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The Concept of Pathogenic TH2 Cells: Collegium Internationale Allergologicum Update 2021.

Int Arch Allergy Immunol 2021 Apr 12;182(5):365-380. Epub 2021 Apr 12.

Department of Dermatology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.

T helper (TH) cells have evolved into distinct subsets that mediate specific immune responses to protect the host against a myriad of infectious and noninfectious challenges. However, if dysregulated, TH-cell subsets can cause inflammatory disease. Emerging evidence now suggests that human allergic disease is caused by a distinct subpopulation of pathogenic TH2 cells. Read More

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In vitro anti-oxidant and cytotoxic activities of gold nanoparticles synthesized from an aqueous extract of the Xylopia aethiopica fruit.

Nanotechnology 2021 Apr 12. Epub 2021 Apr 12.

Physiology, Nelson Mandela University, Port Elizabeth, Eastern Cape, SOUTH AFRICA.

The development of gold nanoparticles (AuNPs) using green approach has drawn a considerable interest in the field of nanomedicine. Its wide application in clinical diagnosis, imaging and therapeutics portrays its importance for human existence. In this study, we reported the biogenic synthesis of AuNPs using aqueous extract of Xylopia aethiopica fruit (AEXAf), which act as both reducing and stabilizing agent. Read More

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A label-free electrochemical aptasensor for breast cancer cell detection based on a reduced graphene oxide-chitosan-gold nanoparticle composite.

Bioelectrochemistry 2021 Mar 26;140:107807. Epub 2021 Mar 26.

Department of Chemistry, University of Isfahan, Isfahan 81746-73441, Iran. Electronic address:

Regarding the cancer fatal consequences, early detection and progression monitoring are the most vital issues in patients' treatment and mortality reduction. Therefore, there is a great demand for fast, inexpensive, and selective detection methods. Herein, a graphene-based aptasensor was designed for sensitive human breast cancer cell detection. Read More

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Is procalcitonin a part of human immunological response to SARS-CoV-2 infection or "just" a marker of bacterial coinfection?

Curr Res Transl Med 2021 Mar 24;69(2):103289. Epub 2021 Mar 24.

Department of Internal Medicine, Faculty of Medicine, Pelita Harapan University, Boulevard Jendral Sudirman, Lippo Karawaci, Tangerang, Banten 15811, Indonesia. Electronic address:

Elevated PCT level in COVID-19 was associated with higher risk of severe disease and higher risk of overall mortality. An increased PCT level of PCT in COVID-19 patients especially in severe cases would be assumed as bacterial coinfection. Could PCT level increase in SARS-CoV-2 infection without bacterial coinfection? Several SARS-CoV-2 proteins activate STAT3-dependent transcriptional pathways particularly in monocytes, that could lead to increased PCT production. Read More

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Transcriptional signatures underlying dynamic phenotypic switching and novel disease biomarkers in a linear cellular model of melanoma progression.

Neoplasia 2021 Apr 9;23(4):439-455. Epub 2021 Apr 9.

Pharmacology Department, Universidade Federal de São Paulo, São Paulo, Brazil. Electronic address:

Despite advances in therapeutics, the progression of melanoma to metastasis still confers a poor outcome to patients. Nevertheless, there is a scarcity of biological models to understand cellular and molecular changes taking place along disease progression. Here, we characterized the transcriptome profiles of a multi-stage murine model of melanoma progression comprising a nontumorigenic melanocyte lineage (melan-a), premalignant melanocytes (4C), nonmetastatic (4C11-) and metastasis-prone (4C11+) melanoma cells. Read More

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Generation of pathogenic TPP1 mutations in human stem cells as a model for neuronal ceroid lipofuscinosis type 2 disease.

Stem Cell Res 2021 Apr 6;53:102323. Epub 2021 Apr 6.

Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, Rhode Island 02912, USA; Center for Translational Neuroscience, Carney Institute for Brain Science and Brown Institute for Translational Science, Brown University, Providence, Rhode Island 02912, USA; Hassenfeld Child Health Innovation Institute, Brown University, Providence, Rhode Island 02912, USA. Electronic address:

Neuronal ceroid lipofuscinosis type 2 (CLN2 disease) is an autosomal recessive neurodegenerative disorder generally with onset at 2 to 4 years of age and characterized by seizures, loss of vision, progressive motor and mental decline, and premature death. CLN2 disease is caused by loss-of-function mutations in the tripeptidyl peptidase 1 (TPP1) gene leading to deficiency in TPP1 enzyme activity. Approximately 60% of patients have one of two pathogenic variants (c. Read More

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Further lead optimization on Bax activators: Design, synthesis and pharmacological evaluation of 2-fluoro-fluorene derivatives for the treatment of breast cancer.

Eur J Med Chem 2021 Apr 3;219:113427. Epub 2021 Apr 3.

Chemical Biology Program, Department of Pharmacology and Toxicology, University of Texas Medical Branch (UTMB), Galveston, TX, 77555, United States; Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch (UTMB), Galveston, TX, 77555, United States. Electronic address:

To further pursue potent Bax activators with better safety profiles for the treatment of breast cancer, structural optimization was conducted based on lead compound CYD-4-61 through several strategies, including scaffold hopping on the 2-nitro-fluorene ring, replacement of the nitro group with bioisosteres to avoid potential toxicity, and further optimization on the upper pyridine by exploring diverse alkylamine linkers as a tail or replacing the pyridine with bioisosteric heterocycles. F-containing compound 22d (GL0388) exhibited a good balance between the activity and toxicity, displaying submicromolar activities against a variety of cancer cell lines with 5.8-10. Read More

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4-4-(Anilinomethyl)-3-[4-(trifluoromethyl)phenyl]-1H-pyrazol-1-ylbenzoic acid derivatives as potent anti-gram-positive bacterial agents.

Eur J Med Chem 2021 Apr 4;219:113402. Epub 2021 Apr 4.

Department of Chemistry and Physics, College of Science and Mathematics, Arkansas State University, Jonesboro, AR, 72467, USA. Electronic address:

A collection of potent antimicrobials consisting of novel 1,3-bis-benzoic acid and trifluoromethyl phenyl derived pyrazoles has been synthesized and tested for antibacterial activity. The majority of trifluoromethyl phenyl derivatives are highly potent growth inhibitors of Gram-positive bacteria and showed low toxicity to human cultured cells. In particular, two compounds (59 and 74) were selected for additional studies. Read More

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Mechanism of thorium-nitrate and thorium-dioxide induced cytotoxicity in normal human lung epithelial cells (WI26): Role of oxidative stress, HSPs and DNA damage.

Environ Pollut 2021 Mar 23;281:116969. Epub 2021 Mar 23.

Radiation Biology & Health Sciences Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400 085, India; Homi Bhabha National Institute, Anushakti Nagar, Mumbai, 400 094, India. Electronic address:

Inhalation represents the most prevalent route of exposure with Thorium-232 compounds (Th-nitrate/Th-dioxide)/Th-containing dust in real occupational scenario. The present study investigated the mechanism of Th response in normal human alveolar epithelial cells (WI26), exposed to Th-nitrate or colloidal Th-dioxide (1-100 μg/ml, 24-72 h). Assessment in terms of changes in cell morphology, cell proliferation (cell count), plasma membrane integrity (lactate dehydrogenase leakage) and mitochondrial metabolic activity (MTT reduction) showed that Th-dioxide was quantitatively more deleterious than Th-nitrate to WI26 cells. Read More

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Single-cell proteomics: A treasure trove in neurobiology.

Biochim Biophys Acta Proteins Proteom 2021 Apr 9:140658. Epub 2021 Apr 9.

Proteomics Unit, Department of Biochemistry, Chemistry Institute, Federal University of Rio de janeiro, 21941-909 Rio de Janeiro, Brazil. Electronic address:

Single-cell analysis came to change the way we look at cell populations. RNA sequencing of single cells allowed us to appreciate the diversity of cell types in the human brain in an unprecedented manner and its power to reveal cell-type specific changes in cell populations has just begun to be explored. In this context, looking at the proteome of single cells promises to bring functional information and contribute to completing the picture. Read More

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In silico and in vitro studies of isolated constituents from Callistemon citrinus leaves: Anti-microbial potential and inhibition of iNOS activity.

Phytochemistry 2021 Apr 9;186:112745. Epub 2021 Apr 9.

National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University, MS, 38677, USA; Division of Pharmacognosy, Department of BioMolecular Sciences, School of Pharmacy, University of Mississippi, University, MS, 38677, USA. Electronic address:

Phytochemical investigation of Callistemon citrinus (Curtis) Skeels (syn. Callistemon lanceolatus (Sm.) Sweet and Melaleuca citrina (Curtis) Dum. Read More

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Neonatal maternal separation increases the number of p27-positive Sertoli cells in prepuberty.

Reprod Toxicol 2021 Apr 9. Epub 2021 Apr 9.

Department of Anatomy, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo, 160-8402, Japan.

Neonatal maternal separation (NMS) is an experimental model for early life stress, which affects the growth and development of various organs, resulting in adverse health effects in humans and animals. In our previous study, we demonstrated that NMS [(0.5-, 1-, 2-h/day NMS, from postnatal day (PND) 1 to 10] induced morphological changes to the male reproductive system, including decreased Sertoli cell numbers in mouse testes at PND 70. Read More

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Cross-reactivity of two human IL-6 family cytokines OSM and LIF explored by protein-protein docking and molecular dynamics simulation.

Biochim Biophys Acta Gen Subj 2021 Apr 9:129907. Epub 2021 Apr 9.

School of Pharmaceutical Sciences, Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Chongqing University, Chongqing 401331, China. Electronic address:

Background: Oncostatin M (OSM) and leukemia inhibitory factor (LIF) are two important pro-inflammatory cytokines of the interleukin-6 (IL-6) family. The two cytokines mediated signaling was recently found to be closely associated with cancer and chronic inflammation, which represent promising therapeutic targets for the treatment of many solid tumors and inflammatory disease. As the most closely related members, cross-reactivity of them may result in undesired activation of off-target cells, leading to toxicity or lack of efficacy of the therapeutic effects. Read More

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TWIST1-mediated transcriptional activation of PDGFRβ in breast cancer stem cells promotes tumorigenesis and metastasis.

Biochim Biophys Acta Mol Basis Dis 2021 Apr 9:166141. Epub 2021 Apr 9.

Department of Applied Biology, CSIR-Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Hyderabad -500 007, TS 500 007, India; Academy of Science and Innovative Research (AcSIR), Ghaziabad, UP - 201 002, India. Electronic address:

Triple-negative breast cancer (TNBC) patients often exhibit poor prognosis and breast cancer relapse due to metastasis. This results in secondary tumor generation at distant-unrelated organs that account for the majority of breast cancer-related deaths. Although breast cancer stem cells (CSCs) have been attributed to metastasis, a mechanistic understanding is essential for developing therapeutic interventions to combat breast cancer relapse. Read More

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Intracellular pathways involved in cell survival are deregulated in mouse and human spinal muscular atrophy motoneurons.

Neurobiol Dis 2021 Apr 9:105366. Epub 2021 Apr 9.

Neuronal Signaling Unit, Experimental Medicine Department, Universitat de Lleida-IRBLleida, Rovira Roure, 80, 25198 Lleida, Spain; Neuronal Signaling Unit, Experimental Medicine Department, Universitat de Lleida-IRBLleida, Rovira Roure, 80, 25198 Lleida, Spain. Electronic address:

Spinal Muscular Atrophy (SMA) is a severe neuromuscular disorder caused by loss of the Survival Motor Neuron 1 gene (SMN1). Due to this depletion of the survival motor neuron (SMN) protein, the disease is characterized by the degeneration of spinal cord motoneurons (MNs), progressive muscular atrophy, and weakness. Nevertheless, the ultimate cellular and molecular mechanisms leading to cell loss in SMN-reduced MNs are only partially known. Read More

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HETEROGENEITY OF NANOMECHANICAL PROPERTIES OF THE HUMAN UMBILICAL VEIN ENDOTHELIAL CELL SURFACE.

Microvasc Res 2021 Apr 9:104168. Epub 2021 Apr 9.

Gomel State Medical University, 5 Lange str., Gomel, BY-246000, Belarus.

Endothelial cells, due to heterogeneity in the cell structure, can potentially form an inhomogeneous on structural and mechanical properties of the inner layer of the capillaries. Using quantitative nanomechanical mapping mode of atomic force microscopy, the parameters of the structural, elastic, and adhesive properties of the cell surface for living and glutaraldehyde-fixed human umbilical vein endothelial cells were studied. A significant difference in the studied parameters for three cell surface zones (peripheral, perinuclear, and nuclear zones) was established. Read More

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Development and qualification of a fast, high-throughput and robust imaging-based neutralization assay for respiratory syncytial virus.

J Immunol Methods 2021 Apr 9:113054. Epub 2021 Apr 9.

Analytical Research & Development, MRL, Merck & Co., Inc., Kenilworth, NJ, USA.

Respiratory syncytial virus (RSV) is a common pathogen causing severe respiratory illness in infants and elder adults. The development of an effective RSV vaccine is an important unmet medical need and an area of active research. The traditional method for testing neutralizing antibodies against RSV in clinical trials is the plaque reduction neutralization test (PRNT), which uses 24-well plates and needs six days post infection to develop viral plaques. Read More

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FasL regulatory B-cells during Mycobacterium tuberculosis infection and TB disease.

J Mol Biol 2021 Apr 9:166984. Epub 2021 Apr 9.

DST-NRF Centre of Excellence for Biomedical Tuberculosis Research; South African Medical Research Council Centre for Tuberculosis Research; Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa, PO Box 241, Cape Town 8000, South Africa. Electronic address:

Tuberculosis (TB) disease remains a major health crisis. Infection with Mycobacterium tuberculosis (M.tb) cause a range of diseases ranging from latent infection to active TB disease. Read More

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PD-1 expression defines epidermal CD8CD103 T cells preferentially producing IL-17A and using skewed TCR repertoire in psoriasis.

J Invest Dermatol 2021 Apr 9. Epub 2021 Apr 9.

Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan; Department of Cellular & Molecular Anatomy, Hamamatsu University School of Medicine, Hamamatsu, Japan. Electronic address:

In psoriasis, CD8CD103 memory T cells residing in the epidermis represent an effector population capable of maintaining the condition and driving a recurrence of the disease. Tissue-infiltrating CD8 T cells expressing programmed cell death protein-1 (PD-1) are regarded as antigen-primed effector cells in others chronic inflammatory diseases. However, the expression and significance of PD-1 on skin-infiltrating CD8 T cells in human psoriasis is not known. Read More

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Fecal microbiota transplantation for recurrent Clostridioides difficile infection associates with functional alterations in circulating microRNAs.

Gastroenterology 2021 Apr 5. Epub 2021 Apr 5.

Department of Biosciences, John van Geest Cancer Research Centre, Centre for Health Aging and Understanding Disease, School of Science and Technology, Nottingham Trent University, Nottingham, UK. Electronic address:

Background And Aims: The molecular mechanisms underlying successful fecal microbiota transplantation (FMT) for recurrent Clostridioides difficile infection (rCDI) remain poorly understood. The primary objective of this study was to characterize alterations in microRNAs (miRs) following FMT for rCDI.

Methods: Sera from two prospective multicentre randomized controlled trials were analyzed for miRNA levels using the Nanostring nCounter platform and quantitative RT-PCR. Read More

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Human microbiota flagellins drive adaptive immune responses in Crohn's disease.

Gastroenterology 2021 Apr 9. Epub 2021 Apr 9.

Department of Medicine, University of Alabama at Birmingham, Birmingham, AL; Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL. Electronic address:

Background And Aims: Crohn's Disease (CD) and ulcerative colitis (UC) are characterized by dysregulated adaptive immune responses to the microbiota in genetically susceptible individuals, but the specificity of these responses remains largely undefined. Therefore, we developed a microbiota antigen microarray to characterize microbial antibody reactivity, particularly to human-derived microbiota flagellins, in inflammatory bowel disease.

Methods: Sera from healthy volunteers at the University of Alabama at Birmingham (UAB), n=87; patients recruited from the Kirklin Clinic of UAB Hospital, including patients with Crohn's disease, n=152; and Ulcerative colitis, n=170; was individually probed against microbiota bacterial flagellins of both mouse and human origin and analyzed for IgG and IgA antibody responses. Read More

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Structure-based phylogeny identifies Avoralstat as a TMPRSS2 inhibitor that prevents SARS-CoV-2 infection in mice.

J Clin Invest 2021 Apr 12. Epub 2021 Apr 12.

Department of Ophthalmology, Stanford University, Palo Alto, United States of America.

Drugs targeting host proteins can act prophylactically to reduce viral burden early in disease and limit morbidity, even with antivirals and vaccination. Transmembrane serine protease 2 (TMPRSS2) is a human protease required for SARS-CoV-2 viral entry and may represent such a target. We hypothesized that drugs selected from proteins related by their tertiary structure, rather than their primary structure, were likely to interact with TMPRSS2. Read More

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PGAM1 and TP53 mRNA levels in canine mammary carcinomas - Short communication.

Acta Vet Hung 2021 Apr 10. Epub 2021 Apr 10.

1Department of Pathology and Veterinary Clinic, Faculty of Veterinary, Universidade Federal Fluminense, Av. Alm. Ary Parreiras, 507, Icaraí, 24220-000, Niterói, RJ, Brazil.

TP53 and PGAM1 genes play a key role in glycolysis which is an essential metabolic pathway of cancer cells for obtaining energy. The purpose of this work was to evaluate PGAM1 and TP53 mRNA expressions in canine mammary carcinomas (CMC) and to correlate them with animal data and tumour histological features. None of the nine samples analysed revealed PGAM1 DNA sequence variations. Read More

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Effect of Photobiomodulation on Restoration of Ionization Radiation-Induced Thyroid Dysfunction Through p53 and Retinoblastoma Signaling.

Photobiomodul Photomed Laser Surg 2021 Apr;39(4):254-264

Beckman Laser Institute Korea, Dankook University, Cheonan, Republic of Korea.

This study aimed to investigate whether photobiomodulation (PBM) restores normal thyroid follicular cells affected by ionizing radiation, and to determine the mechanism of PBM on thyroid function. Despite diverse applications of PBM to medical therapy, there has been no evidence of its involvement with thyroid function. A light emission diode (850 nm) array was used at 2, 5, and 10 J/cm for analysis in human thyroid N-Thy-3. Read More

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The miR-146b-5p promotes Ewing's sarcoma cells progression via suppressing the expression of BTG2.

Sci Prog 2021 Apr-Jun;104(2):368504211002043

Department of Orthopedics Trauma, Zaozhuang Municipal Hospital, Zaozhuang, Shandong, P.R. China.

Ewing sarcoma (ES) is a malignant tumor that occurs mostly in children. However, the underlying mechanisms of ES are still unknown. Analyzing the results of two previous miRNA array reports, we found that miR-146b-5p might be an onco-miRNA in ES progression. Read More

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Progress toward B-Cell Lymphoma 6 BTB Domain Inhibitors for the Treatment of Diffuse Large B-Cell Lymphoma and Beyond.

J Med Chem 2021 Apr 12. Epub 2021 Apr 12.

Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, 20 Penn Street, Baltimore, Maryland 21201, United States.

B-cell lymphoma 6 (BCL6) is a master regulator of germinal center formation that produce antibody-secreting plasma cells and memory B-cells for sustained immune responses. The BTB domain of BCL6 (BCL6) forms a homodimer that mediates transcriptional repression by recruiting its corepressor proteins to form a biologically functional transcriptional complex. The protein-protein interaction (PPI) between the BCL6 and its corepressors has emerged as a therapeutic target for the treatment of DLBCL and a number of other human cancers. Read More

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Targeting Acute Myelogenous Leukemia Using Potent Human Dihydroorotate Dehydrogenase Inhibitors Based on the 2-Hydroxypyrazolo[1,5-]pyridine Scaffold: SAR of the Biphenyl Moiety.

J Med Chem 2021 Apr 12. Epub 2021 Apr 12.

Department of Drug Science and Technology, University of Turin, Via P. Giuria 9, Turin 10125, Italy.

The connection with acute myelogenous leukemia (AML) of dihydroorotate dehydrogenase (DHODH), a key enzyme in pyrimidine biosynthesis, has attracted significant interest from pharma as a possible AML therapeutic target. We recently discovered compound , a potent DHODH inhibitor (IC = 1.2 nM), able to induce myeloid differentiation in AML cell lines (THP1) in the low nM range (EC = 32. Read More

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Anti-SARS-CoV-2 Activity of Extract and Its Major Component Andrographolide in Human Lung Epithelial Cells and Cytotoxicity Evaluation in Major Organ Cell Representatives.

J Nat Prod 2021 Apr 12. Epub 2021 Apr 12.

Excellent Center for Drug Discovery (ECDD), Faculty of Science, Mahidol University, Bangkok 10400, Thailand.

The coronaviruses disease 2019 (COVID-19) caused by a novel coronavirus (SARS-CoV-2) has become a major health problem, affecting more than 50 million people with over one million deaths globally. Effective antivirals are still lacking. Here, we optimized a high-content imaging platform and the plaque assay for viral output study using the legitimate model of human lung epithelial cells, Calu-3, to determine the anti-SARS-CoV-2 activity of extract and its major component, andrographolide. Read More

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