{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T17:02:21Z","timestamp":1772470941209,"version":"3.50.1"},"reference-count":40,"publisher":"Walter de Gruyter GmbH","issue":"3-4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    In the present study, starfish (\n                    <jats:italic>Luidia maculata<\/jats:italic>\n                    ) specimens were collected from bycatch trash fish at a fish landing center, and their pharmacological and cytotoxic potentials were evaluated through acute oral toxicity,\n                    <jats:italic>in\u00a0vivo<\/jats:italic>\n                    anti-nociceptive and locomotor assays, as well as\n                    <jats:italic>in\u00a0vitro<\/jats:italic>\n                    cytotoxicity assay. The crude ethanol extract from starfish\n                    <jats:italic>L.\u00a0maculata<\/jats:italic>\n                    was purified by liquid\u2013liquid partition chromatography using cyclohexane and n-butanol was used to determine the acute oral toxicity (LD\n                    <jats:sub>50<\/jats:sub>\n                    ) and a histopathological examination of the rat. In acute oral toxicity studies, an LD\n                    <jats:sub>50<\/jats:sub>\n                    value of 33.33\u202f% of mortality was observed at 2000\u202fmg\/kg per oral dosage of the extract. Oral administration extract (2000\u202fmg\/kg) revealed significant histopathological alterations in tissues when compared to the control rats. Both in thermal and chemical-induced analgesic methods, administered extract (400\u202fmg\/kg bw) showed the maximum analgesic activity. In the tail flick method, the high dose of the extract significantly elevated the pain threshold throughout the observation period, with all groups showing increased pain tolerance over time. In locomotor activity, the highest percentage reduction (91.16\u202f%) was observed in group IV animals after 90\u202fmin of administration, which showed the potent CNS depressant activity of the extract. The extract exhibited significant cytotoxicity against MCF-7 cells with a low IC\n                    <jats:sub>50<\/jats:sub>\n                    of 6.51\u202f\u00b5g. Hence, the result of the present study showed the anti-nociceptive, CNS depressant cytotoxic properties of starfish\n                    <jats:italic>L.\u00a0maculata.<\/jats:italic>\n                  <\/jats:p>","DOI":"10.1515\/znc-2025-0105","type":"journal-article","created":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T12:56:21Z","timestamp":1755176181000},"page":"281-293","source":"Crossref","is-referenced-by-count":0,"title":["Studies on the pharmacological potential of starfish\n                    <i>Luidia maculata<\/i>\n                    using acute oral toxicity,\n                    <i>in\u00a0vivo<\/i>\n                    anti-nociceptive, locomotor, and\n                    <i>in\u00a0vitro<\/i>\n                    cytotoxic activities"],"prefix":"10.1515","volume":"81","author":[{"given":"Suguna","family":"Anbukkarasu","sequence":"first","affiliation":[{"name":"Centre of Advanced Study in Marine Biology, Faculty of Marine Sciences , Annamalai University , Parangipettai , 608502 , Tamilnadu , India"},{"name":"Department of Microbiology , Bharathidasan University , Tiruchirappalli , 620024 , India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8452-5589","authenticated-orcid":false,"given":"Prabhu","family":"Kolandhasamy","sequence":"additional","affiliation":[{"name":"Marine Toxicology and Bioprospecting Lab, Centre for Global Health Research , Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences , Chennai , Tamil Nadu , India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bragadeeswaran","family":"Subramanian","sequence":"additional","affiliation":[{"name":"Centre of Advanced Study in Marine Biology, Faculty of Marine Sciences , Annamalai University , Parangipettai , 608502 , Tamilnadu , India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3568-2358","authenticated-orcid":false,"given":"Ramachandran","family":"Vinayagam","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Institute of Biotechnology, School of Life and Applied Sciences , Yeungnam University , Gyeongsan , 38541 , Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","published-online":{"date-parts":[[2025,8,15]]},"reference":[{"key":"2026030216130867963_j_znc-2025-0105_ref_001","doi-asserted-by":"crossref","unstructured":"Jimeno, J, Faircloth, G, Fernandez Sousa-Faro, JM, Scheuer, P, Rinehart, K. New marine-derived anticancer therapeutics: a journey from the sea to clinical trials. Mar Drugs 2004;2:14\u201329. https:\/\/doi.org\/10.3390\/md201014.","DOI":"10.3390\/md201014"},{"key":"2026030216130867963_j_znc-2025-0105_ref_002","doi-asserted-by":"crossref","unstructured":"Leal, MC, Madeira, C, Brandao, CA, Puga, J, Calado, R. Bioprospecting of marine invertebrates for new natural products: a chemical and zoogeographical perspective. Molecules 2012;17:9842\u201354. https:\/\/doi.org\/10.3390\/molecules17089842.","DOI":"10.3390\/molecules17089842"},{"key":"2026030216130867963_j_znc-2025-0105_ref_003","doi-asserted-by":"crossref","unstructured":"Koyama, T, Chounan, R, Uemura, D, Yamaguchi, K, Yazawa, K. Hepatoprotective effect of a hot-water extract from the edible thorny oyster Spondylus varius on carbon tetrachloride induced liver injury in mice. Biosci Biotechnol Biochem 2006;70:729\u201331. https:\/\/doi.org\/10.1271\/bbb.70.729.","DOI":"10.1271\/bbb.70.729"},{"key":"2026030216130867963_j_znc-2025-0105_ref_004","doi-asserted-by":"crossref","unstructured":"Prokofieva, NG, Chaikina, EL, Kicha, AA, Ivanchina, NV. Biological activities of steroid glycosides from starfish. Comp Biochem Physiol B 2003;134:695\u2013701. https:\/\/doi.org\/10.1016\/S1096-4959(03)00029-0.","DOI":"10.1016\/S1096-4959(03)00029-0"},{"key":"2026030216130867963_j_znc-2025-0105_ref_005","doi-asserted-by":"crossref","unstructured":"Dong, G, Xu, TH, Yang, B, Lin, XP, Zhou, XF, Yang, XW, et al.. Chemical constituents and bioactivities of starfish. Chem Biodivers 2011;8:740\u201391. https:\/\/doi.org\/10.1002\/cbdv.200900344.","DOI":"10.1002\/cbdv.200900344"},{"key":"2026030216130867963_j_znc-2025-0105_ref_006","unstructured":"Goldsmith, LA. Pharmacological evaluation of an asterosaponin extract from Asterias forbesi (Desor). Kingston, United\u00a0States: University of Rhode Island; 1975:1\u2013100 pp. MSc Thesis."},{"key":"2026030216130867963_j_znc-2025-0105_ref_007","doi-asserted-by":"crossref","unstructured":"Kanagarajan, U, Bragadeeswaran, S, Venkateshwaran, K. On some toxinological aspects of the starfish Stellaster equestris (Retzius, 1805). J\u00a0Venom Anim Toxins Incl Trop Dis 2008;14:435\u201349. https:\/\/doi.org\/10.1590\/s1678-91992008000300005.","DOI":"10.1590\/S1678-91992008000300005"},{"key":"2026030216130867963_j_znc-2025-0105_ref_008","doi-asserted-by":"crossref","unstructured":"Suguna, A, Bragadeeswaran, S, Prabhu, K, Priyatharsini, S, Mohanraj, M, Sivaramakrishnan, S. Cytolytic and antinociceptive activities of starfish Protoreaster linckii (Blainvilli, 1893). Afr J Pharm Pharmacol 2013;7:2734\u201342. https:\/\/doi.org\/10.5897\/AJPP12.1423.","DOI":"10.5897\/AJPP12.1423"},{"key":"2026030216130867963_j_znc-2025-0105_ref_009","doi-asserted-by":"crossref","unstructured":"Nagarajan, P, Sivakumar, AS, Govindasamy, C, El Newehy, AS, Louis, LR, Sivanandham, M, et al.. Molecular perspective on starfish tissue extracts: targeting human carcinoma KB\u00a0cells for anticancer therapy. J\u00a0King Saud Univ Sci 2024;36:103035. https:\/\/doi.org\/10.1016\/j.jksus.2023.103035.","DOI":"10.1016\/j.jksus.2023.103035"},{"key":"2026030216130867963_j_znc-2025-0105_ref_010","doi-asserted-by":"crossref","unstructured":"Zhang, W, Guo, YW, Gu, Y. Secondary metabolites from the South China Sea invertebrates: chemistry and biological activity. Curr Med Chem 2006;13:2041\u201390. https:\/\/doi.org\/10.2174\/092986706777584960.","DOI":"10.2174\/092986706777584960"},{"key":"2026030216130867963_j_znc-2025-0105_ref_011","doi-asserted-by":"crossref","unstructured":"Wikarta, JM, Kim, SM. Anti-inflammatory activity and cytotoxicity of the starfish extracts on cancer cell lines. Med Chem 2016;6:331\u20138. https:\/\/doi.org\/10.4172\/2161-0444.1000366.","DOI":"10.4172\/2161-0444.1000366"},{"key":"2026030216130867963_j_znc-2025-0105_ref_012","doi-asserted-by":"crossref","unstructured":"Parajuli, K, Fahim, N, Mumu, S, Palu, R, Mustafa, A. Antibacterial potential of Luidia clathrata (sea star) tissue extracts against selected pathogenic bacteria. PLoS One 2023;18:e0281889. https:\/\/doi.org\/10.1371\/journal.pone.0281889.","DOI":"10.1371\/journal.pone.0281889"},{"key":"2026030216130867963_j_znc-2025-0105_ref_013","doi-asserted-by":"crossref","unstructured":"Suguna, A, Bragadeeswaran, S, Natarajan, E, Mohanraj, M. Studies on antioxidant properties of starfish Luidia maculata (Muller & Troschel, 1842) off Parangipettai, Southeast coast of India. J\u00a0Coast Life Med 2014;2:694\u20138. https:\/\/doi.org\/10.12980\/JCLM.2.2014JCLM-2014-0014.","DOI":"10.12980\/JCLM.2.2014JCLM-2014-0014"},{"key":"2026030216130867963_j_znc-2025-0105_ref_014","doi-asserted-by":"crossref","unstructured":"Chamundeeswari, K, Saranya, S, Rajagopal, S. Exploration of potential antimicrobial activity of sea star astropecten indicus. J\u00a0Appl Pharm Sci 2012;30:125\u20138.","DOI":"10.7324\/JAPS.2012.2716"},{"key":"2026030216130867963_j_znc-2025-0105_ref_015","doi-asserted-by":"crossref","unstructured":"Thao, NP, Cuong, NX, Luyen, BTT, Nam, NH, Cuong, PV, Thanh, NV, et al.. Steroidal constituents from the starfish Astropecten polyacanthus and their anticancer effects. Chem Pharm Bull 2013;61:1044\u201351. https:\/\/doi.org\/10.1248\/cpb.c13-00490.","DOI":"10.1248\/cpb.c13-00490"},{"key":"2026030216130867963_j_znc-2025-0105_ref_016","unstructured":"Hyman, LH. The invertebrates: IV: echinodermata. New York: McGraw-Hill; 1955:763 p."},{"key":"2026030216130867963_j_znc-2025-0105_ref_017","unstructured":"Clark, AM. Starfishes and their relations, 2nd ed.. London: The British Museum (Natural History); 1968:120 p."},{"key":"2026030216130867963_j_znc-2025-0105_ref_018","doi-asserted-by":"crossref","unstructured":"Braekman, JC, Daloze, D, Stoller, C, Van Soest, RWM. Chemotaxonomy of agelas (Porifera: Demospongiae). Biochem Syst Ecol 1992;20:417\u201331. https:\/\/doi.org\/10.1016\/0305-1978(92)90082-O.","DOI":"10.1016\/0305-1978(92)90082-O"},{"key":"2026030216130867963_j_znc-2025-0105_ref_019","doi-asserted-by":"crossref","unstructured":"D\u2019Amour, FE, Smith, DL. A method for determining loss of pain sensation. J\u00a0Pharmacol Exp Ther 1941;72:74\u20139. https:\/\/doi.org\/10.1016\/s0022-3565-25-03823-6.","DOI":"10.1016\/S0022-3565(25)03823-6"},{"key":"2026030216130867963_j_znc-2025-0105_ref_020","doi-asserted-by":"crossref","unstructured":"Whittle, BA. The use of changes in capillary permeability in mice to distinguish between narcotic and non-narcotic analgesics. Br J Pharmacol Chemother 1964;22:246\u201353. https:\/\/doi.org\/10.1111\/j.1476-5381.1964.tb02030.x.","DOI":"10.1111\/j.1476-5381.1964.tb02030.x"},{"key":"2026030216130867963_j_znc-2025-0105_ref_021","doi-asserted-by":"crossref","unstructured":"Mosmann, T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J\u00a0Immunol Methods 1983;65:55\u201363. https:\/\/doi.org\/10.1016\/0022-1759(83)90303-4.","DOI":"10.1016\/0022-1759(83)90303-4"},{"key":"2026030216130867963_j_znc-2025-0105_ref_022","doi-asserted-by":"crossref","unstructured":"Syed, MH, Gnanakkan, A, Pitchiah, S. Exploration of acute toxicity, analgesic, anti-inflammatory, and anti-pyretic activities of the black tunicate, Phallusia nigra (Savigny, 1816) using mice model. Environ Sci Poll Res 2021;28:5809\u201321. https:\/\/doi.org\/10.1007\/s11356-020-10938-2.","DOI":"10.1007\/s11356-020-10938-2"},{"key":"2026030216130867963_j_znc-2025-0105_ref_023","doi-asserted-by":"crossref","unstructured":"Abu, GO, Weiner, RM, Rice, J, Colwell, RR. Properties of an extracellular adhesive polymer from the marine bacterium Shewanella colwelliana. Biofouling 1991;3:69\u201384. https:\/\/doi.org\/10.1080\/08927019109378163.","DOI":"10.1080\/08927019109378163"},{"key":"2026030216130867963_j_znc-2025-0105_ref_024","doi-asserted-by":"crossref","unstructured":"Ridzwan, BH, Zarina, MZ, Kaswandi, MA, Nadirah, M, Shamsuddin, AF. The antinociceptive effects of extracts from Stichopus chloronotus Brandt. Pak J Biol Sci 2001;4:244\u20136. https:\/\/doi.org\/10.3923\/pjbs.2001.244.246.","DOI":"10.3923\/pjbs.2001.244.246"},{"key":"2026030216130867963_j_znc-2025-0105_ref_025","doi-asserted-by":"crossref","unstructured":"Isaac Dhinakaran, D, Lipton, AP. Pharmacological potentials of sea cucumber Holothuria atra extracts from the Indian Ocean. Asian J Biomed Pharm Sci 2014;4:36\u201343. https:\/\/doi.org\/10.1186\/2193-1801-3-673.","DOI":"10.15272\/ajbps.v4i35.537"},{"key":"2026030216130867963_j_znc-2025-0105_ref_026","doi-asserted-by":"crossref","unstructured":"Ridzwan, BH, Leong, TC, Idid, SZ. The antinociceptive effects of water extracts from sea cucumbers Holothuria leucospilota Brandt, Bohadschia marmorata vitensis Jaeger and coelomic fluid from Stichopus hermanii. Pak J Biol Sci 2003;6:2068\u201372. https:\/\/doi.org\/10.3923\/pjbs.2003.2068.2072.","DOI":"10.3923\/pjbs.2003.2068.2072"},{"key":"2026030216130867963_j_znc-2025-0105_ref_027","doi-asserted-by":"crossref","unstructured":"Deraedt, R, Joughney, S, Delevakee, F, Falhour, M. Release of prostaglandin E and F in an algogenic reaction and its inhibition. Eur J Pharmacol 1980;61:17\u201324. https:\/\/doi.org\/10.1016\/0014-2999(80)90377-5.","DOI":"10.1016\/0014-2999(80)90377-5"},{"key":"2026030216130867963_j_znc-2025-0105_ref_028","doi-asserted-by":"crossref","unstructured":"Tang, HF, Yi, YH, Li, L, Sun, P, Zhang, SQ, Zhao, YP. Asterosaponins from the starfish Culcita novaeguineae and their bioactivities. Fitoterapia 2006;77:28\u201334. https:\/\/doi.org\/10.1016\/j.fitote.2005.07.009.","DOI":"10.1016\/j.fitote.2005.07.009"},{"key":"2026030216130867963_j_znc-2025-0105_ref_029","doi-asserted-by":"crossref","unstructured":"Cheng, G, Zhang, X, Tang, HF, Zhang, Y, Zhang, XH, Cao, WD, et al.. Asterosaponin 1, a cytostatic compound from the starfish Culcita novaeguineae functions by inducing apoptosis in human glioblastoma U87MG cells. J\u00a0Neuro Oncol 2006;79:235\u201341. https:\/\/doi.org\/10.1007\/s11060-006-9136-y.","DOI":"10.1007\/s11060-006-9136-y"},{"key":"2026030216130867963_j_znc-2025-0105_ref_030","doi-asserted-by":"crossref","unstructured":"Ma, N, Tang, HF, Qin, F, Lin, HW, Tian, XR, Yao, MN. Polyhydroxysteroidal glycosides from the starfish Anthenea chinensis. J\u00a0Nat Prod 2010;73:590\u20137. https:\/\/doi.org\/10.1021\/np9007188.","DOI":"10.1021\/np9007188"},{"key":"2026030216130867963_j_znc-2025-0105_ref_031","doi-asserted-by":"crossref","unstructured":"Quang, TH, Lee, DS, Han, SJ, Kim, IC, Yim, JH, Kim, YC, et al.. Steroids from the cold water starfish Ctenodiscus crispatus with cytotoxic and apoptotic effects on human hepatocellular carcinoma and glioblastoma cells. Bull Korean Chem Soc 2014;35:2335\u201341. https:\/\/doi.org\/10.5012\/bkcs.2014.35.8.2335.","DOI":"10.5012\/bkcs.2014.35.8.2335"},{"key":"2026030216130867963_j_znc-2025-0105_ref_032","doi-asserted-by":"crossref","unstructured":"Lee, CC, Hsieh, HJ, Hsieh, CH, Hwang, DF. Plancitoxin I from the venom of crown-of-thorns starfish (Acanthaster planci) induces oxidative and endoplasmic reticulum stress associated cytotoxic A375.S2 cells. Exp Mol Pathol 2015;99:7\u201315. https:\/\/doi.org\/10.1016\/j.yexmp.2015.05.001.","DOI":"10.1016\/j.yexmp.2015.05.001"},{"key":"2026030216130867963_j_znc-2025-0105_ref_033","doi-asserted-by":"crossref","unstructured":"Vien, LT, Ngoan, BT, Hanh, TTH, Vinh, LB, Thung, DC, Thao, DT, et al.. Steroid glycosides from the starfish Pentaceraster gracilis. J\u00a0Asian Nat Prod Res 2016;19:474\u201380. https:\/\/doi.org\/10.1080\/10286020.2016.1235038.","DOI":"10.1080\/10286020.2016.1235038"},{"key":"2026030216130867963_j_znc-2025-0105_ref_034","doi-asserted-by":"crossref","unstructured":"Malyarenko, OS, Dyshlovoy, SA, Kicha, AA, Ivanchina, NV, Malyarenko, TV, Carsten, B, et al.. The inhibitory activity of luzonicosides from the starfish Echinaster luzonicus against human melanoma cells. Mar Drugs 2017;15:227. https:\/\/doi.org\/10.3390\/md15070227.","DOI":"10.3390\/md15070227"},{"key":"2026030216130867963_j_znc-2025-0105_ref_035","doi-asserted-by":"crossref","unstructured":"Malyarenko, TV, Malyarenko, OS, Kicha, AA, Ivanchina, NV, Kalinovsky, AI, Dmitrenok, PS, et al.. In vitro anticancer and proapoptotic activities of steroidal glycosides from the starfish Anthenea aspera. Mar Drugs 2018;16:1\u201314. https:\/\/doi.org\/10.3390\/md16110420.","DOI":"10.3390\/md16110420"},{"key":"2026030216130867963_j_znc-2025-0105_ref_036","doi-asserted-by":"crossref","unstructured":"Ha, DT, Kicha, AA, Kalinovsky, AI, Malyarenko, TV, Popov, RS, Malyarenko, OS, et al.. Asterosaponins from the tropical starfish Acanthaster planci and their cytotoxic and anticancer activities in\u00a0vitro. Nat Prod Res 2019;35:548\u201355. https:\/\/doi.org\/10.1080\/14786419.2019.1585845.","DOI":"10.1080\/14786419.2019.1585845"},{"key":"2026030216130867963_j_znc-2025-0105_ref_037","doi-asserted-by":"crossref","unstructured":"Malyarenko, TV, Malyarenko, OS, Kicha, AA, Kalinovsky, AI, Dmitrenok, PS, Ivanchina, NV. In vitro anticancer and cancer-preventive activity of new triterpene glycosides from the Far Eastern starfish Solaster pacificus. Mar Drugs 2022;20:1\u201324. https:\/\/doi.org\/10.3390\/md20030216.","DOI":"10.3390\/md20030216"},{"key":"2026030216130867963_j_znc-2025-0105_ref_038","doi-asserted-by":"crossref","unstructured":"Malyarenko, TV, Kicha, AA, Malyarenko, OS, Zakharenko, VM, Kotlyarov, IP, Kalinovsky, AI, et al.. New conjugates of polyhydroxysteroids with long-chain fatty acids from the deep-water Far Eastern starfish Ceramaster patagonicus and their anticancer activity. Mar Drugs 2020;18:1\u201314. https:\/\/doi.org\/10.3390\/md18050260.","DOI":"10.3390\/md18050260"},{"key":"2026030216130867963_j_znc-2025-0105_ref_039","doi-asserted-by":"crossref","unstructured":"Kawatake, S, Nakamura, K, Inagaki, M, Higuchi, R. Isolation and structure determination of six glucocerebrosides from the starfish Luidia maculata. Chem Pharm Bull 2002;50:1091\u20136. https:\/\/doi.org\/10.1248\/cpb.50.1091.","DOI":"10.1248\/cpb.50.1091"},{"key":"2026030216130867963_j_znc-2025-0105_ref_040","unstructured":"Husni, A, Byung-Hun, U, Chung, D. Isolation and identification of antioxidants and tyrosinase inhibitors from Stichopus japonicus. Yogyakarta, Indonesia: Department of Fisheries, Faculty of Agriculture, Gadjah Mada University; 2011:1\u201318 pp. MSc Dissertation."}],"container-title":["Zeitschrift f\u00fcr Naturforschung C"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/znc-2025-0105\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/znc-2025-0105\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T16:13:52Z","timestamp":1772468032000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/znc-2025-0105\/html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,15]]},"references-count":40,"journal-issue":{"issue":"3-4","published-online":{"date-parts":[[2025,8,15]]},"published-print":{"date-parts":[[2026,3,26]]}},"alternative-id":["10.1515\/znc-2025-0105"],"URL":"https:\/\/doi.org\/10.1515\/znc-2025-0105","relation":{},"ISSN":["0939-5075","1865-7125"],"issn-type":[{"value":"0939-5075","type":"print"},{"value":"1865-7125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,15]]}}}