Детерминанты ферроптоза – потенциальные предикторы и терапевтические мишени для острого миелоидного лейкоза

Обложка

Цитировать

Полный текст

Аннотация

Ферроптоз (ФП) – один из видов неапоптотической программируемой гибели клеток, связанной с железозависимым перекисным окислением липидов. при нем наблюдаются снижение активности глутатионпероксидазы 4 (GPX4), необходимой для подавления перекисного окисления липидов, накопление редокс-активного железа и окисление фосфолипидов клеточной мембраны, содержащих полиненасыщенные жирные кислоты. ФП играет главную роль в механизмах старения организма человека, регулируя дегенерацию – основную причину повреждения тканей и органной недостаточности. Он вносит значительный вклад в развитие возрастных патологий, включая нейроде генеративные состояния, сердечно-сосудистые заболевания и рак. Особый интерес представляет участие ФП в патогенезе возрастзависимых онкологических заболеваний, включая острый миелоидный лейкоз (ОМЛ). проведенные ранее исследования показывают, что ФП в значительной степени регулирует чувствительность клеток ОМЛ к химио терапевтическим препаратам, а некоторые из генов, связанные с ним, играют жизненно важную роль в онкогенезе ОМЛ. кроме того, представляют интерес исследования влияния иммунной инфильтрации на ФП и прогноз ОМЛ. Таким образом, углубленное изучение уникального механизма ФП при ОМЛ может дать новые представления о диагностике и лечении этого заболевания.

В данном обзоре проанализированы основные регуляторные молекулярные механизмы ФП и его взаимосвязь с возникновением и развитием ОМЛ. кроме того, обобщены последние достижения в изучении роли ФП в прогнозе и терапии данной патологии.

Об авторах

В. Е. Шевченко

ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава России

Автор, ответственный за переписку.
Email: vshev2015@yandex.ru
ORCID iD: 0000-0002-0401-9900

Валерий Евгеньевич Шевченко

115522 Москва, Каширское шоссе, 24

Россия

Т. И. Кушнир

ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава России

Email: fake@neicon.ru
ORCID iD: 0000-0001-9626-6847

115522 Москва, Каширское шоссе, 24

Россия

М. В. Гудкова

ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава России

Email: fake@neicon.ru
ORCID iD: 0000-0003-2694-5232

115522 Москва, Каширское шоссе, 24

Россия

Н. Е. Арноцкая

ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава России

Email: fake@neicon.ru
ORCID iD: 0000-0002-0154-8604

115522 Москва, Каширское шоссе, 24

Россия

Список литературы

  1. Shallis R.M., Wang R., Davidoff A. et al. Epidemiology of acute myeloid leukemia: recent progress and enduring challenges. Blood Rev 2019;36:70–87. doi: 10.1016/j.blre.2019.04.005
  2. Medinger M., Heim D., Halter J.P. et al. Diagnostik und therapie der akuten myeloischen leukämie. Ther Umsch 2019;76(9):481–6. doi: 10.1024/0040-5930/a001126
  3. Pelcovits A., Niroula R. Acute myeloid leukemia: a review. R I Med J (2013) 2020;103(3):38–40.
  4. Döhner H., Wei A.H., Löwenberg B. Towards precision medicine for AML. Nat Rev Clin Oncol 2021;18(9):577–90. doi: 10.1038/s41571-021-00509-w
  5. Ren Y., Mao X., Xu H. et al. Ferroptosis and EMT: key targets for combating cancer progression and therapy resistance. Cell Mol Life Sci 2023;80(9):263. doi: 10.1007/s00018-023-04907-4
  6. Zhang C., Liu X., Jin S. et al. Ferroptosis in cancer therapy: a novel approach to reversing drug resistance. Mol Cancer 2022;21(1):47. doi: 10.1186/s12943-022-01530-y
  7. Mou Y., Wang J., Wu J. et al. Ferroptosis, a new form of cell death: opportunities and challenges in cancer. J Hematol Oncol 2019;12(1):34. doi: 10.1186/s13045-019-0720-y
  8. Lei G., Zhuang L., Gan B. Targeting ferroptosis as a vulnerability in cancer. Nat Rev Cancer 2022;22(7):381–96. doi: 10.1038/s41568-022-00459-0
  9. Liang C., Zhang X., Yang M., Dong X. Recent progress in ferroptosis inducers for cancer therapy. Adv Mater 2019;31(51):e1904197. doi: 10.1002/adma.201904197
  10. Han C., Zheng J., Li F. et al. Novel prognostic signature for acute myeloid leukemia: bioinformatics analysis of combined CNV-driven and ferroptosis-related genes. Front Genet 2022;13:849437. doi: 10.3389/fgene.2022.849437
  11. Yu Y., Meng Y., Xu X. et al. A ferroptosis inducing and leukemic cell targeting drug nanocarrier formed by redox responsive cysteine polymer for acute myeloid leukemia therapy. ACS Nano 2023;17(4):3334–45. doi: 10.1021/acsnano.2c06313
  12. Борисова Л.М., Осипов В.Н., Голубева И.С. и др. Производные 3-гидроксихиназолина, аналоги эрастина, индуцируют ферроптоз в клетках карциномы молочной железы. Успехи молекулярной онкологии 2022;9(1):48–56. doi: 10.17650/2313-805X-2022-9-1-48-56
  13. Liang D., Minikes A.M., Jiang X. Ferroptosis at the intersection of lipid metabolism and cellular signaling. Mol Cell 2022;82(12): 2215–27. doi: 10.1016/j.molcel.2022.03.022
  14. Balihodzic A., Prinz F., Dengler M.A. et al. Non-coding RNAs and ferroptosis: potential implications for cancer therapy. Cell Death Differ 2022;29(6):1094–106. doi: 10.1038/s41418-022-00998-x
  15. Шевченко В.Е., Никифорова З.Н., Кушнир Т.И. и др.. Детерминанты ферроптоза – потенциальные терапевтические мишени стволовых клеток глиобластомы. Успехи молекулярной онкологии 2022;9(3):60–8. doi: 10.17650/2313-805X-2022-9-3-60-68
  16. Li J., Cao F., Yin H.L. et al. Ferroptosis: past, present and future. Cell Death Dis 2020;11:88. doi: 10.1038/s41419-020-2298-2
  17. Chen X., Li J., Kang R. et al. Ferroptosis: machinery and regulation. Autophagy 2021;17(9):2054–81. doi: 10.1080/15548627.2020.1810918
  18. Su Y., Zhao B., Zhou L. et al. Ferroptosis, a novel pharmacological mechanism of anti-cancer drugs. Cancer Lett 2020;483:127–36. doi: 10.1016/j.canlet.2020.02.015
  19. Tang D., Chen X., Kang R. et al. Ferroptosis: molecular mechanisms and health implications. Cell Res 2021;31(2):107–25. doi: 10.1038/s41422-020-00441-1
  20. Liu Y., Wan Y., Jiang Y. et al. GPX4: the hub of lipid oxidation, ferroptosis, disease and treatment. Biochim Biophys Acta Rev Cancer 2023;1878(3):188890. doi: 10.1016/j.bbcan.2023.188890
  21. Forcina G.C., Dixon S.J. GPX4 at the crossroads of lipid homeostasis and ferroptosis. Proteomics 2019;19(18):e1800311. doi: 10.1002/pmic.201800311
  22. Xing K., Bian X., Shi D. et al. miR-612 enhances RSL3-induced ferroptosis of hepatocellular carcinoma cells via mevalonate pathway. J Hepatocell Carcinoma 2023;10:2173–85. doi: 10.2147/JHC.S433332
  23. Ou M., Jiang Y., Ji Y. et al. Role and mechanism of ferroptosis in neurological diseases. Mol Metab 2022;61:101502. doi: 10.1016/j.molmet.2022.101502
  24. Noe R., Inglese N., Romani P. et al. Organic selenium induces ferroptosis in pancreatic cancer cells. Redox Biol 2023;68:102962. doi: 10.1016/j.redox.2023.102962
  25. Zheng J., Conrad M. The metabolic underpinnings of ferroptosis. Cell Metab 2020;32(6):920–37. doi: 10.1016/j.cmet.2020.10.011
  26. Park E., Chung S.W. ROS-mediated autophagy increases intracellular iron levels and ferroptosis by ferritin and transferrin receptor regulation. Cell Death Dis 2019;10(11):822. doi: 10.1038/s41419-019-2064-5
  27. Stockwell B.R. Ferroptosis turns 10: emerging mechanisms, physiological functions, and therapeutic applications. Cell 2022;185(14):2401–21. doi: 10.1016/j.cell.2022.06.003
  28. Fuhrmann D.C., Brune B. A graphical journey through iron metabolism, microRNAs and hypoxia in ferroptosis. Redox Biol 2022;54:102365. doi: 10.1016/j.redox.2022.102365
  29. Bayir H., Dixon S.J., Tyurina Y.Y. et al. Ferroptotic mechanisms and therapeutic targeting of iron metabolism and lipid peroxidation in the kidney. Nat Rev Nephrol 2023;19(5):315–36. doi: 10.1038/s41581-023-00689-x
  30. Grignano E., Birsen R., Chapuis N. From iron chelation to overload as a therapeutic strategy to induce ferroptosis in leukemic cells. Front Oncol 2020;10:586530. doi: 10.3389/fonc.2020.586530
  31. Zeng F., Nijiati S., Tang L. et al. Ferroptosis detection: from approaches to applications. Angew Chem Int Ed 2023;62(35):e202300379. doi: 10.1002/anie.202300379
  32. Chen X., Kang R., Kroemer G. et al. Broadening horizons: the role of ferroptosis in cancer. Nat Rev Clin Oncol 2021;18(5):280–96. doi: 10.1038/s41571-020-00462-0
  33. Koppula P., Zhuang L., Gan B. Cystine transporter SLC7A11/xCT in cancer: ferroptosis, nutrient dependency, and cancer therapy. Protein Cell 2021;12(8):599–620. doi: 10.1007/s13238-020-00789-5
  34. Sun X., Ou Z., Xie M. et al. HSPB1 as a novel regulator of ferroptotic cancer cell death. Oncogene 2015;34(45):5617–25. doi: 10.1038/onc.2015.32
  35. Xia J., Si H., Yao W. et al. Research progress on the mechanism of ferroptosis and its clinical application. Exp Cell Res 2021;409(2):112932. doi: 10.1016/j.yexcr.2021.112932
  36. Liu J., Zhang C., Wang J. et al. The regulation of ferroptosis by tumor suppressor p53 and its pathway. Int J Mol Sci 2020;21(21):8387. doi: 10.3390/ijms21218387
  37. Lei P., Bai T., Sun Y. Mechanisms of ferroptosis and relations with regulated cell death: a review. Front Physiol 2019;10:139. doi: 10.3389/fphys.2019.00139
  38. Xu R., Wang W., Zhang W. Ferroptosis and the bidirectional regulatory factor p53. Cell Death Discov 2023;9(1):197. doi: 10.1038/s41420-023-01517-8
  39. Wang H., Guo M., Wei H. et al. Targeting p53 pathways: mechanisms, structures and advances in therapy. Signal Transduct Target Ther 2023;8(1):92. doi: 10.1038/s41392-023-01347-1
  40. Liu Y., Gu W. p53 in ferroptosis regulation: the new weapon for the old guardian. Cell Death Differ 2022;29(5):895–910. doi: 10.1038/s41418-022-00943-y
  41. Gong D., Chen M., Wang Y. et al. Role of ferroptosis on tumor progression and immunotherapy. Cell Death Discov 2022;8(1):427. doi: 10.1038/s41420-022-01218-8
  42. Liu Y., Gu W. The complexity of p53-mediated metabolic regulation in tumor suppression. Semin Cancer Biol 2022;85:4–32. doi: 10.1016/j.semcancer.2021.03.010
  43. Gao Y., Zhang H., Wang J. et al. Annexin A5 ameliorates traumatic brain injury-induced neuroinflammation and neuronal ferroptosis by modulating the NF-κB/HMGB1 and Nrf2/HO-1 pathways. Int Immunopharmacol 2023;114:109619. doi: 10.1016/j.intimp.2022.109619
  44. Ursini F., Maiorino M. Lipid peroxidation and ferroptosis: the role of GSH and GPx4. Free Radic Biol Med 2020;152:175–85. doi: 10.1016/j.freeradbiomed.2020.02.027
  45. Li D., Li Y. The interaction between ferroptosis and lipid metabolism in cancer. Signal Transduct Target Ther 2020;5(1):108. doi: 10.1038/s41392-020-00216-5
  46. Pope L.E., Dixon S.J. Regulation of ferroptosis by lipid metabolism. Trends Cell Biol 2023;33(12):1077–87. doi: 10.1016/j.tcb.2023.05.003
  47. Zhao L., Zhou X., Xie F. et al. Ferroptosis in cancer and cancer immunotherapy. Cancer Commun (Lond) 2022;42(2):88–116. doi: 10.1002/cac2.12250
  48. Song X., Zhu S., Chen P. et al. AMPK-mediated BECN1 phosphorylation promotes ferroptosis by directly blocking system Xc-activity. Curr Biol 2018;28(15):2388–99. doi: 10.1016/j.cub.2018.05.094
  49. Farge T., Saland E., de Toni F. et al. Chemotherapy-resistant human acute myeloid leukemia cells are not enriched for leukemic stem cells but require oxidative metabolism. Cancer Discov 2017;7(7):716–35. doi: 10.1158/2159-8290.CD-16-0441
  50. Auberger P., Favreau C., Savy C. et al. Emerging role of glutathione peroxidase 4 in myeloid cell lineage development and acute myeloid leukemia. Cell Mol Biol Lett 2024;29(1):98. doi: 10.1186/s11658-024-00613-6
  51. Zhong X., Zhang Z., Shen H. et al. Hepatic NF-κB-inducing kinase and inhibitor of NF-κB kinase subunit α promote liver oxidative stress, ferroptosis, and liver injury. Hepatol Commun 2021;5(10):1704–20. doi: 10.1002/hep4.1757
  52. Rushworth S.A., Zaitseva L., Murray M.Y. et al. High Nrf2 expression in human acute myeloid leukemia is driven by NF-κB and underlies chemo-resistance. Blood 2012;120(26):5188–98. doi: 10.1182/blood-2012-04-422121
  53. Akiyama H., Zhao R., Ostermann L.B. et al. Mitochondrial regulation of GPX4 inhibition-mediated ferroptosis in acute myeloid leukemia. Leukemia 2024;38(4):729–40. doi: 10.1038/s41375-023-02117-2
  54. Pabst T., Kortz L., Fiedler G.M. et al. The plasma lipidome in acute myeloid leukemia at diagnosis in relation to clinical disease features. BBA Clin 2017;7:105–14. doi: 10.1016/j.bbacli.2017.03.002
  55. Yin Z., Li F., Zhou Q. et al. A ferroptosis-related gene signature and immune infiltration patterns predict the overall survival in acute myeloid leukemia patients. Front Mol Biosci 2022;9:959738. doi: 10.3389/fmolb.2022.959738
  56. Prada-Arismendy J., Arroyave J.C., Röthlisberger S. Molecular biomarkers in acute myeloid leukemia. Blood Rev 2017;31(1):63–76. doi: 10.1016/j.blre.2016.08.005
  57. Han C., Zheng J., Li F. et al. Novel prognostic signature for acute myeloid leukemia: bioinformatics analysis of combined CNV-driven and ferroptosis-related genes. Front Genet 2022;13:849437. doi: 10.3389/fgene.2022.849437
  58. Jiang B., Zhao Y., Shi M. et al. DNAJB6 promotes ferroptosis in esophageal squamous cell carcinoma. Dig Dis Sci 2020;65(7):1999–2008. doi: 10.1007/s10620-019-05929-4
  59. Meng E., Shevde L.A., Samant R.S. Retraction: Emerging roles and underlying molecular mechanisms of DNAJB6 in cancer. Oncotarget 2023;14:669. doi: 10.18632/oncotarget.28439
  60. Yan X.S., Sun Y.J., Du J. et al. Effects of ferroptosis-related gene HSPB1 on acute myeloid leukaemia. Int J Lab Hematol 2024;46(5):899–909. doi: 10.1111/ijlh.14319
  61. Ma Z., Ye W., Huang X. et al. The ferroptosis landscape in acute myeloid leukaemia. Aging (Albany NY) 2023;15(22):13486–503. doi: 10.18632/aging.205257
  62. Sun Q., Liu D., Cui W. et al. Cholesterol-mediated ferroptosis suppression reveals essential roles of coenzyme Q and squalene. Commun Biol 2023;6(1):1108. doi: 10.1038/s42003-023-05477-8
  63. Shi J., Wu P., Sheng L. et al. Ferroptosis-related gene signature predicts the prognosis of papillary thyroid carcinoma. Cancer Cell Int 2021;21(1):669. doi: 10.1186/s12935-021-02389-7
  64. Bhanot H., Weisberg E.L., Reddy M.M. et al. Acute myeloid leukemia cells require 6-phosphogluconate dehydrogenase for cell growth and NADPH-dependent metabolic reprogramming. Oncotarget 2017;8(40):67639–50. doi: 10.18632/oncotarget.18797
  65. Song Y., Tian S., Zhang P. et al. Construction and validation of a novel ferroptosis-related prognostic model for acute myeloid leukaemia. Front Genet 2021;12:708699. doi: 10.3389/fgene.2021.708699
  66. Dixon S.J., Patel D.N., Welsch M. et al. Pharmacological inhibition of cystine-glutamate exchange induces endoplasmic-reticulum stress and ferroptosis. eLife 2014;3:e02523. doi: 10.7554/eLife.02523
  67. Zhang X., Peng T., Li C. et al. Inhibition of CISD1 alleviates mitochondrial dysfunction and ferroptosis in mice with acute lung injury. Int Immunopharmacol 2024;130:111685. doi: 10.1016/j.intimp.2024.111685
  68. Xie Y., Zhu S., Song X. et al. The tumour suppressor p53 limits ferroptosis by blocking DPP4 activity. Cell Rep 2017;20(7):1692–704. doi: 10.1016/j.celrep.2017.07.055
  69. Kang R., Kroemer G., Tang D. The tumor suppressor protein p53 and the ferroptosis network. Free Radic Biol Med 2019;133:162–8. doi: 10.1016/j.freeradbiomed.2018.05.074
  70. Shin D., Kim E.H., Lee J. et al. Nrf2 inhibition reverses resistance to GPX4 inhibitor-induced ferroptosis in head and neck cancer. Free Radic Biol Med 2018;129:454–62. doi: 10.1016/j.freeradbiomed.2018.10.426
  71. Wei J., Nai G.Y., Dai Y. et al. Dipetidyl peptidase-4 and transferrin receptor serve as prognostic biomarkers for acute myeloid leukemia. Ann Transl Med 2021;9(17):1381. doi: 10.21037/atm-21-3368
  72. Wei J., Xie Q., Liu X. et al. Identification of the prognostic value of glutathione peroxidases expression levels in acute myeloid leukemia. Ann Transl Med 2020;8(11):678. doi: 10.21037/atm20 3296
  73. Zhang L., Song A., Yang Q.C. et al. Integration of AIEgens into covalent organic frameworks for pyroptosis- and ferroptosis-primed cancer immunotherapy. Nat Commun 2023;14(1):5355. doi: 10.1038/s41467-023-41121-z
  74. Wang J., Zhuo Z., Wang Y. et al. Identification and validation of a prognostic risk-scoring model based on ferroptosis-associated cluster in acute myeloid leukaemia. Front Cell Dev Biol 2021;9:800267. doi: 10.3389/fcell.2021.800267
  75. Ruvolo P.P., Ma H., Ruvolo V.R. et al. LGALS1 acts as a pro-survival molecule in AML. Biochim Biophys Acta Mol Cell Res 2020;1867(10):118785. doi: 10.1016/j.bbamcr.2020.118785
  76. Zhu W., Liu D., Lu Y. et al. PHKG2 regulates RSL3-induced ferroptosis in Helicobacter pylori-related gastric cancer. Arch Biochem Biophys 2023;740:109560. doi: 10.1016/j.abb.2023.109560
  77. Sabatier M., Birsen R., Lauture L. et al. C/EBPα confers dependence on fatty-acid anabolic pathways and vulnerability to lipid oxidative-stress-induced ferroptosis in FLT3-mutant leukaemia. Cancer Discov 2023;13(7):1720–47. doi: 10.1158/2159-8290.CD-22-0411
  78. Chen X., Hu S., Han Y. et al. Ferroptosis-related STEAP3 acts as predictor and regulator in diffuse large B-cell lymphoma through immune infiltration. Clin Exp Med 2023;23(6):2601–17. doi: 10.1007/s10238-023-00996-4
  79. Dai E., Han L., Liu J. et al. Ferroptotic damage promotes pancreatic tumourigenesis through a TMEM173/STING dependent DNA-sensor pathway. Nat Commun 2020;11(1):6339. doi: 10.1038/s41467-020-20154-8
  80. Sadeghi M., Moslehi A., Kheiry H. et al. The sensitivity of acute myeloid leukaemia cells to cytarabine is increased by suppressing the expression of heme oxygenase-1 and hypoxia-inducible factor 1α. Cancer Cell Int 2024;24(1):217. doi: 10.1186/s12935-024-03393-3
  81. Chen X., Song X., Li J. et al. Identification of HPCAL1 as a specific autophagy receptor involved in ferroptosis. Autophagy 2023;19(1):54–74. doi: 10.1080/15548627.2022.2059170
  82. Zhang H., Sun C., Sun Q. et al. Susceptibility of acute myeloid leukaemia cells to ferroptosis and evasion strategies. Front Mol Biosci 2023;10:1275774. doi: 10.3389/fmolb.2023.1275774
  83. Liu J., Kang R., Tang D. Signaling pathways and defence mechanisms of ferroptosis. FEBS J 2022;289(22):7038–50. doi: 10.1111/febs.16059
  84. Cui J., Wang Y., Tian X. et al. LPCAT3 is transcriptionally regulated by YAP/ZEB/EP300 and collaborates with ACSL4 and YAP to determine ferroptosis sensitivity. Antioxid Redox Signal 2023;39(7–9): 491–511. doi: 10.1089/ars.2023.0237
  85. Strickland S.A., Vey N. Diagnosis and treatment of therapy-related acute myeloid leukemia. Crit Rev Oncol Hematol 2022;171:103607. doi: 10.1016/j.critrevonc.2022.103607
  86. Roberts D., Langston A.A., Heffner L.T. Acute myeloid leukemia in young adults: does everyone need a transplant? J Oncol Pract 2019;15(6):315–20. doi: 10.1200/JOP.18.00574
  87. Li Q., Su R., Bao X. et al. Glycyrrhetinic acid nanoparticles combined with ferrotherapy for improved cancer immunotherapy. Acta Biomater 2022;144:109–20. doi: 10.1016/j.actbio.2022.03.030
  88. Diao J., Jia Y., Dai E. et al. Ferroptotic therapy in cancer: benefits, side effects, and risks. Mol Cancer 2024;23(1):89. doi: 10.1186/s12943-024-01999-9
  89. Su R., Dong L., Li Y. et al. Targeting FTO suppresses cancer stem cell maintenance and immune evasion. Cancer Cell 2020;38(1):79–96. doi: 10.1016/j.ccell.2020.04.017
  90. Wen Q., Liu J., Kang R. et al. The release and activity of HMGB1 in ferroptosis. Biochem Biophys Res Commun 2019;510(2):278–83. doi: 10.1016/j.bbrc.2019.01.090
  91. Chen G.Q., Benthani F.A., Wu J. et al. Artemisinin compounds sensitize cancer cells to ferroptosis by regulating iron homeostasis. Cell Death Differ 2020;27(1):242–54. doi: 10.1038/s41418-019-0352-3
  92. Zhu H.Y., Huang Z.X., Chen G.Q. et al. Typhaneoside prevents acute myeloid leukemia through suppressing proliferation and inducing ferroptosis associated with autophagy. Biochem Biophys Res Commun 2019;516(4):1265–71. doi: 10.1016/j.bbrc.2019.06.070
  93. Lai X., Sun Y., Zhang X. et al. Honokiol induces ferroptosis by upregulating HMOX1 in acute myeloid leukemia cells. Front Pharmacol 2022;13:897791. doi: 10.3389/fphar.2022.897791
  94. Bruedigam C., Porter A.H., Song A. et al. Imetelstat-mediated alterations in fatty acid metabolism to induce ferroptosis as a therapeutic strategy for acute myeloid leukemia. Nat Cancer 2024;5(1):47–65. doi: 10.1038/s43018-023-00653-5

Дополнительные файлы

Доп. файлы
Действие
1. JATS XML

© ,



СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 57560 от  08.04.2014.