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Blocking reverse electron transfer-mediated mitochondrial DNA oxidation rescues cells from PANoptosis

Acta Pharmacologica Sinica volume 45, pages 594–608 (2024)Cite this article

Abstract

PANoptosis is a new type of cell death featured with pyroptosis, apoptosis and necroptosis, and is implicated in organ injury and mortality in various inflammatory diseases, such as sepsis and hemophagocytic lymphohistiocytosis (HLH). Reverse electron transport (RET)-mediated mitochondrial reactive oxygen species (mtROS) has been shown to contribute to pyroptosis and necroptosis. In this study we investigated the roles of mtROS and RET in PANoptosis induced by TGF-β–activated kinase 1 (TAK1) inhibitor 5Z-7-oxozeaenol (Oxo) plus lipopolysaccharide (LPS) as well as the effects of anti-RET reagents on PANoptosis. We showed that pretreatment with anti-RET reagents 1-methoxy PMS (MPMS) or dimethyl fumarate (DMF) dose-dependently inhibited PANoptosis in macrophages BMDMs and J774A.1 cells induced by Oxo/LPS treatment assayed by propidium iodide (PI) staining. The three arms of the PANoptosis signaling pathway, namely pyroptosis, apoptosis and necroptosis signaling, as well as the formation of PANoptosomes were all inhibited by MPMS or DMF. We demonstrated that Oxo/LPS treatment induced RET and mtROS in BMDMs, which were reversed by MPMS or DMF pretreatment. Interestingly, the PANoptosome was co-located with mitochondria, in which the mitochondrial DNA was oxidized. MPMS and DMF fully blocked the mtROS production and the formation of PANoptosome induced by Oxo plus LPS treatment. An HLH mouse model was established by poly(I:C)/LPS challenge. Pretreatment with DMF (50 mg·kg−1·d−1, i.g. for 3 days) or MPMS (10 mg·kg−1·d−1, i.p. for 2 days) (DMF i.g. MPMS i.p.) effectively alleviated HLH lesions accompanied by decreased hallmarks of PANoptosis in the liver and kidney. Collectively, RET and mtDNA play crucial roles in PANoptosis induction and anti-RET reagents represent a novel class of PANoptosis inhibitors by blocking oxidation of mtDNA, highlighting their potential application in treating PANoptosis-related inflammatory diseases.

PANoptotic stimulation induces reverse electron transport (RET) and reactive oxygen species (ROS) in mitochondia, while 1-methoxy PMS and dimethyl fumarate can inhibit PANoptosis by suppressing RETmediated oxidation of mitochondrial DNA.

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Fig. 1: DMF inhibits PANoptosis induced by 5Z-7-oxozeaenol plus LPS in macrophages.
Fig. 2: MPMS, instead of WST-8, inhibits PANoptosis induced by 5Z-7-oxozeaenol (Oxo) plus LPS in macrophages.
Fig. 3: MPMS inhibits the signaling pathways of PANoptosis.
Fig. 4: MPMS and DMF inhibit the formation of PANoptosome induced by 5Z-7-oxozeaenol and LPS.
Fig. 5: DMF inhibits the signaling pathways of PANoptosis in RAW 264.7 cells.
Fig. 6: Anti-RET reagents inhibit reactive oxygen species (ROS) production and prevents the oxidization of mitochondrial DNA (mtDNA) induced by PANoptotic stimulation.
Fig. 7: MPMS alleviates HLH by abrogating PANoptosis.

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References

  1. Nössing C, Ryan KM. 50 years on and still very much alive: ‘apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics’. Br J Cancer. 2023;128:426–31.

    Article  PubMed  Google Scholar 

  2. de Vasconcelos NM, Van Opdenbosch N, Van Gorp H, Martín-Pérez R, Zecchin A, Vandenabeele P, et al. An apoptotic caspase network safeguards cell death induction in pyroptotic macrophages. Cell Rep. 2020;32:107959.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Christgen S, Zheng M, Kesavardhana S, Karki R, Malireddi RKS, Banoth B, et al. Identification of the panoptosome: a molecular platform triggering pyroptosis, apoptosis, and necroptosis (PANoptosis). Front Cell Infect Microbiol. 2020;10:237.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Christgen S, Tweedell RE, Kanneganti TD. Programming inflammatory cell death for therapy. Pharmacol Ther. 2022;232:108010.

    Article  CAS  PubMed  Google Scholar 

  5. He S, Liang Y, Shao F, Wang X. Toll-like receptors activate programmed necrosis in macrophages through a receptor-interacting kinase-3-mediated pathway. Proc Natl Acad Sci USA. 2011;108:20054–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Kaiser WJ, Sridharan H, Huang C, Mandal P, Upton JW, Gough PJ, et al. Toll-like receptor 3-mediated necrosis via TRIF,RIP3, and MLKL. J Biol Chem. 2013;288:31268–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Maelfait J, Liverpool L, Bridgeman A, Ragan KB, Upton JW, Rehwinkel J. Sensing of viral and endogenous RNA by ZBP1/DAI induces necroptosis. EMBO J. 2017;36:2529–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Sun L, Wang H, Wang Z, He S, Chen S, Liao D, et al. Mixed lineage kinase domain-like protein mediates necrosis signaling downstream of RIPK3 kinase. Cell. 2012;148:213–27.

    Article  CAS  PubMed  Google Scholar 

  9. Rübbelke M, Hamilton J, Binder F, Bauer M, King J, Nar H, et al. Discovery and structure-based optimization of fragments binding the mixed lineage kinase domain-like protein executioner domain. J Med Chem. 2021;64:15629–38.

    Article  PubMed  Google Scholar 

  10. Zhang T, Yin C, Boyd DF, Quarato G, Ingram JP, Shubina M, et al. Influenza virus Z-RNAs induce ZBP1-mediated necroptosis. Cell. 2020;180:1115–1129.e1113.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Kuriakose T, Man SM, Malireddi RK, Karki R, Kesavardhana S, Place DE, et al. ZBP1/DAI is an innate sensor of influenza virus triggering the NLRP3 inflammasome and programmed cell death pathways. Sci Immunol. 2016;1:aag2045.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Zheng M, Kanneganti TD. The regulation of the ZBP1-NLRP3 inflammasome and its implications in pyroptosis, apoptosis, and necroptosis (PANoptosis). Immunol Rev. 2020;297:26–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Roca FJ, Whitworth LJ, Prag HA, Murphy MP, Ramakrishnan L. Tumor necrosis factor induces pathogenic mitochondrial ROS in tuberculosis through reverse electron transport. Science. 2022;376:eabh2841.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Zhang Y, Su SS, Zhao S, Yang Z, Zhong CQ, Chen X, et al. RIP1 autophosphorylation is promoted by mitochondrial ros and is essential for RIP3 recruitment into necrosome. Nat Commun. 2017;8:14329.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Liu S, Liu H, Johnston A, Hanna-Addams S, Reynoso E, Xiang Y, et al. MLKL forms disulfide bond-dependent amyloid-like polymers to induce necroptosis. Proc Natl Acad Sci USA. 2017;114:E7450–e7459.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Weindel CG, Martinez EL, Zhao X, Mabry CJ, Bell SL, Vail KJ, et al. Mitochondrial ROS promotes susceptibility to infection via gasdermin D-mediated necroptosis. Cell. 2022;185:3214–3231.e3223.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Shi FL, Yuan LS, Wong TS, Li Q, Li YP, Xu R, et al. Dimethyl fumarate inhibits necroptosis and alleviates systemic inflammatory response syndrome by blocking the RIPK1-RIPK3-MLKL axis. Pharmacol Res. 2023;189:106697.

    Article  CAS  PubMed  Google Scholar 

  18. Karki R, Sharma BR, Tuladhar S, Williams EP, Zalduondo L, Samir P, et al. Synergism of TNF-α and IFN-γ triggers inflammatory cell death, tissue damage, and mortality in SARS-CoV-2 infection and cytokine shock syndromes. Cell. 2021;184:149–168.e117.

    Article  CAS  PubMed  Google Scholar 

  19. Yuan F, Cai J, Wu J, Tang Y, Zhao K, Liang F, et al. Z-DNA binding protein 1 promotes heatstroke-induced cell death. Science. 2022;376:609–15.

    Article  CAS  PubMed  Google Scholar 

  20. Griffin G, Shenoi S, Hughes GC. Hemophagocytic lymphohistiocytosis: an update on pathogenesis, diagnosis, and therapy. Best Pract Res Clin Rheumatol. 2020;34:101515.

    Article  PubMed  Google Scholar 

  21. Malireddi RKS, Gurung P, Kesavardhana S, Samir P, Burton A, Mummareddy H, et al. Innate immune priming in the absence of TAK1 drives RIPK1 kinase activity-independent pyroptosis, apoptosis, necroptosis, and inflammatory disease. J Exp Med. 2020;217:jem.20191644.

    Article  PubMed  Google Scholar 

  22. Mohamed MS, Bishr MK, Almutairi FM, Ali AG. Inhibitors of apoptosis: clinical implications in cancer. Apoptosis. 2017;22:1487–509.

    Article  CAS  PubMed  Google Scholar 

  23. Coll RC, Schroder K, Pelegrín P. NLRP3 and pyroptosis blockers for treating inflammatory diseases. Trends Pharmacol Sci. 2022;43:653–68.

    Article  CAS  PubMed  Google Scholar 

  24. Huang Z, Liang J, Chen S, Ng TK, Brelén ME, Liu Q, et al. RIP3-mediated microglial necroptosis promotes neuroinflammation and neurodegeneration in the early stages of diabetic retinopathy. Cell Death Dis. 2023;14:227.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Zhang H, Zhou L, Zhou Y, Wang L, Jiang W, Liu L, et al. Intermittent hypoxia aggravates non-alcoholic fatty liver disease via RIPK3-dependent necroptosis-modulated Nrf2/NFκB signaling pathway. Life Sci. 2021;285:119963.

    Article  CAS  PubMed  Google Scholar 

  26. Cao L, Mu W. Necrostatin-1 and necroptosis inhibition: pathophysiology and therapeutic implications. Pharmacol Res. 2021;163:105297.

    Article  CAS  PubMed  Google Scholar 

  27. Samir P, Malireddi RKS, Kanneganti TD. The panoptosome: a deadly protein complex driving Pyroptosis, Apoptosis, and Necroptosis (PANoptosis). Front Cell Infect Microbiol. 2020;10:238.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Li CG, Zeng QZ, Chen MY, Xu LH, Zhang CC, Mai FY, et al. Evodiamine augments NLRP3 inflammasome activation and anti-bacterial responses through inducing α-tubulin acetylation. Front Pharmacol. 2019;10:290.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Shi FL, Ni ST, Luo SQ, Hu B, Xu R, Liu SY, et al. Dimethyl fumarate ameliorates autoimmune hepatitis in mice by blocking NLRP3 inflammasome activation. Int Immunopharmacol. 2022;108:108867.

    Article  CAS  PubMed  Google Scholar 

  30. Zhong CS, Zeng B, Qiu JH, Xu LH, Zhong MY, Huang YT, et al. Gout-associated monosodium urate crystal-induced necrosis is independent of NLRP3 activity but can be suppressed by combined inhibitors for multiple signaling pathways. Acta Pharmacol Sin. 2022;43:1324–36.

    Article  CAS  PubMed  Google Scholar 

  31. Huang YT, Liang QQ, Zhang HR, Chen SY, Xu LH, Zeng B, et al. Baicalin inhibits necroptosis by decreasing oligomerization of phosphorylated MLKL and mitigates caerulein-induced acute pancreatitis in mice. Int Immunopharmacol. 2022;108:108885.

    Article  CAS  PubMed  Google Scholar 

  32. Hisada R, Yagi T. 1-methoxy-5-methylphenazinium methyl sulfate. A photochemically stable electron mediator between nadh and various electron acceptors. J Biochem. 1977;82:1469–73.

    Article  CAS  PubMed  Google Scholar 

  33. Chen J, Chen ZJ. PtdIns4P on dispersed trans-Golgi network mediates NLRP3 inflammasome activation. Nature. 2018;564:71–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Dubouchaud H, Walter L, Rigoulet M, Batandier C. Mitochondrial NADH redox potential impacts the reactive oxygen species production of reverse electron transfer through complex I. J Bioenerg Biomembr. 2018;50:367–77.

    Article  CAS  PubMed  Google Scholar 

  35. Xian H, Karin M. Oxidized mitochondrial DNA: a protective signal gone awry. Trends Immunol. 2023;44:188–200.

    Article  CAS  PubMed  Google Scholar 

  36. Messaoud-Nacer Y, Culerier E, Rose S, Maillet I, Rouxel N, Briault S, et al. STING agonist diABZI induces PANoptosis and DNA mediated acute respiratory distress syndrome (ARDS). Cell Death Dis. 2022;13:269.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Spinelli JB, Rosen PC, Sprenger HG, Puszynska AM, Mann JL, Roessler JM, et al. Fumarate is a terminal electron acceptor in the mammalian electron transport chain. Science. 2021;374:1227–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Wang YP, Sharda A, Xu SN, van Gastel N, Man CH, Choi U, et al. Malic enzyme 2 connects the krebs cycle intermediate fumarate to mitochondrial biogenesis. Cell Metab. 2021;33:1027–1041.e1028.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Kulkarni RA, Bak DW, Wei D, Bergholtz SE, Briney CA, Shrimp JH, et al. A chemoproteomic portrait of the oncometabolite fumarate. Nat Chem Biol. 2019;15:391–400.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Hooftman A, Peace CG, Ryan DG, Day EA, Yang M, McGettrick AF, et al. Macrophage fumarate hydratase restrains mtRNA-mediated interferon production. Nature. 2023;615:490–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Lin JF, Hu PS, Wang YY, Tan YT, Yu K, Liao K, et al. Phosphorylated NFS1 weakens oxaliplatin-based chemosensitivity of colorectal cancer by preventing PANoptosis. Signal Transduct Target Ther. 2022;7:54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Tong J, Lan XT, Zhang Z, Liu Y, Sun DY, Wang XJ, et al. Ferroptosis inhibitor liproxstatin-1 alleviates metabolic dysfunction-associated fatty liver disease in mice: potential involvement of PANoptosis. Acta Pharmacol Sin. 2022;44:1014–28.

    Article  PubMed  Google Scholar 

  43. Zeng Z, You M, Fan C, Rong R, Li H, Xia X. Pathologically high intraocular pressure induces mitochondrial dysfunction through Drp1 and leads to retinal ganglion cell PANoptosis in glaucoma. Redox Biol. 2023;62:102687.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Billingham LK, Stoolman JS, Vasan K, Rodriguez AE, Poor TA, Szibor M, et al. Mitochondrial electron transport chain is necessary for NLRP3 inflammasome activation. Nat Immunol. 2022;23:692–704.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Zhong Z, Liang S, Sanchez-Lopez E, He F, Shalapour S, Lin XJ, et al. New mitochondrial DNA synthesis enables NLRP3 inflammasome activation. Nature. 2018;560:198–203.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Shimada K, Crother TR, Karlin J, Dagvadorj J, Chiba N, Chen S, et al. Oxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis. Immunity. 2012;36:401–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Xian H, Watari K, Sanchez-Lopez E, Offenberger J, Onyuru J, Sampath H, et al. Oxidized DNA fragments exit mitochondria via mptp- and vdac-dependent channels to activate nlrp3 inflammasome and interferon signaling. Immunity. 2022;55:1370–1385.e1378.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Li L, Tan H, Zou Z, Gong J, Zhou J, Peng N, et al. Preventing necroptosis by scavenging ROS production alleviates heat stress-induced intestinal injury. Int J Hyperth. 2020;37:517–30.

    Article  CAS  Google Scholar 

  49. Saki M, Prakash A. DNA damage related crosstalk between the nucleus and mitochondria. Free Radic Biol Med. 2017;107:216–27.

    Article  CAS  PubMed  Google Scholar 

  50. Saada J, McAuley RJ, Marcatti M, Tang TZ, Motamedi M, Szczesny B. Oxidative stress induces z-DNA-binding protein 1-dependent activation of microglia via mtdna released from retinal pigment epithelial cells. J Biol Chem. 2022;298:101523.

    Article  CAS  PubMed  Google Scholar 

  51. Malireddi RKS, Kesavardhana S, Kanneganti TD. ZBP1 and TAK1: master regulators of NLRP3 inflammasome/Pyroptosis, Apoptosis, and Necroptosis (PAN-optosis). Front Cell Infect Microbiol. 2019;9:406.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Hao Y, Yang B, Yang J, Shi X, Yang X, Zhang D, et al. ZBP1: a powerful innate immune sensor and double-edged sword in host immunity. Int J Mol Sci. 2022;23:10224.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Enzan N, Matsushima S, Ikeda S, Okabe K, Ishikita A, Yamamoto T, et al. ZBP1 protects against mtdna-induced myocardial inflammation in failing hearts. Circ Res. 2023;132:1110–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Dang EV, McDonald JG, Russell DW, Cyster JG. Oxysterol restraint of cholesterol synthesis prevents AIM2 inflammasome activation. Cell. 2017;171:1057–1071.e1011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Subramanian N, Natarajan K, Clatworthy MR, Wang Z, Germain RN. The adaptor MAVS promotes NLRP3 mitochondrial localization and inflammasome activation. Cell. 2013;153:348–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Ichinohe T, Yamazaki T, Koshiba T, Yanagi Y. Mitochondrial protein mitofusin 2 is required for NLRP3 inflammasome activation after rna virus infection. Proc Natl Acad Sci USA. 2013;110:17963–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Iyer SS, He Q, Janczy JR, Elliott EI, Zhong Z, Olivier AK, et al. Mitochondrial cardiolipin is required for NLRP3 inflammasome activation. Immunity. 2013;39:311–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Xu Z, Zhang F, Sun F, Gu K, Dong S, He D. Dimethyl fumarate for multiple sclerosis. Cochrane Database Syst Rev. 2015;Cd011076.

  59. de Carvalho Ribeiro M, Szabo G. Role of the inflammasome in liver disease. Annu Rev Pathol. 2022;17:345–65.

    Article  PubMed  Google Scholar 

  60. Saidu NEB, Kavian N, Leroy K, Jacob C, Nicco C, Batteux F, et al. Dimethyl fumarate, a two-edged drug: Current status and future directions. Med Res Rev. 2019;39:1923–52.

    Article  PubMed  Google Scholar 

  61. Kirby B, Fletcher JM. Mechanism of action of dimethyl fumarate: a small molecule with big effects. Br J Dermatol. 2021;185:483–4.

    Article  CAS  PubMed  Google Scholar 

  62. Sales Conniff A, Encalada G, Patel S, Bhandary M, Al-Takrouri F, Heller L. Poly(I:C) transfection induces a pro-inflammatory cascade in murine mammary carcinoma and fibrosarcoma cells. RNA Biol. 2022;19:841–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Ng SK, Weissbach R, Ronson GE, Scadden AD. Proteins that contain a functional z-DNA-binding domain localize to cytoplasmic stress granules. Nucleic Acids Res. 2013;41:9786–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Fu Y, Comella N, Tognazzi K, Brown LF, Dvorak HF, Kocher O. Cloning of DLM-1, a novel gene that is up-regulated in activated macrophages, using RNA differential display. Gene. 1999;240:157–63.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (Nos. 81873064, 82274167, and 81773965), and Guangzhou Basic and Applied Basic Foundation (202201010725). We also thank Prof. Yong-tang Zheng (Kunming Institute of Zoology, Chinese Academy of Sciences) for his kindly help in this study.

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Authors and Affiliations

  1. Department of Immunobiology, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China

    Fu-li Shi, Qing Li, Rong Xu, Li-sha Yuan, Ying Chen, Ya-ping Li, Zhi-ya Zhou, Xian-hui He & Dong-yun Ou-yang

  2. Department of Fetal Medicine, the First Affiliated Hospital of Jinan University, Guangzhou, 510630, China

    Zi-jian Shi & Qing-bing Zha

  3. Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China

    Li-hui Xu

  4. Department of Clinical Laboratory, the Fifth Affiliated Hospital of Jinan University, Heyuan, 517000, China

    Qing-bing Zha & Xian-hui He

  5. Department of Nephrology, the First Affiliated Hospital of Jinan University, Guangzhou, 510630, China

    Bo Hu

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Contributions

DYOY, XHH, and BH designed this study. FLS, QL, RX,YC carry out the in vitro research. LSY, ZJS, YPL, ZYZ, LHX performed the animal model experiments. QBZ, FLS, DYOY, XHH and BH analyzed the data. DYOY, FLS and XHH prepared and edited the manuscript. DYOY and XHH conceived and supervised the project. All authors contributed to the article and approved the submitted version.

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Correspondence to Bo Hu, Xian-hui He or Dong-yun Ou-yang.

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Shi, Fl., Li, Q., Xu, R. et al. Blocking reverse electron transfer-mediated mitochondrial DNA oxidation rescues cells from PANoptosis. Acta Pharmacol Sin 45, 594–608 (2024). https://doi.org/10.1038/s41401-023-01182-8

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