957,779 results match your criteria kinase rtk

The Effects of M1/M2 Macrophages on the mRNA Expression Profile of Diabetic Glomerular Endothelial Cells.

Nephron 2021 May 6:1-11. Epub 2021 May 6.

Department of Nephrology, the Second Xiangya Hospital of Central South University, Changsha, China.

Objectives: The aim of this study was to explore the effects of M1/M2 macrophages on the mRNA expression profile of glomerular endothelial cells (GECs) treated with advanced glycosylation end products (AGEs).

Methods: We cocultured M1/M2 macrophages and GECs treated with AGEs. The mRNA expression profile was detected by transcriptome sequencing. Read More

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Phlorizin attenuates visceral hypersensitivity and colonic hyperpermeability in a rat model of irritable bowel syndrome.

Biomed Pharmacother 2021 May 3;139:111649. Epub 2021 May 3.

Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1-1-1 Midorigaoka-Higashi, Asahikawa, Hokkaido, 078-8510, Japan; Department of General Medicine, Asahikawa Medical University, 2-1-1-1 Midorigaoka-Higashi, Asahikawa, Hokkaido 078-8510, Japan.

Visceral hypersensitivity and impaired gut barrier are crucial contributors to the pathophysiology of irritable bowel syndrome (IBS), and those are mediated via corticotropin-releasing factor (CRF)-Toll like receptor 4-pro-inflammatory cytokine signaling. Phlorizin is an inhibitor of sodium-linked glucose transporters (SGLTs), and known to have anti-cytokine properties. Thus, we hypothesized that phlorizin may improve these gastrointestinal changes in IBS, and tested this hypothesis in rat IBS models, i. Read More

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Integrated bioinformatic analysis and experiment confirmation of the antagonistic effect and molecular mechanism of ginsenoside Rh2 in metastatic osteosarcoma.

J Pharm Biomed Anal 2021 Apr 19;201:114088. Epub 2021 Apr 19.

Key Laboratory of Diagnostic Medicine Designated by the Chinese Ministry of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China. Electronic address:

This study aimed to compare the gene expression variation of clinical primary osteosarcoma (OS) and metastatic OS, identify expression profiles and signal pathways related to disease classification, and systematically evaluate the potential anticancer effect and molecular mechanism of ginsenoside Rh2 on OS. A raw dataset (GSE14359), which excluded GSM359137 and GSM359138, was downloaded from the Gene Expression Omnibus. Differentially expressed genes (DEGs) and principal component analysis (PCA) were obtained with limma. Read More

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Nicotinamide and its effects on endothelial dysfunction and secretion of antiangiogenic factors by primary human placental cells and tissues.

Placenta 2021 Apr 16;109:28-31. Epub 2021 Apr 16.

Mercy Perinatal, The Department of Obstetrics and Gynaecology, University of Melbourne. Mercy Perinatal, Mercy Hospital for Women 163 Studley Rd, Heidelberg, 3084, Victoria, Australia; Translational Obstetrics Group, The Department of Obstetrics and Gynaecology, University of Melbourne. Mercy Perinatal, Mercy Hospital for Women 163 Studley Rd, Heidelberg, 3084, Victoria, Australia.

Preeclampsia is a serious pregnancy complication associated with elevated antiangiogenic markers and endothelial dysfunction. Recently nicotinamide (vitamin B3) was shown to reduce high blood pressure and proteinuria in mice models of the disease. Using primary human pregnancy tissue we show nicotinamide did not change antiangiogenic factor secretion including soluble fms-like tyrosine kinase 1 or soluble endoglin from primary cytotrophoblasts and placental explants. Read More

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Immunomodulatory effect of pentagalloyl glucose in LPS-stimulated RAW264.7 macrophages and PAO1-induced Caenorhabditis elegans.

Exp Gerontol 2021 May 3:111388. Epub 2021 May 3.

Guangdong Provincial Key Laboratory of Nutraceuticals and Functional Foods, College of Food Science, South China Agricultural University, Guangzhou 510642, Guangdong, China; Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou 510642, Guangdong, China. Electronic address:

Pentagalloyl glucose (PGG) is a valuable natural compound with an array of biological activities, but the immunomodulatory effect and mechanism have not been fully validated yet. In this study, to elucidate comprehensively the function of immunomodulation and its underlying mechanism of PGG in vitro and in vivo, two model systems were conducted, which including lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages cells and Pseudomonas aeruginosa (PAO1)-induced Caenorhabditis elegans (C. Read More

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Efficacy and Safety of Ruxolitinib Cream for the Treatment of Atopic Dermatitis: Results From Two Phase 3, Randomized, Double-Blind Studies.

J Am Acad Dermatol 2021 May 3. Epub 2021 May 3.

Oregon Health & Science University, Portland, OR, USA.

Background: Ruxolitinib (RUX) cream demonstrated potent anti-inflammatory and antipruritic efficacy in a phase 2 study in adults with atopic dermatitis (AD).

Objective: To evaluate 8-week efficacy and safety in two phase 3 studies of RUX cream in patients with AD METHODS: TRuE-AD1 (NCT03745638) and TRuE-AD2 (NCT03745651) enrolled patients aged ≥12 years with AD for ≥2 years, an IGA score of 2/3, and 3% to 20% affected body surface area. Patients were randomized 2:2:1 to twice-daily 0. Read More

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From structure to the dynamic regulation of a molecular switch: A journey over three decades.

J Biol Chem 2021 May 3:100746. Epub 2021 May 3.

Department of Chemistry and Biochemistry, University of California at San Diego, United States; San Diego Supercomputer Center, University of California, San Diego, United States.

It is difficult to imagine where the signaling community would be today without the Protein Data Bank (PDB). This visionary resource, established in the 1970s, has been an essential partner for sharing information between academics and industry for over three decades. We describe here the history of our journey with the protein kinases using cAMP-dependent protein kinase (PKA) as a prototype. Read More

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Modulation of Akt vs Stat3 activity by the focal adhesion kinase in non-neoplastic mouse fibroblasts.

Exp Cell Res 2021 May 3:112601. Epub 2021 May 3.

Department of Biomedical and Molecular Sciences and Department of Pathology and Molecular Medicine, Queen's University, Kingston, Ontario, Canada K7L 3N6.

Adhesion of cells to each other and to the extracellular matrix (ECM) are both required for cellular functions. Cell-to-cell adhesion is mediated by cadherins and their engagement triggers the activation of Stat3, which offers a potent survival signal. Adhesion to the ECM on the other hand, activates FAK which attracts and activates Src, as well as receptor tyrosine kinases (RTKs), the PI3k/Akt and Ras/Erk pathways. Read More

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MiR-205-5p suppresses angiogenesis in gastric cancer by downregulating the expression of VEGFA and FGF1.

Exp Cell Res 2021 May 3:112579. Epub 2021 May 3.

Department of General Surgery, Peking University First Hospital, Beijing 100034, China. Electronic address:

Anti-angiogenic therapy represents one of the most promising treatment modalities for human cancers. However, the response to antiangiogenic therapy in gastric cancer (GC) remains dismal. To help identify new strategies for antiangiogenic therapy in GC, we evaluated miR-205-5p expression in GC tissues from TCGA database and our hospital, and its functions in angiogenesis were explored in vitro and in vivo. Read More

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Evolution of the membrane/particulate guanylyl cyclase: from physicochemical sensors to hormone receptors.

Yoshio Takei

Gen Comp Endocrinol 2021 May 3:113797. Epub 2021 May 3.

Laboratory of Physiology, Department of Marine Bioscience, Atmosphere and Ocean Research Institute, The University of Tokyo, Kashiwa, Chiba 277-8564, Japan. Electronic address:

Guanylyl cyclase (GC) is an enzyme that produces 3',5'-cyclic guanosine monophosphate (cGMP), one of the two canonical cyclic nucleotides used as a second messenger for intracellular signal transduction. The GCs are classified into two groups, particulate/membrane GCs (pGC) and soluble/cytosolic GCs (sGC). In relation to the endocrine system, pGCs include hormone receptors for natriuretic peptides (GC-A and GC-B) and guanylin peptides (GC-C), while sGC is a receptor for nitric oxide and carbon monoxide. Read More

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Case report: Secondary sclerosing cholangitis induced by lapatinib and vinorelbine in a metastasis breast cancer patient.

Thorac Cancer 2021 May 6. Epub 2021 May 6.

Department of Pharmacy, Peking University First Hospital, Beijing, China.

Secondary sclerosing cholangitis (SSC) is a rare cholestatic liver disease that may have a severe clinical course. A 61-year-old woman with a history of metastasis breast cancer was admitted to our hospital for the second cycle of chemotherapy with lapatinib and vinorelbine. The patient had no reports of elevated liver function tests (LFTs) in the previous multiple chemotherapies or history of liver disease. Read More

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Endogenous µ-opioid receptor activity in the lateral and capsular subdivisions of the right central nucleus of the amygdala prevents chronic postoperative pain.

J Neurosci Res 2021 May 6. Epub 2021 May 6.

Department of Anesthesiology and Perioperative Medicine, Pittsburgh Center for Pain Research, Pittsburgh Project to End Opioid Misuse, University of Pittsburgh, Pittsburgh, PA, USA.

Tissue injury induces a long-lasting latent sensitization (LS) of spinal nociceptive signaling that is kept in remission by an opposing µ-opioid receptor (MOR) constitutive activity. To test the hypothesis that supraspinal sites become engaged, we induced hindpaw inflammation, waited 3 weeks for mechanical hypersensitivity to resolve, and then injected the opioid receptor inhibitors naltrexone, CTOP or β-funaltrexamine subcutaneously, and/or into the cerebral ventricles. Intracerebroventricular injection of each inhibitor reinstated hypersensitivity and produced somatic signs of withdrawal, indicative of LS and endogenous opioid dependence, respectively. Read More

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Interleukin-23 reshapes kidney resident cell metabolism and promotes local kidney inflammation.

J Clin Invest 2021 May 6. Epub 2021 May 6.

Department of Medicine, Beth Israel Deaconess Medical Center, Boston, United States of America.

Interstitial kidney inflammation is present in various nephritides in which serum IL-23 is elevated. Here we show that IL-23 receptor (IL-23R) expressing murine and human renal tubular epithelial cells (TEC) respond to IL-23 by inducing intracellular calcium flux, enhanced glycolysis, and the upregulation of calcium/calmodulin kinase IV (CaMK4) which results in suppression of the expression of the arginine degrading enzyme arginase 1 (ARG1) thus increasing in situ levels of free L-Arginine (Arg). Limited availability of Arg suppresses the ability of infiltrating T cells to proliferate and produce inflammatory cytokines. Read More

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A signalling cascade for Ral.

Small GTPases 2021 May 6:1-8. Epub 2021 May 6.

Texas A&M University, Houston, TX, USA.

Ras is the most mutated oncoprotein in cancer. Among the three oncogenic effectors of Ras - Raf, PI3 Kinase and RalGEF>Ral - signalling through RalGEF>Ral (Ras-like) is by far the least well understood. A variety of signals and binding partners have been defined for Ral, yet we know little of how Ral functions . Read More

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Inhibitors of immuno-oncology target HPK1 - a patent review (2016 to 2020).

Expert Opin Ther Pat 2021 May 6. Epub 2021 May 6.

Nimbus Therapeutics, 130 Prospect Street, Suite 301, Cambridge, MA 02139, USA.

Introduction: Hematopoietic progenitor kinase (HPK1), a serine/threonine kinase, which is primarily expressed in hematopoietic cells is a negative regulator of T-cell receptor and B cell signaling. Studies using genetic disruption of HPK1 function show enhanced T-cell signaling, cytokine production and tumor growth inhibition. This profile of enhanced immune response highlights small molecule inhibition of HPK1 as an attractive approach for the immunotherapy of cancer. Read More

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The Kidney-Related Effects of Polystyrene Microplastics on Human Kidney Proximal Tubular Epithelial Cells HK-2 and Male C57BL/6 Mice.

Environ Health Perspect 2021 May 6;129(5):57003. Epub 2021 May 6.

Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.

Background: Understanding the epidemic of chronic kidney disease of uncertain etiology may be critical for health policies and public health responses. Recent studies have shown that microplastics (MPs) contaminate our food chain and accumulate in the gut, liver, kidney, muscle, and so on. Humans manufacture many plastics-related products. Read More

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Coarse-Grained Modeling of Multiple Pathways in Conformational Transitions of Multi-Domain Proteins.

J Chem Inf Model 2021 May 6. Epub 2021 May 6.

Laboratory for Biomolecular Function Simulation, RIKEN Center for Biosystems Dynamics Research, Kobe, Hyogo 650-0047, Japan.

Large-scale conformational transitions in multi-domain proteins are often essential for their functions. To investigate the transitions, it is necessary to explore multiple potential pathways, which involve different intermediate structures. Here, we present a multi-basin (MB) coarse-grained (CG) structure-based Go̅ model for describing transitions in proteins with more than two moving domains. Read More

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p70S6K on astrocytes protects dopamine neurons from 1-methyl-4-phenylpyridinium neurotoxicity.

Glia 2021 May 6. Epub 2021 May 6.

Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul, South Korea.

Our recent finding has demonstrated that astrocytes confer neuroprotection by endogenously producing ciliary neurotrophic factor (CNTF) via transient receptor potential vanilloid 1 (TRPV1) in Parkinson's disease (PD). In this study, the possible molecular target for TRPV1-mediated CNTF production and its neuroprotective effects on dopamine neurons were further investigated. For comparison, glial cell-line derived neurotrophic factor (GDNF) was also examined. Read More

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Glutaredoxin 1 protects neurons from oxygen-glucose deprivation/reoxygenation (OGD/R)-induced apoptosis and oxidative stress via the modulation of GSK-3β/Nrf2 signaling.

J Bioenerg Biomembr 2021 May 6. Epub 2021 May 6.

Department of Anesthesiology, The First Hospital of Yulin, No. 93 Yuxi Street, Yulin, Shaanxi, 719000, China.

Increasing evidence has indicated that glutaredoxin 1 (GRX1) is a potent antioxidant protein that promotes cell survival under conditions of oxidative stress. Oxidative stress-induced neuronal injury contributes to cerebral ischemia/reperfusion injury. However, the role of GRX1-mediated antioxidant defense against neuronal damage during cerebral ischemia/reperfusion injury has not been thoroughly investigated. Read More

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[BRAF-V600E testing in metastatic colorectal cancer and new, chemotherapy-free therapy options. German version].

Pathologe 2021 May 6. Epub 2021 May 6.

Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover, Hannover, Deutschland.

In the past 25 years, treatment of metastatic colorectal cancer (mCRC) has undergone profound changes. The approval of newer chemotherapeutics such as irinotecan and oxaliplatin was followed in 2005 by the first targeted therapies, for example, monoclonal antibodies directed against the epidermal growth factor receptor (EGFR), as cetuximab and panitumumab, or the angiogenesis inhibitors bevacizumab, ramucirumab, and aflibercept. With the rapidly progressing molecular characterization of mCRC in the last 10 years and the classification of the disease in four consensus subtypes, further changes are emerging, which will promote, among other things, the introduction of protein-kinase inhibitors developed for specific molecular aberrations as well as immune checkpoint inhibitors into the treatment algorithm. Read More

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Sit4 and PP2A Dephosphorylate Nitrogen Catabolite Repression-Sensitive Gln3 When TorC1 Is Up- as Well as Downregulated.

Genetics 2019 Aug;212(4):1205-1225

Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, 38163 Tennessee.

Saccharomyces cerevisiae lives in boom and bust nutritional environments. Sophisticated regulatory systems have evolved to rapidly cope with these changes while preserving intracellular homeostasis. Target of Rapamycin Complex 1 (TorC1), is a serine/threonine kinase complex and a principle nitrogen-responsive regulator. Read More

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The TOR Pathway Plays Pleiotropic Roles in Growth and Stress Responses of the Fungal Pathogen Cryptococcus neoformans.

Genetics 2019 Aug;212(4):1241-1258

Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of Korea.

The target of rapamycin (TOR) pathway is an evolutionarily conserved signal transduction system that governs a plethora of eukaryotic biological processes, but its role in Cryptococcus neoformans remains elusive. In this study, we investigated the TOR pathway by functionally characterizing two Tor-like kinases, Tor1 and Tlk1, in C. neoformans. Read More

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Corrigendum to: Mitogen-activated protein kinase kinase 5 (MKK5)-mediated signaling cascade regulates expression of iron superoxide dismutase gene in Arabidopsis under salinity stress.

J Exp Bot 2021 May 6. Epub 2021 May 6.

School of Life Sciences, State Key Laboratory of Agrobiotechnology, and Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China.

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miR-1/133a and miR-206/133b clusters overcome HGF induced gefitinib resistance in non-small cell lung cancers with EGFR sensitive mutations.

J Drug Target 2021 May 6:1-14. Epub 2021 May 6.

The First Clinical Medical College, Wenzhou Medical University, Wenzhou 325000, China.

It has been reported that clustered miRNAs can be transcribed coordinately and exhibit similar functions by regulating the same targets. miR-1/133a and miR-206/133b are well characterized miRNA clusters. However, the effect of these clusters on EGFR-TKI resistance is not clear. Read More

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Establishment of reference intervals of ten commonly used clinical chemistry analytes: a real-world study in China.

Biomark Med 2021 May 6. Epub 2021 May 6.

Department of Epidemiology, Meinian Institute of Health, Beijing, 100191, China.

This real-world study was aimed at establishing reference intervals (RIs) of ten commonly used clinical chemistry analytes (total cholesterol, triglycerides, Apo A1, Apo B, creatine kinase (CK), CK isoenzyme MB, glucose, alkaline phosphatase, γ-glutamyltransferase and blood urea nitrogen) in an apparently healthy population in China.  A total of 17,356 healthy participants aged 18-79 years who underwent check-up at MJ Health Check-up Center were included. The establishment of RIs was performed according to the Clinical and Laboratory Standards Institute EP28-A3c guideline. Read More

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GSK-3β S9A overexpression leads murine hippocampal neural precursors to acquire an astroglial phenotype in vivo.

Dev Neurobiol 2021 May 6. Epub 2021 May 6.

Department of Molecular Neuropathology, Centro de Biología Molecular "Severo Ochoa", CBMSO, CSIC-UAM, Madrid, Spain.

The addition of new neurons to the existing hippocampal circuitry persists in the adult dentate gyrus (DG). During this process, named adult hippocampal neurogenesis (AHN), adult hippocampal progenitor cells (AHPs) give rise to newborn dentate granule cells (DGCs). The acquisition of a neuronal lineage by AHPs is tightly regulated by numerous signaling molecules and transcription factors. Read More

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Anlotinib exerts anti-cancer efficiency on lung cancer stem cells in vitro and in vivo through reducing NF-κB activity.

J Cell Mol Med 2021 May 6. Epub 2021 May 6.

Lung Cancer Center, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, China.

Anlotinib is a multi-target tyrosine kinase inhibitor. Previous studies confirmed that anlotinib exerts anti-cancer efficiency. However, the functional roles of anlotinib on cancer stem cells (CSCs) are yet to be elucidated. Read More

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BRASSINOSTEROID-SIGNALLING KINASES 7 and 8 associate with the FLS2 immune receptor and are required for flg22-induced PTI responses.

Mol Plant Pathol 2021 May 6. Epub 2021 May 6.

School of Plant Sciences and Food Security, Tel-Aviv University, Tel-Aviv, Israel.

Pattern-triggered immunity (PTI) is typically initiated in plants by recognition of pathogen- or damage-associated molecular patterns (PAMP/DAMPs) by cell surface-localized pattern recognition receptors (PRRs). Here, we investigated the role in PTI of Arabidopsis thaliana brassinosteroid-signalling kinases 7 and 8 (BSK7 and BSK8), which are members of the receptor-like cytoplasmic kinase subfamily XII. BSK7 and BSK8 localized to the plant cell periphery and interacted in yeast and in planta with FLS2, but not with other PRRs. Read More

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[Corrigendum] High PLK4 expression promotes tumor progression and induces epithelial‑mesenchymal transition by regulating the Wnt/β‑catenin signaling pathway in colorectal cancer.

Int J Oncol 2021 Jun 6;58(6). Epub 2021 May 6.

Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.

Subsequently to the publication of the above article, the author realized that Fig. 5 on p. 486 contained some errors on account of the figure having been compiled incorrectly; essentially, the published version of the figure contained incorrect images for the panels presented in Fig. Read More

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Predictive significance of STK17A in patients with gastric cancer and association with gastric cancer cell proliferation and migration.

Oncol Rep 2021 Jun 6;45(6). Epub 2021 May 6.

Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.

Gastric cancer (GC) is one of the most frequently diagnosed types of cancer worldwide, and exploring its potential therapeutic targets is particularly important for improving the prognosis of patients with GC. The aim of the present study was to investigate the association between serine/threonine kinase 17a (STK17A) expression and GC prognosis. STK17A expression was measured by quantitative real‑time PCR, western blotting and immunohistochemical staining. Read More

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