{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,8]],"date-time":"2025-11-08T13:36:07Z","timestamp":1762608967433,"version":"3.37.3"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T00:00:00Z","timestamp":1665964800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T00:00:00Z","timestamp":1665964800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100007162","name":"Guangdong Science and Technology Department","doi-asserted-by":"publisher","award":["2021A1515010759"],"award-info":[{"award-number":["2021A1515010759"]}],"id":[{"id":"10.13039\/501100007162","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82201769"],"award-info":[{"award-number":["82201769"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002912","name":"Government of Guangdong Province","doi-asserted-by":"publisher","award":["2019BT02Y276"],"award-info":[{"award-number":["2019BT02Y276"]}],"id":[{"id":"10.13039\/501100002912","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Death Discov."],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Patients with teratozoospermia exhibit low phosducin-like protein (<jats:italic>Pdcl2<\/jats:italic>) expression. As a member of the phosducin family, chaperonin-related <jats:italic>Pdcl2<\/jats:italic>, a germline-specific gene, may be involved in germ cell protein folding. Given that PDCL2 is highly conserved in evolution, it may be indispensable for mammalian spermiogenesis; however, the function of PDCL2 in higher mammalian species remains unknown. To determine the role of PDCL2 in male fertility, we generated <jats:italic>Pdcl2<\/jats:italic> knockout mice using CRISPR\/Cas9. Our results revealed that <jats:italic>Pdcl2<\/jats:italic> heterozygous (<jats:italic>Pdcl2<\/jats:italic><jats:sup><jats:italic>+\/\u2212<\/jats:italic><\/jats:sup>) male mice were normal, but male <jats:italic>Pdcl2<\/jats:italic>-null <jats:italic>(Pdcl2<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup>) mice were infertile. Accordingly, <jats:italic>Pdcl2<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> male mice exhibited lower testis weight, epididymis weight, and sperm number than <jats:italic>Pdcl2<\/jats:italic><jats:sup><jats:italic>+\/+<\/jats:italic><\/jats:sup> mice. Moreover, <jats:italic>Pdcl2<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice displayed malformed and immotile sperm. Apoptotic cells were significantly enhanced in <jats:italic>Pdcl2<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> testes and epididymis when compared with those in wild-type mice. Mechanistically, PDCL2 can interact with the CCT complex, and dysfunction in this complex might lead to infertility in <jats:italic>Pdcl2<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> male mice. Collectively, these findings confirm that <jats:italic>Pdcl2<\/jats:italic> knockout leads to male infertility in mice and that PDCL2 may function as a chaperone to promote protein folding during spermiogenesis.<\/jats:p>","DOI":"10.1038\/s41420-022-01210-2","type":"journal-article","created":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T19:02:46Z","timestamp":1666033366000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["PDCL2 is essential for spermiogenesis and male fertility in mice"],"prefix":"10.1038","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1944-5881","authenticated-orcid":false,"given":"Minyan","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuxi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianping","family":"Ou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3417-1196","authenticated-orcid":false,"given":"Junjiu","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1970-5281","authenticated-orcid":false,"given":"Xiya","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,10,17]]},"reference":[{"key":"1210_CR1","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1016\/S0140-6736(20)32667-2","volume":"397","author":"A Agarwal","year":"2021","unstructured":"Agarwal A, Baskaran S, Parekh N, Cho CL, Henkel R, Vij S, et al. Male infertility. Lancet 2021;397:319\u201333.","journal-title":"Lancet"},{"key":"1210_CR2","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1093\/hmg\/ddm012","volume":"16","author":"AE Platts","year":"2007","unstructured":"Platts AE, Dix DJ, Chemes HE, Thompson KE, Goodrich R, Rockett JC, et al. Success and failure in human spermatogenesis as revealed by teratozoospermic RNAs. Hum Mol Genet. 2007;16:763\u201373.","journal-title":"Hum Mol Genet"},{"key":"1210_CR3","doi-asserted-by":"publisher","first-page":"1751","DOI":"10.1074\/jbc.M207434200","volume":"278","author":"P Lopez","year":"2003","unstructured":"Lopez P, Yaman R, Lopez-Fernandez LA, Vidal F, Puel D, Clertant P, et al. A novel germ line-specific gene of the phosducin-like protein (PhLP) family. A meiotic function conserved from yeast to mice. J Biol Chem. 2003;278:1751\u20137.","journal-title":"J Biol Chem"},{"key":"1210_CR4","doi-asserted-by":"publisher","first-page":"1000","DOI":"10.5713\/ajas.2010.90511","volume":"23","author":"YH Zheng","year":"2010","unstructured":"Zheng YH, Rengaraj D, Park KJ, Lee SI, Han JY. Expression patterns of germ cell-specific Phosducin-like 2 during testicular and ovarian development in chickens. Asian Austral J Anim. 2010;23:1000\u20136.","journal-title":"Asian Austral J Anim"},{"key":"1210_CR5","doi-asserted-by":"publisher","first-page":"7962","DOI":"10.1073\/pnas.112075699","volume":"99","author":"JN McLaughlin","year":"2002","unstructured":"McLaughlin JN, Thulin CD, Hart SJ, Resing KA, Ahn NG, Willardson BM. Regulatory interaction of phosducin-like protein with the cytosolic chaperonin complex. Proc Natl Acad Sci USA. 2002;99:7962\u20137.","journal-title":"Proc Natl Acad Sci USA"},{"key":"1210_CR6","doi-asserted-by":"publisher","first-page":"17410","DOI":"10.1073\/pnas.0405070101","volume":"101","author":"J Martin-Benito","year":"2004","unstructured":"Martin-Benito J, Bertrand S, Hu T, Ludtke PJ, McLaughlin JN, Willardson BM, et al. Structure of the complex between the cytosolic chaperonin CCT and phosducin-like protein. Proc Natl Acad Sci USA. 2004;101:17410\u20135.","journal-title":"Proc Natl Acad Sci USA"},{"key":"1210_CR7","doi-asserted-by":"publisher","first-page":"20042","DOI":"10.1074\/jbc.M409233200","volume":"280","author":"J Humrich","year":"2005","unstructured":"Humrich J, Bermel C, Bunemann MB, Harmark LH, Frost RJA, Quitterer U, et al. Phosducin-like protein regulates G-protein beta gamma folding by interaction with tailless complex polypeptide-1 alpha - Dephosphorylation or splicing of PhLP turns the switch toward regulation of G beta gamma folding. J Biol Chem. 2005;280:20042\u201350.","journal-title":"J Biol Chem"},{"key":"1210_CR8","doi-asserted-by":"publisher","first-page":"22261","DOI":"10.1074\/jbc.M601590200","volume":"281","author":"GL Lukov","year":"2006","unstructured":"Lukov GL, Baker CM, Ludtke PJ, Hu T, Carter MD, Hackett RA, et al. Mechanism of assembly of G protein beta gamma subunits by protein kinase CK2-phosphorylated phosducin-like protein and the cytosolic chaperonin complex. J Biol Chem. 2006;281:22261\u201374.","journal-title":"J Biol Chem"},{"key":"1210_CR9","doi-asserted-by":"publisher","first-page":"20221","DOI":"10.1074\/jbc.M602409200","volume":"281","author":"CA Wells","year":"2006","unstructured":"Wells CA, Dingus J, Hildebrandt JD. Role of the chaperonin CCT\/TRiC complex in G protein beta gamma-dimer assembly. J Biol Chem. 2006;281:20221\u201332.","journal-title":"J Biol Chem"},{"key":"1210_CR10","doi-asserted-by":"publisher","first-page":"2417","DOI":"10.1016\/j.cellsig.2007.06.013","volume":"19","author":"BM Willardson","year":"2007","unstructured":"Willardson BM, Howlett AC. Function of phosducin-like proteins in G protein signaling and chaperone-assisted protein folding. Cell Signal. 2007;19:2417\u201327.","journal-title":"Cell Signal"},{"key":"1210_CR11","doi-asserted-by":"publisher","first-page":"M110 000570","DOI":"10.1074\/mcp.M110.000570","volume":"10","author":"E Posokhova","year":"2011","unstructured":"Posokhova E, Song H, Belcastro M, Higgins L, Bigley LR, Michaud NA, et al. Disruption of the chaperonin containing TCP-1 function affects protein networks essential for rod outer segment morphogenesis and survival. Mol Cell Proteom. 2011;10:M110 000570.","journal-title":"Mol Cell Proteom"},{"key":"1210_CR12","doi-asserted-by":"publisher","first-page":"25760","DOI":"10.1074\/jbc.M113.486258","volume":"288","author":"X Gao","year":"2013","unstructured":"Gao X, Sinha S, Belcastro M, Woodard C, Ramamurthy V, Stoilov P, et al. Splice isoforms of phosducin-like protein control the expression of heterotrimeric G proteins. J Biol Chem. 2013;288:25760\u20138.","journal-title":"J Biol Chem"},{"key":"1210_CR13","doi-asserted-by":"publisher","first-page":"2413","DOI":"10.1073\/pnas.1419595112","volume":"112","author":"RL Plimpton","year":"2015","unstructured":"Plimpton RL, Cuellar J, Lai CW, Aoba T, Makaju A, Franklin S, et al. Structures of the Gbeta-CCT and PhLP1-Gbeta-CCT complexes reveal a mechanism for G-protein beta-subunit folding and Gbetagamma dimer assembly. Proc Natl Acad Sci USA. 2015;112:2413\u20138.","journal-title":"Proc Natl Acad Sci USA"},{"key":"1210_CR14","doi-asserted-by":"publisher","first-page":"2336","DOI":"10.1091\/mbc.e07-01-0069","volume":"18","author":"PC Stirling","year":"2007","unstructured":"Stirling PC, Srayko M, Takhar KS, Pozniakovsky A, Hyman AA, Leroux MR. Functional interaction between phosducin-like protein 2 and cytosolic chaperonin is essential for cytoskeletal protein function and cell cycle progression. Mol Biol Cell. 2007;18:2336\u201345.","journal-title":"Mol Biol Cell"},{"key":"1210_CR15","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1016\/j.jmb.2009.06.003","volume":"391","author":"EA McCormack","year":"2009","unstructured":"McCormack EA, Altschuler GM, Dekker C, Filmore H, Willison KR. Yeast phosducin-like protein 2 acts as a stimulatory co-factor for the folding of actin by the chaperonin CCT via a ternary complex. J Mol Biol. 2009;391:192\u2013206.","journal-title":"J Mol Biol"},{"key":"1210_CR16","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1074\/jbc.M110.166256","volume":"286","author":"SF Stuart","year":"2011","unstructured":"Stuart SF, Leatherbarrow RJ, Willison KR. A two-step mechanism for the folding of actin by the yeast cytosolic chaperonin. J Biol Chem. 2011;286:178\u201384.","journal-title":"J Biol Chem"},{"key":"1210_CR17","doi-asserted-by":"publisher","first-page":"7012","DOI":"10.1074\/jbc.M513235200","volume":"281","author":"PC Stirling","year":"2006","unstructured":"Stirling PC, Cuellar J, Alfaro GA, El Khadali F, Beh CT, Valpuesta JM, et al. PhLP3 modulates CCT-mediated actin and tubulin folding via ternary complexes with substrates. J Biol Chem. 2006;281:7012\u201321.","journal-title":"J Biol Chem"},{"key":"1210_CR18","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1038\/358073a0","volume":"358","author":"PH Bauer","year":"1992","unstructured":"Bauer PH, Muller S, Puzicha M, Pippig S, Obermaier B, Helmreich EJ, et al. Phosducin is a protein kinase A-regulated G-protein regulator. Nature 1992;358:73\u20136.","journal-title":"Nature"},{"key":"1210_CR19","doi-asserted-by":"publisher","first-page":"29825","DOI":"10.1016\/S0021-9258(18)43955-5","volume":"269","author":"BE Hawes","year":"1994","unstructured":"Hawes BE, Touhara K, Kurose H, Lefkowitz RJ, Inglese J. Determination of the G beta gamma-binding domain of phosducin. A regulatable modulator of G beta gamma signaling. J Biol Chem. 1994;269:29825\u201330.","journal-title":"J Biol Chem"},{"key":"1210_CR20","doi-asserted-by":"publisher","first-page":"18462","DOI":"10.1074\/jbc.M002163200","volume":"275","author":"PL Flanary","year":"2000","unstructured":"Flanary PL, DiBello PR, Estrada P, Dohlman HG. Functional analysis of Plp1 and Plp2, two homologues of phosducin in yeast. J Biol Chem. 2000;275:18462\u20139.","journal-title":"J Biol Chem"},{"key":"1210_CR21","doi-asserted-by":"publisher","first-page":"2175","DOI":"10.1002\/jcp.24384","volume":"228","author":"C Bregier","year":"2013","unstructured":"Bregier C, Krzemien-Ojak L, Wloga D, Jerka-Dziadosz M, Joachimiak E, Batko K, et al. PHLP2 is essential and plays a role in ciliogenesis and microtubule assembly in Tetrahymena thermophila. J Cell Physiol. 2013;228:2175\u201389.","journal-title":"J Cell Physiol"},{"key":"1210_CR22","doi-asserted-by":"publisher","first-page":"51091","DOI":"10.1074\/jbc.M409623200","volume":"279","author":"JC Wilkinson","year":"2004","unstructured":"Wilkinson JC, Richter BW, Wilkinson AS, Burstein E, Rumble JM, Balliu B, et al. VIAF, a conserved inhibitor of apoptosis (IAP)-interacting factor that modulates caspase activation. J Biol Chem. 2004;279:51091\u20139.","journal-title":"J Biol Chem"},{"key":"1210_CR23","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1016\/j.tibs.2011.05.003","volume":"36","author":"H Yebenes","year":"2011","unstructured":"Yebenes H, Mesa P, Munoz IG, Montoya G, Valpuesta JM. Chaperonins: Two rings for folding. Trends Biochem Sci. 2011;36:424\u201332.","journal-title":"Trends Biochem Sci"},{"key":"1210_CR24","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1016\/j.tcb.2004.09.015","volume":"14","author":"C Spiess","year":"2004","unstructured":"Spiess C, Meyer AS, Reissmann S, Frydman J. Mechanism of the eukaryotic chaperonin: Protein folding in the chamber of secrets. Trends Cell Biol. 2004;14:598\u2013604.","journal-title":"Trends Cell Biol"},{"key":"1210_CR25","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1038\/ng1366","volume":"36","author":"FW Buaas","year":"2004","unstructured":"Buaas FW, Kirsh AL, Sharma M, McLean DJ, Morris JL, Griswold MD, et al. Plzf is required in adult male germ cells for stem cell self-renewal. Nat Genet. 2004;36:647\u201352.","journal-title":"Nat Genet"},{"key":"1210_CR26","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1038\/ng1367","volume":"36","author":"JA Costoya","year":"2004","unstructured":"Costoya JA, Hobbs RM, Barna M, Cattoretti G, Manova K, Sukhwani M, et al. Essential role of Plzf in maintenance of spermatogonial stem cells. Nat Genet. 2004;36:653\u20139.","journal-title":"Nat Genet"},{"key":"1210_CR27","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1530\/eje.0.1470397","volume":"147","author":"I Ketola","year":"2002","unstructured":"Ketola I, Anttonen M, Vaskivuo T, Tapanainen JS, Toppari J, Heikinheimo M. Developmental expression and spermatogenic stage specificity of transcription factors GATA-1 and GATA-4 and their cofactors FOG-1 and FOG-2 in the mouse testis. Eur J Endocrinol \/ Eur Federation Endocr Societies. 2002;147:397\u2013406.","journal-title":"Eur J Endocrinol \/ Eur Federation Endocr Societies"},{"key":"1210_CR28","doi-asserted-by":"publisher","first-page":"1470","DOI":"10.1210\/endo.140.3.6587","volume":"140","author":"I Ketola","year":"1999","unstructured":"Ketola I, Rahman N, Toppari J, Bielinska M, Porter-Tinge SB, Tapanainen JS, et al. Expression and regulation of transcription factors GATA-4 and GATA-6 in developing mouse testis. Endocrinology 1999;140:1470\u201380.","journal-title":"Endocrinology"},{"key":"1210_CR29","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1159\/000078188","volume":"105","author":"NK Kolas","year":"2004","unstructured":"Kolas NK, Yuan L, Hoog C, Heng HH, Marcon E, Moens PB. Male mouse meiotic chromosome cores deficient in structural proteins SYCP3 and SYCP2 align by homology but fail to synapse and have possible impaired specificity of chromatin loop attachment. Cytogenet Genome Res. 2004;105:182\u20138.","journal-title":"Cytogenet Genome Res"},{"key":"1210_CR30","doi-asserted-by":"publisher","first-page":"2271","DOI":"10.1242\/jcs.02362","volume":"118","author":"A Kouznetsova","year":"2005","unstructured":"Kouznetsova A, Novak I, Jessberger R, Hoog C. SYCP2 and SYCP3 are required for cohesin core integrity at diplotene but not for centromere cohesion at the first meiotic division. J Cell Sci. 2005;118:2271\u20138.","journal-title":"J Cell Sci"},{"key":"1210_CR31","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1083\/jcb.125.4.867","volume":"125","author":"A Cheng","year":"1994","unstructured":"Cheng A, Le T, Palacios M, Bookbinder LH, Wassarman PM, Suzuki F, et al. Sperm-egg recognition in the mouse: characterization of sp56, a sperm protein having specific affinity for ZP3. J Cell Biol. 1994;125:867\u201378.","journal-title":"J Cell Biol."},{"key":"1210_CR32","doi-asserted-by":"publisher","first-page":"746","DOI":"10.2741\/e415","volume":"4","author":"KK Shukla","year":"2012","unstructured":"Shukla KK, Mahdi AA, Rajender S. Apoptosis, spermatogenesis, and male infertility. Front Biosci (Elite Ed). 2012;4:746\u201354.","journal-title":"Front Biosci (Elite Ed)"},{"key":"1210_CR33","doi-asserted-by":"publisher","first-page":"2026","DOI":"10.1126\/science.1092645","volume":"303","author":"P Aloy","year":"2004","unstructured":"Aloy P, Bottcher B, Ceulemans H, Leutwein C, Mellwig C, Fischer S, et al. Structure-based assembly of protein complexes in yeast. Science 2004;303:2026\u20139.","journal-title":"Science"},{"key":"1210_CR34","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1038\/nature04532","volume":"440","author":"AC Gavin","year":"2006","unstructured":"Gavin AC, Aloy P, Grandi P, Krause R, Boesche M, Marzioch M, et al. Proteome survey reveals modularity of the yeast cell machinery. Nature 2006;440:631\u20136.","journal-title":"Nature"},{"key":"1210_CR35","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1016\/S0169-5347(03)00033-8","volume":"18","author":"J Zhang","year":"2003","unstructured":"Zhang J. Evolution by gene duplication: An update. Trends Ecol Evol. 2003;18:292\u20138.","journal-title":"Trends Ecol Evol"},{"key":"1210_CR36","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1186\/1471-213X-9-63","volume":"9","author":"GC Horvath","year":"2009","unstructured":"Horvath GC, Kistler MK, Kistler WS. RFX2 is a candidate downstream amplifier of A-MYB regulation in mouse spermatogenesis. Bmc Dev Biol. 2009;9:63.","journal-title":"Bmc Dev Biol"},{"key":"1210_CR37","doi-asserted-by":"publisher","first-page":"e0143148","DOI":"10.1371\/journal.pone.0143148","volume":"10","author":"M Li","year":"2015","unstructured":"Li M, Huang R, Jiang X, Chen Y, Zhang Z, Zhang X, et al. CRISPR\/Cas9 promotes functional study of testis specific X-linked gene in vivo. PLoS One. 2015;10:e0143148.","journal-title":"PLoS One"}],"container-title":["Cell Death Discovery"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41420-022-01210-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41420-022-01210-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41420-022-01210-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T19:02:59Z","timestamp":1666033379000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41420-022-01210-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,17]]},"references-count":37,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["1210"],"URL":"https:\/\/doi.org\/10.1038\/s41420-022-01210-2","relation":{},"ISSN":["2058-7716"],"issn-type":[{"type":"electronic","value":"2058-7716"}],"subject":[],"published":{"date-parts":[[2022,10,17]]},"assertion":[{"value":"30 May 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 October 2022","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 October 2022","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 October 2022","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"419"}}