{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Fucosyltransferase‐8 (FUT8) is the sole enzyme responsible for catalyzing core fucosylation, that is, the transfer of fucose in an α1,6‐linkage onto the innermost N‐acetylglucosamine of N‐glycans. Core fucosylation is essential for optimal protein folding, stability, and function, and it critically modulates receptor–ligand interactions. For example, FUT8‐mediated fucosylation is indispensable for the proper signaling of multiple receptors—including transforming growth factor‐β (TGF‐β), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), and various integrins—thereby regulating extracellular matrix homeostasis, cell proliferation, adhesion, migration, and even synaptic plasticity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In cancer cells, aberrant FUT8 expression profoundly alters the glycosylation pattern of surface antigens, receptors, and adhesion molecules. Enhanced FUT8 activity has been implicated in the promotion of receptor dimerization and downstream signaling (e.g. of EGFR), epithelial–mesenchymal transition, and the invasive properties of tumor cells in diverse malignancies such as lung, melanoma, thyroid, hepatocellular, colorectal, prostate, and breast cancers, as well as in leukemia stem cells."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "14"}]}, {"type": "t", "text": " In several tumor models, elevated FUT8 expression is linked not only to enhanced invasive and migratory capabilities but also to chemoresistance and immune evasion through modulation of key cell‐surface molecules such as PD‐1 and B7H3."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}, {"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Experimental models further underscore the key role of FUT8 in development and tissue homeostasis. FUT8‐null mice exhibit profound growth retardation, emphysema‐like lung changes, altered integrin‐ and EGF‐receptor signaling, and even neurological deficits resembling schizophrenia, highlighting the enzyme’s importance in normal organogenesis and receptor function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_fs", "start_ref": "17", "end_ref": "19"}]}, {"type": "t", "text": " Moreover, FUT8 deficiency can lead to compensatory changes in other glycosyltransferases and in stress‐response pathways, while genetic alterations in FUT8 have been associated with complex developmental syndromes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "20"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n At the molecular level, advanced structural and biochemical studies have provided insights into FUT8’s substrate specificity and catalytic mechanism, establishing that FUT8 is solely responsible for GnT I–independent core fucosylation. In addition, FUT8 expression is regulated by microRNAs and transcription factors (for instance, Sp1 and miR‑198) that modulate its expression in various pathological contexts, including cancer progression and drug resistance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}, {"type": "fg_f", "ref": "22"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies highlight FUT8 as a central player in modulating receptor function, cell adhesion, immune checkpoint regulation, and tumor progression, as well as in maintaining normal developmental processes. Consequently, targeting aberrant FUT8‐mediated core fucosylation offers a promising therapeutic strategy for a range of pathological conditions, including cancer and immune‐related disorders."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}, {"type": "fg_f", "ref": "24"}, {"type": "fg_f", "ref": "14"}, {"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Xiangchun Wang, Shinya Inoue, Jianguo Gu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dysregulation of TGF-beta1 receptor activation leads to abnormal lung development and emphysema-like phenotype in core fucose-deficient mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0507375102"}], "href": "https://doi.org/10.1073/pnas.0507375102"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16236725"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16236725"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Xiangchun Wang, Jianguo Gu, Hideyuki Ihara, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Core fucosylation regulates epidermal growth factor receptor-mediated intracellular signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M510893200"}], "href": "https://doi.org/10.1074/jbc.M510893200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16316986"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16316986"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Ana García-García, Laura Ceballos-Laita, Sonia Serna, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural basis for substrate specificity and catalysis of α1,6-fucosyltransferase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-020-14794-z"}], "href": "https://doi.org/10.1038/s41467-020-14794-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32080177"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32080177"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Qiang Yang, Lai-Xi Wang "}, {"type": "b", "children": [{"type": "t", "text": "Mammalian α-1,6-Fucosyltransferase (FUT8) Is the Sole Enzyme Responsible for the N-Acetylglucosaminyltransferase I-independent Core Fucosylation of High-mannose N-Glycans."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M116.720789"}], "href": "https://doi.org/10.1074/jbc.M116.720789"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27008861"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27008861"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Ying-Chih Liu, Hsin-Yung Yen, Chien-Yu Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sialylation and fucosylation of epidermal growth factor receptor suppress its dimerization and activation in lung cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1107385108"}], "href": "https://doi.org/10.1073/pnas.1107385108"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21709263"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21709263"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Praveen Agrawal, Barbara Fontanals-Cirera, Elena Sokolova, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A Systems Biology Approach Identifies FUT8 as a Driver of Melanoma Metastasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Cell (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ccell.2017.05.007"}], "href": "https://doi.org/10.1016/j.ccell.2017.05.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28609658"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28609658"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Chien-Yu Chen, Yi-Hua Jan, Yi-Hsiu Juan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Fucosyltransferase 8 as a functional regulator of nonsmall cell lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1220425110"}], "href": "https://doi.org/10.1073/pnas.1220425110"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23267084"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23267084"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Masahiro Okada, Shunsuke Chikuma, Taisuke Kondo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Blockage of Core Fucosylation Reduces Cell-Surface Expression of PD-1 and Promotes Anti-tumor Immune Responses of T Cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2017.07.027"}], "href": "https://doi.org/10.1016/j.celrep.2017.07.027"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28768188"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28768188"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Peter Sidaway "}, {"type": "b", "children": [{"type": "t", "text": "Multiple sclerosis: Concussion during adolescence linked to increased risk of MS."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Rev Neurol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nrneurol.2017.135"}], "href": "https://doi.org/10.1038/nrneurol.2017.135"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28914886"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28914886"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Xiangchun Wang, Jing Chen, Qing Kay Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Overexpression of α (1,6) fucosyltransferase associated with aggressive prostate cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Glycobiology (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/glycob/cwu051"}], "href": "https://doi.org/10.1093/glycob/cwu051"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24906821"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24906821"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "L Cheng, S Luo, C Jin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "FUT family mediates the multidrug resistance of human hepatocellular carcinoma via the PI3K/Akt signaling pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cddis.2013.450"}], "href": "https://doi.org/10.1038/cddis.2013.450"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24232099"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24232099"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Yun Huang, Hai-Liang Zhang, Zhi-Ling Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "FUT8-mediated aberrant N-glycosylation of B7H3 suppresses the immune response in triple-negative breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-021-22618-x"}], "href": "https://doi.org/10.1038/s41467-021-22618-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33976130"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33976130"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Yasuhiro Ito, Akira Miyauchi, Hiroshi Yoshida, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of alpha1,6-fucosyltransferase (FUT8) in papillary carcinoma of the thyroid: its linkage to biological aggressiveness and anaplastic transformation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Lett (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0304-3835(03)00383-5"}], "href": "https://doi.org/10.1016/s0304-3835(03"}, {"type": "t", "text": "00383-5) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14568171"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14568171"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Bing Liu, Hongye Ma, Qianqian Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiR-29b/Sp1/FUT4 axis modulates the malignancy of leukemia stem cells by regulating fucosylation via Wnt/β-catenin pathway in acute myeloid leukemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Clin Cancer Res (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13046-019-1179-y"}], "href": "https://doi.org/10.1186/s13046-019-1179-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31097000"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31097000"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Cinzia Bernardi, Ugo Soffientini, Francesco Piacente, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Effects of microRNAs on fucosyltransferase 8 (FUT8) expression in hepatocarcinoma cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0076540"}], "href": "https://doi.org/10.1371/journal.pone.0076540"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24130780"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24130780"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Naseruddin Höti, Shuang Yang, Yingwei Hu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Overexpression of α (1,6) fucosyltransferase in the development of castration-resistant prostate cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Prostate Cancer Prostatic Dis (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41391-017-0016-7"}], "href": "https://doi.org/10.1038/s41391-017-0016-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29339807"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29339807"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Tomohiko Fukuda, Hirokazu Hashimoto, Natsumi Okayasu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Alpha1,6-fucosyltransferase-deficient mice exhibit multiple behavioral abnormalities associated with a schizophrenia-like phenotype: importance of the balance between the dopamine and serotonin systems."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.172536"}], "href": "https://doi.org/10.1074/jbc.M110.172536"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21471224"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21471224"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Xiangchun Wang, Tomohiko Fukuda, Wenzhe Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Requirement of Fut8 for the expression of vascular endothelial growth factor receptor-2: a new mechanism for the emphysema-like changes observed in Fut8-deficient mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biochem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/jb/mvp022"}], "href": "https://doi.org/10.1093/jb/mvp022"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19179362"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19179362"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Yuqin Wang, Tomohiko Fukuda, Tomoya Isaji, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of α1,6-fucosyltransferase suppressed liver regeneration: implication of core fucose in the regulation of growth factor receptor-mediated cellular signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep08264"}], "href": "https://doi.org/10.1038/srep08264"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25652335"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25652335"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Ayako Kurimoto, Shinobu Kitazume, Yasuhiko Kizuka, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The absence of core fucose up-regulates GnT-III and Wnt target genes: a possible mechanism for an adaptive response in terms of glycan function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M113.502542"}], "href": "https://doi.org/10.1074/jbc.M113.502542"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24619415"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24619415"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Bobby G Ng, Gege Xu, Nandini Chandy, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Biallelic Mutations in FUT8 Cause a Congenital Disorder of Glycosylation with Defective Fucosylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2017.12.009"}], "href": "https://doi.org/10.1016/j.ajhg.2017.12.009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29304374"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29304374"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Minyu Wang, Jilin Wang, Xuan Kong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiR-198 represses tumor growth and metastasis in colorectal cancer by targeting fucosyl transferase 8."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep06145"}], "href": "https://doi.org/10.1038/srep06145"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25174450"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25174450"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Lei Cheng, Shuhang Gao, Xiaobo Song, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Comprehensive N-glycan profiles of hepatocellular carcinoma reveal association of fucosylation with tumor progression and regulation of FUT8 by microRNAs."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.11284"}], "href": "https://doi.org/10.18632/oncotarget.11284"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27533464"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27533464"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Congxiao Gao, Toshitaka Maeno, Fumi Ota, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sensitivity of heterozygous α1,6-fucosyltransferase knock-out mice to cigarette smoke-induced emphysema: implication of aberrant transforming growth factor-β signaling and matrix metalloproteinase gene expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111.315333"}], "href": "https://doi.org/10.1074/jbc.M111.315333"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22433854"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22433854"}]}]}]}