Metals and Metal Complexes in Diseases with a Focus on COVID-19: Facts and Opinions

A special issue of Biology (ISSN 2079-7737). This special issue belongs to the section "Biochemistry and Molecular Biology".

Deadline for manuscript submissions: closed (31 January 2023) | Viewed by 29251

Special Issue Editors


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Guest Editor
Department of Biomedicine and Environmental Research, The John Paul II Catholic University of Lublin, 20-708 Lublin, Poland
Interests: mechanisms of toxicity of selected elements; mechanisms of metal interactions; seeking the most sensitive biomarkers to assess organism reactions to some metals; cytotoxicity of metals; bioelements; oxidative stress; antioxidants; in vivo/in vitro studies; experimental toxicology
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
1. Faculdade de Ciências e Tecnologia (FCT), Campus de Gambelas, Universidade do Algarve, 8005-139 Faro, Portugal
2. CCMAR, Campus de Gambelas, Universidade do Algarve, 8005-139 Faro, Portugal
Interests: metals in molecular sciences; decavanadate biochemistry; polyoxometalate (POM) interactions with proteins; metals and biomedical applications
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Department of Chemistry & Biochemistry, Old Dominion University, Norfolk, VA 23529, USA
Interests: biological and inorganic chemistry; bioinorganic and inorganic reaction mechanisms; synthesis, characterization, and biomedical uses of metal complexes

Special Issue Information

Dear Colleagues, 

The year 2020 was a year like no other, with the COVID-19 pandemic and subsequent health crisis profoundly impacting our lives, not to mention the worldwide consequences for education and research, which will take time to elucidate but are predicted to be particularly dramatic. Add to that the profound loss of loved ones and it is easy to lose hope, but we must hold on to the belief that better times are ahead. 

Professionals in the fields of education and research know that certain trace elements (such as copper, cobalt, nickel, and zinc) are considered potential candidates for therapeutic applications. Vanadium, due to its unique features and multidirectional biological activity, has also been attracting interest in many research centers worldwide as a potential candidate in the treatment of certain human diseases such as cancer and diabetes, as well as bacterial and viral illness. Other metals, which are not essential to life, such as platinum, ruthenium, iridium, rhodium, and gold, are also pharmacologically interesting; hence, they are extensively being investigated in biology and used to biomedical applications.

The number of studies on the use of metals and metal-containing compounds in medicine is continually growing. However, despite the progress made in recent years in the study of the pharmacological activity of various metal-containing complexes, further analyses are needed. There are certain aspects which must be elaborated on before metal-containing species can be used as metallopharmaceuticals in the future. These include an examination of the susceptibility of different cells/tissues to the effects of metal-containing compounds; recognition of key factors (ligands) that may affect the mode of their action; identification of metal-containing species as an important factor in the assessment of their toxicity and the mechanisms of action; examination of well-defined forms of metals in terms of their selectivity, specificity, transport, distribution, interference in the signal transduction pathways, and the mechanisms of absorption and excretion thereof; and direct or indirect correlations between the biological effects of metal-containing compounds (including polyoxometalates) and metal-containing complexes with effects observed in cancer, diabetes, and neurological disorders. Additionally, it has been emphasized that therapeutic targets, pharmacokinetics, and pharmacodynamics have to be clarified in detail in order to design metal-based drugs more efficiently.

We invite authors to submit original research exploring biological metals and diseases, the pharmacological activity of metallodrugs, clinical studies, and/or review reports on promising metals and metal-based drug candidates with a focus on strategies aiming to improve their pharmacological features and on links between metal-based agents and potential therapies for human pathologies with a mechanistic analysis. Bearing in mind the current COVID-19 pandemic, we also invite researchers to submit papers on recent data on critical factors—among others, biologically important metal ions such as Ca2+ and Zn2+—that can influence COVID-19-related susceptibility, severity, and mortality.

Potential topics include but are not limited to:

  • New data on trace element status in COVID-19 patients ;
  • Metals susceptibility and severity of COVID-19;
  • Molecular mechanisms related to COVID-19 and therapeutic strategies;
  • Metal and metal–organic complexes targeting viruses and treatment of a wide range of diseases;
  • Current areas with the most emphasis on metallobased metal center pharmacology;
  • Novel therapeutic metal-based agents having an impact on medicinal practice;
  • Biological metals and diseases;
  • Diseases and symptoms induced by metal implants;
  • Latest progress in the design of pharmacologically active complexes comprising metals and a risk associated with their toxicity;
  • Metal chelation therapy to treat diseases;
  • Metal biological targets and diseases;
  • Design and pharmacological evaluation of novel metal-containing compounds as promising future metallodrugs (synthesis, structure analysis, properties, in vitro/in vivo effects);
  • Identification of molecular targets and mechanistic details of potential metal-based drugs: implications of oxidative stress;
  • Cancer and diabetic mechanistic relationship for metal-containing compounds (including polyoxometalates);
  • Mechanistic relationship between metal and metal-containing compounds (including polyoxometalates) with effects observed in putative biological targets and/or changes in protein expression and/or enzymatic activity;
  • Stability and speciation of metal and metal-containing compounds (including polyoxometalates) in biological solutions.
Dr. Agnieszka Ścibior
Prof. Dr. Manuel Aureliano
Dr. Alvin A. Holder
Prof. Dr. Juan Llopis 
Guest Editors

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Keywords

  • new data on trace element status in COVID-19 patients
  • metals susceptibility and severity of COVID-19
  • molecular mechanisms related to COVID-19 and therapeutic strategies
  • metal and metal–organic complexes targeting viruses and treatment of a wide range of diseases
  • current areas with the most emphasis on metallobased metal center pharmacology
  • novel therapeutic metal-based agents having an impact on medicinal practice
  • biological metals and diseases
  • diseases and symptoms induced by metal implants
  • latest progress in the design of pharmacologically active complexes comprising metals and a risk associated with their toxicity
  • metal chelation therapy to treat diseases
  • metal biological targets and diseases
  • design and pharmacological evaluation of novel metal-containing compounds as promising future metallodrugs (synthesis, structure analysis, properties, in vitro/in vivo effects)
  • identification of molecular targets and mechanistic details of potential metal-based drugs: implications of oxidative stress
  • cancer and diabetic mechanistic relationship for metal-containing compounds (including polyoxometalates)
  • mechanistic relationship between metal and metal-containing compounds (including polyoxometalates) with effects observed in putative biological targets and/or changes in protein expression and/or enzymatic activity
  • stability and speciation of metal and metal-containing compounds (including polyoxometalates) in biological solutions

Published Papers (9 papers)

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Editorial

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5 pages, 652 KiB  
Editorial
Metals and Metal Complexes in Diseases with a Focus on COVID-19: Facts and Opinions
by Agnieszka Ścibior, Manuel Aureliano, Alvin A. Holder and Juan Llopis
Biology 2023, 12(6), 868; https://doi.org/10.3390/biology12060868 - 15 Jun 2023
Viewed by 924
Abstract
In the present Special Issue on “Metals and Metal Complexes in Diseases with a Focus on COVID-19: Facts and Opinions”, an attempt has been made to include reports updating our knowledge of elements considered to be potential candidates for therapeutic applications and certain [...] Read more.
In the present Special Issue on “Metals and Metal Complexes in Diseases with a Focus on COVID-19: Facts and Opinions”, an attempt has been made to include reports updating our knowledge of elements considered to be potential candidates for therapeutic applications and certain metal-containing species, which are extensively being examined towards their potential biomedical use due to their specific physicochemical properties [...] Full article
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Research

Jump to: Editorial, Review

18 pages, 3215 KiB  
Article
The Impact of Long-Term Clinoptilolite Administration on the Concentration Profile of Metals in Rodent Organisms
by Ivan Dolanc, Lejla Ferhatović Hamzić, Tatjana Orct, Vedran Micek, Iva Šunić, Antonija Jonjić, Jasna Jurasović, Saša Missoni, Miran Čoklo and Sandra Kraljević Pavelić
Biology 2023, 12(2), 193; https://doi.org/10.3390/biology12020193 - 26 Jan 2023
Cited by 1 | Viewed by 6200
Abstract
Heavy metals are dangerous systemic toxicants that can induce multiple organ damage, primarily by inducing oxidative stress and mitochondrial damage. Clinoptilolite is a highly porous natural mineral with a magnificent capacity to eliminate metals from living organisms, mainly by ion-exchange and adsorption, thus [...] Read more.
Heavy metals are dangerous systemic toxicants that can induce multiple organ damage, primarily by inducing oxidative stress and mitochondrial damage. Clinoptilolite is a highly porous natural mineral with a magnificent capacity to eliminate metals from living organisms, mainly by ion-exchange and adsorption, thus providing detoxifying, antioxidant and anti-inflammatory medicinal effects. The in vivo efficiency and safety of the oral administration of clinoptilolite in its activated forms, tribomechanically activated zeolite (TMAZ) and Panaceo-Micro-Activated (PMA) zeolite, as well as the impact on the metallic biodistribution, was examined in healthy female rats. Concentration profiles of Al, As, Cd, Co, Pb, Ni and Sr were measured in rat blood, serum, femur, liver, kidney, small and large intestine, and brain using inductively coupled plasma mass spectrometry (ICP-MS) after a 12-week administration period. Our results point to a beneficial effect of clinoptilolite materials on the concentration profile of metals in female rats supplemented with the corresponding natural clinoptilolite materials, TMAZ and PMA zeolite. The observed decrease of measured toxicants in the kidney, femur, and small and large intestine after three months of oral intake occurred concomitantly with their most likely transient release into the bloodstream (serum) indicative of a detoxification process. Full article
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19 pages, 3507 KiB  
Article
The Preyssler-Type Polyoxotungstate Exhibits Anti-Quorum Sensing, Antibiofilm, and Antiviral Activities
by Leonor Faleiro, Ana Marques, João Martins, Luísa Jordão, Isabel Nogueira, Nadiia I. Gumerova, Annette Rompel and Manuel Aureliano
Biology 2022, 11(7), 994; https://doi.org/10.3390/biology11070994 - 30 Jun 2022
Cited by 9 | Viewed by 2100
Abstract
The increase in bacterial resistance to antibiotics has led researchers to find new compounds or find combinations between different compounds with potential antibacterial action and with the ability to prevent the development of antibiotic resistance. Polyoxotungstates (POTs) are inorganic clusters that may fulfill [...] Read more.
The increase in bacterial resistance to antibiotics has led researchers to find new compounds or find combinations between different compounds with potential antibacterial action and with the ability to prevent the development of antibiotic resistance. Polyoxotungstates (POTs) are inorganic clusters that may fulfill that need, either individually or in combination with antibiotics. Herein, we report the ability of the polyoxotungstates (POTs) with Wells-Dawson P2W18, P2W17, P2W15, and Preyssler P5W30 type structures to differently affect Gram-negative and Gram-positive microorganisms, either susceptible or resistant to antibiotics. The compound P5W30 showed the highest activity against the majority of the tested bacterial strains in comparison with the other tested POTs (P2W15, P2W17 and P2W18) that did not show inhibition zones for the Gram-negative bacteria, A. baumanii I73775, E. coli DSM 1077, E. coli I73194, K. pneumoniae I7092374, and P. aeruginosa C46281). Generally, the results evidenced that Gram-positive bacteria are more susceptible to the POTs tested. The compound P5W30 was the one most active against S. aureus ATCC 6538 and MRSA16, reaching <0.83 mg·mL−1 (100 μM) and 4.96 mg·mL−1 (600 μM), respectively. Moreover, it was verified by NMR spectroscopy that the most promising POT, P5W30, remains intact under all the experimental conditions, after 24 h at 37 °C. This prompted us to further evaluate the anti-quorum sensing activity of P5W30 using the biosensor Chromobacterium violaceum CV026, as well as its antibiofilm activity both individually and in combination with the antibiotic cefoxitin against the methicillin-resistant Staphylococcus aureus 16 (MRSA16). P5W30 showed a synergistic antibacterial effect with the antibiotic cefoxitin and chloramphenicol against MRSA16. Moreover, the antibiofilm activity of P5W30 was more pronounced when used individually, in comparison with the combination with the antibiotic cefoxitin. Finally, the antiviral activity of P5W30 was tested using the coliphage Qβ, showing a dose-dependent response. The maximum inactivation was observed at 750 μM (6.23 mg·mL−1). In sum, P5W30 shows anti-quorum sensing and antibiofilm activities besides being a potent antibacterial agent against S. aureus and to exhibit antiviral activities against enteric viruses. Full article
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15 pages, 939 KiB  
Article
Effect of Bis(maltolato)oxovanadium(IV) on Zinc, Copper, and Manganese Homeostasis and DMT1 mRNA Expression in Streptozotocin-Induced Hyperglycemic Rats
by Cristina Sánchez-González, Laura Moreno, Pilar Aranda, María Montes-Bayón, Juan Llopis and Lorenzo Rivas-García
Biology 2022, 11(6), 814; https://doi.org/10.3390/biology11060814 - 25 May 2022
Cited by 5 | Viewed by 1812
Abstract
Our aim was to examine whether vanadium (IV) corrects alterations in zinc, copper and manganese homeostasis, observed in streptozotocin-induced hyperglycemic rats, and whether such changes are related to divalent metal transporter 1 (DMT1) mRNA expression, and antioxidant and proinflammatory parameters. Four groups of [...] Read more.
Our aim was to examine whether vanadium (IV) corrects alterations in zinc, copper and manganese homeostasis, observed in streptozotocin-induced hyperglycemic rats, and whether such changes are related to divalent metal transporter 1 (DMT1) mRNA expression, and antioxidant and proinflammatory parameters. Four groups of Wistar rats were examined: control; hyperglycemic (H); hyperglycemic treated with 1 mg V/day (HV); and hyperglycemic treated with 3 mg V/day (HVH). Vanadium was supplied in drinking water as bis(maltolato)oxovanadium(IV) for five weeks. Zinc, copper and manganese were measured in food, excreta, serum and tissues. DMT1 mRNA expression was quantified in the liver. Hyperglycemic rats showed increased Zn and Cu absorption and content in the liver, serum, kidneys and femurs; DMT1 expression also increased (p < 0.05 in all cases). HV rats showed no changes compared to H rats other than decreased DMT1 expression (p < 0.05). In the HVH group, decreased absorption and tissular content of studied elements (p < 0.05 in all cases) and DMT1 expression compared to H (p < 0.05) were observed. Liver zinc, copper and manganese content correlated positively with glutathione peroxidase activity and negatively with catalase activity (p < 0.05 in both cases). In conclusion, treatment with 3 mg V/d reverted the alterations in zinc and copper homeostasis caused by hyperglycemia, possibly facilitated by decreased DMT1 expression. Full article
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Review

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32 pages, 798 KiB  
Review
Importance of Magnesium Status in COVID-19
by Fernando Guerrero-Romero, Oliver Micke, Luis E. Simental-Mendía, Martha Rodríguez-Morán, Juergen Vormann, Stefano Iotti, Nikolina Banjanin, Andrea Rosanoff, Shadi Baniasadi, Guitti Pourdowlat and Mihai Nechifor
Biology 2023, 12(5), 735; https://doi.org/10.3390/biology12050735 - 18 May 2023
Cited by 10 | Viewed by 5294
Abstract
A large amount of published research points to the interesting concept (hypothesis) that magnesium (Mg) status may have relevance for the outcome of COVID-19 and that Mg could be protective during the COVID disease course. As an essential element, Mg plays basic biochemical, [...] Read more.
A large amount of published research points to the interesting concept (hypothesis) that magnesium (Mg) status may have relevance for the outcome of COVID-19 and that Mg could be protective during the COVID disease course. As an essential element, Mg plays basic biochemical, cellular, and physiological roles required for cardiovascular, immunological, respiratory, and neurological functions. Both low serum and dietary Mg have been associated with the severity of COVID-19 outcomes, including mortality; both are also associated with COVID-19 risk factors such as older age, obesity, type 2 diabetes, kidney disease, cardiovascular disease, hypertension, and asthma. In addition, populations with high rates of COVID-19 mortality and hospitalization tend to consume diets high in modern processed foods, which are generally low in Mg. In this review, we review the research to describe and consider the possible impact of Mg and Mg status on COVID-19 showing that (1) serum Mg between 2.19 and 2.26 mg/dL and dietary Mg intakes > 329 mg/day could be protective during the disease course and (2) inhaled Mg may improve oxygenation of hypoxic COVID-19 patients. In spite of such promise, oral Mg for COVID-19 has thus far been studied only in combination with other nutrients. Mg deficiency is involved in the occurrence and aggravation of neuropsychiatric complications of COVID-19, including memory loss, cognition, loss of taste and smell, ataxia, confusion, dizziness, and headache. Potential of zinc and/or Mg as useful for increasing drug therapy effectiveness or reducing adverse effect of anti-COVID-19 drugs is reviewed. Oral Mg trials of patients with COVID-19 are warranted. Full article
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28 pages, 847 KiB  
Review
COVID-19 in Adult Patients with Hematological Malignancies—Lessons Learned after Three Years of Pandemic
by Iwona Hus, Agnieszka Szymczyk, Joanna Mańko and Joanna Drozd-Sokołowska
Biology 2023, 12(4), 545; https://doi.org/10.3390/biology12040545 - 3 Apr 2023
Cited by 2 | Viewed by 2380
Abstract
The COVID-19 pandemic is undoubtedly the most difficult health challenge of the 21st century with more than 600 million laboratory-confirmed SARS-CoV-2 infections and over 6.5 million deaths worldwide. The coronavirus pandemic contributed to rapid development of mRNA vaccines, which, along with new antiviral [...] Read more.
The COVID-19 pandemic is undoubtedly the most difficult health challenge of the 21st century with more than 600 million laboratory-confirmed SARS-CoV-2 infections and over 6.5 million deaths worldwide. The coronavirus pandemic contributed to rapid development of mRNA vaccines, which, along with new antiviral drugs, have been the subject of extensive research for many decades. Nevertheless, elderly, multi-morbid and immunocompromised patients continue to face a more severe clinical course and a higher risk of death from COVID-19, even now that the risk of COVID-19 in the general population is significantly reduced due to the introduction of global vaccination strategies. In this paper, we present the mechanisms of increased susceptibility to infectious complications and the evolution of the clinical course of COVID-19 in patients with hematological malignancies, taking into account the mutation of the virus and the introduction of vaccines and new antiviral drugs. We also present current recommendations for prophylactic and therapeutic management in patients with hematological malignancies. Full article
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12 pages, 328 KiB  
Review
Interaction of Metals, Menopause and COVID-19—A Review of the Literature
by Tomasz Męcik-Kronenberg, Aleksandra Kuć, Daria Kubik-Machura, Klaudia Kościelecka and Lidia Radko
Biology 2023, 12(3), 350; https://doi.org/10.3390/biology12030350 - 22 Feb 2023
Cited by 1 | Viewed by 1690
Abstract
A growing number of reports point to the possible role of environmental factors in determining the age of onset of menopause. Specific metals, such as mercury, cadmium, arsenic and lead can lead to fertility disorders, to endocrine dysregulation, and in addition, their high [...] Read more.
A growing number of reports point to the possible role of environmental factors in determining the age of onset of menopause. Specific metals, such as mercury, cadmium, arsenic and lead can lead to fertility disorders, to endocrine dysregulation, and in addition, their high blood concentrations correlate with the onset of menopause. Changing concentrations of hormones in the blood during this period of a woman’s life can also have an impact on SARS-CoV-2 infection, and excessively high or low levels of metals may also be an important predictor for the course of COVID-19. Postmenopausal women are exposed to greater risk of serum biochemical changes, and with the possibility of nutritional disturbances, particularly involving trace minerals, the risk of age-related diseases is very high during this period. These adverse changes in serum trace minerals should be taken into consideration for the early diagnosis and prevention of menopause-related diseases. Dietary supplementation may be necessary, especially where levels are significantly reduced. We performed a manual search of scientific articles cited in major electronic databases (PubMed, EMBASE, Web of Science and Google Scholar) in November 2022 to identify studies relevant to the relationship between metals, COVID-19 and menopause. The effects of metals on the course of menopause is a broad topic and should certainly still be a subject of research, due to, among other things, continuing environmental pollution and the use of metals in many areas of life. Full article
15 pages, 1280 KiB  
Review
The Role of Zinc and Copper in Platelet Activation and Pathophysiological Thrombus Formation in Patients with Pulmonary Embolism in the Course of SARS-CoV-2 Infection
by Monika Szewc, Agnieszka Markiewicz-Gospodarek, Aleksandra Górska, Zuzanna Chilimoniuk, Mansur Rahnama, Elżbieta Radzikowska-Buchner, Karolina Strzelec-Pawelczak, Jarosław Bakiera and Ryszard Maciejewski
Biology 2022, 11(5), 752; https://doi.org/10.3390/biology11050752 - 14 May 2022
Cited by 3 | Viewed by 3468
Abstract
To date, many studies have proved that COVID-19 increases the incidence of thrombus formation and coagulopathies but the exact mechanism behind such a disease outcome is not well known. In this review we collect the information and discuss the pathophysiology of thrombus formation [...] Read more.
To date, many studies have proved that COVID-19 increases the incidence of thrombus formation and coagulopathies but the exact mechanism behind such a disease outcome is not well known. In this review we collect the information and discuss the pathophysiology of thrombus formation in patients with pulmonary embolism in the course of COVID-19 disease and the role of zinc and copper in the process. Supplementation of zinc and copper may be beneficial for COVID-19 patients due to its anti-inflammatory and anti-oxidative properties. On the other hand, excess of those microelements in the organism may be harmful, that is why marking the level of those micronutrients should be done at first. We also propose further investigation of diagnostic and therapeutic options of zinc and copper in course of COVID-19 thrombus formation to their potential in patient care, with particular emphasis on the dosage and the duration of their misbalance. Full article
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29 pages, 6269 KiB  
Review
Elements and COVID-19: A Comprehensive Overview of Studies on Their Blood/Urinary Levels and Supplementation with an Update on Clinical Trials
by Agnieszka Ścibior and Ewa Wnuk
Biology 2022, 11(2), 215; https://doi.org/10.3390/biology11020215 - 28 Jan 2022
Cited by 6 | Viewed by 3377
Abstract
The current report provides a brief overview of the clinical features, hematological/biochemical abnormalities, biomarkers, and AI-related strategies in COVID-19; presents in a nutshell the pharmacological and non-pharmacological therapeutic options; and concisely summarizes the most important aspects related to sociodemographic and behavioral factors as [...] Read more.
The current report provides a brief overview of the clinical features, hematological/biochemical abnormalities, biomarkers, and AI-related strategies in COVID-19; presents in a nutshell the pharmacological and non-pharmacological therapeutic options; and concisely summarizes the most important aspects related to sociodemographic and behavioral factors as well as comorbidities having an impact on this disease. It also gives a brief outline of the effect of selected elements on immune response and collects data on the levels of micro-/macro-elements and toxic metals in the blood/urine of SARS-CoV-2 infected patients and on supplementation with minerals in COVID-19 subjects. Moreover, this review provides an overview of clinical trials based on the use of minerals alone or in combination with other agents that can provide effective responses toward SARS-CoV-2 infection. The knowledge compiled in this report lays the groundwork for new therapeutic treatments and further research on biomarkers that should be as informative as possible about the patient’s condition and can provide more reliable information on COVID-19 course and prognosis. The collected results point to the need for clarification of the importance of mineral supplementation in COVID-19 and the relationships of the levels of some minerals with clinical improvement. Full article
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