Chemical Research in Toxicology最新文献

Consensus Modeling for Predicting Chemical Binding to Transthyretin as the Winning Solution of the Tox24 Challenge.

IF 3.7 3区医学

Chemical Research in Toxicology Pub Date : 2025-02-19 DOI: 10.1021/acs.chemrestox.4c00421

Dmitriy M Makarov, Alexander A Ksenofontov, Yury A Budkov

{"title":"Consensus Modeling for Predicting Chemical Binding to Transthyretin as the Winning Solution of the Tox24 Challenge.","authors":"Dmitriy M Makarov, Alexander A Ksenofontov, Yury A Budkov","doi":"10.1021/acs.chemrestox.4c00421","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.4c00421","url":null,"abstract":"The utilization of predictive methodologies for the assessment of toxicological properties represents an alternative approach that facilitates the identification of safe compounds while concurrently reducing the financial costs associated with the process. The objective of the Tox24 Challenge was to assess the progress in computational methods for predicting the activity of chemical binding to transthyretin (TTR). In order to fulfill the requirements of this task, the data set, measured by the Environmental Protection Agency, consisted of 1512 chemical substances of diverse nature. This paper describes the model that won the Tox24 Challenge and the steps taken for its further improvement. The Transformer convolutional neural network (CNN) model achieved the best performance as a standalone solution. Meanwhile, a multitask model built on a graph CNN, trained using 11 additional acute systemic toxicity data sets with increased weighting on the TTR binding activity, showed comparable results on the blind test set. The winning solution was a consensus model consisting of two catBoost models with OEstate and Mold2 descriptor sets, as well as two transformer-based models. The improvement of this solution involved adding a fifth model based on multitask learning using the graph CNN method, which led to a reduction in RMSE on the blind test set to 20.3%. The winning model was developed using the OCHEM web platform and is available online at https://ochem.eu/article/162082.","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447442","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}

引用次数: 0

Vitamin E Acetate Causes Softening of Pulmonary Surfactant Membrane Models.

IF 3.7 3区医学

Chemical Research in Toxicology Pub Date : 2025-02-19 DOI: 10.1021/acs.chemrestox.4c00425

Mitchell DiPasquale, Maksymilian Dziura, Omotayo Gbadamosi, Stuart R Castillo, Ambreen Fahim, Justin Roberto, Jeffrey Atkinson, Natalie Boccalon, Mario Campana, Sai Venkatesh Pingali, P Charukeshi Chandrasekera, Piotr A Zolnierczuk, Michihiro Nagao, Elizabeth G Kelley, Drew Marquardt

{"title":"Vitamin E Acetate Causes Softening of Pulmonary Surfactant Membrane Models.","authors":"Mitchell DiPasquale, Maksymilian Dziura, Omotayo Gbadamosi, Stuart R Castillo, Ambreen Fahim, Justin Roberto, Jeffrey Atkinson, Natalie Boccalon, Mario Campana, Sai Venkatesh Pingali, P Charukeshi Chandrasekera, Piotr A Zolnierczuk, Michihiro Nagao, Elizabeth G Kelley, Drew Marquardt","doi":"10.1021/acs.chemrestox.4c00425","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.4c00425","url":null,"abstract":"The popularity of electronic cigarettes and vaping products has launched the outbreak of a condition affecting the respiratory system of users, known as electronic-cigarette/vaping-associated lung injury (EVALI). The build-up of vitamin E acetate (VEA), a diluent of some illicit vaping oils, in the bronchoalveolar lavage of patients with EVALI provided circumstantial evidence as a target for investigation. In this work, we provide a fundamental characterization of the interaction of VEA with lung cells and pulmonary surfactant (PS) models to explore the mechanisms by which vaping-related lung injuries may be present. We first confirm the localization and uptake of VEA in pulmonary epithelial cells. Further, as PS is vitally responsible for the biophysical functions of the lungs, we explore the effect of added VEA on three increasingly complex models of PS: dipalmitoylphosphatidylcholine (DPPC), a lipid-only synthetic PS, and the biologically derived extract Curosurf. Using high-resolution techniques of small-angle X-ray scattering, small-angle neutron scattering, neutron spin-echo spectroscopy, and neutron reflectometry, we compare the molecular-scale behaviors of these membranes to the bulk viscoelastic properties of surfactant monolayer films as studied by Langmuir monolayer techniques. While VEA does not obviously alter the structure or organization of PS membranes, a consistent softening of membrane systems─regardless of compositional complexity─provides a biophysical explanation for the respiratory distress associated with EVALI and yields a new perspective on the behavior of the PS system.","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456268","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}

引用次数: 0

Identification of Butyrylcholinesterase-Derived Small Molecule Peptides Indicative of Novichok Nerve Agent Exposures. 表明诺维乔克神经毒剂暴露的丁基胆碱酯酶衍生小分子肽的鉴定。

IF 3.7 3区医学

Chemical Research in Toxicology Pub Date : 2025-02-17 Epub Date: 2025-01-14 DOI: 10.1021/acs.chemrestox.4c00397

Susan O Kim, Tonya T Lansing, Jonas W Perez, Brooke G Pantazides, Brian S Crow, Thomas A Blake

{"title":"Identification of Butyrylcholinesterase-Derived Small Molecule Peptides Indicative of Novichok Nerve Agent Exposures.","authors":"Susan O Kim, Tonya T Lansing, Jonas W Perez, Brooke G Pantazides, Brian S Crow, Thomas A Blake","doi":"10.1021/acs.chemrestox.4c00397","DOIUrl":"10.1021/acs.chemrestox.4c00397","url":null,"abstract":"Novichok nerve agents, such as A-230, A-232, and A-234, were classified as Schedule 1 chemicals under the Chemical Weapons Convention (CWC) by the Organisation for the Prohibition of Chemical Weapons (OPCW) following poisoning incidents in 2018. As a result, the production, storage, and use of these chemicals are strictly prohibited by CWC signatory nations. The identification of biomarkers indicating Novichok exposure in humans is crucial for prompt detection and response to potential incidents involving these banned chemical weapons. In this study, BChE was isolated from human serum samples exposed to Novichok nerve agents in vitro using immunomagnetic capture, followed by enzymatic digestion with Pronase or proteinase K to generate new peptide biomarkers indicative of exposure. We identified nine previously unpublished Novichok-adducted peptides generated through enzymatic digestion with proteinase K and Pronase using liquid chromatography-high-resolution mass spectrometry. Two peptides, [Agent]-serine-alanine for proteinase K digestion and [Agent]-serine-alanine-glycine for Pronase digestion, were selected for optimization due to their abundance. The analysis was subsequently transferred to an LC-triple quadrupole system to enhance throughput and detect these new biomarkers at the limits of detection corresponding to BChE inhibition levels of 3.90% or less. These additional biomarkers can improve laboratory preparedness for OPCW-designated biomedical testing laboratories as well as other clinical and investigative laboratories tasked with responding to emergencies involving these highly toxic chemicals.","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":"252-259"},"PeriodicalIF":3.7,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142976840","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}

引用次数: 0

In Utero Perfluorodecanoic Acid Exposure Causes Fetal Leydig Cell Dysfunction via Endoplasmic Reticulum Stress-Mediated Lipid Composition Alteration. 子宫内全氟烷酸暴露通过内质网应激介导的脂质组成改变导致胎儿间质细胞功能障碍。

IF 3.7 3区医学

Chemical Research in Toxicology Pub Date : 2025-02-17 Epub Date: 2025-01-15 DOI: 10.1021/acs.chemrestox.4c00467

Zheyuan Ren, Chengshuang Pan, Yaoyao Dong, Qianjin Fei, Huitao Li, Ren-Shan Ge

{"title":"In Utero Perfluorodecanoic Acid Exposure Causes Fetal Leydig Cell Dysfunction via Endoplasmic Reticulum Stress-Mediated Lipid Composition Alteration.","authors":"Zheyuan Ren, Chengshuang Pan, Yaoyao Dong, Qianjin Fei, Huitao Li, Ren-Shan Ge","doi":"10.1021/acs.chemrestox.4c00467","DOIUrl":"10.1021/acs.chemrestox.4c00467","url":null,"abstract":"Perfluorodecanoic acid (PFDA), a C10 fluorine-containing compound, is used widely and found to be present anywhere. However, whether it has reproductive toxicity for fetal Leydig cells and the underlying mechanisms remain unknown. PFDA was investigated for its effects on fetal Leydig cells (FLCs) following exposure to 0, 1, 2.5, and 5 mg/kg/days (gavage to dams) from day 14 to day 21 during gestation. The study showed that in utero medium-dose PFDA (1, 2.5 mg/kg/days) exposure increased fetal body weight. However, PFDA markedly reduced serum testosterone levels, downregulated FLC genes (Lhcgr, Star, Cyp11a1, Hsd3b1, Cyp17a1, and Insl3), and decreased their protein levels in neonatal rat testes. PFDA at 5 mg/kg/day altered lipid metabolism with upregulation of Elovl1 and downregulation of Scd2, subsequently inducing endoplasmic reticulum stress. Additionally, PFDA exposure downregulated transcription factor Gli1, thereby inhibiting fetal Leydig cell differentiation. Meanwhile, PFDA reduced testosterone biosynthesis in R2C Leydig cells in vitro, and the endoplasmic reticulum stress inhibitor tauroursodeoxycholic acid (TUDCA) reversed this process. In conclusion, PFDA disrupts fetal rat testicular lipid metabolism, induces endoplasmic reticulum stress, and interferes with the steroidogenesis network, leading to fetal Leydig cell dysfunction. This study underscores the potential environmental risk of PFDA exposure on the development of male reproductive function development.","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":"314-324"},"PeriodicalIF":3.7,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996169","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}

引用次数: 0

Chemical Transformation of Vaping Emissions under Indoor Atmospheric Aging Processes. 室内大气老化过程中电子烟排放物的化学转化

IF 3.7 3区医学

Chemical Research in Toxicology Pub Date : 2025-02-17 Epub Date: 2025-01-20 DOI: 10.1021/acs.chemrestox.4c00402

Linhui Tian, Wonsik Woo, Ying-Hsuan Lin

{"title":"Chemical Transformation of Vaping Emissions under Indoor Atmospheric Aging Processes.","authors":"Linhui Tian, Wonsik Woo, Ying-Hsuan Lin","doi":"10.1021/acs.chemrestox.4c00402","DOIUrl":"10.1021/acs.chemrestox.4c00402","url":null,"abstract":"E-cigarette emissions, which contain a variety of hazardous compounds, contribute significantly to indoor air pollution and raise concerns about secondhand exposure to vaping byproducts. Compared to fresh vape emissions, our understanding of chemically aged products in indoor environments remains incomplete. Terpenes are commonly used as flavoring agents in e-liquids, which have the ability to react with the dominant indoor oxidant ozone (O3) to produce reactive oxygenated byproducts and result in new particle formation. In this study, mixtures of propylene glycol (PG), vegetable glycerin (VG), and terpenes as e-liquids were injected into a 2 m3 FEP chamber to simulate the indoor aging process. 100 ppbv O3 was introduced into the chamber and allowed to react with the fresh vape emissions for 1 h. Complementary online and offline analytical techniques were used to characterize the changes in the aerosol size distribution and chemical composition during the aging processes. We observed more ultrafine particles and a greater abundance of highly oxygenated species, such as carbonyls, in aged e-cigarette aerosols. Compared with their fresh counterparts, the aged emissions exhibited greater cytotoxic potential, which can be attributed to the formation of these highly oxygenated compounds that are not present in the fresh emissions. This work highlights the dynamic chemistry and toxicity of e-cigarette aerosols in the indoor environment as well as the indirect risks of secondhand exposure.","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":"260-269"},"PeriodicalIF":3.7,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996244","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}

引用次数: 0

Metabolic Characterization of Sarin, Cyclosarin, and Novichoks (A-230, A-232) in Human Liver Microsomes. 沙林、环沙林和诺维乔克（A-230, A-232）在人肝微粒体中的代谢特性

IF 3.7 3区医学

Chemical Research in Toxicology Pub Date : 2025-02-17 Epub Date: 2025-01-15 DOI: 10.1021/acs.chemrestox.4c00538

Thomas R Lane, David D Koebel, Eric A Lucas, Sean Cleary, Robert Moyer, Sean Ekins

{"title":"Metabolic Characterization of Sarin, Cyclosarin, and Novichoks (A-230, A-232) in Human Liver Microsomes.","authors":"Thomas R Lane, David D Koebel, Eric A Lucas, Sean Cleary, Robert Moyer, Sean Ekins","doi":"10.1021/acs.chemrestox.4c00538","DOIUrl":"10.1021/acs.chemrestox.4c00538","url":null,"abstract":"We have assessed the human liver microsomal (HLM) metabolism of the chemical warfare nerve agents' sarin (GB), cyclosarin (GF), and the Novichok agents A-230 and A-232. In HLM, GB showed drastically decreased stability (t1/2 = 1.4 h). The addition of ethylenediaminetetraacetic acid (EDTA), which inhibits paraoxonase-1 (PON1), reduced the metabolism of GB in HLM suggesting at least a partial role in its metabolism (t1/2 = 2.6 h). The absence of NADPH (a requirement for CYP activity) had a major impact on metabolism, suggesting a role of likely CYP-mediated metabolism, which was rescued with the later addition of NADPH at 4 h. GF was also metabolized readily in HLM (Control t1/2 = 9.7 h; HLM t1/2 = 0.5 h), and this metabolism was mitigated by the addition of EDTA (t1/2 (fast) = 0.7 h, t1/2 (slow) = 4.0 h), suggesting a PON1 role in the metabolism of GF. GF in HLMs also showed a reduced metabolism without NADPH, suggesting a CYP-mediated role. We have described for the first time the clearance of A-230 in HLM (t1/2 (fast) = 0.9 h, t1/2 (slow) = 26.5 h), with a significantly decreased stability from the control (t1/2 = 48.3 h) and with the formation of the A-230 acid as the major metabolite. EDTA also reduced the metabolism of A-230 in HLMs (t1/2 (fast) = 0.8 h, t1/2 (slow) = 62 h). A-232 metabolism was also HLM-dependent (t1/2 (fast) = 1.2 h, t1/2 (slow) = 1190 h), although overall it was dramatically more stable in the control (t1/2 = 2,300 h). The metabolism of A-232 in HLMs also showed some inhibition by EDTA (t1/2 (fast) = 0.5 h, t1/2 (slow) = 1480 h).","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":"353-360"},"PeriodicalIF":3.7,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982335","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}

引用次数: 0

Quantum Chemical Evaluation and QSAR Modeling of N-Nitrosamine Carcinogenicity.

IF 3.7 3区医学

Chemical Research in Toxicology Pub Date : 2025-02-17 Epub Date: 2025-02-06 DOI: 10.1021/acs.chemrestox.4c00476

Sebastian Schieferdecker, Esther Vock

引用次数: 0

Elevating Research and Careers in the Development of Safer Drugs through Artificial Intelligence.

IF 3.7 3区医学

Chemical Research in Toxicology Pub Date : 2025-02-17 DOI: 10.1021/acs.chemrestox.4c00423

Alaa Marwan-Abu-Taha

引用次数: 0

Bisphenol A in Disposable Face Masks: A Novel Human Exposure Pathway and Impact on the Aquatic Environment.

IF 3.7 3区医学

Chemical Research in Toxicology Pub Date : 2025-02-17 Epub Date: 2025-02-03 DOI: 10.1021/acs.chemrestox.4c00535

Hei-Tak Tse, Chun-Kit Au, Wan Chan

{"title":"Bisphenol A in Disposable Face Masks: A Novel Human Exposure Pathway and Impact on the Aquatic Environment.","authors":"Hei-Tak Tse, Chun-Kit Au, Wan Chan","doi":"10.1021/acs.chemrestox.4c00535","DOIUrl":"10.1021/acs.chemrestox.4c00535","url":null,"abstract":"We identified and quantified bisphenol A (BPA), a known estrogen-like endocrine disruptor, in disposable face mask samples collected in Hong Kong. Results revealed that BPA is a common contaminant in face masks, with concentrations reaching up to 2 μg/mask. Although polypropylene, the primary material used in mask production, is generally considered to be BPA-free, the contaminant likely originates from additives, such as flame retardants, added during manufacturing. With a dermal absorption coefficient of 0.59 for BPA, the data indicate that mask-borne BPA is readily absorbed by the skin. Notably, 8 of 85 samples could cause the user to exceed the tolerable daily BPA intake set by the European Food Safety Agency (0.0002 μg/kg body weight per day). Additionally, BPA dissolves completely in landfill leachate in less than 70 days, which poses previously unrecognized health and environmental hazards. Given the extensive use of face masks during the pandemic, their role as personal protective equipment for medical practitioners, and the fact that there are currently no regulations regarding BPA contents in masks, it is imperative to investigate the need for regulations in order to safeguard face mask users and the environment.","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":"347-352"},"PeriodicalIF":3.7,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143077842","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}

引用次数: 0

Early Evaluation of the Interaction and Gender Differences in Combination of Apatinib and Metoprolol Using Humanized CYP2D6 Model. 应用人源化CYP2D6模型早期评价阿帕替尼与美托洛尔联合用药的相互作用及性别差异。

IF 3.7 3区医学

Chemical Research in Toxicology Pub Date : 2025-02-17 Epub Date: 2025-01-15 DOI: 10.1021/acs.chemrestox.4c00433

Yahui Wang, Qihui Kong, Huiyan Chai, Haidan Hu, Qianwen Zhang, Jianchang Qian, Bingbing Chen

{"title":"Early Evaluation of the Interaction and Gender Differences in Combination of Apatinib and Metoprolol Using Humanized CYP2D6 Model.","authors":"Yahui Wang, Qihui Kong, Huiyan Chai, Haidan Hu, Qianwen Zhang, Jianchang Qian, Bingbing Chen","doi":"10.1021/acs.chemrestox.4c00433","DOIUrl":"10.1021/acs.chemrestox.4c00433","url":null,"abstract":"Apatinib, a commonly used tyrosine kinase inhibitor in cancer treatment, can cause adverse reactions such as hypertension. Hypertension, in turn, can increase the risk of certain cancers. The coexistence of these diseases makes the use of combination drugs more common in clinical practice, but the potential interactions and regulatory mechanisms in these drug combinations are poorly understood. We used the humanized CYP2D6 mouse model to predict the effect of apatinib on the pharmacokinetics and pharmacodynamics of metoprolol and investigated the interactional mechanism. The inhibitory effects and mechanisms of apatinib on metoprolol were investigated in vitro by using wild-type mouse liver microsomes (WT MLMs), humanized CYP2D6 mouse liver microsomes (hCYP2D6 MLMs), and human liver microsomes (HLMs). Molecular docking was utilized to explore the structural basis of the observed inhibitory mode. And in vivo interaction between apatinib and metoprolol was assessed by pharmacokinetics study using the humanized CYP2D6 mice. In vitro studies and molecular docking experiments indicated that apatinib competitively inhibited the metabolism of metoprolol. In vivo findings revealed that the administration of apatinib combined with metoprolol resulted in a significant increase in the AUC(0-t), AUC(0-∞) and Cmax of metoprolol; additionally, there was a reduction in the CLz/F and heart rate, indicating that apatinib strongly inhibited metoprolol metabolism. And the homologous CYP2D6 protein in WT mice was more sensitive to apatinib compared to the hCYP2D6 mice. Gender analysis revealed that metoprolol accumulation was more pronounced in male mice when combined with apatinib, indicating a higher susceptibility to cardiotoxicity in males.","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":"296-306"},"PeriodicalIF":3.7,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982333","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}

引用次数: 0