{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T08:36:26Z","timestamp":1791362186348,"version":"4.3.1"},"reference-count":66,"publisher":"Wiley","issue":"42","license":[{"start":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T00:00:00Z","timestamp":1755475200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Degenerative cervical myelopathy (DCM) is the most common cause of spinal cord dysfunction worldwide. Although surgical decompression can halt disease progression and improve neurological function in most patients, there remains a subset for whom functional improvement is limited. Impaired spinal cord perfusion is a pathological hallmark of DCM, which highlights the importance of restoring blood flow to enhance neurological outcomes. Here, this work identifies a novel angiogenesis\u2010associated PIWI\u2010interacting RNA (AGAPIR) that enhances angiogenesis and motor function following spinal cord decompression. Using piRNA sequencing, this work identifies AGAPIR as a key regulator of DCM pathogenesis. This work observes significant upregulation of AGAPIR expression in the spinal cord following surgical decompression, which is correlated with enhanced angiogenesis. Overexpression of AGAPIR markedly improves blood vessel formation and promotes motor function in mice following spinal cord decompression. Using RNA sequencing and cellular validation, this work finds that AGAPIR directly interacts with USP18, leading to an increase in its protein expression level and stabilization of HIF\u20101\u03b1 protein via its deubiquitinating activity. This data demonstrate that AGAPIR is a novel piRNA that further improves the functional status of DCM mice following surgical decompression. These results provide the pioneering evidence and novel insights into piRNA\u2010directed therapeutic strategies for DCM.<\/jats:p>","DOI":"10.1002\/advs.202504246","type":"journal-article","created":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T10:00:16Z","timestamp":1755511216000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["AGAPIR: A Novel PIWI\u2010Interacting RNA Enhancing Post\u2010Decompression Angiogenesis in Degenerative Cervical Myelopathy"],"prefix":"10.1002","volume":"12","author":[{"given":"Yongheng","family":"Xie","sequence":"first","affiliation":[{"name":"Division of Spine Department of Orthopedic Surgery Shenzhen People's Hospital (The First Affiliated Hospital Southern University of Science and Technology The Second Clinical Medical College Jinan University)  Shenzhen 518020 China"},{"name":"The First Affiliated Hospital Jinan University  Guangzhou 510630 China"},{"name":"Shenzhen Key Laboratory of Musculoskeletal Tissue Reconstruction and Function Restoration  Shenzhen 518020 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiling","family":"Peng","sequence":"additional","affiliation":[{"name":"Shenzhen Key Laboratory of Musculoskeletal Tissue Reconstruction and Function Restoration  Shenzhen 518020 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyu","family":"Qin","sequence":"additional","affiliation":[{"name":"Division of Spine Department of Orthopedic Surgery Shenzhen People's Hospital (The First Affiliated Hospital Southern University of Science and Technology The Second Clinical Medical College Jinan University)  Shenzhen 518020 China"},{"name":"Shenzhen Key Laboratory of Musculoskeletal Tissue Reconstruction and Function Restoration  Shenzhen 518020 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuimei","family":"Chen","sequence":"additional","affiliation":[{"name":"Shenzhen Key Laboratory of Musculoskeletal Tissue Reconstruction and Function Restoration  Shenzhen 518020 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenxiao","family":"Ren","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology\/Department of Spine Surgery The First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou 510000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naibo","family":"Feng","sequence":"additional","affiliation":[{"name":"Division of Spine Department of Orthopedic Surgery Shenzhen People's Hospital (The First Affiliated Hospital Southern University of Science and Technology The Second Clinical Medical College Jinan University)  Shenzhen 518020 China"},{"name":"Shenzhen Key Laboratory of Musculoskeletal Tissue Reconstruction and Function Restoration  Shenzhen 518020 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chungeng","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery Guangdong Cardiovascular Institute Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences Southern Medical University  Guangzhou 510000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songlin","family":"Peng","sequence":"additional","affiliation":[{"name":"Division of Spine Department of Orthopedic Surgery Shenzhen People's Hospital (The First Affiliated Hospital Southern University of Science and Technology The Second Clinical Medical College Jinan University)  Shenzhen 518020 China"},{"name":"Shenzhen Key Laboratory of Musculoskeletal Tissue Reconstruction and Function Restoration  Shenzhen 518020 China"},{"name":"Guangdong Provincial Clinical Research Centre for Geriatrics Shenzhen Clinical Research Centre for Geriatrics Department of Geriatrics Shenzhen People's Hospital  Shenzhen 518020 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4480-7298","authenticated-orcid":false,"given":"Houqing","family":"Long","sequence":"additional","affiliation":[{"name":"Division of Spine Department of Orthopedic Surgery Shenzhen People's Hospital (The First Affiliated Hospital Southern University of Science and Technology The Second Clinical Medical College Jinan University)  Shenzhen 518020 China"},{"name":"Shenzhen Key Laboratory of Musculoskeletal Tissue Reconstruction and Function Restoration  Shenzhen 518020 China"},{"name":"Guangdong Provincial Clinical Research Centre for Geriatrics Shenzhen Clinical Research Centre for Geriatrics Department of Geriatrics Shenzhen People's Hospital  Shenzhen 518020 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,18]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-019-0303-0"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/BRS.0000000000000988"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.spinee.2006.04.024"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.2106\/JBJS.L.00589"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.14245\/ns.2448140.070"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-023-00662-1"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/BRS.0000000000005025"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04917"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature06263"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1130164"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.01.043"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-020-09750-w"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202401466"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.123.065213"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s44161-024-00590-1"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s44161-024-00592-z"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-019-0788-4"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2024.08.029"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202414100"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2013.01.032"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-023-00725-w"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.82538"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.13343"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-022-00528-0"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes15060653"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.355819"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2014.135"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.07.012"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0603-677"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2019.08.005"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-29684-9"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s44318-024-00166-6"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1097\/JS9.0000000000000361"},{"key":"e_1_2_9_34_1","volume":"93","author":"Ruck T.","year":"2014","journal-title":"J. Vis. Exp."},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.02.002"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aao2840"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aac6524"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2023.08.025"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2020.0227"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-023-09380-8"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241512498"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23052469"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12929-021-00775-x"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu14071340"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1142612"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019003764"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-023-01010-3"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23992"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku1210"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1860-14.2014"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-81766-8"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1097\/JS9.0000000000001569"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awf257"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aai8030"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.2478\/jtim-2021-0045"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2020.00138"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.92512"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.353485"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms150712061"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2015.08.050"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.31616\/asj.2020.0490"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2013.04.024"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/s44161-022-00046-4"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2006.23.635"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.58364"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12915-023-01679-y"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202504246","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T11:31:23Z","timestamp":1763119883000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202504246"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,18]]},"references-count":66,"journal-issue":{"issue":"42","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1002\/advs.202504246"],"URL":"https:\/\/doi.org\/10.1002\/advs.202504246","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,18]]},"assertion":[{"value":"2025-03-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e04246"}}