Cortisone (BioDeep_00000001526)

 

Secondary id: BioDeep_00000405537

human metabolite PANOMIX_OTCML-2023 Endogenous blood metabolite


代谢物信息卡片


(1S,2R,10S,11S,14R,15S)-14-hydroxy-14-(2-hydroxyacetyl)-2,15-dimethyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadec-6-ene-5,17-dione

化学式: C21H28O5 (360.1936638)
中文名称: 可的松, 皮质醇
谱图信息: 最多检出来源 Homo sapiens(blood) 0.05%

Reviewed

Last reviewed on 2024-07-16.

Cite this Page

Cortisone. BioDeep Database v3. PANOMIX ltd, a top metabolomics service provider from China. https://query.biodeep.cn/s/cortisone (retrieved 2024-09-17) (BioDeep RN: BioDeep_00000001526). Licensed under the Attribution-Noncommercial 4.0 International License (CC BY-NC 4.0).

分子结构信息

SMILES: CC12CCC(=O)C=C1CCC1C2C(=O)CC2(C)C1CCC2(O)C(=O)CO
InChI: InChI=1S/C21H28O5/c1-19-7-5-13(23)9-12(19)3-4-14-15-6-8-21(26,17(25)11-22)20(15,2)10-16(24)18(14)19/h9,14-15,18,22,26H,3-8,10-11H2,1-2H3/t14-,15-,18+,19-,20-,21-/m0/s1

描述信息

A naturally occurring glucocorticoid. It has been used in replacement therapy for adrenal insufficiency and as an anti-inflammatory agent. Cortisone itself is inactive. It is converted in the liver to the active metabolite hydrocortisone. (From Martindale, The Extra Pharmacopoeia, 30th ed, p726) -- Pubchem; Cortisone is a hormone. Chemically it is a corticosteroid with formula C21H28O5 and IUPAC name 17-hydroxy-11-dehydrocorticosterone. It is closely related to corticosterone. -- Wikipedia; One of cortisones effects on the body, and a potentially harmful side effect when administered clinically, is the suppression of the immune system. This is an explanation for the apparent correlation between high stress and sickness. -- Wikipedia [HMDB]
Cortisone is a naturally occurring glucocorticoid. It has been used in replacement therapy for adrenal insufficiency and as an anti-inflammatory agent. Cortisone itself is inactive. It is converted in the liver into the active metabolite cortisol. Cortisone is a corticosteroid hormone released by the adrenal gland in response to stress. One of cortisones effects on the body, and a potentially harmful side effect when administered clinically, is the suppression of the immune system. This is an explanation for the apparent correlation between high stress and sickness.

Cortisone. CAS Common Chemistry. CAS, a division of the American Chemical Society, n.d. https://commonchemistry.cas.org/detail?cas_rn=53-06-5 (retrieved 2024-07-16) (CAS RN: 53-06-5). Licensed under the Attribution-Noncommercial 4.0 International License (CC BY-NC 4.0).
Cortisone (17-Hydroxy-11-dehydrocorticosterone), an oxidized metabolite of Cortisol (a Glucocorticoid). Cortisone acts as an immunosuppressant and anti-inflammatory agent. Cortisone can partially intervene in binding of Glucocorticoid to Glucocorticoid-receptor at high concentrations[1][3][4].

同义名列表

72 个代谢物同义名

(1S,2R,10S,11S,14R,15S)-14-hydroxy-14-(2-hydroxyacetyl)-2,15-dimethyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadec-6-ene-5,17-dione; 17-Hydroxy-3,11,20-trioxopregn-4-en-21-yl acetate; Delta(4)-Pregnene-17alpha,21-diol-3,11,20-trione; 17alpha,21-dihydroxypregn-4-ene-3,11,20-trione; 17alpha,21-Dihydroxy-4-pregnene-3,11,20-trione; delta(4)-Pregnene-17a,21-diol-3,11,20-trione; 17a,21-Dihydroxy-4-pregnene-3,11,20-trione; 17Α,21-dihydroxy-4-pregnene-3,11,20-trione; Pregn-4-en-17alpha,21-diol-3,11,20-trione; 4-Pregnene-17alpha,21-diol-3,11,20-trione; 17,21-Dihydroxypregn-4-ene-3,11,20-trione; Δ(4)-pregnene-17α,21-diol-3,11,20-trione; Δ(4)-pregnene-17a,21-diol-3,11,20-trione; Pregn-4-en-17α,21-diol-3,11,20-trione; 4-Pregnene-17a,21-diol-3,11,20-trione; 4-Pregnene-17α,21-diol-3,11,20-trione; Pregn-4-en-17a,21-diol-3,11,20-trione; 11-Dehydro-17-hydroxycorticosterone; 17-Hydroxy-11-dehydrocorticosterone; Wintersteiners compound F; Reichsteins substance fa; Fludrocortisone acetate; Kendalls compound e; KendallS compound; Cortisone acetate; Locoid lipocream; Cortone acetate; Cortef acetate; Prestwick_132; Reichstein fa; Orabase hca; Solu-cortef; ST 21:4;O5; Compound e; Cortandren; Balneol-HC; Nogenic HC; Anusol HC; Flexicort; Cortisate; Cortadren; Scheroson; Hemsol-HC; Cortivite; Micort-HC; Cortisone; Stie-cort; Dermacort; Cortistal; Westcort; Colocort; Cortisal; Kortison; Texacort; Cortison; Florinef; Incortin; Andreson; Cortogen; Cortone; Dricort; Beta-HC; Glycort; Adreson; CORTRIL; Pandel; Cortef; Hi-cor; Locoid; Corlin; Cortisone; Kendall's compound E



数据库引用编号

98 个数据库交叉引用编号

分类词条

相关代谢途径

Reactome(5)

BioCyc(0)

PlantCyc(0)

代谢反应

106 个相关的代谢反应过程信息。

Reactome(70)

BioCyc(0)

WikiPathways(2)

Plant Reactome(0)

INOH(0)

PlantCyc(0)

COVID-19 Disease Map(0)

PathBank(34)

PharmGKB(0)

3 个相关的物种来源信息

在这里通过桑基图来展示出与当前的这个代谢物在我们的BioDeep知识库中具有相关联信息的其他代谢物。在这里进行关联的信息来源主要有：

  • PubMed: 来源于PubMed文献库中的文献信息，我们通过自然语言数据挖掘得到的在同一篇文献中被同时提及的相关代谢物列表，这个列表按照代谢物同时出现的文献数量降序排序，取前10个代谢物作为相关研究中关联性很高的代谢物集合展示在桑基图中。
  • NCBI Taxonomy: 通过文献数据挖掘，得到的代谢物物种来源信息关联。这个关联信息同样按照出现的次数降序排序，取前10个代谢物作为高关联度的代谢物集合展示在桑吉图上。
  • Chemical Taxonomy: 在物质分类上处于同一个分类集合中的其他代谢物
  • Chemical Reaction: 在化学反应过程中，存在为当前代谢物相关联的生化反应过程中的反应底物或者反应产物的关联代谢物信息。

点击图上的相关代谢物的名称，可以跳转到相关代谢物的信息页面。



文献列表

  • Miwa Suzuki, Noriko Funasaka, Yuki Sato, Daiki Inamori, Yurie Watanabe, Miki Ozaki, Masayuki Hosono, Hideaki Shindo, Keiko Kawamura, Toshiyuki Tatsukawa, Motoi Yoshioka. Association of seasonal changes in circulating cortisol concentrations with the expression of cortisol biosynthetic enzymes and a glucocorticoid receptor in the blubber of common bottlenose dolphin. General and comparative endocrinology. 2024 Jun; 352(?):114516. doi: 10.1016/j.ygcen.2024.114516. [PMID: 38593942]
  • Chang Gao, Jiafeng Fu, Junyi Cui, Tingzhi Zhang, Christos C Zouboulis, Jing Wang, Shaowei Yan. Effects and Stress-Relieving Mechanisms of Dark Tea Polysaccharide in Human HaCaT Keratinocytes and SZ95 Sebocytes. Molecules (Basel, Switzerland). 2023 Aug; 28(16):. doi: 10.3390/molecules28166128. [PMID: 37630380]
  • Camille Pouchieu, Line Pourtau, Julie Brossaud, David Gaudout, Jean-Benoit Corcuff, Lucile Capuron, Nathalie Castanon, Pierre Philip. Acute Effect of a Saffron Extract (Safr'InsideTM) and Its Main Volatile Compound on the Stress Response in Healthy Young Men: A Randomized, Double Blind, Placebo-Controlled, Crossover Study. Nutrients. 2023 Jun; 15(13):. doi: 10.3390/nu15132921. [PMID: 37447245]
  • Rakesh Kumar Mishra, Anas Ahmad, Ajay Kumar, Aneesh Ali, Kanika, Chandrashekhar Jori, Shams Tabrez, Torki A Zughaibi, Majed N Almashjary, Syed Shadab Raza, Rehan Khan. Cortisone-loaded stearoyl ascorbic acid based nanostructured lipid carriers alleviate inflammatory changes in DSS-induced colitis. Biomaterials advances. 2023 May; 148(?):213383. doi: 10.1016/j.bioadv.2023.213383. [PMID: 36958119]
  • Yan Wu, Jianan Ma, Jinghui Shi, Shuting Cao, Jianmei Luo, Tingting Zheng, Min Wang. iTRAQ-Based Quantitative Proteomic Analysis of Arthrobacter simplex in Response to Cortisone Acetate and Its Mutants with Improved Δ1-Dehydrogenation Efficiency. Journal of agricultural and food chemistry. 2023 Apr; 71(16):6376-6388. doi: 10.1021/acs.jafc.3c00417. [PMID: 37043686]
  • Fasih Ullah Haider, Xiukang Wang, Usman Zulfiqar, Muhammad Farooq, Saddam Hussain, Tariq Mehmood, Muhammad Naveed, Yuelin Li, Cai Liqun, Qudsia Saeed, Ishtiaq Ahmad, Adnan Mustafa. Biochar application for remediation of organic toxic pollutants in contaminated soils; An update. Ecotoxicology and environmental safety. 2022 Dec; 248(?):114322. doi: 10.1016/j.ecoenv.2022.114322. [PMID: 36455351]
  • Kathy Tou, Adam Cawley, Christopher Bowen, Kireesan Sornalingam, Shanlin Fu. Measurements of hydrocortisone and cortisone for longitudinal profiling of equine plasma by liquid chromatography-tandem mass spectrometry. Drug testing and analysis. 2022 May; 14(5):943-952. doi: 10.1002/dta.3244. [PMID: 35195373]
  • Tuba Seven Menevse, Yasemin Kendir Demirkol, Busra Gurpinar Tosun, Elvan Bayramoglu, Melek Yildiz, Sezer Acar, Seda Erisen Karaca, Zerrin Orbak, Asan Onder, Elif Sobu, Ahmet Anık, Zeynep Atay, Fuat Bugrul, Ayse Derya Bulus, Korcan Demir, Durmus Dogan, Hamdi Cihan Emeksiz, Heves Kirmizibekmez, Nurhan Ozcan Murat, Akan Yaman, Serap Turan, Abdullah Bereket, Tulay Guran. Steroid Hormone Profiles and Molecular Diagnostic Tools in Pediatric Patients With non-CAH Primary Adrenal Insufficiency. The Journal of clinical endocrinology and metabolism. 2022 04; 107(5):e1924-e1931. doi: 10.1210/clinem/dgac016. [PMID: 35028661]
  • Yu Song, Luting Nie, Dandan Wei, Pengling Liu, Keliang Fan, Li Zhang, Mian Wang, Lulu Wang, Wei Liao, Ning Kang, Qingqing Xu, Juan Wang, Zhenxing Mao, Chongjian Wang, Wenqian Huo. Serum cortisol-to-cortisone ratio and 11-deoxycortisol are associated with hypertension and blood pressure in Chinese rural population: a cross sectional study. Journal of hypertension. 2022 03; 40(3):432-440. doi: 10.1097/hjh.0000000000003028. [PMID: 34670995]
  • Lisanne Rieker, Johannes Hofer, Golo Petzold, Volker Ellenrieder, Ahmad Amanzada. Induction of remission with tacrolimus in a patient with severe acute, cortisone refractory ulcerative colitis and severe Covid-19 pneumonia: a case report. BMC gastroenterology. 2022 Jan; 22(1):22. doi: 10.1186/s12876-022-02094-3. [PMID: 35033015]
  • Wang Lijing, Ke Sujie, Wang Linxi, Huang Lishan, Qi Liqin, Zhan Zhidong, Wu Kejun, Zhang Mengjun, Liu Xiaoying, Liu Xiaohong, Liu Libin. Altered Caffeine Metabolism Is Associated With Recurrent Hypoglycemia in Type 2 Diabetes Mellitus: A UPLC-MS-Based Untargeted Metabolomics Study. Frontiers in endocrinology. 2022; 13(?):843556. doi: 10.3389/fendo.2022.843556. [PMID: 35784552]
  • Annet Vulto, Martijn van Faassen, Michiel N Kerstens, André P van Beek. Susceptibility to Adrenal Crisis Is Associated With Differences in Cortisol Excretion in Patients With Secondary Adrenal Insufficiency. Frontiers in endocrinology. 2022; 13(?):849188. doi: 10.3389/fendo.2022.849188. [PMID: 35518935]
  • Valentina Morelli, Sofia Frigerio, Carmen Aresta, Elena Passeri, Flavia Pugliese, Massimilano Copetti, Anna Maria Barbieri, Silvia Fustinoni, Elisa Polledri, Sabrina Corbetta, Maura Arosio, Alfredo Scillitani, Iacopo Chiodini. Adrenalectomy Improves Blood Pressure and Metabolic Control in Patients With Possible Autonomous Cortisol Secretion: Results of a RCT. Frontiers in endocrinology. 2022; 13(?):898084. doi: 10.3389/fendo.2022.898084. [PMID: 35721734]
  • Soraya Puglisi, Marta Leporati, Eleonora Amante, Alice Parisi, Anna Rosa Pia, Paola Berchialla, Massimo Terzolo, Marco Vincenti, Giuseppe Reimondo. Limited Role of Hair Cortisol and Cortisone Measurement for Detecting Cortisol Autonomy in Patients With Adrenal Incidentalomas. Frontiers in endocrinology. 2022; 13(?):833514. doi: 10.3389/fendo.2022.833514. [PMID: 35222288]
  • Lixia Zhang, Xueyuan Li, Chong Li, Zhifang Wang, Lili Zheng, Guijun Qin, Shoujun Wang, Lijun Xu. Analysis of the Clinical Characteristics and Pituitary Function of Patients in Central China With Rathke's Cleft Cysts. Frontiers in endocrinology. 2022; 13(?):800135. doi: 10.3389/fendo.2022.800135. [PMID: 35295993]
  • G Mayne, E De Bloois, D Dabelea, U Christians. Development and validation of an LC-MS/MS assay for the quantification of allopregnanolone and its progesterone-derived isomers, precursors, and cortisol/cortisone in pregnancy. Analytical and bioanalytical chemistry. 2021 Sep; 413(21):5427-5438. doi: 10.1007/s00216-021-03523-0. [PMID: 34279681]
  • Alejandra Tapia-Castillo, Cristian A Carvajal, Xaviera López-Cortés, Andrea Vecchiola, Carlos E Fardella. Novel metabolomic profile of subjects with non-classic apparent mineralocorticoid excess. Scientific reports. 2021 08; 11(1):17156. doi: 10.1038/s41598-021-96628-6. [PMID: 34433879]
  • Pinar Gumus Balikcioglu, Metin Balikcioglu, Arlette Soros, Stuart Chalew. The 24-hour average concentration of cortisol is elevated in obese African-American youth with type 2 diabetes. Journal of diabetes and its complications. 2021 07; 35(7):107933. doi: 10.1016/j.jdiacomp.2021.107933. [PMID: 33902997]
  • Tania Pilli, Sandro Cardinale, Silvia Cantara, Gilda Dalmazio, Raffaella Forleo, Marco Capezzone, Cristian Bassi, Massimo Negrini, Manuela Ferracin, Maria Grazia Castagna. Preliminary results from whole-genome expression analysis in patients with secondary adrenal insufficiency treated with modified-release hydrocortisone. Endocrine. 2021 07; 73(1):177-185. doi: 10.1007/s12020-020-02578-w. [PMID: 33417142]
  • Janina Tokarz, Stefan M Schmitt, Gabriele Möller, André W Brändli, Jerzy Adamski. Functional characterization of two 20β-hydroxysteroid dehydrogenase type 2 homeologs from Xenopus laevis reveals multispecificity. The Journal of steroid biochemistry and molecular biology. 2021 06; 210(?):105874. doi: 10.1016/j.jsbmb.2021.105874. [PMID: 33722706]
  • Dandan Wei, Shanshan Li, Li Zhang, Pengling Liu, Keliang Fan, Luting Nie, Lulu Wang, Xiaotian Liu, Jian Hou, Songcheng Yu, Linlin Li, Tao Jing, Xing Li, Wenjie Li, Yuming Guo, Chongjian Wang, Wenqian Huo, Zhenxing Mao. Long-term exposure to PM1 and PM2.5 is associated with serum cortisone level and meat intake plays a moderation role. Ecotoxicology and environmental safety. 2021 Jun; 215(?):112133. doi: 10.1016/j.ecoenv.2021.112133. [PMID: 33740488]
  • Yepu He, Liyu Xu, Yanbing Li, Yinying Tang, Shuwen Rao, Rongtian Lin, Zhijun Liu, Heru Chen. Synergistic integration of dihydro-artemisinin with γ-aminobutyric acid results in a more potential anti-depressant. Bioorganic chemistry. 2021 05; 110(?):104769. doi: 10.1016/j.bioorg.2021.104769. [PMID: 33677247]
  • Giulia Carosi, Valentina Morelli, Giulia Del Sindaco, Andreea Liliana Serban, Arianna Cremaschi, Sofia Frigerio, Giulia Rodari, Eriselda Profka, Rita Indirli, Roberta Mungari, Veronica Resi, Emanuela Orsi, Emanuele Ferrante, Alessia Dolci, Claudia Giavoli, Maura Arosio, Giovanna Mantovani. Adrenal Insufficiency at the Time of COVID-19: A Retrospective Study in Patients Referring to a Tertiary Center. The Journal of clinical endocrinology and metabolism. 2021 03; 106(3):e1354-e1361. doi: 10.1210/clinem/dgaa793. [PMID: 34932807]
  • Stéphanie Espiard, Johanna McQueen, Mark Sherlock, Oskar Ragnarsson, Ragnhildur Bergthorsdottir, Pia Burman, Per Dahlqvist, Bertil Ekman, Britt Edén Engström, Stanko Skrtic, Jeanette Wahlberg, Paul M Stewart, Gudmundur Johannsson. Improved Urinary Cortisol Metabolome in Addison Disease: A Prospective Trial of Dual-Release Hydrocortisone. The Journal of clinical endocrinology and metabolism. 2021 03; 106(3):814-825. doi: 10.1210/clinem/dgaa862. [PMID: 33236103]
  • Julie Brossaud, Léa Charret, Delia De Angeli, Magalie Haissaguerre, Amandine Ferriere, Marie Puerto, Blandine Gatta-Cherifi, Jean-Benoît Corcuff, Antoine Tabarin. Hair cortisol and cortisone measurements for the diagnosis of overt and mild Cushing's syndrome. European journal of endocrinology. 2021 Mar; 184(3):445-454. doi: 10.1530/eje-20-1127. [PMID: 33449913]
  • Chisato Shimanoe, Akiko Matsumoto, Megumi Hara, Chiho Akao, Yuichiro Nishida, Mikako Horita, Hinako Nanri, Yasuki Higaki, Keitaro Tanaka. Perceived stress, depressive symptoms, and cortisol-to-cortisone ratio in spot urine in 6878 older adults. Psychoneuroendocrinology. 2021 03; 125(?):105125. doi: 10.1016/j.psyneuen.2020.105125. [PMID: 33429220]
  • Lahari Vuppaladhadiam, Jeannette Lager, Oliver Fiehn, Sandra Weiss, Margaret Chesney, Burcu Hasdemir, Aditi Bhargava. Human Placenta Buffers the Fetus from Adverse Effects of Perceived Maternal Stress. Cells. 2021 02; 10(2):. doi: 10.3390/cells10020379. [PMID: 33673157]
  • Joëlle C Schutten, Peter J Joris, Isidor Minović, Adrian Post, André P van Beek, Martin H de Borst, Ronald P Mensink, Stephan J L Bakker. Long-term magnesium supplementation improves glucocorticoid metabolism: A post-hoc analysis of an intervention trial. Clinical endocrinology. 2021 02; 94(2):150-157. doi: 10.1111/cen.14350. [PMID: 33030273]
  • Julie Brossaud, Jean-Benoît Corcuff, Vanessa Vautier, Aude Bergeron, Aurelie Valade, Anne Lienhardt, Marie-Pierre Moisan, Pascal Barat. Altered Cortisol Metabolism Increases Nocturnal Cortisol Bioavailability in Prepubertal Children With Type 1 Diabetes Mellitus. Frontiers in endocrinology. 2021; 12(?):742669. doi: 10.3389/fendo.2021.742669. [PMID: 34970219]
  • S J Weaver, P I Hynd, C R Ralph, J E Hocking Edwards, C L Burnard, E Narayan, A J Tilbrook. Chronic elevation of plasma cortisol causes differential expression of predominating glucocorticoid in plasma, saliva, fecal, and wool matrices in sheep. Domestic animal endocrinology. 2021 01; 74(?):106503. doi: 10.1016/j.domaniend.2020.106503. [PMID: 32846373]
  • L A Vaira, C Hopkins, A Sandison, A Manca, N Machouchas, D Turilli, J R Lechien, M R Barillari, G Salzano, A Cossu, S Saussez, G De Riu. Olfactory epithelium histopathological findings in long-term coronavirus disease 2019 related anosmia. The Journal of laryngology and otology. 2020 Dec; 134(12):1123-1127. doi: 10.1017/s0022215120002455. [PMID: 33190655]
  • Carina Ankarberg-Lindgren, Mats X Andersson, Jovanna Dahlgren. Determination of estrone sulfate, testosterone, androstenedione, DHEAS, cortisol, cortisone, and 17α-hydroxyprogesterone by LC-MS/MS in children and adolescents. Scandinavian journal of clinical and laboratory investigation. 2020 Dec; 80(8):672-680. doi: 10.1080/00365513.2020.1829699. [PMID: 33258387]
  • Gianmarco Stati, Silvia Sancilio, Mariangela Basile, Antonio Angelini, Roberta Di Pietro. Curcuma longa aqueous extract: A potential solution for the prevention of corneal scarring as a result of pterygium surgical excision (Review). International journal of molecular medicine. 2020 Dec; 46(6):1951-1957. doi: 10.3892/ijmm.2020.4738. [PMID: 33125502]
  • Magdalena Maciuszek, Katarzyna Klak, Leszek Rydz, B M Lidy Verburg-van Kemenade, Magdalena Chadzinska. Cortisol Metabolism in Carp Macrophages: A Role for Macrophage-Derived Cortisol in M1/M2 Polarization. International journal of molecular sciences. 2020 Nov; 21(23):. doi: 10.3390/ijms21238954. [PMID: 33255713]
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  • Joanne E Adaway, James M Hawley, Stephen J Lockhart, Brian G Keevil. Heat Inactivation of Saliva Samples for the Analysis of Cortisol and Cortisone during the COVID-19 Pandemic. The journal of applied laboratory medicine. 2020 Nov; 5(6):1413-1416. doi: 10.1093/jalm/jfaa158. [PMID: 32853331]
  • Tejas Kalaria, Mayuri Agarwal, Sukhbir Kaur, Lauren Hughes, Hayley Sharrod-Cole, Rahul Chaudhari, Carolina Gherman-Ciolac, Roopa Chopra, Victor Okeke, Clare Ford, Harit Buch, Rousseau Gama. Hypothalamic-pituitary-adrenal axis suppression - The value of salivary cortisol and cortisone in assessing hypothalamic-pituitary-adrenal recovery. Annals of clinical biochemistry. 2020 11; 57(6):456-460. doi: 10.1177/0004563220961745. [PMID: 32961064]
  • Vânia Brazão, Fabricia Helena Santello, Rafaela Pravato Colato, Andressa Duarte, Amanda Goulart, Pedro Alexandre Sampaio, Viviani Nardini, Carlos Arterio Sorgi, Lúcia Helena Faccioli, José Clóvis do Prado. Melatonin down-regulates steroidal hormones, thymocyte apoptosis and inflammatory cytokines in middle-aged T. cruzi infected rats. Biochimica et biophysica acta. Molecular basis of disease. 2020 11; 1866(11):165914. doi: 10.1016/j.bbadis.2020.165914. [PMID: 32768678]
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