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1.
J Mol Model ; 28(3): 64, 2022 Feb 18.
Article in English | MEDLINE | ID: covidwho-1699453

ABSTRACT

This paper is a summary of research that looks at the potential of fullerene-like (MO)12 nanoclusters (NCs) in drug-carrying systems using density functional theory. Favipiravir/Zn12O12 (- 34.80 kcal/mol), Favipiravir/Mg12O12 (- 34.98 kcal/mol), and Favipiravir/Be12O12 (- 30.22 kcal/mol) were rated in order of drug adsorption degrees. As a result, Favipiravir attachment to (MgO)12 and (ZnO)12 might be simple, increasing Favipiravir loading efficiency. In addition, the quantum theory of atoms in molecules (QTAIM) assessment was utilized to look at the interactions between molecules. The FMO, ESP, NBO, and Eads reactivity patterns were shown to be in excellent agreement with the QTAIM data. The electrostatic properties of the system with the biggest positive charge on the M atom and the largest Eads were shown to be the best. This system was shown to be the best attraction site for nucleophilic agents. The findings show that (MgO)12 and (ZnO)12 have great carrier potential and may be used in medication delivery.


Subject(s)
Amides/administration & dosage , Amides/chemistry , Antiviral Agents/administration & dosage , Drug Delivery Systems/methods , Nanostructures/chemistry , Pyrazines/administration & dosage , Pyrazines/chemistry , Antiviral Agents/chemistry , COVID-19/drug therapy , Density Functional Theory , Fullerenes/chemistry , Humans , Nanostructures/administration & dosage , Quantum Theory , Spectrophotometry, Ultraviolet , Static Electricity
2.
Small Methods ; 5(5): e2001108, 2021 05.
Article in English | MEDLINE | ID: covidwho-1599126

ABSTRACT

During the global outbreak of COVID-19 pandemic, "cytokine storm" conditions are regarded as the fatal step resulting in most mortality. Hemoperfusion is widely used to remove cytokines from the blood of severely ill patients to prevent uncontrolled inflammation induced by a cytokine storm. This article discoveres, for the first time, that 2D Ti3 C2 Tx MXene sheet demonstrates an ultrahigh removal capability for typical cytokine interleukin-6. In particular, MXene shows a 13.4 times higher removal efficiency over traditional activated carbon absorbents. Molecular-level investigations reveal that MXene exhibits a strong chemisorption mechanism for immobilizing cytokine interleukin-6 molecules, which is different from activated carbon absorbents. MXene sheet also demonstrates excellent blood compatibility without any deleterious side influence on the composition of human blood. This work can open a new avenue to use MXene sheets as an ultraefficient hemoperfusion absorbent to eliminate the cytokine storm syndrome in treatment of severe COVID-19 patients.


Subject(s)
COVID-19/immunology , Cytokine Release Syndrome/drug therapy , Hemoperfusion/methods , Nanostructures/administration & dosage , SARS-CoV-2/immunology , Titanium/administration & dosage , Adsorption , COVID-19/transmission , COVID-19/virology , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/virology , Humans , Interleukin-6/immunology , Nanostructures/chemistry , SARS-CoV-2/isolation & purification , Titanium/chemistry
3.
Molecules ; 26(2)2021 Jan 15.
Article in English | MEDLINE | ID: covidwho-1389464

ABSTRACT

Peptides are fragments of proteins that carry out biological functions. They act as signaling entities via all domains of life and interfere with protein-protein interactions, which are indispensable in bio-processes. Short peptides include fundamental molecular information for a prelude to the symphony of life. They have aroused considerable interest due to their unique features and great promise in innovative bio-therapies. This work focusing on the current state-of-the-art short peptide-based therapeutical developments is the first global review written by researchers from all continents, as a celebration of 100 years of peptide therapeutics since the commencement of insulin therapy in the 1920s. Peptide "drugs" initially played only the role of hormone analogs to balance disorders. Nowadays, they achieve numerous biomedical tasks, can cross membranes, or reach intracellular targets. The role of peptides in bio-processes can hardly be mimicked by other chemical substances. The article is divided into independent sections, which are related to either the progress in short peptide-based theranostics or the problems posing challenge to bio-medicine. In particular, the SWOT analysis of short peptides, their relevance in therapies of diverse diseases, improvements in (bio)synthesis platforms, advanced nano-supramolecular technologies, aptamers, altered peptide ligands and in silico methodologies to overcome peptide limitations, modern smart bio-functional materials, vaccines, and drug/gene-targeted delivery systems are discussed.


Subject(s)
Anti-Infective Agents/pharmacology , Antiviral Agents/pharmacology , Peptides/chemistry , Peptides/pharmacology , Peptides/therapeutic use , Amino Acids/chemistry , Anti-Infective Agents/chemistry , Antiviral Agents/chemistry , COVID-19/drug therapy , Computer Simulation , Cosmeceuticals/chemistry , Cosmeceuticals/therapeutic use , Dietary Supplements , Gene Transfer Techniques , Humans , Lactoferrin/chemistry , Lipid Bilayers , Nanostructures/administration & dosage , Nanostructures/chemistry , Peptides/administration & dosage , Stem Cells , Vaccines, Subunit/chemistry , Vaccines, Subunit/pharmacology
4.
Small Methods ; 5(9): e2100402, 2021 09.
Article in English | MEDLINE | ID: covidwho-1330355

ABSTRACT

In recent years, the main quest of science has been the pioneering of the groundbreaking biomedical strategies needed for achieving a personalized medicine. Ribonucleic acids (RNAs) are outstanding bioactive macromolecules identified as pivotal actors in regulating a wide range of biochemical pathways. The ability to intimately control the cell fate and tissue activities makes RNA-based drugs the most fascinating family of bioactive agents. However, achieving a widespread application of RNA therapeutics in humans is still a challenging feat, due to both the instability of naked RNA and the presence of biological barriers aimed at hindering the entrance of RNA into cells. Recently, material scientists' enormous efforts have led to the development of various classes of nanostructured carriers customized to overcome these limitations. This work systematically reviews the current advances in developing the next generation of drugs based on nanotechnology-assisted RNA delivery. The features of the most used RNA molecules are presented, together with the development strategies and properties of nanostructured vehicles. Also provided is an in-depth overview of various therapeutic applications of the presented systems, including coronavirus disease vaccines and the newest trends in the field. Lastly, emerging challenges and future perspectives for nanotechnology-mediated RNA therapies are discussed.


Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19/therapy , Drug Delivery Systems/methods , Nanostructures/administration & dosage , Nanotechnology/methods , RNA/administration & dosage , SARS-CoV-2/immunology , COVID-19/immunology , COVID-19/prevention & control , COVID-19/virology , COVID-19 Vaccines/immunology , Humans , Nanostructures/chemistry , RNA/chemistry , SARS-CoV-2/isolation & purification
5.
Pharmacol Res ; 172: 105784, 2021 10.
Article in English | MEDLINE | ID: covidwho-1322310

ABSTRACT

It is becoming progressively more understandable that pharmaceutical targeting of drug-resistant cancers is challenging because of intra- and inter-tumor heterogeneity. Interestingly, naturally derived bioactive compounds have unique ability to modulate wide-ranging deregulated oncogenic cell signaling pathways. In this review, we have focused on the available evidence related to regulation of PI3K/AKT/mTOR, Wnt/ß-catenin, NF-κB and TRAIL/TRAIL-R by fisetin in different cancers. Fisetin has also been shown to inhibit the metastatic spread of cancer cells in tumor-bearing mice. We have also summarized how fisetin regulated autophagy in different cancers. In addition, this review also covers fisetin-mediated regulation of VEGF/VEGFR, EGFR, necroptosis and Hippo pathway. Fisetin has entered into clinical trials particularly in context of COVID19-associated inflammations. Furthermore, fisetin mediated effects are also being tested in clinical trials with reference to osteoarthritis and senescence. These developments will surely pave the way for full-fledge and well-designed clinical trials of fisetin in different cancers. However, we still have to comprehensively analyze and fully unlock pharmacological potential of fisetin against different oncogenic signaling cascades and non-coding RNAs. Fisetin has remarkable potential as chemopreventive agent and future studies must converge on the identification of additional regulatory roles of fisetin for inhibition and prevention of cancers.


Subject(s)
Antineoplastic Agents, Phytogenic/administration & dosage , Flavonols/administration & dosage , Nanostructures/administration & dosage , Neoplasms/drug therapy , Animals , Chemoprevention , Humans , Intercellular Signaling Peptides and Proteins/metabolism , NF-kappa B/metabolism , Neoplasms/metabolism , Neoplasms/prevention & control , Receptors, Vascular Endothelial Growth Factor/metabolism , Signal Transduction/drug effects , TOR Serine-Threonine Kinases/metabolism , beta Catenin/metabolism
6.
Proc Natl Acad Sci U S A ; 118(29)2021 07 20.
Article in English | MEDLINE | ID: covidwho-1307382

ABSTRACT

The global coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2), presents an urgent health crisis. More recently, an increasing number of mutated strains of SARS-CoV-2 have been identified globally. Such mutations, especially those on the spike glycoprotein to render its higher binding affinity to human angiotensin-converting enzyme II (hACE2) receptors, not only resulted in higher transmission of SARS-CoV-2 but also raised serious concerns regarding the efficacies of vaccines against mutated viruses. Since ACE2 is the virus-binding protein on human cells regardless of viral mutations, we design hACE2-containing nanocatchers (NCs) as the competitor with host cells for virus binding to protect cells from SARS-CoV-2 infection. The hACE2-containing NCs, derived from the cellular membrane of genetically engineered cells stably expressing hACE2, exhibited excellent neutralization ability against pseudoviruses of both wild-type SARS-CoV-2 and the D614G variant. To prevent SARS-CoV-2 infections in the lung, the most vulnerable organ for COVID-19, we develop an inhalable formulation by mixing hACE2-containing NCs with mucoadhesive excipient hyaluronic acid, the latter of which could significantly prolong the retention of NCs in the lung after inhalation. Excitingly, inhalation of our formulation could lead to potent pseudovirus inhibition ability in hACE2-expressing mouse model, without imposing any appreciable side effects. Importantly, our inhalable hACE2-containing NCs in the lyophilized formulation would allow long-term storage, facilitating their future clinical use. Thus, this work may provide an alternative tactic to inhibit SARS-CoV-2 infections even with different mutations, exhibiting great potential for treatment of the ongoing COVID-19 epidemic.


Subject(s)
COVID-19/prevention & control , Nanostructures/administration & dosage , SARS-CoV-2/drug effects , Adhesives/administration & dosage , Adhesives/chemistry , Adhesives/pharmacokinetics , Administration, Inhalation , Angiotensin-Converting Enzyme 2/metabolism , Animals , Cryoprotective Agents/chemistry , Drug Storage , Epithelial Cells/metabolism , Excipients/administration & dosage , Excipients/chemistry , Excipients/pharmacokinetics , HEK293 Cells , Humans , Hyaluronic Acid/administration & dosage , Hyaluronic Acid/chemistry , Hyaluronic Acid/pharmacokinetics , Lung/drug effects , Lung/metabolism , Lung/virology , Mice , Mice, Transgenic , Nanostructures/chemistry , SARS-CoV-2/genetics , SARS-CoV-2/physiology , Virus Attachment/drug effects
7.
Int J Nanomedicine ; 16: 4063-4072, 2021.
Article in English | MEDLINE | ID: covidwho-1278261

ABSTRACT

BACKGROUND: Ivermectin is an FDA-approved broad-spectrum anti-parasitic agent that has been shown to inhibit SARS-CoV-2 replication in vitro. OBJECTIVE: We aimed to assess the therapeutic efficacy of ivermectin mucoadhesive nanosuspension intranasal spray in treatment of patients with mild COVID-19. METHODS: This clinical trial included 114 patients diagnosed as mild COVID-19. Patients were divided randomly into two age and sex-matched groups; group A comprising 57 patients received ivermectin nanosuspension nasal spray twice daily plus the Egyptian protocol of treatment for mild COVID-19 and group B comprising 57 patients received the Egyptian protocol for mild COVID-19 only. Evaluation of the patients was performed depending on improvement of presenting manifestations, negativity of two consecutive pharyngeal swabs for the COVID-19 nucleic acid via rRT-PCR and assessments of hematological and biochemical parameters in the form of complete blood counts, C-reactive protein, serum ferritin and d-dimer which were performed at presentation and 7 days later. RESULTS: Of the included patients confirmed with mild COVID-19, 82 were males (71.9%) and 32 females (28.1%) with mean age 45.1 ± 18.9. In group A, 54 patients (94.7%) achieved 2 consecutive negative PCR nasopharyngeal swabs in comparison to 43 patients (75.4%) in group B with P = 0.004. The durations of fever, cough, dyspnea and anosmia were significantly shorter in group A than group B, without significant difference regarding the duration of gastrointestinal symptoms. Duration taken for nasopharyngeal swab to be negative was significantly shorter in group A than in group B (8.3± 2.8 days versus 12.9 ± 4.3 days; P = 0.0001). CONCLUSION: Local use of ivermectin mucoadhesive nanosuspension nasal spray is safe and effective in treatment of patients with mild COVID-19 with rapid viral clearance and shortening the anosmia duration. CLINICALTRIALSGOV IDENTIFIER: NCT04716569; https://clinicaltrials.gov/ct2/show/NCT04716569.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , Ivermectin/therapeutic use , Respiratory Tract Diseases/drug therapy , Adult , Antiviral Agents/administration & dosage , COVID-19/etiology , COVID-19 Nucleic Acid Testing , Cough/drug therapy , Cough/virology , Egypt , Female , Fever/drug therapy , Fever/virology , Humans , Ivermectin/administration & dosage , Ivermectin/adverse effects , Male , Middle Aged , Nanostructures/administration & dosage , Nanostructures/chemistry , Nasal Sprays , Nasopharynx/virology , Prospective Studies , Respiratory Tract Diseases/etiology , Respiratory Tract Diseases/virology , Treatment Outcome
8.
Nat Nanotechnol ; 16(8): 942-951, 2021 08.
Article in English | MEDLINE | ID: covidwho-1275929

ABSTRACT

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has grown into a global pandemic, and only a few antiviral treatments have been approved to date. Angiotensin-converting enzyme 2 (ACE2) plays a fundamental role in SARS-CoV-2 pathogenesis because it allows viral entry into host cells. Here we show that ACE2 nanodecoys derived from human lung spheroid cells (LSCs) can bind and neutralize SARS-CoV-2 and protect the host lung cells from infection. In mice, these LSC-nanodecoys were delivered via inhalation therapy and resided in the lungs for over 72 h post-delivery. Furthermore, inhalation of the LSC-nanodecoys accelerated clearance of SARS-CoV-2 mimics from the lungs, with no observed toxicity. In cynomolgus macaques challenged with live SARS-CoV-2, four doses of these nanodecoys delivered by inhalation promoted viral clearance and reduced lung injury. Our results suggest that LSC-nanodecoys can serve as a potential therapeutic agent for treating COVID-19.


Subject(s)
COVID-19/drug therapy , Lung Injury/prevention & control , Nanostructures/administration & dosage , SARS-CoV-2/drug effects , Administration, Inhalation , Angiotensin-Converting Enzyme 2/metabolism , Animals , COVID-19/virology , Cell-Derived Microparticles/metabolism , Cell-Derived Microparticles/transplantation , Disease Models, Animal , Humans , Lung Injury/virology , Macaca fascicularis , Mice , Protein Binding , SARS-CoV-2/metabolism , Spheroids, Cellular/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Viral Load/drug effects
9.
Proc Natl Acad Sci U S A ; 118(19)2021 05 11.
Article in English | MEDLINE | ID: covidwho-1214021

ABSTRACT

To realize RNA interference (RNAi) therapeutics, it is necessary to deliver therapeutic RNAs (such as small interfering RNA or siRNA) into cell cytoplasm. A major challenge of RNAi therapeutics is the endosomal entrapment of the delivered siRNA. In this study, we developed a family of delivery vehicles called Janus base nanopieces (NPs). They are rod-shaped nanoparticles formed by bundles of Janus base nanotubes (JBNTs) with RNA cargoes incorporated inside via charge interactions. JBNTs are formed by noncovalent interactions of small molecules consisting of a base component mimicking DNA bases and an amino acid side chain. NPs presented many advantages over conventional delivery materials. NPs efficiently entered cells via macropinocytosis similar to lipid nanoparticles while presenting much better endosomal escape ability than lipid nanoparticles; NPs escaped from endosomes via a "proton sponge" effect similar to cationic polymers while presenting significant lower cytotoxicity compared to polymers and lipids due to their noncovalent structures and DNA-mimicking chemistry. In a proof-of-concept experiment, we have shown that NPs are promising candidates for antiviral delivery applications, which may be used for conditions such as COVID-19 in the future.


Subject(s)
DNA/chemistry , Drug Delivery Systems , Endosomes/metabolism , Nanostructures/administration & dosage , Amino Acids/chemistry , Cell Survival , Endocytosis , Humans , Nanostructures/chemistry , Nanotubes, Peptide/chemistry , RNA, Small Interfering/administration & dosage , RNA, Small Interfering/chemistry , RNA, Small Interfering/metabolism , RNAi Therapeutics
10.
J Biomater Sci Polym Ed ; 32(9): 1219-1249, 2021 06.
Article in English | MEDLINE | ID: covidwho-1160539

ABSTRACT

The recent coronavirus disease-2019 (COVID-19) outbreak has increased at an alarming rate, representing a substantial cause of mortality worldwide. Respiratory injuries are major COVID-19 related complications, leading to poor lung circulation, tissue scarring, and airway obstruction. Despite an in-depth investigation of respiratory injury's molecular pathogenesis, effective treatments have yet to be developed. Moreover, early detection of viral infection is required to halt the disease-related long-term complications, including respiratory injuries. The currently employed detection technique (quantitative real-time polymerase chain reaction or qRT-PCR) failed to meet this need at some point because it is costly, time-consuming, and requires higher expertise and technical skills. Polymer-based nanobiosensing techniques can be employed to overcome these limitations. Polymeric nanomaterials have the potential for clinical applications due to their versatile features like low cytotoxicity, biodegradability, bioavailability, biocompatibility, and specific delivery at the targeted site of action. In recent years, innovative polymeric nanomedicine approaches have been developed to deliver therapeutic agents and support tissue growth for the inflamed organs, including the lung. This review highlights the most recent advances of polymer-based nanomedicine approaches in infectious disease diagnosis and treatments. This paper also focuses on the potential of novel nanomedicine techniques that may prove to be therapeutically efficient in fighting against COVID-19 related respiratory injuries.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , Nanomedicine/methods , Nanostructures/therapeutic use , Polymers/therapeutic use , SARS-CoV-2/drug effects , Antiviral Agents/administration & dosage , Biosensing Techniques , COVID-19/diagnosis , COVID-19/pathology , COVID-19 Testing , COVID-19 Vaccines , Dendrimers , Drug Carriers/administration & dosage , Drug Carriers/chemistry , Drug Delivery Systems , Early Diagnosis , Humans , Lung/pathology , Lung/physiopathology , Micelles , Nanoconjugates/therapeutic use , Nanoparticles , Nanostructures/administration & dosage , Precision Medicine , Respiratory Distress Syndrome/drug therapy , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/pathology , Tissue Engineering , Treatment Outcome
11.
ACS Appl Mater Interfaces ; 13(13): 14816-14843, 2021 Apr 07.
Article in English | MEDLINE | ID: covidwho-1155690

ABSTRACT

The pandemic outbreak of SARS-CoV-2, with millions of infected patients worldwide, has severely challenged all aspects of public health. In this regard, early and rapid detection of infected cases and providing effective therapeutics against the virus are in urgent demand. Along with conventional clinical protocols, nanomaterial-based diagnostics and therapeutics hold a great potential against coronavirus disease 2019 (COVID-19). Indeed, nanoparticles with their outstanding characteristics would render additional advantages to the current approaches for rapid and accurate diagnosis and also developing prophylactic vaccines or antiviral therapeutics. In this review, besides presenting an overview of the coronaviruses and SARS-CoV-2, we discuss the introduced nanomaterial-based detection assays and devices and also antiviral formulations and vaccines for coronaviruses.


Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19/diagnosis , COVID-19/therapy , Nanostructures/administration & dosage , SARS-CoV-2/drug effects , COVID-19/drug therapy , COVID-19/virology , COVID-19 Testing , Humans , Nanostructures/chemistry , SARS-CoV-2/isolation & purification
12.
J Nanobiotechnology ; 18(1): 125, 2020 Sep 05.
Article in English | MEDLINE | ID: covidwho-745681

ABSTRACT

Incidents of viral outbreaks have increased at an alarming rate over the past decades. The most recent human coronavirus known as COVID-19 (SARS-CoV-2) has already spread around the world and shown R0 values from 2.2 to 2.68. However, the ratio between mortality and number of infections seems to be lower in this case in comparison to other human coronaviruses (such as severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV)). These outbreaks have tested the limits of healthcare systems and have posed serious questions about management using conventional therapies and diagnostic tools. In this regard, the use of nanotechnology offers new opportunities for the development of novel strategies in terms of prevention, diagnosis and treatment of COVID-19 and other viral infections. In this review, we discuss the use of nanotechnology for COVID-19 virus management by the development of nano-based materials, such as disinfectants, personal protective equipment, diagnostic systems and nanocarrier systems, for treatments and vaccine development, as well as the challenges and drawbacks that need addressing.


Subject(s)
Betacoronavirus , Coronavirus Infections , Nanotechnology/methods , Pandemics , Pneumonia, Viral , Antiviral Agents/administration & dosage , Betacoronavirus/isolation & purification , COVID-19 , COVID-19 Testing , COVID-19 Vaccines , Clinical Laboratory Techniques/methods , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Coronavirus Infections/therapy , Disinfection/methods , Drug Carriers , Drug Delivery Systems , Humans , Nanostructures/administration & dosage , Personal Protective Equipment , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Pneumonia, Viral/therapy , SARS-CoV-2 , Viral Vaccines/administration & dosage
13.
IEEE Trans Nanobioscience ; 19(3): 485-497, 2020 07.
Article in English | MEDLINE | ID: covidwho-628414

ABSTRACT

The available antiviral agents and their potential for the management of coronavirus disease 2019 (COVID-19) outbreak are important interventions. A systematic review and meta-analysis was performed to summarize the available evidence on the efficacy of nanoscale materials against coronaviruses in vitro and in animal models. PubMed, Scopus and Wiley Online Library databases were searched up to 4 March 2020. Studies that developed the efficacy of nanoscale materials against coronaviruses were included. Two reviewers independently extracted study characteristics and assessed risk of bias and applicability in the included studies. Meta-analyses were conducted to determine the overall inhibition efficacy of nanoscale materials against coronaviruses. A total of 21 studies were identified. Positive association was found between efficacy of nanoscale materials and coronaviruses in vitro and in animal models. The inhibition efficacy of nanoscale materials against coronavirus in vitro and in animal models were 1.84 (95% CI: 1.57, 2.15) and 1.66 (95% CI: 1.36, 2.02), respectively. Results of subgroup analysis of selected studies revealed that the nanoscale materials with spherical morphology were found to be more antiviral activity than the other morphologies against Middle East respiratory syndrome-coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV). Using systematic review and meta-analysis, our results indicate that nanoscale materials are positive affect against coronaviruses. We might clarify the possible potential for the use of nanoscale materials for SARS-CoV-2.


Subject(s)
Antiviral Agents/administration & dosage , Coronavirus/drug effects , Nanostructures/administration & dosage , Animals , COVID-19 , Coronavirus Infections/drug therapy , Humans , Pandemics , Pneumonia, Viral/drug therapy
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