4,088 results match your criteria wnt signalling

Efficacy and mechanism of the combination of PARP and CDK4/6 inhibitors in the treatment of triple-negative breast cancer.

J Exp Clin Cancer Res 2021 Apr 8;40(1):122. Epub 2021 Apr 8.

Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.

Background: PARP inhibitors (PARPi) benefit only a fraction of breast cancer patients with BRCA mutations, and their efficacy is even more limited in triple-negative breast cancer (TNBC) due to clinical primary and acquired resistance. Here, we found that the efficacy of the PARPi olaparib in TNBC can be improved by combination with the CDK4/6 inhibitor (CDK4/6i) palbociclib.

Methods: We screened primary olaparib-sensitive and olaparib-resistant cell lines from existing BRCA/TNBC cell lines and generated cells with acquired olaparib resistance by gradually increasing the concentration. Read More

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Circulating regulators of the wingless pathway in precapillary pulmonary hypertension.

Respirology 2021 Apr 8. Epub 2021 Apr 8.

Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway.

Background And Objective: Dysregulated Wnt signalling has been implicated in pulmonary hypertension (PH). We hypothesized that plasma levels of secreted Wnt proteins would be increased in patients with precapillary PH, correlate with indices of vascular resistance and cardiac function and give information on long-term prognosis.

Methods: We measured the Wnt ligand Wnt5a and secreted Wnt antagonists Dickkopf (DKK) DKK1, DKK3, secreted frizzled-related protein 3 (sFRP3), Wnt inhibitory factor-1 (WIF1) and sclerostin (SOST) in 106 patients with precapillary PH and 40 healthy controls. Read More

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Vascular endothelial growth factor-mediated peritoneal neoangiogenesis in peritoneal dialysis.

Perit Dial Int 2021 Apr 7:8968608211004683. Epub 2021 Apr 7.

Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.

Peritoneal dialysis (PD) is an important renal replacement therapy for patients with end-stage renal diseases, which is limited by peritoneal neoangiogenesis leading to ultrafiltration failure (UFF). Vascular endothelial growth factor (VEGF) and its receptors are key angiogenic factors involved in almost every step of peritoneal neoangiogenesis. Impaired mesothelial cells are the major sources of VEGF in the peritoneum. Read More

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Role of iron and iron-related proteins in mesenchymal stem cells: Cellular and clinical aspects.

Kosha J Mehta

J Cell Physiol 2021 Apr 5. Epub 2021 Apr 5.

Faculty of Life Sciences and Medicine, Centre for Education, King's College London, London, UK.

Mesenchymal stem cells (MSCs) are located in various tissues where these cells show niche-dependent multilineage differentiation and secrete immunomodulatory molecules to support numerous physiological processes. Due to their regenerative and reparative properties, MSCs are extremely valuable for cell-based therapy in tackling several pathological conditions including COVID-19. Iron is essential for MSC processes but iron-loading, which is common in several chronic conditions, hinders normal MSC functionality. Read More

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Systematic expression analysis of the CELSR family reveals the importance of CELSR3 in human lung adenocarcinoma.

J Cell Mol Med 2021 Apr 3. Epub 2021 Apr 3.

Department of Thoracic Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, China.

Cadherin EGF LAG seven-pass G-type receptors (CELSRs) are involved in the progression of various types of cancer. CELSR3, a crucial signalling molecule in the WNT/PCP pathway, is believed to be associated with tumorigenesis and metastasis. However, its role in lung adenocarcinoma (LUAD) remains unclear. Read More

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Temporal Quantitative Proteomics Analysis of Neuroblastoma Cells Treated with Bovine Milk-Derived Extracellular Vesicles Highlights the Anti-Proliferative Properties of Milk-Derived Extracellular Vesicles.

Cells 2021 Mar 29;10(4). Epub 2021 Mar 29.

Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria 3086, Australia.

Neuroblastoma (NBL) is a pediatric cancer that accounts for 15% of childhood cancer mortality. Amplification of the oncogene N-Myc occurs in 20% of NBL patients and is considered high risk as it correlates with aggressiveness, treatment resistance and poor prognosis. Even though the treatment strategies have improved in the recent years, the survival rate of high-risk NBL patients remain poor. Read More

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USP42 protects ZNRF3/RNF43 from R-spondin-dependent clearance and inhibits Wnt signalling.

EMBO Rep 2021 Mar 30:e51415. Epub 2021 Mar 30.

Centre for Organismal Studies (COS), Heidelberg University, Heidelberg, Germany.

The tumour suppressors RNF43 and ZNRF3 play a central role in development and tissue homeostasis by promoting the turnover of the Wnt receptors LRP6 and Frizzled (FZD). The stem cell growth factor R-spondin induces auto-ubiquitination and membrane clearance of ZNRF3/RNF43 to promote Wnt signalling. However, the deubiquitinase stabilising ZNRF3/RNF43 at the plasma membrane remains unknown. Read More

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A Wnt-mediated phenotype switch along the epithelial-mesenchymal axis defines resistance and invasion downstream of ionising radiation in oral squamous cell carcinoma.

Br J Cancer 2021 Mar 30. Epub 2021 Mar 30.

Discipline of Oral Biosciences, School of Dentistry, Faculty of Medicine and Health, University of Sydney, Westmead Hospital, Westmead, NSW, Australia.

Background: Dynamic transitions of tumour cells along the epithelial-mesenchymal axis are important in tumorigenesis, metastasis and therapy resistance.

Methods: In this study, we have used cell lines, 3D spheroids and tumour samples in a variety of cell biological and transcriptome analyses to highlight the cellular and molecular dynamics of OSCC response to ionising radiation.

Results: Our study demonstrates a prominent hybrid epithelial-mesenchymal state in oral squamous cell carcinoma cells and tumour samples. Read More

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Down-regulation of long non-coding RNA antisense non-coding RNA in the INK4 locus suppresses OVCAR-3 cells proliferation and induction of apoptosis by Wnt/β -catenin.

J Pharm Pharmacol 2021 Mar 27. Epub 2021 Mar 27.

Department of Gynecology, Maternal and Child Health Care Hospital of Shandong Province, Jinan City, Shandong Province,  China.

Objectives: Ovarian cancer is a lethal gynecological malignancy. Long non-coding RNA antisense non-coding RNA in the INK4 locus (lncRNA ANRIL) was reported to have a critical role in cancer advancement. The ANRIL-mediated oncogenic underlying molecular mechanisms are not fully understood in ovarian cancer. Read More

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A role for Dynlt3 in melanosome movement, distribution, acidity and transfer.

Commun Biol 2021 Mar 26;4(1):423. Epub 2021 Mar 26.

Normal and Pathological Development of Melanocytes, Institut Curie, CNRS UMR3347, Inserm U1021, Université PSL, Orsay, France.

Skin pigmentation is dependent on cellular processes including melanosome biogenesis, transport, maturation and transfer to keratinocytes. However, how the cells finely control these processes in space and time to ensure proper pigmentation remains unclear. Here, we show that a component of the cytoplasmic dynein complex, Dynlt3, is required for efficient melanosome transport, acidity and transfer. Read More

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MiR-155 promotes colitis-associated intestinal fibrosis by targeting HBP1/Wnt/β-catenin signalling pathway.

J Cell Mol Med 2021 Mar 26. Epub 2021 Mar 26.

Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China.

Intestinal fibrosis is the most common complication of Crohn's disease (CD) that is one major disorder of inflammatory bowel disease (IBD), but the precise mechanism remains unclear. MiR-155 has been involved in fibrotic diseases. Here, we determined the role of miR-155 in regulating intestinal fibrosis. Read More

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A single-cell survey of the human glomerulonephritis.

J Cell Mol Med 2021 Mar 22. Epub 2021 Mar 22.

Department of Nephrology, Molecular Cell Laboratory for Kidney Disease, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Glomerulonephritis is the one of the major causes of the end-stage kidney disease, whereas the pathological process of glomerulonephritis is still not completely understood. Single-cell RNA sequencing (scRNA-seq) emerges to be a powerful tool to evaluate the full heterogeneity of kidney diseases. To reveal cellular gene expression profiles of glomerulonephritis, we performed scRNA-seq of 2 human kidney transplantation donor samples, 4 human glomerulonephritis samples, 1 human malignant hypertension (MH) sample and 1 human chronic interstitial nephritis (CIN) sample, all tissues were taken from the biopsy. Read More

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The HOTAIR lncRNA: A remarkable oncogenic promoter in human cancer metastasis.

Oncol Lett 2021 Apr 17;21(4):302. Epub 2021 Feb 17.

Department of Medical Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, P.R. China.

Long non-coding RNA (lncRNA) is a new type of non-coding RNA that has an important regulatory influence on several human diseases, including cancer metastasis. HOX antisense intergenic RNA (HOTAIR), a newly discovered lncRNA, has an important effect on tumour proliferation, migration and metastasis. HOTAIR regulates cell proliferation, changes gene expression, and promotes tumour cell invasion and migration. Read More

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Endogenous suppression of WNT signalling in human embryonic stem cells leads to low differentiation propensity towards definitive endoderm.

Sci Rep 2021 Mar 17;11(1):6137. Epub 2021 Mar 17.

Research Group Reproduction and Genetics, Vrije Universiteit Brussel, 1090, Brussels, Belgium.

Low differentiation propensity towards a targeted lineage can significantly hamper the utility of individual human pluripotent stem cell (hPSC) lines in biomedical applications. Here, we use monolayer and micropatterned cell cultures, as well as transcriptomic profiling, to investigate how variability in signalling pathway activity between human embryonic stem cell lines affects their differentiation efficiency towards definitive endoderm (DE). We show that endogenous suppression of WNT signalling in hPSCs at the onset of differentiation prevents the switch from self-renewal to DE specification. Read More

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Wnt/β-Catenin Antagonist Pyrvinium Exerts Cardioprotective Effects in Polymicrobial Sepsis Model by Attenuating Calcium Dyshomeostasis and Mitochondrial Dysfunction.

Cardiovasc Toxicol 2021 Mar 15. Epub 2021 Mar 15.

Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab, India.

Calcium dysregulation and mitochondrial dysfunction are key elements in the development of sepsis-induced cardiac dysfunction. Evidences have suggested that inhibition of Wnt/β-Catenin signalling prevents cardiac dysfunction and remodelling in surgical, hypertension and pressure overload models. The present study investigated the effects of Wnt/β-Catenin inhibitor on calcium overload and mitochondrial dysfunction in rat sepsis model of cardiomyopathy. Read More

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TGF-β-induced DACT1 biomolecular condensates repress Wnt signalling to promote bone metastasis.

Nat Cell Biol 2021 Mar 9;23(3):257-267. Epub 2021 Mar 9.

Department of Molecular Biology, Princeton University, Princeton, NJ, USA.

The complexity of intracellular signalling requires both a diversity of molecular players and the sequestration of activity to unique compartments within the cell. Recent findings on the role of liquid-liquid phase separation provide a distinct mechanism for the spatial segregation of proteins to regulate signalling pathway crosstalk. Here, we discover that DACT1 is induced by TGFβ and forms protein condensates in the cytoplasm to repress Wnt signalling. Read More

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Bone marrow stromal cells from MDS and AML patients show increased adipogenic potential with reduced Delta-like-1 expression.

Sci Rep 2021 Mar 15;11(1):5944. Epub 2021 Mar 15.

Department of Medicine III: Hematology and Oncology, School of Medicine, Klinikum Rechts Der Isar, Technical University of Munich, Ismaninger Str. 22, 81675, Munich, Germany.

Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are clonal hematopoietic stem cell disorders with a poor prognosis, especially for elderly patients. Increasing evidence suggests that alterations in the non-hematopoietic microenvironment (bone marrow niche) can contribute to or initiate malignant transformation and promote disease progression. One of the key components of the bone marrow (BM) niche are BM stromal cells (BMSC) that give rise to osteoblasts and adipocytes. Read More

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A modified protein marker panel to identify four consensus molecular subtypes in colorectal cancer using immunohistochemistry.

Pathol Res Pract 2021 Apr 5;220:153379. Epub 2021 Mar 5.

Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden. Electronic address:

Colorectal cancer (CRC) is a heterogeneous disease with different genetic and molecular backgrounds, leading to a diverse patient prognosis and treatment response. Four consensus molecular subtypes (CMS 1-4) have recently been proposed based on transcriptome profiling. A clinically practical immunohistochemistry (IHC) based CMS classifier consisting of the four markers FRMD6, ZEB1, HTR2B, and CDX2 was then demonstrated. Read More

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Redox-sensitive signalling pathways regulated by human papillomavirus in HPV-related cancers.

Rev Med Virol 2021 Mar 11:e2230. Epub 2021 Mar 11.

Laboratorio F-315, Departamento de Biología, Facultad de Química, Universidad Nacional Autónoma de México, México City, México.

High-risk human papillomavirus (HR-HPV) chronic infection is associated with the induction of different HPV-related cancers, such as cervical, anus, vaginal, vulva, penis and oropharynx. HPV-related cancers have been related to oxidative stress (OS), where OS has a significant role in cancer development and maintenance. Surgical resection is the treatment of choice for localised HPV-related cancers; however, these malignancies commonly progress to metastasis. Read More

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Calcium calmodulin kinase II activity is required for cartilage homeostasis in osteoarthritis.

Sci Rep 2021 Mar 11;11(1):5682. Epub 2021 Mar 11.

Barts and the London School of Medicine and Dentistry, William Harvey Research Institute, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK.

WNT ligands can activate several signalling cascades of pivotal importance during development and regenerative processes. Their de-regulation has been associated with the onset of different diseases. Here we investigated the role of the WNT/Calcium Calmodulin Kinase II (CaMKII) pathway in osteoarthritis. Read More

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Alpha synuclein (SNCA) rs7684318 variant contributes to Parkinson's disease risk by altering transcription factor binding related with Notch and Wnt signaling.

Neurosci Lett 2021 04 8;750:135802. Epub 2021 Mar 8.

Department of Clinical Pharmacology and Therapeutics, Nizam's Institute of Medical Sciences, Hyderabad, India.

In view of inconsistencies in the association studies of alpha synuclein (SNCA) rs7684318 (chr4: 90655003 T > C) with Parkinson's disease (PD), we conducted a meta-analysis to establish the association of this variant with PD and examined changes in transcription factor binding. SNCA rs7684318 C-allele was identified as genetic risk factor for PD in fixed (OR: 1.53, 95 % CI: 1. Read More

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A gradient of Wnt activity positions the neurosensory domains of the inner ear.

Elife 2021 Mar 11;10. Epub 2021 Mar 11.

UCL Ear Institute, University College London, London, United Kingdom.

The auditory and vestibular organs of the inner ear and the neurons that innervate them originate from Sox2-positive and Notch-active neurosensory domains specified at early stages of otic development. Sox2 is initially present throughout the otic placode and otocyst, and then it becomes progressively restricted to a ventro-medial domain. Using gain- and loss-of-function approaches in the chicken otocyst, we show that these early changes in Sox2 expression are regulated in a dose-dependent manner by Wnt/beta-catenin signalling. Read More

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DAAM2 is elevated in the circulation and placenta in pregnancies complicated by fetal growth restriction and is regulated by hypoxia.

Sci Rep 2021 Mar 10;11(1):5540. Epub 2021 Mar 10.

Therapeutics Discovery and Vascular Function in Pregnancy Group, Mercy Hospital for Women, Heidelberg, VIC, 3084, Australia.

Previously, we identified increased maternal circulating DAAM2 mRNA in pregnancies complicated by preterm fetal growth restriction (FGR). Here, we assessed whether circulating DAAM2 mRNA could detect FGR, and whether the DAAM2 gene, known to play roles in the Wnt signalling pathway is expressed in human placenta and associated with dysfunction and FGR. We performed linear regression analysis to calculate area under the ROC curve (AUC) for DAAM2 mRNA expression in the maternal circulation of pregnancies complicated by preterm FGR. Read More

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Culture and differentiation of rabbit intestinal organoids and organoid-derived cell monolayers.

Sci Rep 2021 Mar 8;11(1):5401. Epub 2021 Mar 8.

Health and Biosecurity, Commonwealth Scientific and Industrial Research Organisation, Canberra, 2601, Australia.

Organoids emulate many aspects of their parental tissue and are therefore used to study pathogen-host interactions and other complex biological processes. Here, we report a robust protocol for the isolation, maintenance and differentiation of rabbit small intestinal organoids and organoid-derived cell monolayers. Our rabbit intestinal spheroid and monolayer cultures grew most efficiently in L-WRN-conditioned medium that contained Wnt, R-spondin and Noggin, and that had been supplemented with ROCK and TGF-β inhibitors. Read More

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Gene expression profiling of giant fibroadenomas of the breast.

Surg Oncol 2021 Mar 2;37:101536. Epub 2021 Mar 2.

Center for Cancer and Stem Cell Research, Institute for Research, Development and Innovation (IRDI), International Medical University, Kuala Lumpur, Malaysia; School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia. Electronic address:

Introduction: Fibroadenomas of the breast present as two phenotypic variants. The usual variety is 5 cm or less in diameter and there is another large variant called giant fibroadenoma which is greater than 5 cm in diameter. Despite of its large size, it is not malignant. Read More

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Implication of TrkC-miR2 in neurotrophin signalling pathway regulation through NGFR transcript targeting.

J Cell Mol Med 2021 Apr 6;25(7):3381-3390. Epub 2021 Mar 6.

Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.

TrkC and NGFR neurotrophin receptors are associated with cell death, cancer and differentiation. TrkC-miR2, which is located in TrkC gene, is known to regulate Wnt signalling pathway, and its influence on other signalling pathways is under investigation. Here, through RT-qPCR, dual-luciferase assay and Western blotting we reveal that TrkC-miR2 targets NGFR. Read More

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Subversion of Niche-Signalling Pathways in Colorectal Cancer: What Makes and Breaks the Intestinal Stem Cell.

Cancers (Basel) 2021 Feb 27;13(5). Epub 2021 Feb 27.

Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.

The intestinal epithelium fulfils pleiotropic functions in nutrient uptake, waste elimination, and immune surveillance while also forming a barrier against luminal toxins and gut-resident microbiota. Incessantly barraged by extraneous stresses, the intestine must continuously replenish its epithelial lining and regenerate the full gamut of specialized cell types that underpin its functions. Homeostatic remodelling is orchestrated by the intestinal stem cell (ISC) niche: a convergence of epithelial- and stromal-derived cues, which maintains ISCs in a multipotent state. Read More

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February 2021

Understanding the binding affinities between SFRP1, SFRP1, Wnt and frizzled receptors 2, 3 and 7 using MD simulations.

J Biomol Struct Dyn 2021 Mar 5:1-14. Epub 2021 Mar 5.

Stem Cell Biology Group, Waghmare Lab, Cancer Research Institute, Advanced Centre for Treatment Research and Education in Cancer (ACTREC), Tata Memorial Centre, Navi Mumbai, India.

cWnt-signalling plays a crucial role in stem cell maintenance and tissue homeostasis. Secreted frizzled-related proteins(SFRP), Wnt inhibitors consist of the N-terminal cysteine rich domain(CRD) and the C-terminal netrin(NTR) domain. SFRP1 binds to the Wnt ligands and frizzled receptors(FZ) either through its SFRP1CRD or through its SFRP1Netrin domains; however, very little is known on these binding affinities. Read More

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Developmental regulation of barrier- and non-barrier blood vessels in the CNS.

A Ben-Zvi S Liebner

J Intern Med 2021 Mar 4. Epub 2021 Mar 4.

Institute of Neurology (Edinger Institute), University Hospital, Goethe University Frankfurt, Frankfurt am Main, Germany.

The blood-brain barrier (BBB) is essential for creating and maintaining tissue homeostasis in the central nervous system (CNS), which is key for proper neuronal function. In most vertebrates, the BBB is localized to microvascular endothelial cells that acquire barrier properties during angiogenesis of the neuroectoderm. Complex and continuous tight junctions, and the lack of fenestrae combined with low pinocytotic activity render the BBB endothelium a tight barrier for water-soluble molecules that may only enter the CNS via specific transporters. Read More

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Spermatozoal transcripts associated with oxidative stress and mitochondrial membrane potential differ between high- and low-fertile crossbred bulls.

Andrologia 2021 Mar 4:e14029. Epub 2021 Mar 4.

Animal Genomics Laboratory, ICAR - National Dairy Research Institute, Karnal, Haryana, India.

The presence of various forms of RNAs having roles in fertilisation and early embryonic development is well documented in mammalian spermatozoa. In the present study, using Agilent microarray platform, we compared sperm mRNA expression profiles between high- and low-fertile crossbred bulls with normal semen parameters. Microarray data acquisition and analysis were performed using GeneSpring GX version software, wherein spermatozoa from high-fertile bulls were kept as control while spermatozoa from low-fertile bulls were considered as treatment group. Read More

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