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Hypothermic-oxygenated machine perfusion (HOPE) has the potential to counterbalance the detrimental consequences of cold and warm ischemia time in both brain death donors (DBD) and donors after circulatory death (DCD). Herein, we investigated the protective effects of HOPE in extended criteria (ECD) DBD and over-extended warm ischemia time (WIT) DCD grafts. The present retrospective case-series study included 50 livers subjected to end-ischemic HOPE or dual (D)HOPE in two liver transplant (LT) Centers from January 2018 to December 2019. All DCD donors were subjected to normothermic regional perfusion before organ procurement. Results are expressed as median (IQR). In the study period, 21 grafts derived from over-extended WIT DCD donors (total WIT 54 (40-60) min and 75% classified as futile), while 29 from ECD DBD. Three biliary complications and one case of ischemia-type biliary lesions were diagnosed. The rate of early allograft dysfunction (EAD) was 20% and those patients had higher comprehensive-complication index. Through a changing point analysis, cold preservation time (CPT) &gt;9h was associated with prolonged hospital stay (p=0.02), higher rate of EAD (p=0.009) and worst post-LT complications (p=0.02). Logistic regression analyses indicated a significant relationship between CPT and early allograft dysfunction. No differences were showed in terms of early post-LT results between LT performed with DCD and BDB. Overall, our data are fully comparable with benchmark criteria in LT. In conclusion, the application of (D)HOPE allowed to obtain satisfactory and promising results using ECD-DBD and over-extended DCD grafts. Our findings indicate the need to reduce CPT also in the setting of DHOPE, particularly for grafts showing poor quality.The C-X-C motif chemokine CXCL8 (interleukin-8, IL-8) and its receptor chemokine receptor 2 (CXCR2) mediate neutrophil migration during cell development and inflammatory responses and thus are related to numerous inflammatory diseases and cancers. We have determined the cryo-electron microscopy structure of CXCL8 bound CXCR2 coupled to Gi protein, as well as the crystal structure of inactive CXCR2 in complex with a designed allosteric antagonist. These results reveal the binding modes between CXCL8 and CXCR2, CXCR2 and G protein, and the detailed binding pattern of the allosteric antagonist, 00767013. Further structural analysis of the inactive- and active- states of CXCR2 reveals the unique shallow-pocket activation mechanism of C-X-C chemokine receptors and promotes our understanding on how a G protein-coupled receptor (GPCR) is activated by an endogenous protein molecule. In addition, the cholesterol molecule is observed in the activated CXCR2 structure, providing the structural basis of the potential allosteric modulation role of cholesterol in chemokine receptors.<br /><br /> Early detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients who could develop a severe form of COVID-19 must be considered of great importance to carry out adequate care and optimise the use of limited resources.<br /><br /> To use several machine learning classification models to analyse a series of non-critically ill COVID-19 patients admitted to a general medicine ward to verify if any clinical variables recorded could predict the clinical outcome.<br /><br /> We retrospectively analysed non-critically ill patients with COVID-19 admitted to the general ward of the hospital in Pordenone from 1 March 2020 to 30 April 2020. Patients' characteristics were compared based on clinical outcomes. Through several machine learning classification models, some predictors for clinical outcome were detected.<br /><br /> In the considered period, we analysed 176 consecutive patients admitted 119 (67.6%) were discharged, 35 (19.9%) dead and 22 (12.5%) were transferred to intensive care unit. The most accurate models were a random forest model (M2) and a conditional inference tree model (M5) (accuracy = 0.79; 95% confidence interval 0.64-0.90, for both). For M2, glomerular filtration rate and creatinine were the most accurate predictors for the outcome, followed by age and fraction-inspired oxygen. For M5, serum sodium, body temperature and arterial pressure of oxygen and inspiratory fraction of oxygen ratio were the most reliable predictors.<br /><br /> In non-critically ill COVID-19 patients admitted to a medical ward, glomerular filtration rate, creatinine and serum sodium were promising predictors for the clinical outcome. Some factors not determined by COVID-19, such as age or dementia, influence clinical outcomes.<br /><br />In non-critically ill COVID-19 patients admitted to a medical ward, glomerular filtration rate, creatinine and serum sodium were promising predictors for the clinical outcome. Some factors not determined by COVID-19, such as age or dementia, influence clinical outcomes.Preeclampsia (PE), a common disorder of pregnancy, is characterized by insufficient trophoblast migration and inadequate vascular remodelling, such that promotion of trophoblast proliferation might ameliorate PE. In the current study, we sought to study the underlying mechanism of extracellular vesicle (EV)-derived microRNA-18 (miR-18b) in PE. Human umbilical cord mesenchymal stem cells (HUCMSCs) isolated from placental tissues were verified through osteogenic, adipogenic and chondrogenic differentiation assays. Bioinformatics analyses and dual-luciferase reporter gene assay were adopted to confirm the targeting relationship between miR-18b and Notch2. The functional roles of EV-derived miR-18b and Notch2 in trophoblasts were determined using loss- and gain-of-function experiments, and trophoblast proliferation and migration were assayed using CCK-8 and Transwell tests. In vivo experiments were conducted to determine the effect of EV-derived miR-18b, Notch2 and TIM3/mTORC1 in a rat model of PE, with monitoring of blood pressure and urine proteinuria. TUNEL staining was conducted to observe the cell apoptosis of placental tissues of PE rats. [https://www.selleckchem.com/products/oxidopamine-hydrobromide.html this website] We found down-regulated miR-18b expression, and elevated Notch2, TIM3 and mTORC1 levels in the placental tissues of PE patients compared with normal placenta. miR-18b was delivered to trophoblasts and targeted Notch2 and negatively its expression, whereas Notch2 positively mediated the expression of TIM3/mTORC1. EV-derived miR-18b or Notch2 down-regulation enhanced trophoblast proliferation and migration in vitro and decreased blood pressure and 24 hours urinary protein in PE rats by deactivating the TIM3/mTORC1 axis in vivo. In summary, EV-derived miR-18b promoted trophoblast proliferation and migration via down-regulation of Notch2-dependent TIM3/mTORC1.