COLON CANCER CELL-DERIVED EXOSOMES INDUCE MACROPHAGES TO ACQUIRE AN IMMUNOSUPPRESSIVE PHENOTYPE BY UPREGULATING PD-L1 EXPRESSION

Tumor-associated macrophages (TAMs) are a prominent component of cancer microenvironment having a key role in promoting tumor progression. Several studies have demonstrated that TAMs phenotypically and functionally correspond to M2-polarized macrophages thus they exert immunosuppressive functions also associated to the expression of programmed cell death ligand 1 (PD-L1). Within the local tumor microenvironment, tumor-derived exosomes (TDEs) are well known to play a key role in modulating the properties and the behavior of surrounding cells such as TAMs. Even if several studies demonstrated the ability of TDEs to induce M2-like macrophage polarization, few data are available about their involvement in regulating the expression of PD-L1 in TAMs. The aim of the current study was to investigate the ability of exosomes derived from SW480 human colon cancer cells to modulate the properties of TAMs by using non-polarized macrophages (M0-M) differentiated from THP-1 as in vitro model. Our results indicate that after 48h treatment, exosomes derived from SW480 cells (SW480exos) significantly upregulate the expression of surface markers of M2-like phenotype (CD163 and CD206) as well as of PD-L1, inducing macrophages to acquire an immunosuppressive phenotype. In parallel, we found that SW480exos were able to induce a significant increase of interleukin 6 (IL6) expression at both mRNA and protein level. Finally, according to the known ability of PD-1/PD-L1 axis to induce T cell dysfunction, we found that CD3+ T cells co-cultured with M0-M pre-treated with SW480exos significantly increased their apoptotic rate in comparison to those grown in presence of no-treated M0-M. Cumulatively, these preliminary data suggest that within local colon cancer microenvironment TDEs can act as positive modulators of the immunosuppressive status of TAMs, actively promoting the immunotolerance necessary to favor tumor growth and progression

Key role of chemistry versus bias in electrocatalytic oxygen evolution

The oxygen evolution reaction has an important role in many alternative-energy schemes because it supplies the protons and electrons required for converting renewable electricity into chemical fuels. Electrocatalysts accelerate the reaction by facilitating the required electron transfer, as well as the formation and rupture of chemical bonds5. This involvement in fundamentally different processes results in complex electrochemical kinetics that can be challenging to understand and control, and that typically depends exponentially on overpotential. Such behaviour emerges when the applied bias drives the reaction in line with the phenomenological Butler–Volmer theory, which focuses on electron transfer, enabling the use of Tafel analysis to gain mechanistic insight under quasi-equilibrium or steady-state assumptions. However, the charging of catalyst surfaces under bias also affects bond formation and rupture, the effect of which on the electrocatalytic rate is not accounted for by the phenomenological Tafel analysis8 and is often unknown. Here we report pulse voltammetry and operando X-ray absorption spectroscopy measurements on iridium oxide to show that the applied bias does not act directly on the reaction coordinate, but affects the electrocatalytically generated current through charge accumulation in the catalyst. We find that the activation free energy decreases linearly with the amount of oxidative charge stored, and show that this relationship underlies electrocatalytic performance and can be evaluated using measurement and computation. We anticipate that these findings and our methodology will help to better understand other electrocatalytic materials and design systems with improved performance

Catalyst design for natural-gas upgrading through oxybromination chemistry

ISSN:1755-4349ISSN:1755-433

Simple parameters from complete blood count predict in-hospital mortality in covid-19

Introduction. The clinical course of Coronavirus Disease 2019 (COVID-19) is highly heterogenous, ranging from asymptomatic to fatal forms. The identification of clinical and laboratory predictors of poor prognosis may assist clinicians in monitoring strategies and therapeutic decisions. Materials and Methods. In this study, we retrospectively assessed the prognostic value of a simple tool, the complete blood count, on a cohort of 664 patients (F 260; 39%, median age 70 (56-81) years) hospitalized for COVID-19 in Northern Italy. We collected demographic data along with complete blood cell count; moreover, the outcome of the hospital in-stay was recorded. Results. At data cut-off, 221/664 patients (33.3%) had died and 453/664 (66.7%) had been discharged. Red cell distribution width (RDW) (χ2 10.4; p < 0:001), neutrophil-to-lymphocyte (NL) ratio (χ2 7.6; p = 0:006), and platelet count (χ2 5.39; p = 0:02), along with age (χ2 87.6; p < 0:001) and gender (χ2 17.3; p < 0:001), accurately predicted in-hospital mortality. Hemoglobin levels were not associated with mortality. We also identified the best cut-off for mortality prediction: a NL ratio > 4:68 was characterized by an odds ratio for in-hospital mortality ðORÞ = 3:40 (2.40-4.82), while the OR for a RDW > 13:7% was 4.09 (2.87-5.83); a platelet count > 166,000/μL was, conversely, protective (OR: 0.45 (0.32-0.63)). Conclusion. Our findings arise the opportunity of stratifying COVID-19 severity according to simple lab parameters, which may drive clinical decisions about monitoring and treatment