Figure 1

1.Singer, M. et al. The third worldwide consensus definitions for sepsis and septic shock (Sepsis-Three). JAMA 315, 801–810, (2016).2.Shankar-Hari, M. et al. Creating a brand new definition and assessing new medical standards for septic shock: for the Third Worldwide Consensus Definitions for Sepsis and Septic Shock (Sepsis-Three). JAMA 315, 775–787, (2016).Three.Seymour, C. W. et al. Evaluation of medical standards for cepsis: for the Third Worldwide Consensus Definitions for Sepsis and Septic Shock (Sepsis-Three). JAMA 315, 762–774, (2016).Four.Fleischmann, C. et al. Evaluation of world incidence and mortality of hospital-treated sepsis. Present estimates and limitations. Am J Respir Crit Care Med 193, 259–272, (2016).5.Corridor, M. J., Williams, S. N., DeFrances, C. J. & Golosinskiy, A. 1–eight (Nationwide Middle for Well being Statistics Hyattsville, MD, 2011).6.Levy, M. M. et al. The Surviving Sepsis Marketing campaign: outcomes of a world guideline-based efficiency enchancment program focusing on extreme sepsis. Crit Care Med 38, 367–374, (2010).7.Masewu, A. et al. Acute kidney harm is a strong unbiased predictor of mortality in critically in poor health sufferers: a multicenter potential cohort examine from Kinshasa, the Democratic Republic of Congo. BMC Nephrol 17, 118, (2016).eight.Sevransky, J. E. et al. Pulmonary vs nonpulmonary sepsis and mortality in acute lung harm. Chest 134, 534–538, (2008).9.Martin, G. S., Mannino, D. M. & Moss, M. The impact of age on the event and end result of grownup sepsis. Crit Care Med 34, 15–21, doi:00003246-200601000-Zero0003 [pii] (2006).10.Dombrovskiy, V. Y., Martin, A. A., Sunderram, J. & Paz, H. L. Fast enhance in hospitalization and mortality charges for extreme sepsis in america: a pattern evaluation from 1993 to 2003. Crit Care Med 35, 1244–1250, (2007).11.US Meals and Drug Administration. (Silver Spring, MD, 2011).12.Gotts, J. E. & Matthay, M. A. Sepsis: pathophysiology and medical administration. BMJ 353, i1585, (2016).13.Khan, M. M., Yang, W. L., Brenner, M., Bolognese, A. C. & Wang, P. Chilly-inducible RNA-binding protein (CIRP) causes sepsis-associated acute lung harm through induction of endoplasmic reticulum stress. Sci Rep 7, 41363, (2017).14.Wellmann, S. et al. Oxygen-regulated expression of the RNA-binding proteins RBM3 and CIRP by a HIF-1-independent mechanism. J Cell Sci 117, 1785–1794, (2004).15.Al-Fageeh, M. B. & Smales, C. M. Various promoters regulate chilly inducible RNA-binding (CIRP) gene expression and improve transgene expression in mammalian cells. Mol Biotechnol 54, 238–249, (2013).16.De Leeuw, F. et al. The cold-inducible RNA-binding protein migrates from the nucleus to cytoplasmic stress granules by a methylation-dependent mechanism and acts as a translational repressor. Exp Cell Res 313, 4130–4144, (2007).17.Morf, J. et al. Chilly-inducible RNA-binding protein modulates circadian gene expression posttranscriptionally. Science 338, 379–383, (2012).18.Qiang, X. et al. Chilly-inducible RNA-binding protein (CIRP) triggers inflammatory responses in hemorrhagic shock and sepsis. Nat Med 19, 1489–1495, (2013).19.Zhou, Y. et al. The cold-inducible RNA-binding protein (CIRP) stage in peripheral blood predicts sepsis end result. PLoS One 10, e0137721, (2015).20.Yang, W. L. et al. Chilly-inducible RNA-binding protein causes endothelial dysfunction through activation of Nlrp3 inflammasome. Sci Rep 6, 26571, (2016).21.Aird, W. C. The function of the endothelium in extreme sepsis and a number of organ dysfunction syndrome. Blood 101, 3765–3777, (2003).22.Cen, C. et al. Deficiency of cold-inducible ribonucleic acid-binding protein reduces renal harm after ischemia-reperfusion. Surgical procedure 160, 473–483, (2016).23.Shin, H. J. et al. Kinetics of binding of LPS to recombinant CD14, TLR4, and MD-2 proteins. Mol Cells 24, 119–124 (2007).24.Yang, H. et al. A vital cysteine is required for HMGB1 binding to Toll-like receptor Four and activation of macrophage cytokine launch. Proc Natl Acad Sci USA 107, 11942–11947, (2010).25.Angele, M. Ok., Schwacha, M. G., Ayala, A. & Chaudry, I. H. Impact of gender and intercourse hormones on immune responses following shock. Shock 14, 81–90 (2000).26.Diodato, M. D., Knoferl, M. W., Schwacha, M. G., Bland, Ok. I. & Chaudry, I. H. Gender variations within the inflammatory response and survival following haemorrhage and subsequent sepsis. Cytokine 14, 162–169, (2001).27.Luiking, Y. C., Hallemeesch, M. M., Vissers, Y. L., Lamers, W. H. & Deutz, N. E. In vivo entire physique and organ arginine metabolism throughout endotoxemia (sepsis) depends on mouse pressure and gender. J Nutr 134, 2768S–2774S, dialogue 2796S–2797S (2004).28.Aoyama, M., Kotani, J. & Usami, M. Gender distinction in granulocyte dynamics and apoptosis and the function of IL-18 throughout endotoxin-induced systemic irritation. Shock 32, 401–409, (2009).29.Zhang, F., Yang, W.-L., Brenner, M. & Wang, P. Attenuation of hemorrhage-associated lung harm by adjuvant therapy with C23, an oligopeptide derived from cold-inducible RNA-binding protein (CIRP). J Trauma Acute Care Surg. (2017).30.Hirano, Y. et al. Neutralization of osteopontin attenuates neutrophil migration in sepsis-induced acute lung harm. Crit Care 19, 53, (2015).31.Livak, Ok. J. & Schmittgen, T. D. Evaluation of relative gene expression knowledge utilizing real-time quantitative PCR and the two(-Delta Delta C(T)) Technique. Strategies 25, 402–408, (2001).32.Giannini, E. G., Testa, R. & Savarino, V. Liver enzyme alteration: a information for clinicians. CMAJ 172, 367–379, (2005).33.Nishiyama, H. et al. Cloning and characterization of human CIRP (cold-inducible RNA-binding protein) cDNA and chromosomal task of the gene. Gene 204, 115–120, doi:S0378-1119(97)00530-1 [pii] (1997).34.Yang, C. & Service, F. The UV-inducible RNA-binding protein A18 (A18 hnRNP) performs a protecting function within the genotoxic stress response. J Biol Chem 276, 47277–47284, (2001).35.Yang, R. et al. Useful significance for a heterogenous ribonucleoprotein A18 signature RNA motif within the Three′-untranslated area of ataxia telangiectasia mutated and Rad3-related (ATR) transcript. J Biol Chem 285, 8887–8893, (2010).36.Nishiyama, H. et al. Decreased expression of cold-inducible RNA-binding protein (CIRP) in male germ cells at elevated temperature. Am J Pathol 152, 289–296 (1998).37.Nishiyama, H. et al. Diurnal change of the cold-inducible RNA-binding protein (Cirp) expression in mouse mind. Biochem Biophys Res Commun 245, 534–538, (1998).38.Xue, J. H. et al. Results of ischemia and H2O2 on the chilly stress protein CIRP expression in rat neuronal cells. Free Radic Biol Med 27, 1238-1244, doi:S0891-5849(99)00158-6 [pii] (1999).39.Fornace, A. J. Jr, Alamo, I. Jr. & Hollander, M. C. DNA damage-inducible transcripts in mammalian cells. Proc Natl Acad Sci USA 85, 8800–8804 (1988).40.Sheikh, M. S. et al. Identification of a number of human homologs of hamster DNA damage-inducible transcripts. Cloning and characterization of a novel UV-inducible cDNA that codes for a putative RNA-binding protein. J Biol Chem 272, 26720–26726 (1997).41.Barenco, M. et al. Ranked prediction of p53 targets utilizing hidden variable dynamic modeling. Genome biology 7, R25, (2006).42.Godwin, A. et al. Blocking cold-inducible RNA-binding protein protects liver from ischemia-reperfusion harm. Shock 43, 24–30, (2015).43.Zhou, M., Yang, W. L., Ji, Y., Qiang, X. & Wang, P. Chilly-inducible RNA-binding protein mediates neuroinflammation in cerebral ischemia. Biochim Biophys Acta 1840, 2253–2261. (2014).44.Nesseler, N. et al. Scientific assessment: The liver in sepsis. Crit Care 16, 235, (2012).45.Kellum, J. A. et al. Understanding the inflammatory cytokine response in pneumonia and sepsis: outcomes of the Genetic and Inflammatory Markers of Sepsis (GenIMS) Examine. Arch Intern Med 167, 1655–1663, (2007).46.Hwaiz, R. et al. Rac1 signaling regulates sepsis-induced pathologic irritation within the lung through attenuation of Mac-1 expression and CXC chemokine formation. J Surg Res 183, 798–807, (2013).47.Dolinay, T. et al. Inflammasome-regulated cytokines are vital mediators of acute lung harm. Am J Respir Crit Care Med 185, 1225–1234, (2012).48.Rudkowski, J. C. et al. Roles of iNOS and nNOS in sepsis-induced pulmonary apoptosis. Am J Physiol Lung Cell Mol Physiol 286, L793–800, (2004).49.Gill, S. E., Rohan, M. & Mehta, S. Function of pulmonary microvascular endothelial cell apoptosis in murine sepsis-induced lung harm in vivo. Respir Res 16, 109, (2015).50.Zhang, H. T. et al. Chilly-inducible RNA-binding protein inhibits neuron apoptosis by the suppression of mitochondrial apoptosis. Mind Res 1622, 474–483, (2015).51.Lujan, D. A. et al. Chilly-inducible RNA binding protein in mouse mammary gland growth. Tissue & cell 48, 577–588. (2016).52.Lee, H. N., Ahn, S. M. & Jang, H. H. Chilly-inducible RNA-binding protein, CIRP, inhibits DNA damage-induced apoptosis by regulating p53. Biochem Biophys Res Commun 464, 916–921, (2015).53.Liao, Y., Feng, J., Zhang, Y., Tang, L. & Wu, S. The mechanism of CIRP in inhibition of keratinocytes development arrest and apoptosis following low dose UVB radiation. Mol Carcinog 56, 1554–1569, (2017).54.Han, W. Ok. et al. Urinary biomarkers within the early prognosis of acute kidney harm. Kidney Int 73, 863–869, (2008).55.Han, M., Li, Y., Liu, M., Li, Y. & Cong, B. Renal neutrophil gelatinase related lipocalin expression in lipopolysaccharide-induced acute kidney harm within the rat. BMC Nephrol 13, 25, (2012).56.Ko, G. J. et al. Transcriptional evaluation of kidneys throughout restore from AKI reveals attainable roles for NGAL and KIM-1 as biomarkers of AKI-to-CKD transition. Am J Physiol Renal Physiol 298, F1472–1483, (2010).57.Sprenkle, P. & Russo, P. Molecular markers for ischemia, do we now have one thing higher then creatinine and glomerular filtration charge? Arch Esp Urol 66, 99–114 (2013).58.Zhang, M. et al. Toll-like receptor Four is important to preserving cardiac perform and survival in low-grade polymicrobial sepsis. Anesthesiology 121, 1270–1280, (2014).59.Deng, M. et al. Lipopolysaccharide clearance, bacterial clearance, and systemic inflammatory responses are regulated by cell type-specific capabilities of TLR4 throughout sepsis. J Immunol 190, 5152–5160, (2013).60.Entezari, M. et al. Inhibition of high-mobility group field 1 protein (HMGB1) enhances bacterial clearance and protects in opposition to Pseudomonas Aeruginosa pneumonia in cystic fibrosis. Mol Med 18, 477–485, (2012).61.Rice, T. W. et al. A randomized, double-blind, placebo-controlled trial of TAK-242 for the therapy of extreme sepsis. Crit Care Med 38, 1685–1694, (2010).62.Opal, S. M. et al. Impact of eritoran, an antagonist of MD2-TLR4, on mortality in sufferers with extreme sepsis: the ACCESS randomized trial. JAMA 309, 1154–1162, (2013).63.Sakurai, T. et al. Cirp protects in opposition to tumor necrosis factor-alpha-induced apoptosis through activation of extracellular signal-regulated kinase. Biochim Biophys Acta 1763, 290–295, (2006).64.Masuda, T. et al. Chilly-inducible RNA-binding protein (Cirp) interacts with Dyrk1b/Mirk and promotes proliferation of immature male germ cells in mice. Proc Natl Acad Sci USA 109, 10885–10890, (2012).


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