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Advances in the study of GPCRs by F NMR.

Curr Opin Struct Biol 2021 Jun 12;69:169-176. Epub 2021 Jun 12.

Department of Chemistry, University of Toronto, Canada. Electronic address:

Crystallography and cryo-electron microscopy have advanced atomic resolution perspectives of inactive and active states of G protein-coupled receptors (GPCRs), alone and in complex with G proteins or arrestin. F NMR can play a role in ascertaining activation mechanisms and understanding the complete energy landscape associated with signal transduction. Fluorinated reporters are introduced biosynthetically via fluorinated amino acid analogs or chemically, via thiol-specific fluorinated reporters. Read More

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Nutrient status and growth in vegan children.

Nutr Res 2021 May 18;91:13-25. Epub 2021 May 18.

Institute of Evolutionary Medicine, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland. Electronic address:

Vegan diets have risen in popularity over the past 9 years. However, few studies have examined nutrient status and the effect of a vegan diet on the growth of children. This study analysed the existing literature on the health impact and growth impact of selected nutrients in vegan children. Read More

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Effects of dynamic adsorption on bubble formation and coalescence in partitioned-EDGE devices.

J Colloid Interface Sci 2021 Jun 4;602:316-324. Epub 2021 Jun 4.

Wageningen University, Food Process Engineering Group, Bornse Weilanden 9, 6708 WG Wageningen, The Netherlands. Electronic address:

Hypothesis: Dynamic adsorption effects can play a crucial role in bubble formation and stabilization. We hypothesize that microfluidic tools provide direct insights to these effects, and that the final bubble size depends on the intersection of time scales for bubble formation versus adsorption of proteins.

Experiments: We use a microfluidic device to study Laplace pressure-driven formation of bubbles that are stabilized by whey proteins. Read More

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Anti-flagellin IgY antibodies protect against Pseudomonas aeruginosa infection in both acute pneumonia and burn wound murine models in a non-type-specific mode.

Mol Immunol 2021 Jun 12;136:118-127. Epub 2021 Jun 12.

Medicinal Plants Research Center, Shahed University, Tehran, Iran.

Pseudomonas aeruginosa (PA) is one of the most dominant causes of nosocomial infections in burn patients. Increasing emergence of antibiotic-resistant strains highlights the need for novel antimicrobial agents. Flagellin, the main component protein of flagellum, is determined as the major antigen interacting with anti-P. Read More

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Peroxiredomin-4 ameliorates lipotoxicity-induced oxidative stress and apoptosis in diabetic cardiomyopathy.

Biomed Pharmacother 2021 Jun 12;141:111780. Epub 2021 Jun 12.

Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China. Electronic address:

Diabetic cardiomyopathy (DCM), one severe complication in the diabetes, leads to high mortality in the diabetic patients. However, the understanding of molecular mechanisms underlying DCM is far from completion. Herein, we investigated the disease-related differences in the proteomes of DCM based on db/db mice and verified the protective roles of peroxiredoxin-4 (Prdx4) in H9c2 cardiomyocytes treated by palmitic acid (PA). Read More

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Knockdown of CDK5 down-regulates PD-L1 via the ubiquitination-proteasome pathway and improves antitumor immunity in lung adenocarcinoma.

Transl Oncol 2021 Jun 12;14(9):101148. Epub 2021 Jun 12.

Department of Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 Huaihai West Road, Shanghai 200030, PR China. Electronic address:

Although immunotherapy (anti-PD-1/PD-L1 antibodies) has been approved for clinical treatment of lung cancer, only a small proportion of patients respond to monotherapy. Hence, understanding the regulatory mechanism of PD-L1 is particularly important to identify optimal combinations. In this study, we found that inhibition of CDK5 induced by shRNA or CDK5 inhibitor leads to reduced expression of PD-L1 protein in human lung adenocarcinoma cells, while the mRNA level is not substantially altered. Read More

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Deeply Mining a Universe of Peptides Encoded by Long Noncoding RNAs.

Mol Cell Proteomics 2021 Jun 12:100109. Epub 2021 Jun 12.

Laboratory of Protein and Peptide Pharmaceuticals & Laboratory of Proteomics, institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:

Many small open reading frames (smORFs) embedded in lncRNA transcripts have been shown to encode biologically functional polypeptides (smORFs-encoded polypeptides, SEPs) in different organisms. Despite significant advances in genomics, bioinformatics and proteomics that largely enabled the discovery of novel SEPs, their identification across different biological samples is still hampered by their poor predictability, diminutive size and low relative abundance. Here, we take advantage of NONCODE, a repository containing the most complete collection and annotation of lncRNA transcripts from different species, to build a novel database that attempts to maximize a collection of SEPs from human and mouse lncRNA transcripts. Read More

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In silico screening and exploration into phenotypic alterations of deleterious oncogenic single nucleotide polymorphisms in HSPB1 gene.

Genomics 2021 Jun 12. Epub 2021 Jun 12.

Amity Institute of Biotechnolgy, Amity University Kolkata, India. Electronic address:

A small heat shock protein, HSP27, encoded by HSPB1 gene strongly favors survival, proliferation and metastasis of cancer cells and its expression is dependent on post-translational modifications like phosphorylation. This study performed an extensive in silico screening of 20 deleterious non-synonymous SNPs in the coding region of HSPB1 gene, among which four were identified to be cancer associated. The SNP variant I181S introduced a new phosphorylation site in position 181, which might elevate the protein's activation potential. Read More

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Cryo-EM structure of an open conformation of a gap junction hemichannel in lipid bilayer nanodiscs.

Structure 2021 Jun 11. Epub 2021 Jun 11.

Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, Sheridan G. Snyder Translational Research Building, Rm 320, 480 Ray C. Hunt Drive, Charlottesville, VA 22908, USA; Center for Membrane Biology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA; Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA 22908, USA; Department of Medicine, Division of Cardiovascular Medicine, University of Virginia School of Medicine, Charlottesville, VA 22908, USA. Electronic address:

To mediate cell-to-cell communication via gap junction channels (GJCs), connexins (Cx) traffic as hexameric hemichannels to the plasma membrane, which dock end-to-end between adjacent cell membranes, thereby forming a dodecameric intercellular conduit. Hemichannels also function independently to mediate the passage of contents between the cytoplasm and extracellular space. To generate hemichannels, the mutation N176Y was introduced into the second extracellular loop of Cx26. Read More

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Basement Membrane Extracellular Matrix Proteins in Pulmonary Vascular and Right Ventricular Remodeling in Pulmonary Hypertension.

Am J Respir Cell Mol Biol 2021 Jun 15. Epub 2021 Jun 15.

Johns Hopkins University School of Medicine, 1500, Division of Pulmonary and Critical Care Medicine, Baltimore, Maryland, United States;

The extracellular matrix (ECM), a highly organized network of structural and non-structural proteins, plays a pivotal role in cellular and tissue homeostasis. Changes in the ECM are critical for normal tissue repair, while dysregulation contributes to aberrant tissue remodeling. Pulmonary arterial hypertension (PAH) is a severe disorder of the pulmonary vasculature characterized by pathologic remodeling of the pulmonary vasculature and right ventricle (RV), increased production and deposition of structural and non-structural proteins, and altered expression of ECM growth factors and proteases. Read More

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Solid-State NMR Study to Probe the Effects of Divalent Metal Ions (Ca and Mg) on the Magnetic Alignment of Polymer-Based Lipid Nanodiscs.

Langmuir 2021 Jun 15. Epub 2021 Jun 15.

Biophysics Program and Department of Chemistry, Biomedical Engineering, and Macromolecular Science and Engineering, The University of Michigan, Ann Arbor, Michigan 48109-1055, United States.

Divalent cations, especially Ca and Mg, play a vital role in the function of biomolecules and making them important to be constituents in samples for in vitro biophysical and biochemical characterizations. Although lipid nanodiscs are becoming valuable tools for structural biology studies on membrane proteins and for drug delivery, most types of nanodiscs used in these studies are unstable in the presence of divalent metal ions. To avoid the interaction of divalent metal ions with the belt of the nanodiscs, synthetic polymers have been designed and demonstrated to form stable lipid nanodiscs under such unstable conditions. Read More

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Self-Assembled Nanobodies as Selectively Targeted, Nanostructured, and Multivalent Materials.

ACS Appl Mater Interfaces 2021 Jun 15. Epub 2021 Jun 15.

Laboratory for Environmental and Life Sciences, University of Nova Gorica Nova Gorica 5000, Slovenia.

Nanobodies represent valuable tools in advanced therapeutic strategies but their small size (∼2.5 × ∼ 4 nm) and limited valence for interactions might pose restrictions for applications, especially regarding their modest capacity for multivalent and cooperative interaction. In this work, modular protein constructs have been designed, in which nanobodies are fused to protein domains to provide further functionalities and to favor oligomerization into stable self-assembled nanoparticles. Read More

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Loss of Selenoprotein Iodothyronine Deiodinase 3 Expression Correlates with Progression of Complete Hydatidiform Mole to Gestational Trophoblastic Neoplasia.

Reprod Sci 2021 Jun 15. Epub 2021 Jun 15.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, 75 Francis St., Boston, MA, 02115, USA.

To investigate if differences in imprinting at tropho-microRNA (miRNA) genomic clusters can distinguish between pre-gestational trophoblastic neoplasia cases (pre-GTN) and benign complete hydatidiform mole (CHM) cases at the time of initial uterine evacuation. miRNA sequencing was performed on frozen tissue from 39 CHM cases including 9 GTN cases. DIO3, DLK1, RTL1, and MEG 3 mRNA levels were assessed by qRT-PCR. Read More

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The potential role of Keap1-Nrf2 pathway in the pathogenesis of Alzheimer's disease, type 2 diabetes, and type 2 diabetes-related Alzheimer's disease.

Authors:
Ling He Yi Sun

Metab Brain Dis 2021 Jun 15. Epub 2021 Jun 15.

Department of Pharmacology, School of Pharmacy, China Pharmaceutical University, 639 Longmian Avenue, Nanjing, 211198, China.

Kelch-like ECH associated-protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway is thought to be the key regulatory process defensing oxidative stress in multiple organs. Type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) are both serious global health problems with high prevalence. A growing number of literatures have suggested a possible link between Keap1-Nrf2 signaling pathway and the pathological changes of T2DM, AD as well as T2DM-related AD. Read More

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Impacts of OrX and cAMP-insensitive Orco to the insect olfactory heteromer activity.

Mol Biol Rep 2021 Jun 11. Epub 2021 Jun 11.

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia.

Insect odorant receptors (ORs) have been suggested to function as ligand-gated cation channels, with OrX/Orco heteromers combining ionotropic and metabotropic activity. The latter is mediated by different G proteins and results in Orco self-activation by cyclic nucleotide binding. In this contribution, we co-express the odor-specific subunits DmOr49b and DmOr59b with either wild-type Orco or an Orco-PKC mutant lacking cAMP activation heterologously in mammalian cells. Read More

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Subcellular dynamics of estrogen-related receptors involved in transrepression through interactions with scaffold attachment factor B1.

Histochem Cell Biol 2021 Jun 15. Epub 2021 Jun 15.

Department of Anatomy and Neurobiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, 602-8566, Japan.

Estrogen-related receptor (ERR), a member of the nuclear receptor superfamily, consists of three subtypes (α, β, γ) and has strong homology with estrogen receptor. No endogenous ligands have been identified for ERRs, but they play key roles in metabolic, hormonal, and developmental processes as transcription factors without ligand binding. Although subnuclear dynamics are essential for nuclear events including nuclear receptor-mediated transcriptional regulation, the dynamics of ERRs are poorly understood. Read More

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The converging path of protein SUMOylation in phytohormone signalling: highlights and new frontiers.

Plant Cell Rep 2021 Jun 15. Epub 2021 Jun 15.

National Agri-Food Biotechnology Institute (NABI), Sector-81 (Knowledge City), S.A.S. Nagar, Mohali, Punjab, 140306, India.

Key Message: The intersection of phytohormone signalling pathways with SUMOylation, a key post-translational modification, offers an additional layer of control to the phytohormone signalling for sophisticated regulation of plant development. Plants live in a constantly changing environment that are often challenging for the growth and development of plants. Phytohormones play a critical role in modulating molecular-level changes for enabling plants to resist climatic aberrations. Read More

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Tankyrase regulates epithelial lumen formation via suppression of Rab11 GEFs.

J Cell Biol 2021 Jul 15;220(7). Epub 2021 Jun 15.

Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.

Rab11 GTPase proteins are required for cytokinesis, ciliogenesis, and lumenogenesis. Rab11a is critical for apical delivery of podocalyxin (PODXL) during lumen formation in epithelial cells. SH3BP5 and SH3BP5L are guanine nucleotide exchange factors (GEFs) for Rab11. Read More

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Phenotypic spectrum and mechanism analysis of Schaff Yang syndrome: A case report on new mutation of MAGEL2 gene.

Medicine (Baltimore) 2021 Jun;100(24):e26309

Department of Endocrinology, Shandong Provincial Hospital affiliated to Shandong First Medical University.

Rationale: The Schaaf-Yang syndrome (SYS) is an autosomal dominant multi-system genetic disease caused by melanoma antigen L2 (MAGEL2) gene mutations imprinted by mothers and expressed by fathers on the 15q11-15q13 chromosomes in the critical region of Prader-Willi. MAGEL2 is a single exon gene and one of the protein-coding genes of the Prader-Willi domain. MAGEL2 is a matrilineal imprinted gene (i. Read More

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Rapid Increase of SARS-CoV-2 Variant B.1.1.7 Detected in Sewage Samples from England between October 2020 and January 2021.

mSystems 2021 Jun 15:e0035321. Epub 2021 Jun 15.

Division of Virology, National Institute for Biological Standards and Control, South Mimms, Potters Bar, Hertfordshire, UK.

SARS-CoV-2 variants with multiple amino acid mutations in the spike protein are emerging in different parts of the world, raising concerns regarding their possible impact on human immune response and vaccine efficacy against the virus. Recently, a variant named lineage B.1. Read More

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LA14 Alleviates Liver Injury.

mSystems 2021 Jun 15:e0038421. Epub 2021 Jun 15.

Key Laboratory of Nutrition of Zhejiang Province, Institute of Health Food, Hangzhou Medical College, Hangzhou, China.

Although the probiotic Lactobacillus acidophilus LA14 is used worldwide, its effect on liver diseases remains unelucidated. Here, 32 rats were divided into four groups, gavaged with L. acidophilus LA14 (3 × 10 CFU) or phosphate-buffered saline for 7 days, and then intraperitoneally injected with d-galactosamine or saline. Read More

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Detecting FRET in living cells by conventional and spectral flow cytometry.

Cytometry A 2021 Jun 14. Epub 2021 Jun 14.

Department of Lymphoma and Myeloma, The University of Texas-MD Anderson Cancer Center, Houston, TX, USA.

Assays based on Förster resonance energy transfer (FRET) can be used to study many processes in cell biology. Although this is most often done with microscopy for fluorescence detection, we report two ways to measure FRET in living cells by flow cytometry. Using a conventional flow cytometer and the "3-cube method" for intensity-based calculation of FRET efficiency, we measured the enzymatic activity of specific kinases in cells expressing a genetically-encoded reporter. Read More

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Recent advances (2019-2021) of capillary electrophoresis-mass spectrometry for multilevel proteomics.

Mass Spectrom Rev 2021 Jun 15. Epub 2021 Jun 15.

Department of Chemistry, Michigan State University, East Lansing, Michigan, USA.

Multilevel proteomics aims to delineate proteins at the peptide (bottom-up proteomics), proteoform (top-down proteomics), and protein complex (native proteomics) levels. Capillary electrophoresis-mass spectrometry (CE-MS) can achieve highly efficient separation and highly sensitive detection of complex mixtures of peptides, proteoforms, and even protein complexes because of its substantial technical progress. CE-MS has become a valuable alternative to the routinely used liquid chromatography-mass spectrometry for multilevel proteomics. Read More

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Lanosterol reduces the aggregation propensity of ultraviolet-damaged human γD-crystallins: a molecular dynamics study.

Phys Chem Chem Phys 2021 Jun 15. Epub 2021 Jun 15.

State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China.

Ultraviolet (UV) radiation-induced oxidation of tryptophan (Trp) to kynurenine (KN) (TRP > KN) in human γD-crystallins (HγD-Crys) promotes the conversion of proteins into partially unfolded species that act as important precursors for sequential large-scale aggregation. Herein, we report that lanosterol shows protective activity to the structure of the TRP > KN mutant HγD-Crys, particularly its N-terminal domain (N-td), by using all-atom molecular dynamics simulations. The Trp68 > KN mutation significantly destabilizes the originally highly stable "Tyr55-Trp68-Tyr62" cluster, thereby causing loop2, where the mutation occurs, to become very flexible. Read More

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Type I Interferon Transcriptional Network Regulates Expression of Coinhibitory Receptors in Human T cells.

Res Sq 2021 Jun 8. Epub 2021 Jun 8.

While inhibition of T cell co-inhibitory receptors has revolutionized cancer therapy, the mechanisms governing their expression on human T cells have not been elucidated. Type 1 interferon (IFN-I) modulates T cell immunity in viral infection, autoimmunity, and cancer, and may facilitate induction of T cell exhaustion in chronic viral infection. Here we show that IFN-I regulates co-inhibitory receptor expression on human T cells, inducing PD-1/TIM-3/LAG-3 while surprisingly inhibiting TIGIT expression. Read More

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Plasma Proteomics of COVID-19 Associated Cardiovascular Complications: Implications for Pathophysiology and Therapeutics.

Res Sq 2021 Jun 8. Epub 2021 Jun 8.

Cardiovascular complications are common in COVID-19 and strongly associated with disease severity and mortality. However, the mechanisms driving cardiac injury and failure in COVID-19 are largely unknown. We performed plasma proteomics on 80 COVID-19 patients and controls, grouped according to disease severity and cardiac involvement. Read More

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Fine-mapping, trans-ancestral and genomic analyses identify causal variants, cells, genes and drug targets for type 1 diabetes.

Nat Genet 2021 Jun 14. Epub 2021 Jun 14.

Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL, USA.

We report the largest and most diverse genetic study of type 1 diabetes (T1D) to date (61,427 participants), yielding 78 genome-wide-significant (P < 5 × 10) regions, including 36 that are new. We define credible sets of T1D-associated variants and show that they are enriched in immune-cell accessible chromatin, particularly CD4 effector T cells. Using chromatin-accessibility profiling of CD4 T cells from 115 individuals, we map chromatin-accessibility quantitative trait loci and identify five regions where T1D risk variants co-localize with chromatin-accessibility quantitative trait loci. Read More

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Cryo-EM structures of Lassa and Machupo virus polymerases complexed with cognate regulatory Z proteins identify targets for antivirals.

Nat Microbiol 2021 Jun 14. Epub 2021 Jun 14.

Savaid Medical School, University of Chinese Academy of Sciences, Beijing, China.

Zoonotic arenaviruses can lead to life-threating diseases in humans. These viruses encode a large (L) polymerase that transcribes and replicates the viral genome. At the late stage of replication, the multifunctional Z protein interacts with the L polymerase to shut down RNA synthesis and initiate virion assembly. Read More

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Reconstituting T cell receptor selection in-silico.

Genes Immun 2021 Jun 14. Epub 2021 Jun 14.

Department of Population and Data Sciences, UT Southwestern Medical Center, Dallas, TX, USA.

Each T cell receptor (TCR) gene is created without regard for which substances (antigens) the receptor can recognize. T cell selection culls developing T cells when their TCRs (i) fail to recognize major histocompatibility complexes (MHCs) that act as antigen presenting platforms or (ii) recognize with high affinity self-antigens derived from healthy cells and tissue. While T cell selection has been thoroughly studied, little is known about which TCRs are retained or removed by this process. Read More

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Inhibition of translation initiation factor eIF4a inactivates heat shock factor 1 (HSF1) and exerts anti-leukemia activity in AML.

Leukemia 2021 Jun 14. Epub 2021 Jun 14.

Department of Leukemia, Section of Molecular Hematology and Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Eukaryotic initiation factor 4A (eIF4A), the enzymatic core of the eIF4F complex essential for translation initiation, plays a key role in the oncogenic reprogramming of protein synthesis, and thus is a putative therapeutic target in cancer. As important component of its anticancer activity, inhibition of translation initiation can alleviate oncogenic activation of HSF1, a stress-inducible transcription factor that enables cancer cell growth and survival. Here, we show that primary acute myeloid leukemia (AML) cells exhibit the highest transcript levels of eIF4A1 compared to other cancer types. Read More

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