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Acute hemolytic transfusion reaction caused by anti-Yt.

Immunohematology 2021 Mar;37(1):13-17

Department of Transfusion Medicine and Transplantation Biology, University Clinical Hospital Zagreb , Zagreb , Croatia .

Many patients with anti-Yt receive multiple transfusions of Yt(a+) red blood cells (RBCs) with no ill effects. However, anti-Yt has been implicated in hemolytic transfusion reactions. Antibody identification typically determines specificity of antibodies and their clinical significance to justify blood requirements for antigen-negative blood when clinically significant antibodies are involved. Read More

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Neither gonadotropin nor cumulus cell expansion is needed for the maturation of competent porcine oocytes in vitro.

Biol Reprod 2021 May 7. Epub 2021 May 7.

Division of Animal Sciences, University of Missouri, Columbia, MO 65211.

In vitro maturation of oocytes from immature females is widely used in assisted reproductive technologies. Here we illustrate that cumulus cell (CC) expansion, once considered a key indicator of oocyte quality, is not needed for oocytes to mature to the metaphase II (MII) stage and to gain nuclear and cytoplasmic competence to produce offspring. Juvenile pig oocytes were matured in four different media: 1) Basal (-gonadotropins (GN)-FLI); 2) -GN + FLI (supplement of FGF2, LIF, and IGF1); 3) + GN-FLI; 4) + GN + FLI. Read More

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Quality by design to define critical process parameters for mesenchymal stem cell expansion.

Biotechnol Adv 2021 May 4:107765. Epub 2021 May 4.

Laboratoire Réactions et Génie des Procédés, Université de Lorraine, CNRS, Nancy, France. Electronic address:

Stem cell-based therapeutic products could be the key to treat the deadliest current pathologies, ranging from neuro-degenerative to respiratory diseases. However, in order to bring these innovative therapeutics to a commercialization stage, reproducible manufacturing of high quality cell products is required. Although advances in cell culture techniques have led to more robust production processes and dramatically accelerated the development of early-phase clinical studies, challenges remain before regulatory approval, particularly to define and implement science-based quality standards (essential pre-requisites for national health agencies). Read More

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Targeting lipid metabolism is an emerging strategy to enhance the efficacy of anti-HER2 therapies in HER2-positive breast cancer.

Cancer Lett 2021 May 4. Epub 2021 May 4.

Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133, Milan, Italy; IFOM, the FIRC Institute of Molecular Oncology, Via Adamello 16, Milan, Italy. Electronic address:

De novo or acquired resistance of cancer cells to currently available Human Epidermal Growth Factor Receptor 2 (HER2) inhibitors represents a clinical challenge. Several resistance mechanisms have been identified in recent years, with lipid metabolism reprogramming, a well-established hallmark of cancer, representing the last frontier of preclinical and clinical research in this field. Fatty Acid Synthase (FASN), the key enzyme required for fatty acids (FAs) biosynthesis, is frequently overexpressed/activated in HER2-positive (HER2+) breast cancer (BC), and it crucially sustains HER2+ BC cell growth, proliferation and survival. Read More

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Neuroglian regulates Drosophila intestinal stem cell proliferation through enhanced signaling via the epidermal growth factor receptor.

Stem Cell Reports 2021 May 5. Epub 2021 May 5.

Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address:

The Drosophila intestine is an excellent system for elucidating mechanisms regulating stem cell behavior. Here we show that the septate junction (SJ) protein Neuroglian (Nrg) is expressed in intestinal stem cells (ISCs) and enteroblasts (EBs) within the fly intestine. SJs are not present between ISCs and EBs, suggesting Nrg plays a different role in this tissue. Read More

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Astrocyte-Endotheliocyte Axis in the Regulation of the Blood-Brain Barrier.

Neurochem Res 2021 May 7. Epub 2021 May 7.

Department of Stem Cell Biology, State Research Institute Centre for Innovative Medicine, 01102, Vilnius, Lithuania.

The evolution of blood-brain barrier paralleled centralisation of the nervous system: emergence of neuronal masses required control over composition of the interstitial fluids. The barriers were initially created by glial cells, which employed septate junctions to restrict paracellular diffusion in the invertebrates and tight junctions in some early vertebrates. The endothelial barrier, secured by tight and adherent junctions emerged in vertebrates and is common in mammals. Read More

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Temperature Dependence of Lithium Anode Voiding in Argyrodite Solid-State Batteries.

ACS Appl Mater Interfaces 2021 May 7. Epub 2021 May 7.

Department of Materials, University of Oxford, Parks Road, Oxford OX1 3PH, U.K.

Void formation at the Li/ceramic electrolyte interface of an all-solid-state battery on discharge results in high local current densities, dendrites on charge, and cell failure. Here, we show that such voiding is reduced at the Li/LiPSCl interface at elevated temperatures, sufficient to increase the critical current before voiding and cell failure from <0.25 mA cm at 25 °C to 0. Read More

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Detection of mcr-1-positive Escherichia coli in slaughterhouse wastewater collected from Dawen river.

Vet Med Sci 2021 May 7. Epub 2021 May 7.

College of Animal Science and Technology, Shandong Agricultural University, Tai'an, China.

Background: Low levels of mcr-1 were detected in Escherichia coli from wastewater samples across the world; hence, further monitoring and management of accumulation of mcr-1-positive bacteria in wastewater are urgently recommended.

Objectives: In this study, we have reported the detection of E. coli strains carrying the colistin resistance gene mcr-1 in slaughterhouse wastewater discharged into Dawen river. Read More

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Gyroid-Nanostructured All-Solid Polymer Films Combining High H Conductivity with Low H Permeability.

Macromol Rapid Commun 2021 May 7:e2100115. Epub 2021 May 7.

Department of Biotechnology, Tokyo University of Agriculture and Technology, Naka-cho, Koganei, Tokyo, 184-8588, Japan.

Gyroid-nanostructured all-solid polymer films with exceedingly high proton conductivity and low H gas permeability have been created via crosslinking polymerization of mixtures of a zwitterionic amphiphilic monomer and a polymerizable imide-type acid that co-organize into bicontinuous cubic liquid-crystalline phases. The gyroid nanostructures are visualized by reconstructing a 3D electron map from the synchrotron X-ray diffraction patterns. These films exhibit high proton conductivity of the order of 10 S cm and extremely low H gas permeability of the order of 10 mol m m s Pa . Read More

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Regulation of CTLA-4 recycling by LRBA and Rab11.

Immunology 2021 May 7. Epub 2021 May 7.

Institute of Immunity and Transplantation, University College London, London, United Kingdom.

CTLA-4 is an essential regulator of T cell immune responses whose intracellular trafficking is a hallmark of its expression. Defects in CTLA-4 trafficking due to LRBA deficiency cause profound autoimmunity in humans. CTLA-4 rapidly internalises via a clathrin-dependent pathway followed by poorly characterised recycling and degradation fates. Read More

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Helios serves as a suppression marker to reduce regulatory T cell function in pancreatic cancer patients.

Immunol Res 2021 May 6. Epub 2021 May 6.

Department of Gastrointestinal Surgery, Shanghai Tenth People's Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

Destabilizing and reprogramming regulatory T (Treg) cells have become a potential strategy to treat tumor. Mounting evidence indicates that the transcription factor Helios is required for the stable differentiation of Treg lineage. Hence, we investigated whether Helios suppression could be a potential treatment option for pancreatic cancer patients. Read More

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The cholesterol metabolite 27-hydroxycholesterol increases the secretion of extracellular vesicles which promote breast cancer progression.

Endocrinology 2021 May 7. Epub 2021 May 7.

Department of Molecular and Integrative Physiology, University of Illinois Urbana-Champaign, Urbana, IL.

Cholesterol has been implicated in the clinical progression of breast cancer, a disease that continues to be the most commonly diagnosed cancer in women. Previous work has identified the cholesterol metabolite, 27-hydroxycholesterol (27HC), as a major mediator of the effects of cholesterol on breast tumor growth and progression. 27HC can act as an estrogen receptor (ER) modulator to promote the growth of ERα+ tumors, and a liver x receptor (LXR) ligand in myeloid immune cells to establish an immune-suppressive program. Read More

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Sweet Melody or Jazz? Transcription Around DNA Double-Strand Breaks.

Front Mol Biosci 2021 20;8:655786. Epub 2021 Apr 20.

Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom.

Genomic integrity is continuously threatened by thousands of endogenous and exogenous damaging factors. To preserve genome stability, cells developed comprehensive DNA damage response (DDR) pathways that mediate the recognition of damaged DNA lesions, the activation of signaling cascades, and the execution of DNA repair. Transcription has been understood to pose a threat to genome stability in the presence of DNA breaks. Read More

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Lansoprazole Alone or in Combination With Gefitinib Shows Antitumor Activity Against Non-small Cell Lung Cancer A549 Cells and .

Front Cell Dev Biol 2021 20;9:655559. Epub 2021 Apr 20.

Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin, China.

Lansoprazole (Lpz) is an FDA-approved proton pump inhibitor (PPI) drug for the therapy of acid-related diseases. Aiming to explore the new application of old drugs, we recently investigated the antitumor effect of Lpz. We demonstrated that the PPI Lpz played a tumor suppressive role in non-small cell lung cancer (NSCLC) A549 cells. Read More

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Evolving Roles of Muscle-Resident Fibro-Adipogenic Progenitors in Health, Regeneration, Neuromuscular Disorders, and Aging.

Front Physiol 2021 20;12:673404. Epub 2021 Apr 20.

Departamento de Biología Celular y Molecular, Center for Aging and Regeneration (CARE-ChileUC), Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.

Normal skeletal muscle functions are affected following trauma, chronic diseases, inherited neuromuscular disorders, aging, and cachexia, hampering the daily activities and quality of life of the affected patients. The maladaptive accumulation of fibrous intramuscular connective tissue and fat are hallmarks of multiple pathologies where chronic damage and inflammation are not resolved, leading to progressive muscle replacement and tissue degeneration. Muscle-resident fibro-adipogenic progenitors are adaptable stromal cells with multilineage potential. Read More

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C/EBPβ is a MYB- and p300-cooperating pro-leukemogenic factor and promising drug target in acute myeloid leukemia.

Oncogene 2021 May 6. Epub 2021 May 6.

Institute for Biochemistry, Westfälische-Wilhelms-Universität, Münster, Germany.

Transcription factor MYB has recently emerged as a promising drug target for the treatment of acute myeloid leukemia (AML). Here, we have characterized a group of natural sesquiterpene lactones (STLs), previously shown to suppress MYB activity, for their potential to decrease AML cell proliferation. Unlike what was initially thought, these compounds inhibit MYB indirectly via its cooperation partner C/EBPβ. Read More

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Mitochondrial calcium uniporter is essential for hearing and hair cell preservation in congenic FVB/NJ mice.

Sci Rep 2021 May 6;11(1):9660. Epub 2021 May 6.

Department of Otolaryngology-Head and Neck Surgery, School of Medicine, Case Western Reserve University and University Hospitals Cleveland Medical Center, 11100 Euclid Ave., Cleveland, OH, 44106, USA.

Mitochondrial Ca regulates a wide range of cell processes, including morphogenesis, metabolism, excitotoxicity, and survival. In cochlear hair cells, the activation of mechano-electrical transduction and voltage-gated Ca channels result in a large influx of Ca. The intracellular rise in Ca is partly balanced by the mitochondria which rapidly uptakes Ca via a highly selective channel comprised of the main pore-forming subunit, the mitochondrial Ca uniporter (MCU), and associated regulatory proteins. Read More

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Natural products targeting the synthesis of β(1,3)-D-glucan and chitin of the fungal cell wall. Existing drugs and recent findings.

Phytomedicine 2021 Mar 27:153556. Epub 2021 Mar 27.

Instituto de Biología Funcional y Genómica and Departamento de Microbiología y Genética, Consejo Superior de Investigaciones Científicas (CSIC)/Universidad de Salamanca, Salamanca, Spain. Electronic address:

Background: During the last three decades systemic fungal infections associated to immunosuppressive therapies have become a serious healthcare problem. Clinical development of new antifungals is an urgent requirement. Since fungal but not mammalian cells are encased in a carbohydrate-containing cell wall, which is required for the growth and viability of fungi, the inhibition of cell wall synthesizing machinery, such as β(1,3)-D-glucan synthases (GS) and chitin synthases (CS) that catalyze the synthesis of β(1-3)-D-glucan and chitin, respectively, represent an ideal mode of action of antifungal agents. Read More

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Tumor reversion: a dream or a reality.

Biomark Res 2021 May 6;9(1):31. Epub 2021 May 6.

Amity Stem Cell Institute, Amity Medical School, Amity University Haryana, Panchgaon, Haryana, Manesar (Gurugram), -122413, India.

Reversion of tumor to a normal differentiated cell once considered a dream is now at the brink of becoming a reality. Different layers of molecules/events such as microRNAs, transcription factors, alternative RNA splicing, post-transcriptional, post-translational modifications, availability of proteomics, genomics editing tools, and chemical biology approaches gave hope to manipulation of cancer cells reversion to a normal cell phenotype as evidences are subtle but definitive. Regardless of the advancement, there is a long way to go, as customized techniques are required to be fine-tuned with precision to attain more insights into tumor reversion. Read More

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Three-dimensional cell printed lock-key structure for oral soft and hard tissue regeneration.

Tissue Eng Part A 2021 May 6. Epub 2021 May 6.

University of Michigan School of Dentistry, 43800, Ann Arbor, Michigan, United States;

Alveolar ridge absorbs rapidly following tooth extraction. To promote implant rehabilitation, an adequate bone and soft tissue volume are required. Three-dimensional (3D) cell printing technique provides the advantages of precise spatial distribution and personalization. Read More

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Lycium barbarum mitigates radiation injury via regulation of the immune function, gut microbiota, and related metabolites.

Biomed Pharmacother 2021 May 3;139:111654. Epub 2021 May 3.

Tianjin University of Traditional Chinese Medicine, Tianjin, China; Beijing Institute of Radiation Medicine, Beijing, China. Electronic address:

Previous studies have suggested that Lycium barbarum (L. barbarum) has a radioprotective function, although more in-depth investigation is still required. We investigated the radioprotective efficacy of extract of the fruits of L. Read More

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Ultrasensitive detection and quantification of viral nucleic acids with raindance droplet digital PCR (ddPCR).

Methods 2021 May 3. Epub 2021 May 3.

AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, MD, 21702, United States.

Sensitive detection of viral nucleic acids is critically important for diagnosis and monitoring of the progression of infectious diseases such as those caused by SARS-CoV2, HIV-1, and other viruses. In HIV-1 infection cases, assessing the efficacy of treatment interventions that are superimposed on combination antiretroviral therapy (cART) has benefited tremendously from the development of sensitive HIV-1 DNA and RNA quantitation assays. Simian immunodeficiency virus (SIV) infection of Rhesus macaques is similar in many key aspects to human HIV-1 infection and consequently this non-human primate (NHP) model has and continues to prove instrumental in evaluating HIV prevention, treatment and eradication approaches. Read More

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Seeing the PDB.

J Biol Chem 2021 May 3:100742. Epub 2021 May 3.

Department of Integrative and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA; Research Collaboratory for Structural Bioinformatics Protein Data Bank, Rutgers, the State University of New Jersey, Piscataway, NJ, USA. Electronic address:

Ever since the first structures of proteins were determined in the 1960s, structural biologists have required methods to visualize biomolecular structures, both as an essential tool for their research and also to promote 3D comprehension of structural results by a wide audience of researchers, students, and the general public. In this review to celebrate the 50 anniversary of the Protein Data Bank, we present our own experiences in developing and applying methods of visualization and analysis to the ever-expanding archive of protein and nucleic acid structures in the worldwide PDB. Across that timespan, Jane and David Richardson have concentrated on the organization inside and between the macromolecules, with ribbons to show the overall backbone "fold" and contact dots to show how the all-atom details fit together locally. Read More

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Targeted truncation of the ADAM17 cytoplasmic domain in mice results in protein destabilization and a hypomorphic phenotype.

J Biol Chem 2021 May 3:100733. Epub 2021 May 3.

Physiology, Biophysics and Systems Biology Program, Weill Cornell Medicine, New York, NY, 10021, USA; Arthritis and Tissue Degeneration Program, Hospital for Special Surgery, New York, NY, 10021, USA; Institute for Advanced Study, Technische Universität München, D-85748 Garching, Germany; Department of Medicine, Physiology and Systems Biology, Weill Cornell Medicine, New York, NY, 10021, USA; Department of Biophysics, Physiology and Systems Biology, Weill Cornell Medicine, New York, NY 10021, USA. Electronic address:

A disintegrin and metalloprotease 17 (ADAM17) is a cell-surface metalloprotease that serves as the principle sheddase for Tumor necrosis factor α (TNFα), interleukin-6 receptor (IL-6R) and several ligands of the epidermal growth factor receptor (EGFR), regulating these crucial signaling pathways. ADAM17 activation requires its transmembrane domain, but not its cytoplasmic domain, and little is known about the role of this domain in vivo. To investigate, we used CRISPR-Cas9 to mutate the endogenous Adam17 locus in mice to produce a mutant ADAM17 lacking its cytoplasmic domain (Adam17Δcyto). 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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MyD88 oligomer size functions as a physical threshold to trigger IL1R Myddosome signaling.

J Cell Biol 2021 Jul 6;220(7). Epub 2021 May 6.

Max Planck Institute for Infection Biology, Berlin, Germany.

A recurring feature of innate immune receptor signaling is the self-assembly of signaling proteins into oligomeric complexes. The Myddosome is an oligomeric complex that is required to transmit inflammatory signals from TLR/IL1Rs and consists of MyD88 and IRAK family kinases. However, the molecular basis for how Myddosome proteins self-assemble and regulate intracellular signaling remains poorly understood. 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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Bistability in the polarity circuit of yeast.

Mol Biol Cell 2021 May 6:mbcE20070445. Epub 2021 May 6.

Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

Cells polarize their growth or movement in many different physiological contexts. A key driver of polarity is the Rho GTPase Cdc42, which when activated becomes clustered or concentrated at polar sites. Multiple models for polarity establishment have been proposed. Read More

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Oligodendrocyte progenitor cell maturation is dependent on dual function of MCT8 in the transport of thyroid hormone across brain barriers and the plasma membrane.

Glia 2021 May 6. Epub 2021 May 6.

The Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.

Inactivating mutations in the thyroid hormone (TH) transporter monocarboxylate transporter 8 (MCT8) causes a rare and debilitating form of X-linked psychomotor disability known as Allan Herndon Dudley syndrome (AHDS). One of the most prominent pathophysiological symptoms of MCT8-deficiency is hypomyelination. Here, patient-derived induced pluripotent stem cells (iPSCs) were used to study the role of MCT8 and TH on the maturation of oligodendrocytes. Read More

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GIMAP5 maintains liver endothelial cell homeostasis and prevents portal hypertension.

J Exp Med 2021 Jul 6;218(7). Epub 2021 May 6.

Department of Internal Medicine (Digestive Diseases), Yale School of Medicine, New Haven, CT.

Portal hypertension is a major contributor to decompensation and death from liver disease, a global health problem. Here, we demonstrate homozygous damaging mutations in GIMAP5, a small organellar GTPase, in four families with unexplained portal hypertension. We show that GIMAP5 is expressed in hepatic endothelial cells and that its loss in both humans and mice results in capillarization of liver sinusoidal endothelial cells (LSECs); this effect is also seen when GIMAP5 is selectively deleted in endothelial cells. Read More

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