{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T07:31:00Z","timestamp":1785915060824,"version":"3.56.0"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2026,3,24]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Tissue-specific regulatory T cells (Tregs) accumulate in the heart after myocardial infarction (MI) and play a vital role in limiting inflammation and promoting tissue repair. However, the developmental trajectory of heart Tregs and the molecular cues that guide their recruitment to the heart remain poorly understood, impeding therapeutic strategies that leverage Treg-mediated cardiac protection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>\n                      We used single-cell and bulk RNA sequencing in a murine MI model to delineate the differentiation trajectory of Tregs from mediastinal lymph nodes to the heart. Functional validation was performed using Treg-specific\n                      <jats:italic toggle=\"yes\">Ccr8<\/jats:italic>\n                      (CC motif chemokine receptor 8) knockout mice (\n                      <jats:italic toggle=\"yes\">Ccr8<\/jats:italic>\n                      <jats:sup>flox\/flox<\/jats:sup>\n                      <jats:italic toggle=\"yes\">Foxp3<\/jats:italic>\n                      <jats:sup>Cre<\/jats:sup>\n                      ),\n                      <jats:italic toggle=\"yes\">Ccl1<\/jats:italic>\n                      (CC motif chemokine ligand 1) knockout mice (\n                      <jats:italic toggle=\"yes\">Ccl1<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      ), macrophage-targeted\n                      <jats:italic toggle=\"yes\">Ccl1<\/jats:italic>\n                      knockdown mice,\n                      <jats:italic toggle=\"yes\">Ccl1<\/jats:italic>\n                      -overexpressing mice, and DEREG mice. The CCL1-CCR8 axis was evaluated in cardiac tissues and circulating blood from patients with MI.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      Single-cell RNA sequencing revealed a stepwise differentiation of mediastinal lymph node\u2013derived naive Tregs into heart Tregs, marked by the progressive acquisition of CCR8 expression and reparative capacity. CCR8\n                      <jats:sup>+<\/jats:sup>\n                      Tregs in the heart exhibited enhanced immunosuppressive and tissue-repair signatures. Treg-specific\n                      <jats:italic toggle=\"yes\">Ccr8<\/jats:italic>\n                      deletion led to reduced Treg accumulation and worsened cardiac function after MI, along with increased proinflammatory macrophage features and number of CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells and natural killer cells. In addition, Tregs promoted a shift of macrophages toward an anti-inflammatory phenotype by secreting IL-1R2 (interleukin 1 receptor, type 2). We identified cardiac macrophages as the main source of CCL1, which was essential for CCR8\n                      <jats:sup>+<\/jats:sup>\n                      Treg recruitment.\n                      <jats:italic toggle=\"yes\">Ccl1<\/jats:italic>\n                      deficiency or macrophage-specific\n                      <jats:italic toggle=\"yes\">Ccl1<\/jats:italic>\n                      knockdown impaired Treg infiltration and aggravated ventricular remodeling;\n                      <jats:italic toggle=\"yes\">Ccl1<\/jats:italic>\n                      overexpression promoted Treg recruitment and improved cardiac outcomes. Moreover, the cardioprotective effects of CCL1 were abolished in DEREG mice upon Treg depletion and\n                      <jats:italic toggle=\"yes\">Ccr8<\/jats:italic>\n                      <jats:sup>flox\/flox<\/jats:sup>\n                      <jats:italic toggle=\"yes\">Foxp3<\/jats:italic>\n                      <jats:sup>Cre<\/jats:sup>\n                      mice, establishing a CCR8\n                      <jats:sup>+<\/jats:sup>\n                      Treg-dependent mechanism. Furthermore, circulating CCR8\n                      <jats:sup>+<\/jats:sup>\n                      Tregs and cardiac CCL1 were elevated in humans with MI, and the presence of CCR8\n                      <jats:sup>+<\/jats:sup>\n                      Tregs and CCL1-expressing macrophages was confirmed in the hearts of patients with MI, suggesting important clinical relevance.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>Our findings reveal a 2-phase Treg specialization process and establish the CCL1-CCR8 axis as a crucial pathway for Treg recruitment and function in the infarcted heart. Therapeutic targeting of this axis may improve immune-regulated cardiac repair after MI.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.125.076426","type":"journal-article","created":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T10:00:14Z","timestamp":1770976814000},"page":"922-940","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":6,"title":["CCR8 Expression on Regulatory T Cells Reveals Trajectories of Tissue Adaptation and Protects Against Myocardial Infarction\u2013Induced Tissue Damage"],"prefix":"10.1161","volume":"153","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9933-8674","authenticated-orcid":true,"given":"Nana","family":"Li","sequence":"first","affiliation":[{"name":"Department of Cardiology (N.L., Z.H., H.Y., M.L., J.H., R.G., Y.S., Z.C., Y.L., T.T., M.Z., J.J., F.Y., J.L., M.G., N.X., X.C.), Huazhong University of Science and Technology, Wuhan, Hubei, China."},{"name":"Hubei Key Laboratory of Biological Targeted Therapy (N.L., Z.H., H.Y., M.L., J.H., R.G., Y.S., Z.C., Y.L., T.T., M.Z., J.J., F.Y., J.L., M.G., N.X., X.C.), Huazhong University of Science and Technology, Wuhan, Hubei, China."},{"name":"Hubei Engineering Research Center for Immunological Diagnosis and Therapy of Cardiovascular Diseases (N.L., Z.H., H.Y., M.L., J.H., R.G., Y.S., Z.C., Y.L., T.T., M.Z., J.J., F.Y., J.L., M.G., N.X., X.C.), Huazhong University of Science and Technology, Wuhan, Hubei, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiheng","family":"Hao","sequence":"additional","affiliation":[{"name":"Department of Cardiology (N.L., Z.H., H.Y., M.L., J.H., R.G., Y.S., Z.C., Y.L., T.T., M.Z., J.J., F.Y., J.L., M.G., N.X., X.C.), Huazhong University of Science and Technology, Wuhan, Hubei, China."},{"name":"Hubei Key Laboratory of Biological Targeted Therapy (N.L., Z.H., H.Y., M.L., J.H., R.G., Y.S., Z.C., Y.L., T.T., M.Z., J.J., F.Y., J.L., M.G., N.X., X.C.), Huazhong University of Science and Technology, Wuhan, Hubei, China."},{"name":"Hubei Engineering Research Center for Immunological Diagnosis and Therapy of Cardiovascular Diseases (N.L., Z.H., H.Y., M.L., J.H., R.G., Y.S., Z.C., Y.L., T.T., M.Z., J.J., F.Y., J.L., M.G., N.X., X.C.), Huazhong University of Science and Technology, Wuhan, Hubei, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoyi","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Cardiology (N.L., Z.H., H.Y., M.L., J.H., R.G., Y.S., Z.C., Y.L., T.T., M.Z., J.J., F.Y., J.L., M.G., N.X., X.C.), Huazhong University of Science and Technology, Wuhan, Hubei, China."},{"name":"Hubei Key Laboratory of Biological Targeted Therapy (N.L., Z.H., H.Y., M.L., J.H., R.G., Y.S., Z.C., Y.L., T.T., M.Z., J.J., F.Y., J.L., M.G., N.X., X.C.), Huazhong University of Science and Technology, Wuhan, Hubei, China."},{"name":"Hubei Engineering Research Center for Immunological Diagnosis and Therapy of Cardiovascular Diseases (N.L., Z.H., H.Y., M.L., J.H., R.G., Y.S., Z.C., Y.L., T.T., M.Z., J.J., F.Y., J.L., M.G., N.X., X.C.), Huazhong University of Science and Technology, Wuhan, Hubei, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Cai","sequence":"additional","affiliation":[{"name":"Tongji Medical College; and Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Cardio-X Institute (Q.W.), Huazhong University of Science and Technology, Wuhan, Hubei, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meilin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cardiology (N.L., Z.H., H.Y., M.L., J.H., R.G., Y.S., Z.C., Y.L., T.T., M.Z., J.J., F.Y., J.L., M.G., N.X., X.C.), Huazhong University of Science and Technology, Wuhan, Hubei, China."},{"name":"Hubei Key Laboratory of Biological Targeted Therapy (N.L., Z.H., H.Y., M.L., J.H., R.G., Y.S., Z.C., Y.L., T.T., M.Z., J.J., F.Y., J.L., M.G., N.X., X.C.), Huazhong University of Science and Technology, Wuhan, Hubei, China."},{"name":"Hubei Engineering Research Center for Immunological Diagnosis and Therapy of Cardiovascular Diseases (N.L., Z.H., H.Y., M.L., J.H., R.G., Y.S., Z.C., Y.L., T.T., M.Z., J.J., F.Y., J.L., M.G., N.X., X.C.), Huazhong University of Science and Technology, Wuhan, Hubei, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0545-3784","authenticated-orcid":true,"given":"Junyi","family":"He","sequence":"additional","affiliation":[{"name":"Department of Cardiology (N.L., Z.H., H.Y., M.L., J.H., R.G., Y.S., Z.C., Y.L., T.T., M.Z., J.J., F.Y., J.L., M.G., N.X., X.C.), Huazhong University of Science and Technology, Wuhan, Hubei, China."},{"name":"Hubei Key Laboratory of Biological Targeted Therapy (N.L., Z.H., H.Y., M.L., J.H., R.G., Y.S., Z.C., Y.L., T.T., M.Z., J.J., F.Y., J.L., M.G., N.X., X.C.), Huazhong University of Science and Technology, Wuhan, Hubei, China."},{"name":"Hubei Engineering Research Center for Immunological Diagnosis and Therapy of Cardiovascular Diseases (N.L., Z.H., H.Y., M.L., J.H., R.G., Y.S., Z.C., Y.L., T.T., M.Z., J.J., F.Y., J.L., M.G., N.X., X.C.), Huazhong University of Science and Technology, Wuhan, Hubei, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Cardiology (N.L., Z.H., H.Y., M.L., J.H., R.G., Y.S., Z.C., Y.L., T.T., M.Z., J.J., F.Y., J.L., M.G., N.X., X.C.), Huazhong University of Science and Technology, Wuhan, Hubei, China."},{"name":"Hubei Key Laboratory of Biological Targeted Therapy (N.L., Z.H., H.Y., M.L., J.H., R.G., Y.S., Z.C., Y.L., T.T., M.Z., J.J., F.Y., J.L., M.G., N.X., X.C.), Huazhong University of Science and Technology, Wuhan, Hubei, China."},{"name":"Hubei Engineering Research Center for Immunological Diagnosis and Therapy of Cardiovascular Diseases (N.L., Z.H., H.Y., M.L., J.H., R.G., Y.S., Z.C., Y.L., T.T., M.Z., J.J., F.Y., J.L., M.G., N.X., X.C.), Huazhong University of Science and Technology, Wuhan, Hubei, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0550-6725","authenticated-orcid":true,"given":"Yuhan","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Cardiology (N.L., Z.H., H.Y., M.L., J.H., R.G., Y.S., Z.C., Y.L., T.T., M.Z., J.J., F.Y., J.L., M.G., N.X., X.C.), Huazhong University of Science and Technology, Wuhan, Hubei, China."},{"name":"Hubei Key Laboratory of Biological Targeted Therapy (N.L., Z.H., H.Y., M.L., J.H., R.G., Y.S., Z.C., Y.L., T.T., M.Z., J.J., F.Y., J.L., M.G., N.X., X.C.), Huazhong University of Science and Technology, Wuhan, Hubei, China."},{"name":"Hubei Engineering Research Center for Immunological Diagnosis and Therapy of Cardiovascular Diseases (N.L., Z.H., H.Y., M.L., J.H., R.G., Y.S., Z.C., Y.L., T.T., M.Z., J.J., F.Y., J.L., M.G., N.X., X.C.), Huazhong University of Science and Technology, Wuhan, Hubei, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3379-7802","authenticated-orcid":true,"given":"Zhehao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiology (N.L., Z.H., H.Y., M.L., J.H., R.G., Y.S., Z.C., Y.L., T.T., M.Z., J.J., F.Y., J.L., M.G., N.X., X.C.), Huazhong University of Science and Technology, Wuhan, Hubei, China."},{"name":"Hubei Key Laboratory of Biological Targeted Therapy (N.L., Z.H., H.Y., M.L., J.H., R.G., Y.S., Z.C., Y.L., T.T., M.Z., J.J., F.Y., J.L., M.G., N.X., X.C.), Huazhong University of Science and Technology, Wuhan, Hubei, China."},{"name":"Hubei Engineering Research Center for Immunological Diagnosis and Therapy of Cardiovascular Diseases (N.L., Z.H., H.Y., M.L., J.H., R.G., Y.S., Z.C., Y.L., T.T., M.Z., J.J., F.Y., J.L., M.G., N.X., X.C.), Huazhong University of Science and Technology, Wuhan, Hubei, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzhi","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Cardiology (N.L., Z.H., H.Y., M.L., J.H., R.G., Y.S., Z.C., Y.L., T.T., M.Z., J.J., F.Y., J.L., M.G., N.X., X.C.), Huazhong University of Science and Technology, Wuhan, Hubei, China."},{"name":"Hubei Key Laboratory of Biological Targeted Therapy (N.L., Z.H., H.Y., M.L., J.H., R.G., Y.S., Z.C., Y.L., T.T., M.Z., J.J., F.Y., J.L., M.G., N.X., X.C.), Huazhong University of Science and Technology, Wuhan, Hubei, China."},{"name":"Hubei Engineering Research Center for Immunological Diagnosis and Therapy of Cardiovascular Diseases (N.L., Z.H., H.Y., M.L., J.H., R.G., Y.S., Z.C., Y.L., T.T., M.Z., J.J., F.Y., J.L., M.G., N.X., X.C.), Huazhong University of Science and Technology, Wuhan, Hubei, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5667-6737","authenticated-orcid":true,"given":"Tingting","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Cardiology (N.L., Z.H., H.Y., M.L., J.H., R.G., Y.S., Z.C., Y.L., T.T., M.Z., J.J., F.Y., J.L., M.G., N.X., X.C.), Huazhong University of Science and Technology, Wuhan, Hubei, China."},{"name":"Hubei Key Laboratory of Biological Targeted Therapy (N.L., Z.H., H.Y., M.L., J.H., R.G., Y.S., Z.C., Y.L., T.T., M.Z., J.J., F.Y., J.L., M.G., N.X., X.C.), Huazhong University of Science and Technology, Wuhan, Hubei, China."},{"name":"Hubei Engineering Research Center for Immunological Diagnosis and Therapy of Cardiovascular Diseases (N.L., Z.H., H.Y., M.L., J.H., R.G., Y.S., Z.C., Y.L., T.T., M.Z., J.J., F.Y., J.L., M.G., N.X., X.C.), Huazhong University of Science and Technology, Wuhan, Hubei, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology (N.L., Z.H., H.Y., M.L., J.H., R.G., Y.S., Z.C., Y.L., T.T., M.Z., J.J., F.Y., J.L., M.G., N.X., X.C.), Huazhong University of Science and Technology, Wuhan, Hubei, China."},{"name":"Hubei Key Laboratory of Biological Targeted Therapy (N.L., Z.H., H.Y., M.L., J.H., R.G., Y.S., Z.C., Y.L., T.T., M.Z., J.J., F.Y., J.L., M.G., N.X., X.C.), Huazhong University of Science and Technology, Wuhan, Hubei, China."},{"name":"Hubei Engineering Research Center for Immunological Diagnosis and Therapy of Cardiovascular Diseases (N.L., Z.H., H.Y., M.L., J.H., R.G., Y.S., Z.C., Y.L., T.T., M.Z., J.J., F.Y., J.L., M.G., N.X., X.C.), Huazhong University of Science and Technology, Wuhan, Hubei, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4845-9023","authenticated-orcid":true,"given":"Jiao","family":"Jiao","sequence":"additional","affiliation":[{"name":"Department of Cardiology (N.L., Z.H., H.Y., M.L., J.H., R.G., Y.S., Z.C., Y.L., T.T., M.Z., J.J., F.Y., J.L., M.G., N.X., X.C.), Huazhong University of Science and Technology, Wuhan, Hubei, China."},{"name":"Hubei Key Laboratory of Biological Targeted Therapy (N.L., Z.H., H.Y., M.L., J.H., R.G., Y.S., Z.C., Y.L., T.T., M.Z., J.J., F.Y., J.L., M.G., N.X., X.C.), Huazhong University of Science and Technology, Wuhan, Hubei, China."},{"name":"Hubei Engineering Research Center for Immunological Diagnosis and Therapy of Cardiovascular Diseases (N.L., Z.H., H.Y., M.L., J.H., R.G., Y.S., Z.C., Y.L., T.T., M.Z., J.J., F.Y., J.L., M.G., N.X., X.C.), Huazhong University of Science and Technology, Wuhan, Hubei, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1970-3270","authenticated-orcid":true,"given":"Fen","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Cardiology (N.L., Z.H., H.Y., M.L., J.H., R.G., Y.S., Z.C., Y.L., T.T., M.Z., J.J., F.Y., J.L., M.G., N.X., X.C.), Huazhong University of Science and Technology, Wuhan, Hubei, China."},{"name":"Hubei Key Laboratory of Biological Targeted Therapy (N.L., Z.H., H.Y., M.L., J.H., R.G., Y.S., Z.C., Y.L., T.T., M.Z., J.J., F.Y., J.L., M.G., N.X., X.C.), Huazhong University of Science and Technology, Wuhan, Hubei, China."},{"name":"Hubei Engineering Research Center for Immunological Diagnosis and Therapy of Cardiovascular Diseases (N.L., Z.H., H.Y., M.L., J.H., R.G., Y.S., Z.C., Y.L., T.T., M.Z., J.J., F.Y., J.L., M.G., N.X., X.C.), Huazhong University of Science and Technology, Wuhan, Hubei, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0228-7028","authenticated-orcid":true,"given":"Jingyong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cardiology (N.L., Z.H., H.Y., M.L., J.H., R.G., Y.S., Z.C., Y.L., T.T., M.Z., J.J., F.Y., J.L., M.G., N.X., X.C.), Huazhong University of Science and Technology, Wuhan, Hubei, China."},{"name":"Hubei Key Laboratory of Biological Targeted Therapy (N.L., Z.H., H.Y., M.L., J.H., R.G., Y.S., Z.C., Y.L., T.T., M.Z., J.J., F.Y., J.L., M.G., N.X., X.C.), Huazhong University of Science and Technology, Wuhan, Hubei, China."},{"name":"Hubei Engineering Research Center for Immunological Diagnosis and Therapy of Cardiovascular Diseases (N.L., Z.H., H.Y., M.L., J.H., R.G., Y.S., Z.C., Y.L., T.T., M.Z., J.J., F.Y., J.L., M.G., N.X., X.C.), Huazhong University of Science and Technology, Wuhan, Hubei, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muyang","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Cardiology (N.L., Z.H., H.Y., M.L., J.H., R.G., Y.S., Z.C., Y.L., T.T., M.Z., J.J., F.Y., J.L., M.G., N.X., X.C.), Huazhong University of Science and Technology, Wuhan, Hubei, China."},{"name":"Hubei Key Laboratory of Biological Targeted Therapy (N.L., Z.H., H.Y., M.L., J.H., R.G., Y.S., Z.C., Y.L., T.T., M.Z., J.J., F.Y., J.L., M.G., N.X., X.C.), Huazhong University of Science and Technology, Wuhan, Hubei, China."},{"name":"Hubei Engineering Research Center for Immunological Diagnosis and Therapy of Cardiovascular Diseases (N.L., Z.H., H.Y., M.L., J.H., R.G., Y.S., Z.C., Y.L., T.T., M.Z., J.J., F.Y., J.L., M.G., N.X., X.C.), Huazhong University of Science and Technology, Wuhan, Hubei, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9608-0310","authenticated-orcid":true,"given":"Desheng","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Integrated Traditional Chinese and Western Medicine (D.H.), Huazhong University of Science and Technology, Wuhan, Hubei, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1085-3766","authenticated-orcid":true,"given":"Weimin","family":"Wang","sequence":"additional","affiliation":[{"name":"Union Hospital; Department of Immunology, School of Basic Medicine (W.W.), Huazhong University of Science and Technology, Wuhan, Hubei, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Wang","sequence":"additional","affiliation":[{"name":"Tongji Medical College; and Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center 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