Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Targeting HINT1 to improve synaptic plasticity: toward loganin as a new antidepressant strategy

Molecular Psychiatry volume 30, pages 3695–3707 (2025)Cite this article

Subjects

Abstract

Histidine triad nucleotide-binding protein 1 (HINT1) is related to depression. However, the underlying mechanisms and whether HINT1 is a therapeutic target for depression remain unclear. In this study, we report that loganin, an antidepressant candidate from our previous research, directly targets HINT1 to alleviate depressive-like behaviors. Overexpression of HINT1 in the hippocampus induces depressive-like behaviors. Mechanistically, HINT1 hinders sigma-1 receptor (Sigma-1R) binding to N-methyl-D-aspartate receptor (NMDAR), promotes  postsynaptic density protein (PSD95) binding to NMDAR, inhibits  brain derived neurotrophic factor (BDNF) signaling, and impairs synaptic plasticity. The interaction between HINT1 and NMDAR is disturbed by loganin. The antidepressant-like effects of loganin are reversed by HINT1 overexpression, Sigma-1R inhibitor and tropomyosin kinase receptor B (TrkB) inhibitor. These results not only indicate that HINT1 induces depression via impairing synaptic plasticity but also provide a candidate targeting HINT1 for depression therapy.

Zhang et al. reported that a natural compound, loganin, improves synaptic plasticity and reduces depressive-like behaviors via its direct target HINT1. Mechanistically, overexpressed HINT1 hinders NMDAR/Sigma-1R interactions and increases NMDAR/PSD95 interactions, and HINT1/NMDAR interactions are disrupted by loganin treatment.

Access through your institution
Buy or subscribe

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Loganin improves BDNF signaling and synaptic plasticity in neurons against CORT.
Fig. 2: HINT1 is the target of loganin.
Fig. 3: HINT1 modulating Sigma-1R/NMDAR and PSD95/NMDAR inhibits BDNF signaling and synaptic plasticity.
Fig. 4: Loganin inhibits HINT1/NMDAR complex.
Fig. 5: Sigma-1R and Trkb are required for the antidepressant-like effects of loganin.
Fig. 6: HINT1 is required for the antidepressant-like effects of loganin.

Similar content being viewed by others

Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request. Some data may not be made available because of privacy or ethical restrictions. Supplementary information is available at MP’s website.

References

  1. Herrman H, Kieling C, McGorry P, Horton R, Sargent J, Patel V. Reducing the global burden of depression: a lancet-world psychiatric association commission. Lancet. 2019;393:e42–3.

    Article  PubMed  Google Scholar 

  2. Otte C, Gold SM, Penninx BW, Pariante CM, Etkin A, Fava M, et al. Major depressive disorder. Nat Rev Dis Primers. 2016;2:16065.

    Article  PubMed  Google Scholar 

  3. Gaynes BN, Lux L, Gartlehner G, Asher G, Forman-Hoffman V, Green J, et al. Defining treatment-resistant depression. Depress Anxiety. 2020;37:134–45.

    Article  PubMed  Google Scholar 

  4. Kim JW, Suzuki K, Kavalali ET, Monteggia LM. Bridging rapid and sustained antidepressant effects of ketamine. Trends Mol Med. 2023;29:364–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Jha MK, Mathew SJ. Pharmacotherapies for treatment-resistant depression: how antipsychotics fit in the rapidly evolving therapeutic landscape. Am J Psychiatry. 2023;180:190–9.

    Article  PubMed  Google Scholar 

  6. Ling S, Ceban F, Lui LMW, Lee Y, Teopiz KM, Rodrigues NB, et al. Molecular mechanisms of psilocybin and implications for the treatment of depression. CNS Drugs. 2022;36:17–30.

    Article  CAS  PubMed  Google Scholar 

  7. Liu P, Liu Z, Wang J, Ma X, Dang Y. HINT1 in neuropsychiatric diseases: a potential neuroplastic mediator. Neural Plast. 2017;2017:5181925.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Dillenburg M, Smith J, Wagner CR. The many faces of histidine triad nucleotide binding protein 1 (HINT1). ACS Pharmacol Transl Sci. 2023;6:1310–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Barbier E, Wang JB. Anti-depressant and anxiolytic like behaviors in PKCI/HINT1 knockout mice associated with elevated plasma corticosterone level. BMC Neurosci. 2009;10:132.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Rodríguez-Muñoz M, Cortés-Montero E, Onetti Y, Sánchez-Blázquez P, Garzón-Niño J. The σ1 Receptor and the HINT1 protein control α2δ1 binding to glutamate NMDA receptors: implications in neuropathic pain. Biomolecules. 2021;11:1681.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Pabba M, Sibille E. Sigma-1 and N-Methyl-d-Aspartate receptors: a partnership with beneficial outcomes. Mol Neuropsychiatry. 2015;1:47–51.

    PubMed  PubMed Central  Google Scholar 

  12. Cai Q, Zeng M, Wu X, Wu H, Zhan Y, Tian R, et al. CaMKIIα-driven, phosphatase-checked postsynaptic plasticity via phase separation. Cell Res. 2021;31:37–51.

    Article  CAS  PubMed  Google Scholar 

  13. Zhang F, Yan Y, Zhang J, Li L, Wang YW, Xia CY, et al. Phytochemistry, synthesis, analytical methods, pharmacological activity, and pharmacokinetics of loganin: a comprehensive review. Phytother Res. 2022;36:2272–99.

    Article  CAS  PubMed  Google Scholar 

  14. Guo Y-X, Xia C-Y, Yan Y, Han Y, Shi R, He J, et al. Loganin improves chronic unpredictable mild stress-induced depressive-like behaviors and neurochemical dysfunction. J Ethnopharmacol. 2023;308:116288.

    Article  CAS  PubMed  Google Scholar 

  15. Pan CH, Xia CY, Yan Y, Han Y, Shi R, He J, et al. Loganin ameliorates depression-like behaviors of mice via modulation of serotoninergic system. Psychopharmacology (Berl). 2021;238:3063–70.

    Article  CAS  PubMed  Google Scholar 

  16. Shi R, Han Y, Yan Y, Qiao HY, He J, Lian WW, et al. Loganin exerts sedative and hypnotic effects via modulation of the serotonergic system and GABAergic neurons. Front Pharmacol. 2019;10:409.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Zhang WK, Xu JK, He J, Qiao HY, Ye XS Application of loganin in the preparation of drugs for the prevention and treatment of depression, anxiety and other mental disorders.

  18. Zhang WK, Xu JK, He J, Ye XS, Qiao HY, Pan XG A kind of preparation method of loganin raw material drug.

  19. Sun JD, Liu Y, Yuan YH, Li J, Chen NH. Gap junction dysfunction in the prefrontal cortex induces depressive-like behaviors in rats. Neuropsychopharmacology. 2012;37:1305–20.

    Article  CAS  PubMed  Google Scholar 

  20. Su SH, Wu YF, Lin Q, Wang DP, Hai J. URB597 protects against NLRP3 inflammasome activation by inhibiting autophagy dysfunction in a rat model of chronic cerebral hypoperfusion. J Neuroinflammation. 2019;16:260.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Cheng X, Yan J, Liu Y, Wang J, Taubert S. eVITTA: a web-based visualization and inference toolbox for transcriptome analysis. Nucleic Acids Res. 2021;49:W207–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Zhang X, Xu H, Bi X, Hou G, Liu A, Zhao Y, et al. Src acts as the target of matrine to inhibit the proliferation of cancer cells by regulating phosphorylation signaling pathways. Cell Death Dis. 2021;12:931.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Ye Z, Wang J, Fang F, Wang Y, Liu Z, Shen C, et al. Zhi-Zi-Hou-Po decoction alleviates depressive-like behavior and promotes hippocampal neurogenesis in chronic unpredictable mild stress induced mice via activating the BDNF/TrkB/CREB pathway. J Ethnopharmacol. 2024;319:117355.

    Article  CAS  PubMed  Google Scholar 

  24. Liaqat H, Parveen A, Kim SY. Antidepressive effect of natural products and their derivatives targeting BDNF-TrkB in Gut-Brain Axis. Int J Mol Sci. 2022;23:14968.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Zhou X, Chou TF, Aubol BE, Park CJ, Wolfenden R, Adams J, et al. Kinetic mechanism of human histidine triad nucleotide binding protein 1. Biochemistry. 2013;52:3588–600.

    Article  CAS  PubMed  Google Scholar 

  26. Rodríguez-Muñoz M, Sánchez-Blázquez P, Herrero-Labrador R, Martínez-Murillo R, Merlos M, Vela JM, et al. The σ1 receptor engages the redox-regulated HINT1 protein to bring opioid analgesia under NMDA receptor negative control. Antioxid Redox Signal. 2015;22:799–818.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Pabba M, Wong AY, Ahlskog N, Hristova E, Biscaro D, Nassrallah W, et al. NMDA receptors are upregulated and trafficked to the plasma membrane after sigma-1 receptor activation in the rat hippocampus. J Neurosci. 2014;34:11325–38.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Yang ZJ, Carter EL, Torbey MT, Martin LJ, Koehler RC. Sigma receptor ligand 4-phenyl-1-(4-phenylbutyl)-piperidine modulates neuronal nitric oxide synthase/postsynaptic density-95 coupling mechanisms and protects against neonatal ischemic degeneration of striatal neurons. Exp Neurol. 2010;221:166–74.

    Article  CAS  PubMed  Google Scholar 

  29. Szeszko PR, Lipsky R, Mentschel C, Robinson D, Gunduz-Bruce H, Sevy S, et al. Brain-derived neurotrophic factor val66met polymorphism and volume of the hippocampal formation. Mol Psychiatry. 2005;10:631–6.

    Article  CAS  PubMed  Google Scholar 

  30. Notaras M, van den Buuse M. Neurobiology of BDNF in fear memory, sensitivity to stress, and stress-related disorders. Mol Psychiatry. 2020;25:2251–74.

    Article  PubMed  Google Scholar 

  31. Castrén E, Monteggia LM. Brain-Derived neurotrophic factor signaling in depression and antidepressant action. Biol Psychiatry. 2021;90:128–36.

    Article  PubMed  Google Scholar 

  32. Thompson Ray M, Weickert CS, Wyatt E, Webster MJ. Decreased BDNF, trkB-TK+ and GAD67 mRNA expression in the hippocampus of individuals with schizophrenia and mood disorders. J Psychiatry Neurosci. 2011;36:195–203.

    Article  PubMed  Google Scholar 

  33. Taliaz D, Stall N, Dar DE, Zangen A. Knockdown of brain-derived neurotrophic factor in specific brain sites precipitates behaviors associated with depression and reduces neurogenesis. Mol Psychiatry. 2010;15:80–92.

    Article  CAS  PubMed  Google Scholar 

  34. Sun Z, Jia L, Shi D, He Y, Ren Y, Yang J, et al. Deep brain stimulation improved depressive-like behaviors and hippocampal synapse deficits by activating the BDNF/mTOR signaling pathway. Behav Brain Res. 2022;419:113709.

    Article  CAS  PubMed  Google Scholar 

  35. Larsen MH, Mikkelsen JD, Hay-Schmidt A, Sandi C. Regulation of brain-derived neurotrophic factor (BDNF) in the chronic unpredictable stress rat model and the effects of chronic antidepressant treatment. J Psychiatr Res. 2010;44:808–16.

    Article  PubMed  Google Scholar 

  36. Kowiański P, Lietzau G, Czuba E, Waśkow M, Steliga A, Moryś J. BDNF: a key factor with multipotent impact on brain signaling and synaptic plasticity. Cell Mol Neurobiol. 2018;38:579–93.

    Article  PubMed  Google Scholar 

  37. Yan XB, Hou HL, Wu LM, Liu J, Zhou JN. Lithium regulates hippocampal neurogenesis by ERK pathway and facilitates recovery of spatial learning and memory in rats after transient global cerebral ischemia. Neuropharmacology. 2007;53:487–95.

    Article  CAS  PubMed  Google Scholar 

  38. Vara H, Onofri F, Benfenati F, Sassoè-Pognetto M, Giustetto M. ERK activation in axonal varicosities modulates presynaptic plasticity in the CA3 region of the hippocampus through synapsin I. Proc Natl Acad Sci USA. 2009;106:9872–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Doucet MV, Harkin A, Dev KK. The PSD-95/nNOS complex: new drugs for depression? Pharmacol Ther. 2012;133:218–29.

    Article  CAS  PubMed  Google Scholar 

  40. Compans B, Camus C, Kallergi E, Sposini S, Martineau M, Butler C, et al. NMDAR-dependent long-term depression is associated with increased short term plasticity through autophagy mediated loss of PSD-95. Nat Commun. 2021;12:2849.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Xue SG, He JG, Lu LL, Song SJ, Chen MM, Wang F, et al. Enhanced TARP-γ8-PSD-95 coupling in excitatory neurons contributes to the rapid antidepressant-like action of ketamine in male mice. Nat Commun. 2023;14:7971.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Dang YH, Liu P, Ma R, Chu Z, Liu YP, Wang JB, et al. HINT1 is involved in the behavioral abnormalities induced by social isolation rearing. Neurosci Lett. 2015;607:40–5.

    Article  CAS  PubMed  Google Scholar 

  43. Liu F, Dong YY, Lei G, Zhou Y, Liu P, Dang YH. HINT1 is involved in the chronic mild stress elicited oxidative stress and apoptosis through the PKC ε/ALDH-2/4HNE pathway in prefrontal cortex of rats. Front Behav Neurosci. 2021;15:690344.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Martins-de-Souza D, Guest PC, Harris LW, Vanattou-Saifoudine N, Webster MJ, Rahmoune H, et al. Identification of proteomic signatures associated with depression and psychotic depression in post-mortem brains from major depression patients. Transl Psychiatry. 2012;2:e87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Zhou Y, Li SF, Deng LS, Ma YK, Lei G, Dang YH. HINT1 deficiency in aged mice reduces anxiety-like and depression-like behaviours and enhances cognitive performances. Exp Gerontol. 2022;159:111683.

    Article  CAS  PubMed  Google Scholar 

  46. Sun L, Liu P, Liu F, Zhou Y, Chu Z, Li Y, et al. Effects of Hint1 deficiency on emotional-like behaviors in mice under chronic immobilization stress. Brain Behav. 2017;7:e00831.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Jackson KJ, Wang JB, Barbier E, Chen X, Damaj MI. Acute behavioral effects of nicotine in male and female HINT1 knockout mice. Genes Brain Behav. 2012;11:993–1000.

    Article  CAS  PubMed  Google Scholar 

  48. Tian M, Stroebel D, Piot L, David M, Ye S, Paoletti P. GluN2A and GluN2B NMDA receptors use distinct allosteric routes. Nat Commun. 2021;12:4709.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Monyer H, Sprengel R, Schoepfer R, Herb A, Higuchi M, Lomeli H, et al. Heteromeric NMDA receptors: molecular and functional distinction of subtypes. Science. 1992;256:1217–21.

    Article  CAS  PubMed  Google Scholar 

  50. Gao M, Wu Y, Yang L, Chen F, Li L, Li Q, et al. Anti-depressant-like effect of fermented Gastrodia elata Bl. by regulating monoamine levels and BDNF/NMDAR pathways in mice. J Ethnopharmacol. 2023;301:115832.

    Article  CAS  PubMed  Google Scholar 

  51. Liu B, Du Y, Xu C, Liu Q, Zhang L. Antidepressant effects of repeated s-ketamine administration as NMDAR antagonist: involvement of CaMKIIα and mTOR signaling in the hippocampus of CUMS mice. Brain Res. 2023;1811:148375.

    Article  CAS  PubMed  Google Scholar 

  52. Ma S, Chen M, Jiang Y, Xiang X, Wang S, Wu Z, et al. Sustained antidepressant effect of ketamine through NMDAR trapping in the LHb. Nature. 2023;622:802–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Rodríguez-Muñoz M, Cortés-Montero E, Pozo-Rodrigálvarez A, Sánchez-Blázquez P, Garzón-Niño J. The ON:OFF switch, σ1R-HINT1 protein, controls GPCR-NMDA receptor cross-regulation: implications in neurological disorders. Oncotarget. 2015;6:35458–77.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Valkov E, Sharpe T, Marsh M, Greive S, Hyvönen M. Targeting protein-protein interactions and fragment-based drug discovery. Top Curr Chem. 2012;317:145–79.

    Article  CAS  PubMed  Google Scholar 

  55. Shi X, Zhou XZ, Chen G, Luo WF, Zhou C, He TJ, et al. Targeting the postsynaptic scaffolding protein PSD-95 enhances BDNF signaling to mitigate depression-like behaviors in mice. Sci Signal. 2024;17:eadn4556.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Luo CX, Lin YH, Qian XD, Tang Y, Zhou HH, Jin X, et al. Interaction of nNOS with PSD-95 negatively controls regenerative repair after stroke. J Neurosci. 2014;34:13535–48.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Fishback JA, Robson MJ, Xu Y-T, Matsumoto RR. Sigma receptors: potential targets for a new class of antidepressant drug. Pharmacol Ther. 2010;127:271–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Yang K, Sun T. The roles of chaperone proteins, sigma receptors, in Parkinson’s disease (PD) and major depressive disorder (MDD). Front Pharmacol. 2019;10:528.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Vavers E, Zvejniece L, Maurice T, Dambrova M. Allosteric modulators of sigma-1 receptor: a review. Front Pharmacol. 2019;10:223.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Liu X, Qu C, Shi S, Ye T, Wang L, Liu S, et al. The reversal effect of Sigma-1 receptor (S1R) agonist, SA4503, on atrial fibrillation after depression and its underlying mechanism. Front Physiol. 2019;10:1346.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Volz H-P, Stoll K. Clinical trials with sigma ligands. Pharmacopsychiatry. 2004;37:214–20.

    Article  Google Scholar 

  62. Di T, Zhang S, Hong J, Zhang T, Chen L. Hyperactivity of hypothalamic-pituitary-adrenal axis due to dysfunction of the hypothalamic glucocorticoid receptor in sigma-1 receptor knockout mice. Front Mol Neurosci. 2017;10:287.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Fujimoto M, Hayashi T, Urfer R, Mita S, Su T-P. Sigma-1 receptor chaperones regulate the secretion of brain-derived neurotrophic factor. Synapse. 2012;66:630–9.

    Article  CAS  PubMed  Google Scholar 

  64. Ji LL, Peng JB, Fu CH, Tong L, Wang ZY. Sigma-1 receptor activation ameliorates anxiety-like behavior through NR2A-CREB-BDNF signaling pathway in a rat model submitted to single-prolonged stress. Mol Med Rep. 2017;16:4987–93.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by National High Level & Elite Medical Professionals Project of China-Japan Friendship Hospital (2024-NHLHCRF-JBGS-WZ-07, 2023-NHLHCRF-CXYW-01, ZRJY2021-QM16, ZRJY2024-BJ01), National Natural Science Foundation of China (82474100, 82273815, 82273809, 82073731), and Beijing Key Laboratory of Mental Disorders (2022JSJB03).

Author information

Author notes

  1. These authors contributed equally: Congyuan Xia, Guoyan Zuo.

Authors and Affiliations

  1. Institute of Clinical Medical Sciences & Department of Pharmacy, China-Japan Friendship Hospital, Beijing, 100029, P. R. China

    Congyuan Xia, Honglin Xiang, Jun He & Weiku Zhang

  2. School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 100029, P. R. China

    Guoyan Zuo, Manni Wang, Yuming Wang, Yuxuan Guo, Yan Han & Jiekun Xu

  3. Department of Pharmacology, School of Medicine, Yale University, Connecticut, New Haven, USA

    Yungchi Cheng

Authors
  1. Congyuan Xia
    View author publications

    Search author on:PubMed Google Scholar

  2. Guoyan Zuo
    View author publications

    Search author on:PubMed Google Scholar

  3. Manni Wang
    View author publications

    Search author on:PubMed Google Scholar

  4. Yuming Wang
    View author publications

    Search author on:PubMed Google Scholar

  5. Yuxuan Guo
    View author publications

    Search author on:PubMed Google Scholar

  6. Yan Han
    View author publications

    Search author on:PubMed Google Scholar

  7. Honglin Xiang
    View author publications

    Search author on:PubMed Google Scholar

  8. Yungchi Cheng
    View author publications

    Search author on:PubMed Google Scholar

  9. Jiekun Xu
    View author publications

    Search author on:PubMed Google Scholar

  10. Jun He
    View author publications

    Search author on:PubMed Google Scholar

  11. Weiku Zhang
    View author publications

    Search author on:PubMed Google Scholar

Contributions

GY Zuo and YX Guo. performed the cellular and animal experiments. GY Zuo, MN Wang and YM Wang. wrote the manuscript. CY Xia and HL Xiang. performed bioinformatics analysis. GY Zuo, YM Wang and Y Han assisted with animal experiments and prepared mouse models. CY Xia, GY Zuo, YM Wang and MN Wang analyzed the data. WK Zhang, JK Xu., J He and, CY Xia provided the idea and designed the experiments. WK Zhang, JK Xu, J He, CY Xia and YC Cheng reviewed and checked the final paper. All the authors have read and approved the final paper.

Corresponding authors

Correspondence to Jiekun Xu, Jun He or Weiku Zhang.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xia, C., Zuo, G., Wang, M. et al. Targeting HINT1 to improve synaptic plasticity: toward loganin as a new antidepressant strategy. Mol Psychiatry 30, 3695–3707 (2025). https://doi.org/10.1038/s41380-025-02959-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41380-025-02959-5

Search

Advanced search

Quick links