{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T23:28:57Z","timestamp":1789428537897,"version":"build-2803163510"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Lipids Health Dis"],"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Fucoxanthin is a xanthophyll present in brown seaweeds and has several beneficial effects, including anti-obesity and anti-diabetic effects. However, we and another group previously observed that fucoxanthin increases serum cholesterol levels in rodents. Cholesterol is an important component of cell membranes and biosynthesis of bile acids. Serum cholesterol levels are also closely associated with atherosclerosis. Therefore, we sought to identify the mechanism underlying the increase in serum cholesterol levels by fucoxanthin.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Diabetic\/obese KK-<jats:italic>A<\/jats:italic>\n              <jats:sup>\n                <jats:italic>y<\/jats:italic>\n              <\/jats:sup> mice were fed a diet containing 0.2% fucoxanthin for 4\u2009weeks. The mice were sacrificed, and total blood samples were collected for the measurement of serum total cholesterol, HDL-cholesterol and non-HDL-cholesterol levels. Cholesterol content in tissues was also analyzed. Real-time PCR and Western blotting were performed to determine hepatic mRNA and protein expression of genes involved in cholesterol metabolism, respectively.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Dietary fucoxanthin significantly increased serum HDL and non-HDL cholesterol levels, and reduced hepatic cholesterol content. In liver, the expression of SREBP1, SREBP2 and their target genes involved in cholesterol biosynthesis significantly increased and tended to increase in the fucoxanthin-fed mice, respectively. In contrast, hepatic levels of LDLR and SR-B1 proteins which is important factors for LDL-cholesterol and HDL-cholesterol uptake in the liver from serum, decreased to 60% and 80% in the fucoxanthin-fed mice, respectively, compared with the control mice. Further, we found that dietary fucoxanthin significantly increased the mRNA expression of proprotein convertase subtilisin\/kexin type 9 (PCSK9), which enhances intracellular degradation of LDLR in lysosomes.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Fucoxanthin increased HDL-cholesterol and non-HDL-cholesterol levels in KK-<jats:italic>A<\/jats:italic>\n              <jats:sup>\n                <jats:italic>y<\/jats:italic>\n              <\/jats:sup> mice by inducing SREBP expression and reduced cholesterol uptake in the liver via down-regulation of LDLR and SR-B1, resulted in increased serum cholesterol in the mice.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1476-511x-11-112","type":"journal-article","created":{"date-parts":[[2012,9,10]],"date-time":"2012-09-10T12:14:06Z","timestamp":1347279246000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["Effects of dietary fucoxanthin on cholesterol metabolism in diabetic\/obese KK-A\n                y\n               mice"],"prefix":"10.1186","volume":"11","author":[{"given":"Fumiaki","family":"Beppu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Hosokawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshimi","family":"Niwano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuo","family":"Miyashita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2012,9,10]]},"reference":[{"key":"741_CR1","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/j.bbagen.2004.08.012","volume":"1675","author":"M Hosokawa","year":"2004","unstructured":"Hosokawa M, Kudo M, Maeda H, Kohno H, Tanaka T, Miyashita K: Fucoxanthin induces apoptosis and enhances the antiproliferative effect of the PPARgamma ligand, troglitazone, on colon cancer cells. Biochim Biophys Acta. 2004, 1675: 113-119. 10.1016\/j.bbagen.2004.08.012","journal-title":"Biochim Biophys Acta"},{"key":"741_CR2","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1016\/j.exer.2005.03.002","volume":"81","author":"K Shiratori","year":"2005","unstructured":"Shiratori K, Ohgami K, Ilieva I, Jin XH, Koyama Y, Miyashita K, Yoshida K, Kase S, Ohno S: Effects of fucoxanthin on lipopolysaccharide-induced inflammation in vitro and in vivo. Exp Eye Res. 2005, 81: 422-428. 10.1016\/j.exer.2005.03.002","journal-title":"Exp Eye Res"},{"key":"741_CR3","doi-asserted-by":"publisher","first-page":"8516","DOI":"10.1021\/jf071848a","volume":"55","author":"NM Sachindra","year":"2007","unstructured":"Sachindra NM, Sato E, Maeda H, Hosokawa M, Niwano Y, Kohno M, Miyashita K: Radical scavenging and singlet oxygen quenching activity of marine carotenoid fucoxanthin and its metabolites. J Agric Food Chem. 2007, 55: 8516-8522. 10.1021\/jf071848a","journal-title":"J Agric Food Chem"},{"key":"741_CR4","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.abb.2010.05.031","volume":"504","author":"M Hosokawa","year":"2010","unstructured":"Hosokawa M, Miyashita T, Nishikawa S, Emi S, Tsukui T, Beppu F, Okada T, Miyashita K: Fucoxanthin regulates adipocytokine mRNA expression in white adipose tissue of diabetic\/obese KK-Ay mice. Arch Biochem Biophys. 2010, 504: 17-25. 10.1016\/j.abb.2010.05.031","journal-title":"Arch Biochem Biophys"},{"key":"741_CR5","doi-asserted-by":"publisher","first-page":"304","DOI":"10.3136\/nskkk.55.304","volume":"55","author":"T Kadekaru","year":"2008","unstructured":"Kadekaru T, Toyama H, Yasumoto T: Safety evaluation of fucoxanthin purified from undariapinnatifida. Nippon Shokuhin Kagaku Kogaku Kaishi. 2008, 55: 304-308. 10.3136\/nskkk.55.304. 10.3136\/nskkk.55.304","journal-title":"Nippon Shokuhin Kagaku Kogaku Kaishi"},{"key":"741_CR6","doi-asserted-by":"publisher","first-page":"501","DOI":"10.2131\/jts.34.501","volume":"34","author":"F Beppu","year":"2009","unstructured":"Beppu F, Niwano Y, Tsukui T, Hosokawa M, Miyashita K: Single and repeated oral dose toxicity study of fucoxanthin (FX), a marine carotenoid, in mice. J Toxicol Sci. 2009, 34: 501-510. 10.2131\/jts.34.501","journal-title":"J Toxicol Sci"},{"key":"741_CR7","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1016\/j.cbi.2010.05.006","volume":"186","author":"MN Woo","year":"2010","unstructured":"Woo MN, Jeon SM, Kim HJ, Lee MK, Shin SK, Shin YC, Park YB, Choi MS: Fucoxanthin supplementation improves plasma and hepatic lipid metabolism and blood glucose concentration in high-fat fed C57BL\/6\u2009N mice. Chem Biol Interact. 2010, 186: 316-322. 10.1016\/j.cbi.2010.05.006","journal-title":"Chem Biol Interact"},{"key":"741_CR8","doi-asserted-by":"publisher","first-page":"5025","DOI":"10.1021\/jf070110q","volume":"55","author":"T Tsukui","year":"2007","unstructured":"Tsukui T, Konno K, Hosokawa M, Maeda H, Sashima T, Miyashita K: Fucoxanthin and fucoxanthinol enhance the amount of docosahexaenoic acid in the liver of KKAy obese\/diabetic mice. J Agric Food Chem. 2007, 55: 5025-5029. 10.1021\/jf070110q","journal-title":"J Agric Food Chem"},{"key":"741_CR9","doi-asserted-by":"publisher","first-page":"961","DOI":"10.1002\/biot.201000215","volume":"5","author":"SM Jeon","year":"2010","unstructured":"Jeon SM, Kim HJ, Woo MN, Lee MK, Shin YC, Park YB, Choi MS: Fucoxanthin-rich seaweed extract suppresses body weight gain and improves lipid metabolism in high-fat-fed C57BL\/6\u2009J mice. Biotechnol J. 2010, 5: 961-969. 10.1002\/biot.201000215","journal-title":"Biotechnol J"},{"key":"741_CR10","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0021-9258(18)64849-5","volume":"226","author":"J Folch","year":"1957","unstructured":"Folch J, Lees M, Sloane Stanley GH: A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem. 1957, 226: 497-509.","journal-title":"J Biol Chem"},{"key":"741_CR11","doi-asserted-by":"publisher","first-page":"11603","DOI":"10.1073\/pnas.90.24.11603","volume":"90","author":"X Hua","year":"1993","unstructured":"Hua X, Yokoyama C, Wu J, Briggs MR, Brown MS, Goldstein JL, Wang X: SREBP-2, a second basic-helix-loop-helix-leucine zipper protein that stimulates transcription by binding to a sterol regulatory element. Proc Natl Acad Sci USA. 1993, 90: 11603-11607. 10.1073\/pnas.90.24.11603","journal-title":"Proc Natl Acad Sci USA"},{"key":"741_CR12","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1016\/S0092-8674(00)80213-5","volume":"89","author":"MS Brown","year":"1997","unstructured":"Brown MS, Goldstein JL: The SREBP pathway: regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor. Cell. 1997, 89: 331-340. 10.1016\/S0092-8674(00)80213-5","journal-title":"Cell"},{"key":"741_CR13","first-page":"52","volume":"24","author":"JM Timmins","year":"2004","unstructured":"Timmins JM, Lee JY, Mulya A: Tissue-specific hepatic deletion of ABCA1 indicates that the liver is the primary site for HDL formation in vivo [abstract]. Arterioscler Thromb Vasc Biol. 2004, 24: 52-","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"741_CR14","doi-asserted-by":"publisher","first-page":"1721","DOI":"10.1126\/science.1125884","volume":"311","author":"MS Brown","year":"2006","unstructured":"Brown MS, Goldstein JL: Lowering LDL \u2013 not only how low, but how long?. Science. 2006, 311: 1721-1723. 10.1126\/science.1125884","journal-title":"Science"},{"key":"741_CR15","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1016\/j.cmet.2005.04.006","volume":"1","author":"AD Attie","year":"2005","unstructured":"Attie AD, Seidah NG: Dual regulation of the LDL receptor\u2013some clarity and new questions. Cell Metab. 2005, 1: 290-292. 10.1016\/j.cmet.2005.04.006","journal-title":"Cell Metab"},{"key":"741_CR16","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1016\/j.bbrc.2005.05.002","volume":"332","author":"H Maeda","year":"2005","unstructured":"Maeda H, Hosokawa M, Sashima T, Funayama K, Miyashita K: Fucoxanthin from edible seaweed, Undaria pinnatifida, shows antiobesity effect through UCP1 expression in white adipose tissues. Biochem Biophys Res Commun. 2005, 332: 392-397. 10.1016\/j.bbrc.2005.05.002","journal-title":"Biochem Biophys Res Commun"},{"key":"741_CR17","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1111\/j.1463-1326.2009.01132.x","volume":"12","author":"M Abidov","year":"2010","unstructured":"Abidov M, Ramazanov Z, Seifulla R, Grachev S: The effects of Xanthigen in the weight management of obese premenopausal women with non-alcoholic fatty liver disease and normal liver fat. Diabetes Obes Metab. 2010, 12: 72-81. 10.1111\/j.1463-1326.2009.01132.x","journal-title":"Diabetes Obes Metab"},{"key":"741_CR18","doi-asserted-by":"publisher","first-page":"12610","DOI":"10.1073\/pnas.94.23.12610","volume":"94","author":"A Rigotti","year":"1997","unstructured":"Rigotti A, Trigatti BL, Penman M, Rayburn H, Herz J, Krieger M: A targeted mutation in the murine gene encoding the high density lipoprotein (HDL) receptor scavenger receptor class B type I reveals its key role in HDL metabolism. Proc Natl Acad Sci USA. 1997, 94: 12610-12615. 10.1073\/pnas.94.23.12610","journal-title":"Proc Natl Acad Sci USA"},{"key":"741_CR19","doi-asserted-by":"publisher","first-page":"4619","DOI":"10.1073\/pnas.95.8.4619","volume":"95","author":"ML Varban","year":"1998","unstructured":"Varban ML, Rinninger F, Wang N, Fairchild-Huntress V, Dunmore JH, Fang Q, Gosselin ML, Dixon KL, Deeds JD, Acton SL, Tall AR, Huszar D: Targeted mutation reveals a central role for SR-BI in hepatic selective uptake of high density lipoprotein cholesterol. Proc Natl Acad Sci USA. 1998, 95: 4619-4624. 10.1073\/pnas.95.8.4619","journal-title":"Proc Natl Acad Sci USA"},{"key":"741_CR20","doi-asserted-by":"publisher","first-page":"32920","DOI":"10.1074\/jbc.273.49.32920","volume":"273","author":"N Wang","year":"1998","unstructured":"Wang N, Arai T, Ji Y, Rinninger F, Tall AR: Liver-specific overexpression of scavenger receptor BI decreases levels of very low density lipoprotein ApoB, low density lipoprotein ApoB, and high density lipoprotein in transgenic mice. J Biol Chem. 1998, 273: 32920-32926. 10.1074\/jbc.273.49.32920","journal-title":"J Biol Chem"},{"key":"741_CR21","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1126\/science.3513311","volume":"232","author":"MS Brown","year":"1986","unstructured":"Brown MS, Goldstein JL: A receptor-mediated pathway for cholesterol homeostasis. Science. 1986, 232: 34-47. 10.1126\/science.3513311","journal-title":"Science"},{"key":"741_CR22","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1210\/er.2001-0037","volume":"24","author":"A Rigotti","year":"2003","unstructured":"Rigotti A, Miettinen HE, Krieger M: The role of the high-density lipoprotein receptor SR-BI in the lipid metabolism of endocrine and other tissues. Endocr Rev. 2003, 24: 357-387. 10.1210\/er.2001-0037","journal-title":"Endocr Rev"},{"key":"741_CR23","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1191\/1358863x05vm593ra","volume":"10","author":"S Soumian","year":"2005","unstructured":"Soumian S, Albrecht C, Davies AH, Gibbs RG: ABCA1 and atherosclerosis. Vasc Med. 2005, 10: 109-119. 10.1191\/1358863x05vm593ra","journal-title":"Vasc Med"},{"key":"741_CR24","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/S0022-2275(20)39534-1","volume":"12","author":"E Quint\u00e3o","year":"1971","unstructured":"Quint\u00e3o E, Grundy SM, Ahrens EH: Effects of dietary cholesterol on the regulation of total body cholesterol in man. J Lipid Res. 1971, 12: 233-247.","journal-title":"J Lipid Res"},{"key":"741_CR25","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/S0022-2275(20)36894-2","volume":"14","author":"J Farkas","year":"1973","unstructured":"Farkas J, Angel A, Avigan MI: Studies on the compartmentation of lipid in adipose cells. II. Cholesterol accumulation and distribution in adipose tissue components. J Lipid Res. 1973, 14: 344-356.","journal-title":"J Lipid Res"},{"key":"741_CR26","doi-asserted-by":"publisher","first-page":"48865","DOI":"10.1074\/jbc.M409699200","volume":"279","author":"S Benjannet","year":"2004","unstructured":"Benjannet S, Rhainds D, Essalmani R, Mayne J, Wickham L, Jin W, Asselin MC, Hamelin J, Varret M, Allard D, Trillard M, Abifadel M, Tebon A, Attie AD, Rader DJ, Boileau C, Brissette L, Chr\u00e9tien M, Prat A, Seidah NG: NARC-1\/PCSK9 and its natural mutants: zymogen cleavage and effects on the low density lipoprotein (LDL) receptor and LDL cholesterol. J Biol Chem. 2004, 279: 48865-48875. 10.1074\/jbc.M409699200","journal-title":"J Biol Chem"},{"key":"741_CR27","doi-asserted-by":"publisher","first-page":"50630","DOI":"10.1074\/jbc.M410077200","volume":"279","author":"SW Park","year":"2004","unstructured":"Park SW, Moon YA, Horton JD: Post-transcriptional regulation of low density lipoprotein receptor protein by proprotein convertase subtilisin\/kexin type 9a in mouse liver. J Biol Chem. 2004, 279: 50630-50638. 10.1074\/jbc.M410077200","journal-title":"J Biol Chem"},{"key":"741_CR28","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1126\/science.1168974","volume":"325","author":"N Zelcer","year":"2009","unstructured":"Zelcer N, Hong C, Boyadjian R, Tontonoz P: LXR regulates cholesterol uptake through Idol-dependent ubiquitination of the LDL receptor. Science. 2009, 325: 100-104. 10.1126\/science.1168974","journal-title":"Science"},{"key":"741_CR29","doi-asserted-by":"publisher","first-page":"928","DOI":"10.1073\/pnas.0335507100","volume":"100","author":"NG Seidah","year":"2003","unstructured":"Seidah NG, Benjannet S, Wickham L, Marcinkiewicz J, Jasmin SB, Stifani S, Basak A, Prat A, Chretien M: The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): liver regeneration and neuronal differentiation. Proc Natl Acad Sci USA. 2003, 100: 928-933. 10.1073\/pnas.0335507100","journal-title":"Proc Natl Acad Sci USA"},{"key":"741_CR30","doi-asserted-by":"publisher","first-page":"18602","DOI":"10.1074\/jbc.M702027200","volume":"282","author":"DW Zhang","year":"2007","unstructured":"Zhang DW, Lagace TA, Garuti R, Zhao Z, McDonald M, Horton JD, Cohen JC, Hobbs HH: Binding of proprotein convertase subtilisin\/kexin type 9 to epidermal growth factor-like repeat A of low density lipoprotein receptor decreases receptor recycling and increases degradation. J Biol Chem. 2007, 282: 18602-18612. 10.1074\/jbc.M702027200","journal-title":"J Biol Chem"},{"key":"741_CR31","doi-asserted-by":"publisher","first-page":"50630","DOI":"10.1074\/jbc.M410077200","volume":"279","author":"SW Park","year":"2004","unstructured":"Park SW, Moon YA, Horton JD: Post-transcriptional regulation of low density lipoprotein receptor protein by proprotein convertase subtilisin\/kexin type 9a in mouse liver. J Biol Chem. 2004, 279: 50630-50638. 10.1074\/jbc.M410077200","journal-title":"J Biol Chem"},{"key":"741_CR32","doi-asserted-by":"publisher","first-page":"12027","DOI":"10.1073\/pnas.1534923100","volume":"100","author":"JD Horton","year":"2003","unstructured":"Horton JD, Shah NA, Warrington JA, Anderson NN, Park SW, Brown MS, Goldstein JL: Combined analysis of oligonucleotide microarray data from transgenic and knockout mice identifies direct SREBP target genes. Proc Natl Acad Sci USA. 2003, 100: 12027-12032. 10.1073\/pnas.1534923100","journal-title":"Proc Natl Acad Sci USA"},{"key":"741_CR33","doi-asserted-by":"publisher","first-page":"2109","DOI":"10.1194\/jlr.M300203-JLR200","volume":"44","author":"KN Maxwell","year":"2003","unstructured":"Maxwell KN, Soccio RE, Duncan EM, Sehayek E, Breslow JL: Novel putative SREBP and LXR target genes identified by microarray analysis in liver of cholesterol-fed mice. J Lipid Res. 2003, 44: 2109-2119. 10.1194\/jlr.M300203-JLR200","journal-title":"J Lipid Res"},{"key":"741_CR34","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1097\/00041433-200004000-00004","volume":"11","author":"B Trigatti","year":"2000","unstructured":"Trigatti B, Rigotti A, Krieger M: The role of the high-density lipoprotein receptor SR-BI in cholesterol metabolism. Curr Opin Lipidol. 2000, 11: 123-131. 10.1097\/00041433-200004000-00004","journal-title":"Curr Opin Lipidol"},{"key":"741_CR35","doi-asserted-by":"publisher","first-page":"916","DOI":"10.1016\/S0006-291X(02)02760-2","volume":"299","author":"L Maler\u00f8d","year":"2002","unstructured":"Maler\u00f8d L, Juvet LK, Hanssen-Bauer A, Eskild W, Berg T: Oxysterol-activated LXRalpha\/RXR induces hSR-BI-promoter activity in hepatoma cells and preadipocytes. Biochem Biophys Res Commun. 2002, 299: 916-923. 10.1016\/S0006-291X(02)02760-2","journal-title":"Biochem Biophys Res Commun"},{"key":"741_CR36","doi-asserted-by":"publisher","first-page":"7884","DOI":"10.1074\/jbc.M211627200","volume":"278","author":"P Mardones","year":"2003","unstructured":"Mardones P, Pilon A, Bouly M, Duran D, Nishimoto T, Arai H, Kozarsky KF, Altayo M, Miquel JF, Luc G, Clavey V, Staels B, Rigotti A: Fibrates down-regulate hepatic scavenger receptor class B type I protein expression in mice. J Biol Chem. 2003, 278: 7884-7890. 10.1074\/jbc.M211627200","journal-title":"J Biol Chem"}],"container-title":["Lipids in Health and Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1476-511X-11-112.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,2]],"date-time":"2021-09-02T19:13:53Z","timestamp":1630610033000},"score":1,"resource":{"primary":{"URL":"https:\/\/lipidworld.biomedcentral.com\/articles\/10.1186\/1476-511X-11-112"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,9,10]]},"references-count":36,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2012,12]]}},"alternative-id":["741"],"URL":"https:\/\/doi.org\/10.1186\/1476-511x-11-112","relation":{},"ISSN":["1476-511X"],"issn-type":[{"value":"1476-511X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,9,10]]},"assertion":[{"value":"1 August 2012","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 September 2012","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 September 2012","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"112"}}