Jean Chen Shih, PhD

TitleUniversity Professor
InstitutionUniversity of Southern California
DepartmentPharmacology and Pharmaceutical Sciences
AddressPSC 518
Health Sciences Campus
Los Angeles CA 90089-9121
Phone+1 323 442 1441
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    Dr. Shih received her B.S. in biochemistry from the National Taiwan University, where she graduated as the valedictorian. She earned her Ph.D. in biochemistry from a joint program at the University of California, Riverside (UCR) and Los Angeles (UCLA). Dr. Shih continued as a postdoctoral research fellow at UCLA and, in 1974, she joined the School of Pharmacy faculty at USC.

    She is currently a University Professor and holds the Boyd and Elsie Welin endowed chair. She is the founding Director of USC – Taiwan Center for Translational Research
    She has received numerous honors: She received two Research Scientist Awards and two MERIT awards from the National Institutes of Health (NIH), each providing a 10-year support to investigators whose research competence and productivity are distinctly superior and who are likely to continue to perform in an outstanding manner. The MERIT award is given to the top 1% investigators of the country. She is a Fellow of Academia Sinica, Taiwan , Fellow of the American College of Neuropsychopharmacology; a recipient of the Volwiler Research Achievement Award from the American Association of Colleges of Pharmacy (AACP); USC. Associates Award for Creativity in Research and Scholarship; among many others. A Distinguish Series Kaiser Lecturer at University of Hawaii.

    Dr. Shih is a member of the NIH study sections (Psycho Clinical Biology, 1984-88; Neurobiology, 1990-94; NICHD Mental Retardation Committee, 1997-2001). She is also a member of the International Brain Research Committee of the National Academy of Sciences (1995-2000). She is a current member and past president of the Society of Chinese Bioscientists in America (2002-2004). She is a mentor of American. NIH Director and Pioneer Award review committee (2011-2014).

    Research objectives in Shih Lab are to understand the roles of neurotransmitters on gene expression, signal transduction behaviors and ultimately diseases. They are studying the role of serotonin and dopamine in neuronal development, regulation of transcription factors in a series of monoamine oxidase (MAO) gene knock-out mice, which are animal models for anxiety, aggression and autistic-like-behavior and aggression. Recently, they showed these gene knockout mice also slowed down the progression and metastasis of prostate and brain cancers Thus provides unique animal models to study the interaction between tumors and microenvironment. Currently, Shih Lab used these KO mice model to develop novel targets for the treatment and early diagnosis of autistic-like behaviors and prostate and brain cancer.

    Recent work from the lab of Dr. Shih has shown that elimination of the gene that encodes monoamine oxidase (MAO) prevents the growth of prostate cancer in mice. As MAO is an important regulator of mood and motivation in the brain, there are already a number of drugs that effectively inhibit its function, called MAOI (MAO inhibitors), which are used clinically as antidepressants.Given the urgent and unmet need for more effective target-based therapies to significantly reduce the lethal outcome of prostate cancer, the repurposing of these drugs may represent a rapid and cost-effective solution. This presents an extraordinary opportunity to translate scientific discovery to patient therapies on an accelerated timeframe.

    Collapse Research 
    Collapse Research Activities and Funding
    NIH/NIMH R01MH067968Aug 1, 2004 - Jun 30, 2010
    Role: Principal Investigator
    NIH/NIMH K05MH000796Apr 1, 1989 - Apr 30, 2000
    Role: Principal Investigator
    Two Types of Monoamine Oxidase
    NIH/NIMH R01MH039085Sep 1, 1985 - Nov 30, 2014
    Role: Principal Investigator
    NIH/NIMH R37MH039085Sep 1, 1985 - Dec 28, 2008
    Role: Principal Investigator
    NIH/NIMH R01MH037020May 1, 1982 - Dec 31, 2003
    Role: Principal Investigator

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    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
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    1. Bortolato M, Floris G, Shih J. From aggression to autism: new perspectives on the behavioral sequelae of monoamine oxidase deficiency. J Neural Transm (Vienna). 2018 May 10. PMID: 29748850.
      View in: PubMed
    2. Chen K, Kardys A, Chen Y, Flink S, Tabakoff B, Shih J. Altered gene expression in early postnatal monoamine oxidase A knockout mice. Brain Res. 2017 Aug 15; 1669:18-26. PMID: 28535982.
      View in: PubMed
    3. Lin YC, Chang YT, Campbell M, Lin TP, Pan CC, Lee HC, Shih J, Chang PC. MAOA-a novel decision maker of apoptosis and autophagy in hormone refractory neuroendocrine prostate cancer cells. Sci Rep. 2017 Apr 12; 7:46338. PMID: 28402333.
      View in: PubMed
    4. Hintiryan H, Foster NN, Bowman I, Bay M, Song MY, Gou L, Yamashita S, Bienkowski MS, Zingg B, Zhu M, Yang XW, Shih J, Toga AW, Dong HW. The mouse cortico-striatal projectome. Nat Neurosci. 2016 08; 19(8):1100-14. PMID: 27322419.
      View in: PubMed
    5. Oanca G, Purg M, Mavri J, Shih J, Stare J. Insights into enzyme point mutation effect by molecular simulation: phenylethylamine oxidation catalyzed by monoamine oxidase A. Phys Chem Chem Phys. 2016 05 21; 18(19):13346-56. PMID: 27121693.
      View in: PubMed
    6. Kushal S, Wang W, Vaikari VP, Kota R, Chen K, Yeh TS, Jhaveri N, Groshen SL, Olenyuk BZ, Chen TC, Hofman FM, Shih J. Monoamine oxidase A (MAO A) inhibitors decrease glioma progression. Oncotarget. 2016 Mar 22; 7(12):13842-53. PMID: 26871599; PMCID: PMC4924682.
    7. Godar SC, Bortolato M, Richards SE, Li FG, Chen K, Wellman CL, Shih J. Monoamine Oxidase A is Required for Rapid Dendritic Remodeling in Response to Stress. Int J Neuropsychopharmacol. 2015 Apr 08; 18(9). PMID: 25857821; PMCID: PMC4576521.
    8. Wu JB, Lin TP, Gallagher JD, Kushal S, Chung LW, Zhau HE, Olenyuk BZ, Shih J. Monoamine oxidase A inhibitor-near-infrared dye conjugate reduces prostate tumor growth. J Am Chem Soc. 2015 Feb 18; 137(6):2366-74. PMID: 25585152.
      View in: PubMed
    9. Wu JB, Shao C, Li X, Li Q, Hu P, Shi C, Li Y, Chen YT, Yin F, Liao CP, Stiles BL, Zhau HE, Shih J, Chung LW. Monoamine oxidase A mediates prostate tumorigenesis and cancer metastasis. J Clin Invest. 2014 Jul; 124(7):2891-908. PMID: 24865426; PMCID: PMC4071401.
    10. Godar SC, Bortolato M, Castelli MP, Casti A, Casu A, Chen K, Ennas MG, Tambaro S, Shih J. The aggression and behavioral abnormalities associated with monoamine oxidase A deficiency are rescued by acute inhibition of serotonin reuptake. J Psychiatr Res. 2014 Sep; 56:1-9. PMID: 24882701; PMCID: PMC4114985.
    11. Bortolato M, Godar SC, Tambaro S, Li FG, Devoto P, Coba MP, Chen K, Shih J. Early postnatal inhibition of serotonin synthesis results in long-term reductions of perseverative behaviors, but not aggression, in MAO A-deficient mice. Neuropharmacology. 2013 Dec; 75:223-32. PMID: 23871843; PMCID: PMC3849223.
    12. Singh C, Bortolato M, Bali N, Godar SC, Scott AL, Chen K, Thompson RF, Shih J. Cognitive abnormalities and hippocampal alterations in monoamine oxidase A and B knockout mice. Proc Natl Acad Sci U S A. 2013 Jul 30; 110(31):12816-21. PMID: 23858446; PMCID: PMC3732950.
    13. Davis DA, Bortolato M, Godar SC, Sander TK, Iwata N, Pakbin P, Shih J, Berhane K, McConnell R, Sioutas C, Finch CE, Morgan TE. Prenatal exposure to urban air nanoparticles in mice causes altered neuronal differentiation and depression-like responses. PLoS One. 2013; 8(5):e64128. PMID: 23734187; PMCID: PMC3667185.
    14. Kaludercic N, Carpi A, Nagayama T, Sivakumaran V, Zhu G, Lai EW, Bedja D, De Mario A, Chen K, Gabrielson KL, Lindsey ML, Pacak K, Takimoto E, Shih J, Kass DA, Di Lisa F, Paolocci N. Monoamine oxidase B prompts mitochondrial and cardiac dysfunction in pressure overloaded hearts. Antioxid Redox Signal. 2014 Jan 10; 20(2):267-80. PMID: 23581564; PMCID: PMC3887464.
    15. Alzghoul L, Bortolato M, Delis F, Thanos PK, Darling RD, Godar SC, Zhang J, Grant S, Wang GJ, Simpson KL, Chen K, Volkow ND, Lin RC, Shih J. Altered cerebellar organization and function in monoamine oxidase A hypomorphic mice. Neuropharmacology. 2012 Dec; 63(7):1208-17. PMID: 22971542; PMCID: PMC3442946.
    16. Bortolato M, Godar SC, Alzghoul L, Zhang J, Darling RD, Simpson KL, Bini V, Chen K, Wellman CL, Lin RC, Shih J. Monoamine oxidase A and A/B knockout mice display autistic-like features. Int J Neuropsychopharmacol. 2013 May; 16(4):869-88. PMID: 22850464; PMCID: PMC3517692.
    17. Bortolato M, Godar SC, Melis M, Soggiu A, Roncada P, Casu A, Flore G, Chen K, Frau R, Urbani A, Castelli MP, Devoto P, Shih J. NMDARs mediate the role of monoamine oxidase A in pathological aggression. J Neurosci. 2012 Jun 20; 32(25):8574-82. PMID: 22723698; PMCID: PMC3417343.
    18. O'Leary RE, Shih J, Hyland K, Kramer N, Asher YJ, Graham JM. De novo microdeletion of Xp11.3 exclusively encompassing the monoamine oxidase A and B genes in a male infant with episodic hypotonia: a genomics approach to personalized medicine. Eur J Med Genet. 2012 May; 55(5):349-53. PMID: 22365943; PMCID: PMC3468330.
    19. Zhang J, Darling RD, Paul IA, Simpson KL, Chen K, Shih J, Lin RC. Altered expression of tyrosine hydroxylase in the locus coeruleus noradrenergic system in citalopram neonatally exposed rats and monoamine oxidase a knock out mice. Anat Rec (Hoboken). 2011 Oct; 294(10):1685-97. PMID: 21901841; PMCID: PMC3177426.
    20. Bortolato M, Chen K, Godar SC, Chen G, Wu W, Rebrin I, Farrell MR, Scott AL, Wellman CL, Shih J. Social deficits and perseverative behaviors, but not overt aggression, in MAO-A hypomorphic mice. Neuropsychopharmacology. 2011 Dec; 36(13):2674-88. PMID: 21832987; PMCID: PMC3230491.
    21. Wu JB, Shih J. Valproic acid induces monoamine oxidase A via Akt/forkhead box O1 activation. Mol Pharmacol. 2011 Oct; 80(4):714-23. PMID: 21775495; PMCID: PMC3187529.
    22. Wang ZQ, Chen K, Ying QL, Li P, Shih J. Monoamine oxidase A regulates neural differentiation of murine embryonic stem cells. J Neural Transm (Vienna). 2011 Jul; 118(7):997-1001. PMID: 21607742; PMCID: PMC3435112.
    23. Bonnin A, Goeden N, Chen K, Wilson ML, King J, Shih J, Blakely RD, Deneris ES, Levitt P. A transient placental source of serotonin for the fetal forebrain. Nature. 2011 Apr 21; 472(7343):347-50. PMID: 21512572; PMCID: PMC3084180.
    24. Li D, London SJ, Liu J, Lee W, Jiang X, Van Den Berg D, Bergen AW, Nishita D, Waleh N, Swan GE, Gallaher P, Chou CP, Shih J, Unger JB, Gauderman WJ, Gilliland F, Johnson CA, Conti DV. Association of the calcyon neuron-specific vesicular protein gene (CALY) with adolescent smoking initiation in China and California. Am J Epidemiol. 2011 May 01; 173(9):1039-48. PMID: 21415033; PMCID: PMC3121219.
    25. Shih J, Wu JB, Chen K. Transcriptional regulation and multiple functions of MAO genes. J Neural Transm (Vienna). 2011 Jul; 118(7):979-86. PMID: 21359973; PMCID: PMC3125068.
    26. Bortolato M, Shih J. Behavioral outcomes of monoamine oxidase deficiency: preclinical and clinical evidence. Int Rev Neurobiol. 2011; 100:13-42. PMID: 21971001; PMCID: PMC3371272.
    27. Godar SC, Bortolato M, Frau R, Dousti M, Chen K, Shih J. Maladaptive defensive behaviours in monoamine oxidase A-deficient mice. Int J Neuropsychopharmacol. 2011 Oct; 14(9):1195-207. PMID: 21156093; PMCID: PMC3435117.
    28. Chen K, Ou XM, Wu JB, Shih J. Transcription factor E2F-associated phosphoprotein (EAPP), RAM2/CDCA7L/JPO2 (R1), and simian virus 40 promoter factor 1 (Sp1) cooperatively regulate glucocorticoid activation of monoamine oxidase B. Mol Pharmacol. 2011 Feb; 79(2):308-17. PMID: 20980443; PMCID: PMC3033708.
    29. Cheng A, Scott AL, Ladenheim B, Chen K, Ouyang X, Lathia JD, Mughal M, Cadet JL, Mattson MP, Shih J. Monoamine oxidases regulate telencephalic neural progenitors in late embryonic and early postnatal development. J Neurosci. 2010 Aug 11; 30(32):10752-62. PMID: 20702706; PMCID: PMC2967387.
    30. Ou XM, Stockmeier CA, Meltzer HY, Overholser JC, Jurjus GJ, Dieter L, Chen K, Lu D, Johnson C, Youdim MB, Austin MC, Luo J, Sawa A, May W, Shih J. A novel role for glyceraldehyde-3-phosphate dehydrogenase and monoamine oxidase B cascade in ethanol-induced cellular damage. Biol Psychiatry. 2010 May 01; 67(9):855-63. PMID: 20022592; PMCID: PMC2854240.
    31. Kaludercic N, Takimoto E, Nagayama T, Feng N, Lai EW, Bedja D, Chen K, Gabrielson KL, Blakely RD, Shih J, Pacak K, Kass DA, Di Lisa F, Paolocci N. Monoamine oxidase A-mediated enhanced catabolism of norepinephrine contributes to adverse remodeling and pump failure in hearts with pressure overload. Circ Res. 2010 Jan 08; 106(1):193-202. PMID: 19910579; PMCID: PMC2804073.
    32. Yin HS, Chen K, Shih J, Tien TW. Down-regulated GABAergic expression in the olfactory bulb layers of the mouse deficient in monoamine oxidase B and administered with amphetamine. Cell Mol Neurobiol. 2010 May; 30(4):511-9. PMID: 19902350; PMCID: PMC2875355.
    33. Bortolato M, Godar SC, Davarian S, Chen K, Shih J. Behavioral disinhibition and reduced anxiety-like behaviors in monoamine oxidase B-deficient mice. Neuropsychopharmacology. 2009 Dec; 34(13):2746-57. PMID: 19710633; PMCID: PMC2783894.
    34. Wu JB, Chen K, Li Y, Lau YF, Shih J. Regulation of monoamine oxidase A by the SRY gene on the Y chromosome. FASEB J. 2009 Nov; 23(11):4029-38. PMID: 19661285; PMCID: PMC2775015.
    35. Ou XM, Lu D, Johnson C, Chen K, Youdim MB, Rajkowska G, Shih J. Glyceraldehyde-3-phosphate dehydrogenase-monoamine oxidase B-mediated cell death-induced by ethanol is prevented by rasagiline and 1-R-aminoindan. Neurotox Res. 2009 Aug; 16(2):148-59. PMID: 19526291; PMCID: PMC2862453.
    36. Wu JB, Chen K, Ou XM, Shih J. Retinoic acid activates monoamine oxidase B promoter in human neuronal cells. J Biol Chem. 2009 Jun 19; 284(25):16723-35. PMID: 19401466; PMCID: PMC2719307.
    37. Bortolato M, Chen K, Shih J. Monoamine oxidase inactivation: from pathophysiology to therapeutics. Adv Drug Deliv Rev. 2008 Oct-Nov; 60(13-14):1527-33. PMID: 18652859; PMCID: PMC2630537.
    38. Scott AL, Bortolato M, Chen K, Shih J. Novel monoamine oxidase A knock out mice with human-like spontaneous mutation. Neuroreport. 2008 May 07; 19(7):739-43. PMID: 18418249; PMCID: PMC3435113.
    39. Guo G, Ou XM, Roettger M, Shih J. The VNTR 2 repeat in MAOA and delinquent behavior in adolescence and young adulthood: associations and MAOA promoter activity. Eur J Hum Genet. 2008 May; 16(5):626-34. PMID: 18212819; PMCID: PMC2922855.
    40. Shih J. Monoamine oxidases: from tissue homogenates to transgenic mice. Neurochem Res. 2007 Oct; 32(10):1757-61. PMID: 17551828.
      View in: PubMed
    41. Yin HS, Chen K, Kalpana S, Shih J. Differential effects of chronic amphetamine and baclofen administration on cAMP levels and phosphorylation of CREB in distinct brain regions of wild type and monoamine oxidase B-deficient mice. Synapse. 2006 Dec 15; 60(8):573-84. PMID: 16983645.
      View in: PubMed
    42. Chen K, Cases O, Rebrin I, Wu W, Gallaher TK, Seif I, Shih J. Forebrain-specific expression of monoamine oxidase A reduces neurotransmitter levels, restores the brain structure, and rescues aggressive behavior in monoamine oxidase A-deficient mice. J Biol Chem. 2007 Jan 05; 282(1):115-23. PMID: 17090537; PMCID: PMC2844870.
    43. Guo G, Roettger ME, Shih J. Contributions of the DAT1 and DRD2 genes to serious and violent delinquency among adolescents and young adults. Hum Genet. 2007 Mar; 121(1):125-36. PMID: 17120049.
      View in: PubMed
    44. Wang TJ, Huang SY, Lin WW, Lo HY, Wu PL, Wang YS, Wu YS, Ko HC, Shih J, Lu RB. Possible interaction between MAOA and DRD2 genes associated with antisocial alcoholism among Han Chinese men in Taiwan. Prog Neuropsychopharmacol Biol Psychiatry. 2007 Jan 30; 31(1):108-14. PMID: 17007976.
      View in: PubMed
    45. Agatsuma S, Lee M, Zhu H, Chen K, Shih J, Seif I, Hiroi N. Monoamine oxidase A knockout mice exhibit impaired nicotine preference but normal responses to novel stimuli. Hum Mol Genet. 2006 Sep 15; 15(18):2721-31. PMID: 16893910.
      View in: PubMed
    46. Ou XM, Chen K, Shih J. Monoamine oxidase A and repressor R1 are involved in apoptotic signaling pathway. Proc Natl Acad Sci U S A. 2006 Jul 18; 103(29):10923-8. PMID: 16829576; PMCID: PMC1544150.
    47. Ou XM, Chen K, Shih J. Glucocorticoid and androgen activation of monoamine oxidase A is regulated differently by R1 and Sp1. J Biol Chem. 2006 Jul 28; 281(30):21512-25. PMID: 16728402.
      View in: PubMed
    48. Squires LN, Jakubowski JA, Stuart JN, Rubakhin SS, Hatcher NG, Kim WS, Chen K, Shih J, Seif I, Sweedler JV. Serotonin catabolism and the formation and fate of 5-hydroxyindole thiazolidine carboxylic acid. J Biol Chem. 2006 May 12; 281(19):13463-70. PMID: 16537538.
      View in: PubMed
    49. Zhang Z, Chen K, Shih J, Teng CT. Estrogen-related receptors-stimulated monoamine oxidase B promoter activity is down-regulated by estrogen receptors. Mol Endocrinol. 2006 Jul; 20(7):1547-61. PMID: 16484337.
      View in: PubMed
    50. Yi H, Akao Y, Maruyama W, Chen K, Shih J, Naoi M. Type A monoamine oxidase is the target of an endogenous dopaminergic neurotoxin, N-methyl(R)salsolinol, leading to apoptosis in SH-SY5Y cells. J Neurochem. 2006 Jan; 96(2):541-9. PMID: 16336631.
      View in: PubMed
    51. Chen K, Ou XM, Chen G, Choi SH, Shih J. R1, a novel repressor of the human monoamine oxidase A. J Biol Chem. 2005 Mar 25; 280(12):11552-9. PMID: 15654081; PMCID: PMC2861901.
    52. Yeung Lam P, Chen K, Shih J. The circadian rhythm of 5-HT biosynthetic and degradative enzymes in immortalized mouse neuroendocrine pineal cell line--a model for studying circadian rhythm. Life Sci. 2004 Nov 05; 75(25):3017-26. PMID: 15474553.
      View in: PubMed
    53. Shih J, Chen K. Regulation of MAO-A and MAO-B gene expression. Curr Med Chem. 2004 Aug; 11(15):1995-2005. PMID: 15279563.
      View in: PubMed
    54. Chen K, Holschneider DP, Wu W, Rebrin I, Shih J. A spontaneous point mutation produces monoamine oxidase A/B knock-out mice with greatly elevated monoamines and anxiety-like behavior. J Biol Chem. 2004 Sep 17; 279(38):39645-52. PMID: 15272015; PMCID: PMC2861902.
    55. Maragos WF, Young KL, Altman CS, Pocernich CB, Drake J, Butterfield DA, Seif I, Holschneider DP, Chen K, Shih J. Striatal damage and oxidative stress induced by the mitochondrial toxin malonate are reduced in clorgyline-treated rats and MAO-A deficient mice. Neurochem Res. 2004 Apr; 29(4):741-6. PMID: 15098936.
      View in: PubMed
    56. Ou XM, Chen K, Shih J. Dual functions of transcription factors, transforming growth factor-beta-inducible early gene (TIEG)2 and Sp3, are mediated by CACCC element and Sp1 sites of human monoamine oxidase (MAO) B gene. J Biol Chem. 2004 May 14; 279(20):21021-8. PMID: 15024015.
      View in: PubMed
    57. Shih J. Cloning, after cloning, knock-out mice, and physiological functions of MAO A and B. Neurotoxicology. 2004 Jan; 25(1-2):21-30. PMID: 14697877.
      View in: PubMed
    58. Vitalis T, Alvarez C, Chen K, Shih J, Gaspar P, Cases O. Developmental expression pattern of monoamine oxidases in sensory organs and neural crest derivatives. J Comp Neurol. 2003 Sep 22; 464(3):392-403. PMID: 12900932.
      View in: PubMed
    59. Wong WK, Chen K, Shih J. Decreased methylation and transcription repressor Sp3 up-regulated human monoamine oxidase (MAO) B expression during Caco-2 differentiation. J Biol Chem. 2003 Sep 19; 278(38):36227-35. PMID: 12855685.
      View in: PubMed
    60. Lu RB, Lin WW, Lee JF, Ko HC, Shih J. Neither antisocial personality disorder nor antisocial alcoholism is associated with the MAO-A gene in Han Chinese males. Alcohol Clin Exp Res. 2003 Jun; 27(6):889-93. PMID: 12824808.
      View in: PubMed
    61. Wong WK, Ou XM, Chen K, Shih J. Activation of human monoamine oxidase B gene expression by a protein kinase C MAPK signal transduction pathway involves c-Jun and Egr-1. J Biol Chem. 2002 Jun 21; 277(25):22222-30. PMID: 11956220; PMCID: PMC2861899.
    62. Lu RB, Lee JF, Ko HC, Lin WW, Chen K, Shih J. No association of the MAOA gene with alcoholism among Han Chinese males in Taiwan. Prog Neuropsychopharmacol Biol Psychiatry. 2002 Apr; 26(3):457-61. PMID: 11999895.
      View in: PubMed
    63. Geha RM, Chen K, Wouters J, Ooms F, Shih J. Analysis of conserved active site residues in monoamine oxidase A and B and their three-dimensional molecular modeling. J Biol Chem. 2002 May 10; 277(19):17209-16. PMID: 11861643; PMCID: PMC2844881.
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