differences in susceptibility to 23 environmental toxicants. These findings can inform the discovery of conserved susceptibility genes and the development of biomarkers that improve chemical risk assessment by accounting for genetic differences among humans.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13462801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146221048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A systematic review of nervous system effects of ethylbenzene exposure in animal models.","authors":"Laura V Dishaw, Michele M Taylor, Deborah Segal, Laura M Carlson","doi":"10.1093/toxsci/kfag016","DOIUrl":"10.1093/toxsci/kfag016","url":null,"abstract":"<p><p>Ethylbenzene is a high-production-volume chemical. Exposure occurs in the general population, but there is potential for additional exposure in certain groups, such as workers in petrochemical industries or individuals living near contaminated areas. This paper presents a systematic review of currently available evidence in animals focused on potential nervous system-related effects of ethylbenzene exposure. A broad literature search was conducted. A total of 9,679 studies were screened for inclusion based on Populations, Exposures, Comparators, and Outcomes (PECO) criteria. Included studies were evaluated for potential concerns related to risk of bias and sensitivity, and informative studies moved forward for data extraction and evidence synthesis. Twenty-one animal toxicology studies were identified that evaluated nervous system effects, including auditory effects, neurotransmitters, neurobehavior, brain weight, and histopathology. Six studies rated medium or low confidence showed consistent concentration- and exposure duration-related effects on cochlear hair cells and hearing thresholds. The evidence for the other nervous system outcomes is inconclusive. Although some studies showed effects on neurotransmitters and neurobehavior, they were rated low confidence, and findings were inconsistent. Relative brain weight changes were observed, but the direction of the effect was inconsistent. No changes were observed in absolute brain weights, which is considered the more reliable measure for evaluating effects on brain weight. No changes in brain histopathology were reported.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146158498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}