8,037 results match your criteria Archives Of Toxicology[Journal]


The potential of remdesivir to affect function, metabolism and proliferation of cardiac and kidney cells in vitro.

Arch Toxicol 2022 May 17. Epub 2022 May 17.

Institute of Pharmacology and Toxicology, University of Würzburg, Würzburg, Germany.

Remdesivir is a prodrug of a nucleoside analog and the first antiviral therapeutic approved for coronavirus disease. Recent cardiac safety concerns and reports on remdesivir-related acute kidney injury call for a better characterization of remdesivir toxicity and understanding of the underlying mechanisms. Here, we performed an in vitro toxicity assessment of remdesivir around clinically relevant concentrations (C 9 µM) using H9c2 rat cardiomyoblasts, neonatal mouse cardiomyocytes (NMCM), rat NRK-52E and human RPTEC/TERT1 cells as cell models for the assessment of cardiotoxicity or nephrotoxicity, respectively. Read More

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News and views : AUTOTACs join the arena for targeted protein degradation.

Arch Toxicol 2022 May 17. Epub 2022 May 17.

Institute of Toxicology, Mainz University Medical Center, Mainz, Germany.

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rVSV-ΔG-SARS-CoV-2-S vaccine: repeated intramuscular (IM) toxicity, local tolerance, immunogenicity and biodistribution study in NZW rabbits.

Arch Toxicol 2022 May 17. Epub 2022 May 17.

Department of Pharmacology, Israel Institute for Biological Research, Ness Ziona, Israel.

BriLife, a vector-based vaccine that utilizes the recombinant vesicular stomatitis virus (VSV) platform to express and present the spike antigen of SARS-CoV-2, is undergoing testing in a phase 2 clinical trial in Israel. A nonclinical repeated-dose (GLP) toxicity study in New Zealand white rabbits was performed to evaluate the potential toxicity, local tolerance, immunogenicity and biodistribution of the vaccine. rVSV-ΔG-SARS-CoV-2-S (or vehicle) was administered intramuscularly to two groups of animals (10, 10 PFU/animal, n = 10/sex/group) on three occasions, at 2-week intervals, followed by a 3-week recovery period. Read More

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Highly stable peptide adducts from hard keratins as biomarkers to verify local sulfur mustard exposure of hair by high-resolution mass spectrometry.

Arch Toxicol 2022 May 16. Epub 2022 May 16.

Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstrasse 11, 80937, Munich, Germany.

In the recent past, the blister agent sulfur mustard (SM) deployed by the terroristic group Islamic State has caused a huge number of civilian and military casualties in armed conflicts in the Middle East. The vaporized or aerolized agent might be inhaled and have direct contact to skin and hair. Reaction products of SM with plasma proteins (adducts) represent well-established systemic targets for the bioanalytical verification of exposure. Read More

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Excretion time courses of lambda-cyhalothrin metabolites in the urine of strawberry farmworkers and effect of coexposure with captan.

Arch Toxicol 2022 May 14. Epub 2022 May 14.

Department of Environmental and Occupational Health, Chair in Toxicological Risk Assessment and Management, and Public Health Research Center (CReSP), University of Montreal, Roger-Gaudry Building, Main Station, P.O. Box 6128, Montreal, QC, U436H3C 3J7, Canada.

There are limited literature data on the impact of coexposure on the toxicokinetics of pesticides in agricultural workers. Using the largely employed pyrethroid lambda-cyhalothrin (LCT) and fungicide captan as sentinel pesticides, we compared individual temporal profiles of biomarkers of exposure to LCT in strawberry field workers following an application episode of LCT alone or in coexposure with captan. Participants provided all urine voided over a 3-day period after an application of a pesticide formulation containing LCT alone (E1) or LCT mixed with captan (E2), and in some cases following re-entry in treated field (E3). Read More

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The EU chemicals strategy for sustainability: an opportunity to develop new approaches for hazard and risk assessment.

Arch Toxicol 2022 May 11. Epub 2022 May 11.

Department of Bioanalytical Ecotoxicology, Helmholtz Centre for Environmental Research-UFZ, Permoserstr. 15, 04318, Leipzig, Germany.

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Chicken heterophils extracellular traps act as early effectors against cyclopiazonic acid dependent upon NADPH oxidase, ROS and glycolysis.

Arch Toxicol 2022 May 4. Epub 2022 May 4.

College of Life Sciences and Engineering, Foshan University, Foshan, 528231, Guangdong, People's Republic of China.

Cyclopiazonic acid (CPA) is a secondary metabolite produced by Aspergillus and Penicillium, which is present in contaminated crops and food, causing severe toxicity to humans and animals. Heterophil extracellular traps (HETs) are a novel host innate immune mechanism of chicken heterophils against pathogen infection. However, whether CPA can cause immunotoxicity of heterophils on HETs release remains unclear. Read More

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Salivary nitrate/nitrite and acetaldehyde in humans: potential combination effects in the upper gastrointestinal tract and possible consequences for the in vivo formation of N-nitroso compounds-a hypothesis.

Arch Toxicol 2022 Jun 4;96(6):1905-1914. Epub 2022 May 4.

Institut für Agrar- und Ernährungswissenschaften, Martin-Luther-Universität Halle-Wittenberg, Weinbergweg 22, 06120, Halle (Saale), Germany.

Subsequent to the dietary uptake of nitrate/nitrite in combination with acetaldehyde/ethanol, combination effects resulting from the sustained endogenous exposure to nitrite and acetaldehyde may be expected. This may imply locoregional effects in the upper gastrointestinal tract as well as systemic effects, such as a potential influence on endogenous formation of N-nitroso compounds (NOC). Salivary concentrations of the individual components nitrate and nitrite and acetaldehyde are known to rise after ingestion, absorption and systemic distribution, thereby reflecting their respective plasma kinetics and parallel secretion through the salivary glands as well as the microbial/enzymatic metabolism in the oral cavity. Read More

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Replacement of animal testing by integrated approaches to testing and assessment (IATA): a call for in vivitrosi.

Arch Toxicol 2022 May 3. Epub 2022 May 3.

Center for Alternatives to Animal Testing (CAAT), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA.

Alternative methods to animal use in toxicology are evolving with new advanced tools and multilevel approaches, to answer from one side to 3Rs requirements, and on the other side offering relevant and valid tests for drugs and chemicals, considering also their combination in test strategies, for a proper risk assessment.While stand-alone methods, have demonstrated to be applicable for some specific toxicological predictions with some limitations, the new strategy for the application of New Approach Methods (NAM), to solve complex toxicological endpoints is addressed by Integrated Approaches for Testing and Assessment (IATA), aka Integrated Testing Strategies (ITS) or Defined Approaches for Testing and Assessment (DA). The central challenge of evidence integration is shared with the needs of risk assessment and systematic reviews of an evidence-based Toxicology. Read More

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microRNAs signatures as potential biomarkers of structural cardiotoxicity in human-induced pluripotent stem-cell derived cardiomyocytes.

Arch Toxicol 2022 Apr 29. Epub 2022 Apr 29.

UCB Biopharma SRL, Braine L'Alleud, Belgium.

Identification of early biomarkers of heart injury and drug-induced cardiotoxicity is important to eliminate harmful drug candidates early in preclinical development and to prevent severe drug effects. The main objective of this study was to investigate the expression of microRNAs (miRNAs) in human-induced pluripotent stem cell cardiomyocytes (hiPSC-CM) in response to a broad range of cardiotoxic drugs. Next generation sequencing was applied to hiPSC-CM treated for 72 h with 40 drugs falling into the categories of functional (i. Read More

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Recommendations on dose level selection for repeat dose toxicity studies.

Arch Toxicol 2022 Apr 29. Epub 2022 Apr 29.

Syngenta Ltd., Bracknell, UK.

Prior to registering and marketing any new pharmaceutical, (agro)chemical or food ingredient product manufacturers must, by law, generate data to ensure human safety. Safety testing requirements vary depending on sector, but generally repeat-dose testing in animals form the basis for human health risk assessments. Dose level selection is an important consideration when designing such studies, to ensure that exposure levels that lead to relevant hazards are identified. Read More

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Pharmacological evaluation and forensic case series of N-pyrrolidino etonitazene (etonitazepyne), a newly emerging 2-benzylbenzimidazole 'nitazene' synthetic opioid.

Arch Toxicol 2022 Jun 28;96(6):1845-1863. Epub 2022 Apr 28.

Laboratory of Toxicology, Department of Bioanalysis, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.

Novel synthetic opioids continue to emerge on recreational drug markets worldwide. In response to legislative bans on fentanyl analogues, non-fentanyl structural templates, such as 2-benzylbenzimidazoles ('nitazenes'), are being exploited to create new μ-opioid receptor (MOR) agonists. Here, we pharmacologically characterize an emerging cyclic analogue of etonitazene, called N-pyrrolidino etonitazene (etonitazepyne), using in vitro and in vivo methods. Read More

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Mechanisms of opioid-induced respiratory depression.

Arch Toxicol 2022 Apr 26. Epub 2022 Apr 26.

University of Sydney, Sydney, NSW, Australia.

Opioid-induced respiratory depression (OIRD), the primary cause of opioid-induced death, is the neural depression of respiratory drive which, together with a decreased level of consciousness and obstructive sleep apnea, cause ventilatory insufficiency. Variability of responses to opioids and individual differences in physiological and neurological states (e.g. Read More

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First identification, chemical analysis and pharmacological characterization of N-piperidinyl etonitazene (etonitazepipne), a recent addition to the 2-benzylbenzimidazole opioid subclass.

Arch Toxicol 2022 Jun 21;96(6):1865-1880. Epub 2022 Apr 21.

Laboratory of Toxicology, Department of Bioanalysis, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.

N-Piperidinyl etonitazene ('etonitazepipne') represents a recent addition to the rapidly expanding class of 2-benzylbenzimidazole 'nitazene' opioids. Following its first identification in an online-sourced powder and in biological samples from a patient seeking help for detoxification, this report details its in-depth chemical analysis and pharmacological characterization. Analysis of the powder via different techniques (LC-HRMS, GC-MS, UHPLC-DAD, FT-IR) led to the unequivocal identification of N-piperidinyl etonitazene. Read More

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Renal hypoxia-HIF-PHD-EPO signaling in transition metal nephrotoxicity: friend or foe?

Arch Toxicol 2022 Jun 21;96(6):1573-1607. Epub 2022 Apr 21.

Physiology and Pathophysiology of Cells and Membranes, Medical School EWL, Bielefeld University, R.1 B2-13, Morgenbreede 1, 33615 Bielefeld, Germany.

The kidney is the main organ that senses changes in systemic oxygen tension, but it is also the key detoxification, transit and excretion site of transition metals (TMs). Pivotal to oxygen sensing are prolyl-hydroxylases (PHDs), which hydroxylate specific residues in hypoxia-inducible factors (HIFs), key transcription factors that orchestrate responses to hypoxia, such as induction of erythropoietin (EPO). The essential TM ion Fe is a key component and regulator of the hypoxia-PHD-HIF-EPO (HPHE) signaling axis, which governs erythropoiesis, angiogenesis, anaerobic metabolism, adaptation, survival and proliferation, and hence cell and body homeostasis. Read More

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Comprehensive interpretation of in vitro micronucleus test results for 292 chemicals: from hazard identification to risk assessment application.

Arch Toxicol 2022 Apr 21. Epub 2022 Apr 21.

Environmental Health Science and Research Bureau, Environmental and Radiation Health Sciences Directorate, Healthy Environment and Consumer Safety Branch, Health Canada, Ottawa, ON, Canada.

Risk assessments are increasingly reliant on information from in vitro assays. The in vitro micronucleus test (MNvit) is a genotoxicity test that detects chromosomal abnormalities, including chromosome breakage (clastogenicity) and/or whole chromosome loss (aneugenicity). In this study, MNvit datasets for 292 chemicals, generated by the US EPA's ToxCast program, were evaluated using a decision tree-based pipeline for hazard identification. Read More

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Reversal of genetic brain iron accumulation by N,N'-bis(2-mercaptoethyl)isophthalamide, a lipophilic metal chelator, in mice.

Arch Toxicol 2022 Apr 21. Epub 2022 Apr 21.

Department of Biomedical and Nutritional Sciences, University of Massachusetts Lowell, Lowell, MA, USA.

N,N'-bis(2-mercaptoethyl)isophthalamide (NBMI) is a novel lipophilic metal chelator and antioxidant used in mercury poisoning. Recent studies have suggested that NBMI may also bind to other metals such as lead and iron. Since NBMI can enter the brain, we evaluated if NBMI removes excess iron from the iron-loaded brain and ameliorates iron-induced oxidative stress. Read More

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Assessment of multiple mycotoxin exposure and its association with food consumption: a human biomonitoring study in a pregnant cohort in rural Bangladesh.

Arch Toxicol 2022 Apr 19. Epub 2022 Apr 19.

Institute of Public Health, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117, Berlin, Germany.

Aflatoxins (AFs), ochratoxin A (OTA), citrinin (CIT), fumonisin B (FB), zearalenone (ZEN), and deoxynivalenol (DON) are mycotoxins that may contaminate diets, especially in low-income settings, with potentially severe health consequences. This study investigates the exposure of 439 pregnant women in rural Bangladesh to 35 mycotoxins and their corresponding health risks and links their exposure to certain foods and local stimulants. Overall, 447 first-morning urine samples were collected from pregnant women between July 2018 and November 2019. Read More

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Dapagliflozin protects against doxorubicin-induced cardiotoxicity by restoring STAT3.

Arch Toxicol 2022 Apr 19. Epub 2022 Apr 19.

Division of Cardiology, Department of Internal Medicine, Chi-Mei Medical Center, Tainan, Taiwan.

Doxorubicin (Dox), an effective therapy in different types of cancer, is known to exhibit cardiotoxic effects. Despite previous studies indicating the benefits of dapagliflozin (DAPA) in patients experiencing heart failure, it remains uncertain whether DAPA exerts a protective effect on Dox-induced cardiac dysfunction. Signal transducer and activator of transcription 3 (STAT3) participates in various mechanisms of cardioprotection. Read More

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Identification of environmental chemicals that activate p53 signaling after in vitro metabolic activation.

Arch Toxicol 2022 Apr 18. Epub 2022 Apr 18.

National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Rockville, MD, 20850, USA.

Currently, approximately 80,000 chemicals are used in commerce. Most have little-to-no toxicity information. The U. Read More

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Circular RNA circNIPBL promotes NNK-induced DNA damage in bronchial epithelial cells via the base excision repair pathway.

Arch Toxicol 2022 Apr 18. Epub 2022 Apr 18.

State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China.

Environmental chemical exposure often causes DNA damage, which leads to cellular dysfunction and the development of diseases. 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a tobacco-specific carcinogen that is known to cause DNA damage, while remains unknown about the underlying mechanism. In this study, simulated doses of NNK exposure in smokers, ranging from 50 to 300 μM, were used to detect the DNA damage effects of NNK in two human bronchial epithelial cells, 16HBE and BEAS-2B. Read More

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Extending the viability of human precision-cut intestinal slice model for drug metabolism studies.

Arch Toxicol 2022 Jun 15;96(6):1815-1827. Epub 2022 Apr 15.

Department of Pharmaceutical Technology and Biopharmacy, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, The Netherlands.

Human Precision-cut intestinal slices (hPCIS) are used to study intestinal physiology, pathophysiology, drug efficacy, toxicology, kinetics, and metabolism. However, the use of this ex vivo model is restricted to approximately a 24 h timeframe because of declining viability of the hPCIS during traditional culture. We hypothesized that we could extend the hPCIS viability by using organoid medium. Read More

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Research for type 2 diabetes mellitus in endemic arsenism areas in central China: role of low level of arsenic exposure and KEAP1 rs11545829 polymorphism.

Arch Toxicol 2022 Jun 14;96(6):1673-1683. Epub 2022 Apr 14.

Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, No. 157 Baojian Road, Nangang District, Harbin, 150081, Heilongjiang Province, China.

Type 2 diabetes mellitus (T2DM) is one of the major public health problems worldwide; both genetic and environmental factors are its risk factors. Arsenic, an environmental pollutant, might be a risk factor for T2DM, but the association of low-to-moderate level arsenic exposure with the risk of T2DM is still inconsistent. Single nucleotide polymorphisms (SNPs) can affect the development of T2DM, but the study on KEAP1 rs11545829 (G>A) SNP is few. Read More

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Towards better prediction of xenobiotic genotoxicity: CometChip technology coupled with a 3D model of HepaRG human liver cells.

Arch Toxicol 2022 Apr 13. Epub 2022 Apr 13.

Fougères Laboratory, Toxicology of Contaminants Unit, ANSES, French Agency for Food, Environmental and Occupational Health and Safety, 10 B rue Claude Bourgelat, 35306, Fougères, France.

Toxicology is facing a major change in the way toxicity testing is conducted by moving away from animal experimentation towards animal-free methods. To improve the in vitro genotoxicity assessment of chemical and physical compounds, there is an urgent need to accelerate the development of 3D cell models in high-throughput DNA damage detection platforms. Among the alternative methods, hepatic cell lines are a relevant in vitro model for studying the functions of the liver. Read More

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The pro-radical hydrogen peroxide as a stable hydroxyl radical distributor: lessons from pancreatic beta cells.

Arch Toxicol 2022 Apr 13. Epub 2022 Apr 13.

Institute of Biochemistry, University of Greifswald, Greifswald, Germany.

The toxic potential of HO is limited, even if intracellular concentrations of HO under conditions of oxidative stress increase to the micromolar concentration range. Its toxicity is mostly restricted to the oxidation of highly reactive thiol groups, some of which are functionally very important. Subsequently, the HO radical is generated spontaneously from HO in the Fenton reaction. Read More

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In silico, in vitro, and in vivo human metabolism of acetazolamide, a carbonic anhydrase inhibitor and common "diuretic and masking agent" in doping.

Arch Toxicol 2022 Apr 11. Epub 2022 Apr 11.

Department of Excellence of Biomedical Sciences and Public Health, Section of Legal Medicine, Unit of Forensic Toxicology, Marche Polytechnic University, Via Tronto 10/a, 60126, Ancona, AN, Italy.

Acetazolamide (ACZ) is a carbonic anhydrase inhibitor prescribed for the treatment of various pathologies. It is also used in doping and is prohibited in and out of sportive competitions. ACZ was reported not to undergo metabolization. Read More

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Polymorphisms of an oncogenic gene, mesothelin, predict the risk and prognosis of gastric cancer in a Chinese Han population.

Arch Toxicol 2022 Apr 9. Epub 2022 Apr 9.

Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China.

Mesothelin (MSLN) is a cell surface protein associated with tumor invasion and metastasis. This study aims to explore the biological function of MSLN in gastric cancer and to evaluate the association of MSLN polymorphism (rs3764247, rs3764246, rs12597489, rs1057147, rs3765319) with the risk and prognosis of gastric cancer. Small interfering RNA (siRNA) transfection and MSLN overexpression were performed in human gastric cancer cell lines, respectively. Read More

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New aspects in deriving health-based guidance values for bromate in swimming pool water.

Arch Toxicol 2022 Jun 6;96(6):1623-1659. Epub 2022 Apr 6.

Institute of Environmental Toxicology, University of Halle, Halle/Saale, Germany.

Bromate, classified as a EU CLP 1B carcinogen, is a typical by-product of the disinfection of drinking and swimming pool water. The aim of this study was (a) to provide data on the occurrence of bromate in pool water, (b) to re-evaluate the carcinogenic MOA of bromate in the light of existing data, (c) to assess the possible exposure to bromate via swimming pool water and (d) to inform the derivation of cancer risk-related bromate concentrations in swimming pool water. Measurements from monitoring analysis of 229 samples showed bromate concentrations in seawater pools up to 34 mg/L. Read More

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Liver transcriptome analyses of acute poisoning and recovery of male ICR mice exposed to the mushroom toxin α-amanitin.

Arch Toxicol 2022 Jun 6;96(6):1751-1766. Epub 2022 Apr 6.

Chinese Center for Disease Control and Prevention, National Institute for Occupational Health and Poison Control, Beijing, 100050, China.

Approximately 70-90% of mushroom poisoning deaths are caused by α-amanitin-induced liver injury resulting from RNA polymerase II (RNAP II) inhibition. Liver regeneration ability may contribute greatly to individual survival after α-amanitin poisoning. However, it is unclear what cellular pathways are activated to stimulate regeneration. Read More

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Pharmacokinetics and toxicity evaluation following oral exposure to bisphenol F.

Arch Toxicol 2022 Jun 4;96(6):1711-1728. Epub 2022 Apr 4.

Bio Technology Division, GLP 2 Center, Korea Conformity Laboratories (KCL), 8, Gaetbeol-ro 145 beon-gil, Yeonsu-gu, Incheon, 21999, South Korea.

Bisphenol F is a substitute material for bisphenol A and is widely used in household products as a raw material for polycarbonate resin, epoxy resin, and plastic reinforcement. It is known to be mainly used in food containers, thermal paper for receipts, and coatings for water pipes. In some countries, bisphenol F has been detected in drinking water and human urine samples. Read More

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