{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T14:05:11Z","timestamp":1791813911097,"version":"4.3.4"},"reference-count":49,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2024,10,27]],"date-time":"2024-10-27T00:00:00Z","timestamp":1729987200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research &amp; Development Program of China","award":["2023YFC2507800"],"award-info":[{"award-number":["2023YFC2507800"]}]},{"name":"National Key Research &amp; Development Program of China","award":["81130008"],"award-info":[{"award-number":["81130008"]}]},{"name":"National Key Research &amp; Development Program of China","award":["81820108003"],"award-info":[{"award-number":["81820108003"]}]},{"name":"National Key Research &amp; Development Program of China","award":["81770117"],"award-info":[{"award-number":["81770117"]}]},{"name":"National Key Research &amp; Development Program of China","award":["82070121"],"award-info":[{"award-number":["82070121"]}]},{"name":"National Key Research &amp; Development Program of China","award":["GSWS2022008"],"award-info":[{"award-number":["GSWS2022008"]}]},{"name":"National Natural Science Foundation of China","award":["2023YFC2507800"],"award-info":[{"award-number":["2023YFC2507800"]}]},{"name":"National Natural Science Foundation of China","award":["81130008"],"award-info":[{"award-number":["81130008"]}]},{"name":"National Natural Science Foundation of China","award":["81820108003"],"award-info":[{"award-number":["81820108003"]}]},{"name":"National Natural Science Foundation of China","award":["81770117"],"award-info":[{"award-number":["81770117"]}]},{"name":"National Natural Science Foundation of China","award":["82070121"],"award-info":[{"award-number":["82070121"]}]},{"name":"National Natural Science Foundation of China","award":["GSWS2022008"],"award-info":[{"award-number":["GSWS2022008"]}]},{"name":"Gusu Health Talent","award":["2023YFC2507800"],"award-info":[{"award-number":["2023YFC2507800"]}]},{"name":"Gusu Health Talent","award":["81130008"],"award-info":[{"award-number":["81130008"]}]},{"name":"Gusu Health Talent","award":["81820108003"],"award-info":[{"award-number":["81820108003"]}]},{"name":"Gusu Health Talent","award":["81770117"],"award-info":[{"award-number":["81770117"]}]},{"name":"Gusu Health Talent","award":["82070121"],"award-info":[{"award-number":["82070121"]}]},{"name":"Gusu Health Talent","award":["GSWS2022008"],"award-info":[{"award-number":["GSWS2022008"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Septic patients, coupling severe disseminated intravascular coagulation (DIC) and thrombocytopenia, have poor prognoses and higher mortality. The platelet glycoprotein Ib\u03b1 (GPIb\u03b1) is involved in thrombosis, hemostasis, and inflammation response. However, it remains unclear whether the GPIb\u03b1 cytoplasmic tail regulates sepsis-mediated platelet activation and inflammation, especially in Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) infections. Using a mouse model of S. aureus-induced bacteremia, we found that both 10 amino acids of GPIb\u03b1 C-terminal sequence deficiency and pharmacologic inhibition of protein kinase C (PKC) alleviated pathogenesis by diminishing platelet activation and aggregate formation. Furthermore, the GPIb\u03b1 cytoplasmic tail promoted the phagocytosis of platelets by Kupffer cells in vivo. The genetically deficient GPIb\u03b1 cytoplasmic tail also downregulated inflammatory cytokines and reduced liver damage, ultimately improving the survival rate of the septic mice. Our results illustrate that the platelet GPIb\u03b1 cytoplasmic domain exacerbates excessive platelet activation and inflammation associated with sepsis through a PKC-dependent pathway. Thus, our findings provide insights for the development of effective therapeutic strategies using PKC inhibitor treatment against bacterial infection.<\/jats:p>","DOI":"10.3390\/ijms252111548","type":"journal-article","created":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T04:15:02Z","timestamp":1730088902000},"page":"11548","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Platelet Glycoprotein Ib\u03b1 Cytoplasmic Tail Exacerbates Thrombosis During Bacterial Sepsis"],"prefix":"10.3390","volume":"25","author":[{"given":"Yue","family":"Xia","sequence":"first","affiliation":[{"name":"Jiangsu Institute of Hematology, Cyrus Tang Medical Institute, Suzhou Medical College of Soochow University, NHC Key Laboratory of Thrombosis and Hemostasis, National Clinical Research Center for Hematological Diseases, Suzhou 215123, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenglin","family":"Sun","sequence":"additional","affiliation":[{"name":"Jiangsu Institute of Hematology, Cyrus Tang Medical Institute, Suzhou Medical College of Soochow University, NHC Key Laboratory of Thrombosis and Hemostasis, National Clinical Research Center for Hematological Diseases, Suzhou 215123, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kangxi","family":"Zhou","sequence":"additional","affiliation":[{"name":"Jiangsu Institute of Hematology, Cyrus Tang Medical Institute, Suzhou Medical College of Soochow University, NHC Key Laboratory of Thrombosis and Hemostasis, National Clinical Research Center for Hematological Diseases, Suzhou 215123, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Shen","sequence":"additional","affiliation":[{"name":"Jiangsu Institute of Hematology, Cyrus Tang Medical Institute, Suzhou Medical College of Soochow University, NHC Key Laboratory of Thrombosis and Hemostasis, National Clinical Research Center for Hematological Diseases, Suzhou 215123, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaojiao","family":"Li","sequence":"additional","affiliation":[{"name":"Jiangsu Institute of Hematology, Cyrus Tang Medical Institute, Suzhou Medical College of Soochow University, NHC Key Laboratory of Thrombosis and Hemostasis, National Clinical Research Center for Hematological Diseases, Suzhou 215123, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuxia","family":"Huang","sequence":"additional","affiliation":[{"name":"Jiangsu Institute of Hematology, Cyrus Tang Medical Institute, Suzhou Medical College of Soochow University, NHC Key Laboratory of Thrombosis and Hemostasis, National Clinical Research Center for Hematological Diseases, Suzhou 215123, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahao","family":"Du","sequence":"additional","affiliation":[{"name":"Jiangsu Institute of Hematology, Cyrus Tang Medical Institute, Suzhou Medical College of Soochow University, NHC Key Laboratory of Thrombosis and Hemostasis, National Clinical Research Center for Hematological Diseases, Suzhou 215123, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sai","family":"Zhang","sequence":"additional","affiliation":[{"name":"Jiangsu Institute of Hematology, Cyrus Tang Medical Institute, Suzhou Medical College of Soochow University, NHC Key Laboratory of Thrombosis and Hemostasis, National Clinical Research Center for Hematological Diseases, Suzhou 215123, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang","family":"Sun","sequence":"additional","affiliation":[{"name":"Jiangsu Institute of Hematology, Cyrus Tang Medical Institute, Suzhou Medical College of Soochow University, NHC Key Laboratory of Thrombosis and Hemostasis, National Clinical Research Center for Hematological Diseases, Suzhou 215123, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renping","family":"Hu","sequence":"additional","affiliation":[{"name":"Jiangsu Institute of Hematology, Cyrus Tang Medical Institute, Suzhou Medical College of Soochow University, NHC Key Laboratory of Thrombosis and Hemostasis, National Clinical Research Center for Hematological Diseases, Suzhou 215123, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Yan","sequence":"additional","affiliation":[{"name":"Jiangsu Institute of Hematology, Cyrus Tang Medical Institute, Suzhou Medical College of Soochow University, NHC Key Laboratory of Thrombosis and Hemostasis, National Clinical Research Center for Hematological Diseases, Suzhou 215123, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kesheng","family":"Dai","sequence":"additional","affiliation":[{"name":"Jiangsu Institute of Hematology, Cyrus Tang Medical Institute, Suzhou Medical College of Soochow University, NHC Key Laboratory of Thrombosis and Hemostasis, National Clinical Research Center for Hematological Diseases, Suzhou 215123, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/S1473-3099(17)30117-2","article-title":"Application of the Third International Consensus Definitions for Sepsis (Sepsis-3) Classification: A retrospective population-based cohort study","volume":"17","author":"Donnelly","year":"2017","journal-title":"Lancet Infect. Dis."},{"key":"ref_2","unstructured":"GBD 2019 Antimicrobial Resistance Collaborators (2022). Global mortality associated with 33 bacterial pathogens in 2019: A systematic analysis for the Global Burden of Disease Study 2019. Lancet, 400, 2221\u20132248."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1002\/ncp.10892","article-title":"Intravenous fluid therapy in sepsis","volume":"37","author":"Seitz","year":"2022","journal-title":"Nutr. Clin. Pract."},{"key":"ref_4","first-page":"7","article-title":"Developments in the production of platelets from stem cells (Review)","volume":"23","author":"Yang","year":"2021","journal-title":"Mol. Med. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Mandel, J., Casari, M., Stepanyan, M., Martyanov, A., and Deppermann, C. (2022). Beyond Hemostasis: Platelet Innate Immune Interactions and Thromboinflammation. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23073868"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1038\/nri2956","article-title":"Platelets and the immune continuum","volume":"11","author":"Semple","year":"2011","journal-title":"Nat. Rev. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1016\/j.smim.2016.10.005","article-title":"Platelets and infection","volume":"28","author":"Deppermann","year":"2016","journal-title":"Semin. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1007\/s00018-009-0207-z","article-title":"Platelet-bacterial interactions","volume":"67","author":"Kerrigan","year":"2010","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Cox, D. (2023). Sepsis-it is all about the platelets. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1210219"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1055\/s-0033-1353390","article-title":"Bernard-Soulier syndrome: An update","volume":"39","author":"Andrews","year":"2013","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1097\/MOH.0b013e3280dce51a","article-title":"Signaling and regulation of the platelet glycoprotein Ib-IX-V complex","volume":"14","author":"Du","year":"2007","journal-title":"Curr. Opin. Hematol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1975","DOI":"10.1182\/blood-2005-01-0440","article-title":"A critical role for 14-3-3\u03b6 protein in regulating the VWF binding function of platelet glycoprotein Ib-IX and its therapeutic implications","volume":"106","author":"Dai","year":"2005","journal-title":"Blood"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1161\/CIRCRESAHA.109.204669","article-title":"Identification of a novel 14-3-3\u03b6 binding site within the cytoplasmic domain of platelet glycoprotein Ib\u03b1 that plays a key role in regulating the von Willebrand factor binding function of glycoprotein Ib-IX","volume":"105","author":"Yuan","year":"2009","journal-title":"Circ. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4580","DOI":"10.1182\/blood-2007-09-111096","article-title":"A functional 14-3-3\u03b6-independent association of PI3-kinase with glycoprotein Ib \u03b1, the major ligand-binding subunit of the platelet glycoprotein Ib-IX-V complex","volume":"111","author":"Mu","year":"2008","journal-title":"Blood"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1038\/ni.2631","article-title":"Nucleation of platelets with blood-borne pathogens on Kupffer cells precedes other innate immunity and contributes to bacterial clearance","volume":"14","author":"Wong","year":"2013","journal-title":"Nat. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"15559","DOI":"10.1038\/ncomms15559","article-title":"Leukocyte integrin Mac-1 regulates thrombosis via interaction with platelet GPIb\u03b1","volume":"8","author":"Wang","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/j.celrep.2019.06.062","article-title":"Platelets Promote Macrophage Polarization toward Pro-inflammatory Phenotype and Increase Survival of Septic Mice","volume":"28","author":"Carestia","year":"2019","journal-title":"Cell Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1182\/blood.V100.2.509","article-title":"A role for glycoprotein Ib in Streptococcus sanguis-induced platelet aggregation","volume":"100","author":"Kerrigan","year":"2002","journal-title":"Blood"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1002\/ana.24146","article-title":"Streptococcus pneumoniae worsens cerebral ischemia via interleukin 1 and platelet glycoprotein Ib\u03b1","volume":"75","author":"Pradillo","year":"2014","journal-title":"Ann. Neurol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2529","DOI":"10.1161\/ATVBAHA.113.302339","article-title":"Role for platelet glycoprotein Ib-IX and effects of its inhibition in endotoxemia-induced thrombosis, thrombocytopenia, and mortality","volume":"33","author":"Yin","year":"2013","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1161\/ATVBAHA.114.303367","article-title":"Platelet GPIb-IX has suppressive effects on septic inflammation","volume":"34","author":"Semple","year":"2014","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1161\/ATVBAHA.113.303113","article-title":"Platelet glycoprotein Ib-IX as a regulator of systemic inflammation","volume":"34","author":"Corken","year":"2014","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_23","first-page":"933","article-title":"The GPIb\u03b1 intracellular tail\u2014Role in transducing VWF- and collagen\/GPVI-mediated signaling","volume":"107","author":"Wang","year":"2022","journal-title":"Haematologica"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2657","DOI":"10.1038\/ncomms3657","article-title":"Platelets protect from septic shock by inhibiting macrophage-dependent inflammation via the cyclooxygenase 1 signalling pathway","volume":"4","author":"Xiang","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1097\/01.shk.0000108399.56565.e7","article-title":"Antibiotics improve survival in sepsis independent of injury severity but do not change mortality in mice with markedly elevated interleukin 6 levels","volume":"21","author":"Turnbull","year":"2004","journal-title":"Shock"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s40560-019-0387-z","article-title":"Sepsis-associated disseminated intravascular coagulation and its differential diagnoses","volume":"7","author":"Iba","year":"2019","journal-title":"J. Intensive Care."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.jinf.2018.12.002","article-title":"The clinical significance of thrombocytopenia complicating sepsis: A meta-analysis","volume":"78","author":"Xie","year":"2019","journal-title":"J. Infect."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3388","DOI":"10.1182\/bloodadvances.2023012308","article-title":"Essential role of glycoprotein Ib\u03b1 in platelet activation","volume":"8","author":"Yan","year":"2024","journal-title":"Blood Adv."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.jss.2004.04.005","article-title":"PKC-\u03b6 is essential for endotoxin-induced macrophage activation","volume":"121","author":"Cuschieri","year":"2004","journal-title":"J. Surg. Res."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Liverani, E., Mondrinos, M.J., Sun, S., Kunapuli, S.P., and Kilpatrick, L.E. (2018). Role of Protein Kinase C-delta in regulating platelet activation and platelet-leukocyte interaction during sepsis. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0195379"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1712","DOI":"10.1007\/s11605-007-0314-9","article-title":"Protein kinase C-zeta (PKC-\u03b6) regulates Kupffer cell apoptosis during experimental sepsis","volume":"11","author":"Peng","year":"2007","journal-title":"J. Gastrointest. Surg."},{"key":"ref_32","first-page":"399","article-title":"PKC\u03b1 regulates platelet granule secretion and thrombus formation in mice","volume":"119","author":"Konopatskaya","year":"2009","journal-title":"J. Clin. Investig."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2102","DOI":"10.1182\/blood-2002-03-0997","article-title":"Amelioration of the macrothrombocytopenia associated with the murine Bernard-Soulier syndrome","volume":"100","author":"Kanaji","year":"2002","journal-title":"Blood"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.jtha.2022.10.022","article-title":"Communication from the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis on sepsis-induced coagulopathy in the management of sepsis","volume":"21","author":"Iba","year":"2023","journal-title":"J. Thromb. Haemost."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2626","DOI":"10.1182\/blood.2021014966","article-title":"S100A8\/A9 drives the formation of procoagulant platelets through GPIb\u03b1","volume":"140","author":"Colicchia","year":"2022","journal-title":"Blood"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Chen, X., Li, J., Liu, P., Zhou, Y., Zhang, T., Li, L., Shi, J., Deng, X., Sheng, Y., and Chen, W. (2024). Inflammasome-Independent Mechanism of NLRP3 Is Critical for Platelet GPIb-IX Function and Thrombosis. Thromb. Haemost.","DOI":"10.1055\/a-2263-8372"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"6528","DOI":"10.1128\/IAI.72.11.6528-6537.2004","article-title":"The Streptococcus gordonii surface proteins GspB and Hsa mediate binding to sialylated carbohydrate epitopes on the platelet membrane glycoprotein Ib\u03b1","volume":"72","author":"Bensing","year":"2004","journal-title":"Infect. Immun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"111614","DOI":"10.1016\/j.celrep.2022.111614","article-title":"Platelet p110\u03b2 mediates platelet-leukocyte interaction and curtails bacterial dissemination in pneumococcal pneumonia","volume":"41","author":"Schrottmaier","year":"2022","journal-title":"Cell Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1165\/rcmb.2017-0083OC","article-title":"Platelet Depletion Impairs Host Defense to Pulmonary Infection with Pseudomonas aeruginosa in Mice","volume":"58","author":"Amison","year":"2018","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"4831","DOI":"10.1111\/j.1742-4658.2006.05482.x","article-title":"Staphylococcus aureus protein A binding to von Willebrand factor A1 domain is mediated by conserved IgG binding regions","volume":"273","author":"Kerrigan","year":"2006","journal-title":"FEBS J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/cc1854","article-title":"Bench-to-bedside review: Functional relationships between coagulation and the innate immune response and their respective roles in the pathogenesis of sepsis","volume":"7","author":"Opal","year":"2003","journal-title":"Crit. Care"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.thromres.2013.07.002","article-title":"Use of antiplatelet agents in sepsis: A glimpse into the future","volume":"133","author":"Akinosoglou","year":"2014","journal-title":"Thromb. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.thromres.2018.04.007","article-title":"Platelet activation and antiplatelet therapy in sepsis: A narrative review","volume":"166","author":"Wang","year":"2018","journal-title":"Thromb. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1160\/TH07-12-0718","article-title":"Platelet GPIb complex as a target for anti-thrombotic drug development","volume":"99","author":"Clemetson","year":"2008","journal-title":"Thromb. Haemost."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Li, B.X., Dai, X., Xu, X.R., Adili, R., Neves, M.A.D., Lei, X., Shen, C., Zhu, G., Wang, Y., and Zhou, H. (2021). In vitro assessment and phase I randomized clinical trial of anfibatide a snake venom derived anti-thrombotic agent targeting human platelet GPIb\u03b1. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-91165-8"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2118","DOI":"10.4049\/jimmunol.2100229","article-title":"Macrophagic Extracellular Vesicle CXCL2 Recruits and Activates the Neutrophil CXCR2\/PKC\/NOX4 Axis in Sepsis","volume":"207","author":"Wang","year":"2021","journal-title":"J. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1097\/00024382-200201000-00008","article-title":"Alteration of protein kinase C isoforms in the liver of septic rat","volume":"17","author":"Hsu","year":"2002","journal-title":"Shock"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"132","DOI":"10.21037\/atm-21-6497","article-title":"Inhibition of protein kinase C alpha attenuates lipopolysaccharide-triggered acute lung injury by alleviating the hyperinflammatory response and oxidative stress","volume":"10","author":"Chen","year":"2022","journal-title":"Ann. Transl. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1097\/SHK.0000000000001212","article-title":"Minimum Quality Threshold in Pre-Clinical Sepsis Studies (MQTiPSS): An International Expert Consensus Initiative for Improvement of Animal Modeling in Sepsis","volume":"50","author":"Osuchowski","year":"2018","journal-title":"Shock"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/21\/11548\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:21:46Z","timestamp":1760113306000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/21\/11548"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,27]]},"references-count":49,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["ijms252111548"],"URL":"https:\/\/doi.org\/10.3390\/ijms252111548","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,27]]}}}