المؤلفون: Huijie, Zhang, Zhixin, He, Ping, Deng, Muxue, Lu, Chao, Zhou, Lingling, Yang, Zhengping, Yu

المصدر: Toxicology Research. 11:628-643

مصطلحات موضوعية: Health, Toxicology and Mutagenesis, Toxicology

الوصف: Arsenic, a widely existing environmental contaminant, is recognized to be toxic to multiple organs. Exposure to arsenic results in liver damage via excessive production of reactive oxidative species (ROS). PIN1 regulates the levels of ROS. N-acetyl-L-cysteine (NAC) is an ROS scavenger that protects the hepatic functions. Whether PIN1 plays a regulatory role in NAC-mediated antagonism against arsenic hepatotoxicity remains largely unknown. In our study, the protective effects of NAC against arsenic (NaAsO2)-induced hepatotoxicity were evaluated in vitro and in vivo. Arsenic exposure induced cytotoxicity by increasing the intracellular ROS production, impairing mitochondrial function and inducing apoptosis in L02 hepatocytes. Overexpression of PIN1 markedly protected against arsenic cytotoxicity, decreased ROS levels, and mitigated mitochondrial dysfunction and apoptosis in L02 cells. However, loss of PIN1 further aggravated arsenic-induced cytotoxicity and abolished the protective effects of NAC in L02 cells. An in vivo study showed that pretreatment with NAC rescued arsenic-induced liver injury by restoring liver function and suppressing hepatic oxidative stress. Overexpression of PIN1 in mice transfected with AAV-Pin1 relieved arsenic-induced liver dysfunction and hepatic oxidative stress. Taken together, our study identified PIN1 as a novel intervention target for antagonizing arsenic-induced hepatotoxicity, highlighting a new pharmacological mechanism of NAC targeting PIN1 in antagonism against arsenic toxicity.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f8643b96db57c124b66e4ae21b00a5b5Test
https://doi.org/10.1093/toxres/tfac040Test

المؤلفون: Houxiang Hu, Rongchuan Yue, Zhengping Yu, Chao Zhou, Shengzhong Lu, Xi Yu, Mengyu Liu, Zhou Zhou, Hao Liang, Jing Zeng

المصدر: Journal of Applied Toxicology. 41:775-788

مصطلحات موضوعية: medicine.medical_specialty, Endothelium, 010501 environmental sciences, Toxicology, 01 natural sciences, 03 medical and health sciences, Internal medicine, Lipid droplet, medicine, Animals, Humans, Endothelial dysfunction, Beta oxidation, Triglycerides, 030304 developmental biology, 0105 earth and related environmental sciences, Membrane Potential, Mitochondrial, chemistry.chemical_classification, 0303 health sciences, Reactive oxygen species, Endothelial Cells, Lipid metabolism, Lipid Metabolism, medicine.disease, Mitochondria, medicine.anatomical_structure, Endocrinology, chemistry, Lipogenesis, Environmental Pollutants, Reactive Oxygen Species, Homeostasis, Cadmium

الوصف: Cadmium (Cd) is an occupational and environmental heavy metal pollutant derived from many sources that is linked to endothelial homeostasis. The endothelium is an important site of Cd deposition, while increasing evidence has revealed there is a close relationship between endothelial dysfunction and abnormal lipid metabolism. However, the effects of the alterations in lipid metabolism on endothelial cells (ECs) after Cd exposure still remain unclear. In our study, human microvascular endothelial cells (HMEC-1) were exposed to 40-μM Cd for 6, 12, or 24 h or 10-, 20-, or 40-μM Cd for 24 h, respectively. The Cd exposure accelerated the decomposition of triglyceride (TG) and resulted in the accumulation of free fatty acids (FFAs). These changes stimulated cytotoxicity, impaired fatty acid oxidation (FAO), induced reactive oxygen species (ROS) generation, altered the mitochondrial membrane potential (MMP), and decreased the ATP content, which eventually led to endothelial dysfunction and cell death. In summary, exposure to cadmium caused endothelial dysfunction by disrupting lipid metabolism in HMEC-1. These changes were mainly due to FFA accumulation and FAO inhibition, which further induced ROS generation and mitochondrial dysfunction. Moreover, our results provide novel insight into understanding the alterations of lipid metabolism induced by Cd exposure in ECs.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::04dddea4cc3b0e4d1b839c4cb625a94aTest
https://doi.org/10.1002/jat.4115Test

المؤلفون: Huifeng Pi, Yang Yue, Zhengping Yu, Lingzhi Liao, Yan Luo, Liting Wang, Yidan Liang, Miduo Tan, Ping Deng, Li Tian, Yu Xi, Zhou Zhou, Mingliang Chen, Jia Xie, Mengyan Chen

المصدر: Environmental Pollution. 273:116504

مصطلحات موضوعية: 010504 meteorology & atmospheric sciences, Chemistry, Cell growth, Health, Toxicology and Mutagenesis, Autophagy, ATG5, General Medicine, 010501 environmental sciences, Cadmium chloride, Toxicology, medicine.disease, 01 natural sciences, Pollution, Metastasis, chemistry.chemical_compound, Acetylation, ACSS2, Cancer research, medicine, Carcinogen, 0105 earth and related environmental sciences

الوصف: Cadmium (Cd), which is considered a carcinogenic metal, promotes breast cancer (BC) progression, but the precise mechanism remains unclear. Herein, MCF-7 and T47-D cells were treated with 0.1, 1, and 10 μM cadmium chloride (CdCl2) for 24, 48 and 72 h. In our study, Cd exposure significantly accelerated the proliferation, migration and invasion of MCF-7 and T47-D cells. Notably, Cd inhibited autophagic flux by suppressing ATG5-dependent autophagosome formation but had no significant effect on autophagosome-lysosome fusion and lysosomal function. The genetic enhancement of autophagy through ATG5 overexpression suppressed the Cd-mediated increases in proliferation, migration and invasion, which indicated a carcinogenic role of autophagy impairment in Cd-exposed BC cells. GSEA and GeneMANIA were utilized to demonstrate that the Cd-induced decrease in ACSS2 expression mechanistically inhibited ATG5-dependent autophagy in BC cells. Importantly, ACSS2 overexpression increased the level of H3K27 acetylation in the promoter region of ATG5, and this result maintained autophagic flux and abolished the Cd-induced increases in proliferation, migration and invasion. We also verified that the expression of ACSS2 in BC tissues was low and positively related to ATG5 expression. These findings indicated that the promoting effect of Cd on BC cell proliferation, migration and invasion through the impairment of ACSS2/ATG5-dependent autophagic flux suggests a new mechanism for BC cell proliferation and metastasis stimulated by Cd.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::113aa40e17a527b20df30d2386e64617Test
https://doi.org/10.1016/j.envpol.2021.116504Test

المؤلفون: Lingling Yang, Yidan Liang, Ping Deng, Zhengping Yu, Li Pang, Jing-yu Qian, Zhou Zhou, Li-chuan Wu

المصدر: Toxicol Res (Camb)

مصطلحات موضوعية: chemistry.chemical_classification, 0303 health sciences, Reactive oxygen species, Health, Toxicology and Mutagenesis, Alpha-Lipoic Acid, Pharmacology, Toxicology, medicine.disease, medicine.disease_cause, Nitric oxide, 03 medical and health sciences, chemistry.chemical_compound, Lipoic acid, Chemistry, 0302 clinical medicine, chemistry, Paraquat, 030220 oncology & carcinogenesis, Toxicity, medicine, Endothelial dysfunction, Oxidative stress, 030304 developmental biology

الوصف: Paraquat (PQ) is a widely used herbicide in the agricultural field. The lack of an effective antidote is the significant cause of high mortality in PQ poisoning. Here, we investigate the antagonistic effects of alpha lipoic acid (α-LA), a naturally existing antioxidant, on PQ toxicity in human microvascular endothelial cells (HMEC-1). All the doses of 250, 500 and 1000 μM α-LA significantly inhibited 1000 μM PQ-induced cytotoxicity in HMEC-1 cells. α-LA pretreatment remarkably diminished the damage to cell migration ability, recovered the declined levels of the vasodilator factor nitric oxide (NO), elevated the expression level of endothelial nitric oxide synthases (eNOS), and inhibited the upregulated expression of vasoconstrictor factor endothelin-1 (ET-1). Moreover, α-LA pretreatment inhibited reactive oxygen species (ROS) generation, suppressed the damage to the mitochondrial membrane potential (ΔΨm) and mitigated the inhibition of adenosine triphosphate (ATP) production in HMEC-1 cells. These results suggested that α-LA could alleviate PQ-induced endothelial dysfunction by suppressing oxidative stress. In summary, our present study provides novel insight into the protective effects and pharmacological potential of α-LA against PQ toxicity in microvascular endothelial cells.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c022f09db0cfcbe1c6d050d3c60a63dbTest
https://pubmed.ncbi.nlm.nih.gov/32774841Test

المؤلفون: Mindi He, Chunhai Chen, Yonghui Lu, Min Li, Lingling Yang, Zhou Zhou, Lei Zhang, Zhi-Yu Chen, Chuan Liu, Zhengping Yu

المصدر: Cellular Physiology and Biochemistry, Vol 39, Iss 3, Pp 961-974 (2016)

مصطلحات موضوعية: 0301 basic medicine, Physiology, Cytotoxicity, medicine.disease_cause, lcsh:Physiology, DNA Glycosylases, Histones, Toxicology, Mice, chemistry.chemical_compound, Bisphenol A, Cadmium Chloride, lcsh:QD415-436, Phosphorylation, OGG1, chemistry.chemical_classification, Cadmium, lcsh:QP1-981, G2 Phase Cell Cycle Checkpoints, Drug Combinations, Comet Assay, Poly(ADP-ribose) Polymerases, hormones, hormone substitutes, and hormone antagonists, endocrine system, Cell Survival, DNA damage, Poly ADP ribose polymerase, chemistry.chemical_element, Air Pollutants, Occupational, Cadmium chloride, lcsh:Biochemistry, 03 medical and health sciences, Phenols, medicine, Animals, Estrogens, Non-Steroidal, Benzhydryl Compounds, Reactive oxygen species, L-Lactate Dehydrogenase, urogenital system, Molecular biology, Comet assay, 030104 developmental biology, Gene Expression Regulation, chemistry, DNA glycosylase, NIH 3T3 Cells, Genotoxicity, Reactive Oxygen Species, DNA Damage

الوصف: Background: Both cadmium (Cd) and bisphenol A (BPA) are commonly encountered in humans' daily activities, but their combined genotoxic effects remain unclear. Methods: In the present study, we exposed a mouse embryonic fibroblast cell line (NIH3T3) to Cd for 24 h, followed by a 24 h BPA exposure to evaluate toxicity. The cytotoxicity was evaluated by viability with CCK-8 assay and lactate dehydrogenase (LDH) release. Reactive oxygen species (ROS) production was measured by 2′,7′-dichlorofluorescein diacetate (DCFH-DA). And DNA damage was measured by 8-hydroxydeoxyguanosine (8-OHdG), phosphorylated H2AX (γH2AX) and the comet assay. The flow cytometry was used to detect cell cycle distribution, and apoptosis was determined by TUNEL assay and western blot against poly-ADP-ribose polymerase (PARP). Results: The results showed that Cd or BPA treatments alone (with the exception of BPA exposure at 50 μM) did not alter cell viability. However, pre-treatment with Cd aggravated the BPA-induced reduction in cell viability; increased BPA-induced LDH release, ROS production, DNA damage and G2 phase arrest; and elevated BPA-induced TUNEL-positive cells and the expression levels of cleaved PARP. Cd exposure concurrently decreased the expression of 8-oxoguanine-DNA glycosylase-1 (OGG1), whereas OGG1 over-expression abolished the enhancement of Cd on BPA-induced genotoxicity and cytotoxicity. Conclusion: These findings indicate that Cd exposure aggravates BPA-induced genotoxicity and cytotoxicity through OGG1 inhibition.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::544ee9bb44708eb338f3ea755c3033c2Test
https://doi.org/10.1159/000447804Test

المؤلفون: Chunhai Chen, Yu Xi, Zhengping Yu, Ping Deng, Min Lin, Zhou Zhou, Lingling Yang, Qinlong Ma

المصدر: Toxicology in Vitro. 62:104686

مصطلحات موضوعية: 0301 basic medicine, Cell cycle checkpoint, Neurogenesis, Gene Expression, chemistry.chemical_element, Apoptosis, Biology, Toxicology, Transcriptome, Mice, 03 medical and health sciences, 0302 clinical medicine, Neural Stem Cells, Pregnancy, Neurosphere, Animals, Viability assay, Progenitor cell, Mice, Inbred BALB C, Cadmium, High-Throughput Nucleotide Sequencing, Cell Cycle Checkpoints, General Medicine, Cell cycle, Embryonic stem cell, Cell biology, 030104 developmental biology, chemistry, 030220 oncology & carcinogenesis, RNA, Female, Neurotoxicity Syndromes, Signal Transduction

الوصف: Cadmium exposure has raised great public concern. Extensive studies have revealed the neurotoxic effects of cadmium exposure during brain development. However, more evidence is still needed to reach a consistent conclusion and uncover the underlying mechanisms. Here, we used primary mouse embryonic neural stem/progenitor cells (NSPCs) as a cell model and exposed the cells to 0, 1, 2 or 4 μM cadmium. High-throughput mRNA-seq technology was used to explore the global transcriptome changes in NSPCs after exposure to 2 μM cadmium. We found that cadmium exposure remarkably influenced the expression of genes involved in cell growth, proliferation, cell cycle and survival. Pathway-Act-Network analysis revealed that these altered genes were targeted to the P53, PI3K-AKT, MAPK, calcium, and NF-kappa B signaling pathways. In vitro experiments using cultured NSPCs verified that cadmium exposure reduced cell viability, proliferation, neurosphere formation and caused cell cycle arrest at low concentrations (≤ 2 μM), while induced cell apoptosis at high concentrations (≥ 4 μM). Real-time PCR results confirmed the concentration-dependent effects of cadmium exposure on the expression of critical genes in the above signaling pathways. Together, our results provide transcriptomic insight into cadmium-induced developmental neurotoxic effects and the underlying mechanisms.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::717516c64d0ca5eee01c9d1d4b0e02bfTest
https://doi.org/10.1016/j.tiv.2019.104686Test

المؤلفون: Zhengping Yu, Huifeng Pi, Yu Xi, Zhiqi Yang, Zhou Zhou, Jia Xie, Min Li

المصدر: Toxicology letters. 295

مصطلحات موضوعية: 0301 basic medicine, Time Factors, Autophagy-Related Proteins, Apoptosis, Cadmium chloride, Toxicology, Cathepsin B, Permeability, 03 medical and health sciences, chemistry.chemical_compound, Mice, Cadmium Chloride, Cell Line, Tumor, medicine, Autophagy, Animals, Neurons, biology, Dose-Response Relationship, Drug, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Cytochrome c, Neurotoxicity, Cytochromes c, General Medicine, Intracellular Membranes, medicine.disease, Cell biology, Mitochondria, Cytosol, 030104 developmental biology, chemistry, biology.protein, Environmental Pollutants, Neurotoxicity Syndromes, Apoptosis Regulatory Proteins, Lysosomes, Flux (metabolism), Signal Transduction

الوصف: Cadmium (Cd), is a well-known environmental and occupational hazard with a potent neurotoxic action. However, the mechanism underlying cadmium-induced neurotoxicity remains unclear. Herein, we exposed Neuro-2a cells to different concentrations of cadmium chloride (CdCl2) (12.5, 25 and 50 μM) for 24 h and found that Cd significantly induced lysosomal membrane permeabilization (LMP) with the release of cathepsin B (CTSB) to the cytosol, which in turn caused the release of mitochondrial cytochrome c (Cyt c) and eventually triggered caspase-dependent apoptosis. Interestingly, Cd decreased TFE3 expression but induced the nuclear translocation of TFE3 and TFE3 target-gene expression, which might be associated with lysosomal stress mediated by Cd. Notably, Tfe3 overexpression protected against Cd-induced neurotoxicity by maintaining the lysosomal-mitochondrial axis, and the protective effect of TFE3 is not dependent on the restoration of autophagic flux. In conclusion, our study demonstrated for the first time that lysosomal-mitochondrial axis dependent apoptosis, a neglected mechanism, may be the most important reason for Cd-induced neurotoxicity and that manipulation of TFE3 signaling may be a potential therapeutic approach for treatment of Cd-induced neurotoxicity.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ac783535cf8b96bee3d22b9699ab2337Test
https://pubmed.ncbi.nlm.nih.gov/30030080Test

المؤلفون: Lei Zhang, Chunhai Chen, Yonghui Lu, Zhou Zhou, Lin Mao, Huifeng Pi, Weixia Duan, Chuan Liu, Yuming Li, Zhengping Yu, Feng-Hua Qian, Zhengwang Cao, Mindi He

المصدر: Toxicology and Applied Pharmacology. 286:80-91

مصطلحات موضوعية: Pharmacology, Caspase 3, Cell Survival, Chemistry, Down-Regulation, Apoptosis, Bronchi, Epithelial Cells, Transfection, Resveratrol, Toxicology, Cell Line, Cell biology, chemistry.chemical_compound, Sirtuin 1, Biochemistry, Nickel, Annexin, Acetylation, Toxicity, Humans, Nanoparticles, Viability assay, Cytotoxicity

الوصف: With application of nano-sized nickel-containing particles (Nano-Ni) expanding, the health concerns about their adverse effects on the pulmonary system are increasing. However, the mechanisms for the pulmonary toxicity of these materials remain unclear. In the present study, we focused on the impacts of NiO nanoparticles (NiONPs) on sirtuin1 (SIRT1), a NAD-dependent deacetylase, and investigated whether SIRT1 was involved in NiONPs-induced apoptosis. Although the NiONPs tended to agglomerate in fluid medium, they still entered into the human bronchial epithelial cells (BEAS-2B) and released Ni(2+) inside the cells. NiONPs at doses of 5, 10, and 20μg/cm(2) inhibited the cell viability. NiONPs' produced cytotoxicity was demonstrated through an apoptotic process, indicated by increased numbers of Annexin V positive cells and caspase-3 activation. The expression of SIRT1 was markedly down-regulated by the NiONPs, accompanied by the hyperacetylation of p53 (tumor protein 53) and overexpression of Bax (Bcl-2-associated X protein). However, overexpression of SIRT1 through resveratrol treatment or transfection clearly attenuated the NiONPs-induced apoptosis and activation of p53 and Bax. Our results suggest that the repression of SIRT1 may underlie the NiONPs-induced apoptosis via p53 hyperacetylation and subsequent Bax activation. Because SIRT1 participates in multiple biologic processes by deacetylation of dozens of substrates, this knowledge of the impact of NiONPs on SIRT1 may lead to an improved understanding of the toxic mechanisms of Nano-Ni and provide a molecular target to antagonize Nano-Ni toxicity.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a2b4f8884de2765bba0b0d0d34442088Test
https://doi.org/10.1016/j.taap.2015.03.024Test

المؤلفون: Liping Pei, Gao Peng, Lin Liu, Zhou Zhou, Lei Zhang, Qi-Zhong Qin, Qi Zhao, Hui-feng Pi, Yu Chen, Yonghui Lu, Xiang Mei, Zhengping Yu, Zhao-hui Zhang, Min Li, Yue-ming Jiang

المصدر: Cellular Physiology and Biochemistry, Vol 40, Iss 3-4, Pp 633-643 (2016)

مصطلحات موضوعية: 0301 basic medicine, inorganic chemicals, Adult, Male, medicine.medical_specialty, Multivariate analysis, Physiology, Epidemiology, chemistry.chemical_element, 010501 environmental sciences, 01 natural sciences, lcsh:Physiology, Toxicology, lcsh:Biochemistry, 03 medical and health sciences, Environmental health, Occupational Exposure, medicine, Odds Ratio, Prevalence, Humans, lcsh:QD415-436, 0105 earth and related environmental sciences, Dyslipidemias, Pollutant, Cadmium, lcsh:QP1-981, business.industry, Odds ratio, medicine.disease, Lipids, CADMIUM EXPOSURE, 030104 developmental biology, chemistry, Dyslipidemia, Multivariate Analysis, Female, Occupational exposure, business

الوصف: Background: Cadmium is a widespread environmental and occupational pollutant that accumulates in human body with a biological half-life exceeding 10 years. Cadmium exposure has been demonstrated to increase rates of cardiovascular diseases. Whether occupational cadmium exposure is associated with the increase in the prevalence of dyslipidemia and hence contributes to the risk of cardiovascular diseases is still equivocal. To test the hypothesis that exposure to cadmium is related to the prevalence of dyslipidemia, we examined the associations between blood cadmium concentration and the prevalence of dyslipidemia in workers occupationally exposed to cadmium in China. Methods: A cross-sectional survey on demographic data, blood cadmium level and lipid profile in cadmium exposed workers from seven cadmium smelting factories in central and southwestern China was conducted. We measured blood cadmium concentration and lipid components of 1489 cadmium exposed workers. The prevalence of dyslipidemia was compared across blood cadmium quartiles. Associations between the blood cadmium concentrations and the prevalence of dyslipidemia were assessed using confounder adjusted linear and logistic regressions. Results: The blood cadmium concentration was 3.61±0.84µg/L ( mean ±SD). The prevalence of dyslipidemia in this occupational population was 66.3%. Mean blood cadmium concentration of workers with dyslipedemia was significantly higher than that of workers without dyslipidemia (p

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7924ed69d5ec9e44ae0913f85debba9bTest
https://pubmed.ncbi.nlm.nih.gov/27898410Test

المؤلفون: Shangcheng Xu, Yan Wang, Xiao Zhang, Zhengping Yu, Lei Zhang, Yonghui Lu, Zhou Zhou, Xin Zhang, Jia-Chuan Xiong, Mindi He

المصدر: NeuroToxicology. 38:9-16

مصطلحات موضوعية: Iron-Sulfur Proteins, Male, inorganic chemicals, medicine.medical_specialty, Cellular respiration, Down-Regulation, Morris water navigation task, Oxidative phosphorylation, Toxicology, medicine.disease_cause, Aconitase, Superoxide dismutase, Mice, Adenosine Triphosphate, Oxygen Consumption, Nickel, Internal medicine, medicine, Animals, Lactic Acid, Maze Learning, Aconitate Hydratase, Cerebral Cortex, chemistry.chemical_classification, Reactive oxygen species, biology, Chemistry, General Neuroscience, Neurotoxicity, Brain, NAD, medicine.disease, Aerobiosis, Oxidative Stress, Endocrinology, Biochemistry, Exploratory Behavior, biology.protein, Oxidative stress

الوصف: The oral ingestion of soluble nickel compounds leads to neurological symptoms in humans. Deficiencies in aerobic metabolism induced by neurotoxic stimulus can cause an energy crisis in the brain that results in a variety of neurotoxic effects. In the present study, we focused on the aerobic metabolic states to investigate whether disturbance of aerobic metabolism was involved in nickel-induced neurological effects in mice. Mice were orally administered nickel chloride, and neurobehavioral performance was evaluated using the Morris water maze and open field tests at different time points. Aerobic metabolic states in the cerebral cortex were analyzed at the same time points at which neurobehavioral changes were evident. We found that nickel exposure caused deficits in both spatial memory and exploring activity in mice and that nickel was deposited in their cerebral cortex. Deficient aerobic metabolism manifested as decreased O2 consumption and ATP concentrations, lactate and NADH accumulation, and oxidative stress. Meanwhile, the activity of prototypical iron-sulfur clusters (ISCs) containing enzymes that are known to control aerobic metabolism, including complex I and aconitase, and the expression of ISC assembly scaffold protein (ISCU) were inhibited following nickel deposition. Overall, these data suggest that aerobic metabolic disturbances, which accompanied the neurobehavioral changes, may participate in nickel-induced neurologic effects. The inactivation of ISC containing metabolic enzymes may result in the disturbance of aerobic metabolism. A better understanding of how nickel impacts the energy metabolic processes may provide insight into the prevention of nickel neurotoxicity.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7c74d44a78f381f635605f8d3fe91065Test
https://doi.org/10.1016/j.neuro.2013.05.011Test