In Vitro Evaluation of Antiviral Activities of Funicone-like Compounds Vermistatin and Penisimplicissin against Canine Coronavirus Infection

Recent studies have demonstrated that 3-O-methylfunicone (OMF), a fungal secondary metabolite from Talaromyces pinophilus belonging to the class of funicone-like compounds, has antiviral activity against canine coronaviruses (CCoV), which causes enteritis in dogs. Herein, we selected two additional funicone-like compounds named vermistatin (VER) and penisimplicissin (PS) and investigated their inhibitory activity towards CCoV infection. Thus, both compounds have been tested for their cytotoxicity and for antiviral activity against CCoV in A72 cells, a fibrosarcoma cell line suitable for investigating CCoV. Our findings showed an increase in cell viability, with an improvement of morphological features in CCoV-infected cells at the non-toxic doses of 1 μM for VER and 0.5 μM for PS. In addition, we observed that these compounds caused a strong inhibition in the expression of the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor which is activated during CCoV infection. Our results also showed the alkalinization of lysosomes in the presence of VER or PS, which may be involved in the observed antiviral activities

Incidence and severity of primary graft dysfunction after lung transplantation using rejected grafts reconditioned with ex vivo lung perfusion.

Ex vivo lung perfusion (EVLP) is a novel technique used to evaluate and recondition marginal or rejected grafts. Primary graft dysfunction (PGD) is a major early complication after lung transplantation (LTx). The use of marginal or initially rejected grafts may increase its incidence and severity. The aim of this study is to evaluate the incidence of PGD after LTx using rejected grafts reconditioned with EVLP.PGD has been evaluated immediately after LTx (t0) and after 72 h (t72) in patients receiving standard (Group A) or reconditioned (Group B) grafts. EVLP was performed using a controlled acellular perfusion according to the Toronto technique.From July 2011 to February 2013, 36 LTxs have been performed: 28 patients (21 M/7 F, mean age 51.7 ± 14.7 years) in Group A and 8 (6 M/2 F, mean age 46.6 ± 9.8 years) in Group B (successful recondition rate of 73\%, 8 of 11 cases). Incidence rate of PGD 3 at t0 and at t72 (Group A versus Group B) was 50 vs 37\% (P = NS) and 25 vs 0\% (P = NS), respectively. Post-transplant extracorporeal membrane oxygenation was required in 5 and 2 patients in Groups A and B, respectively (P = NS).The use of initially rejected grafts treated with EVLP does not increase the incidence and severity of PGD after LTx. Although comparison of PGD 3 incidence in the two groups did not reach a statistical difference, all EVLP patients suffering from severe PGD early after transplant recovered normal lung function at 72 h, suggesting a protective role of EVLP against PGD occurrence and severity

The Effectiveness of Cyrene as a Solvent in Exfoliating 2D TMDs Nanosheets

The pursuit of environmentally friendly solvents has become an essential research topic in sustainable chemistry and nanomaterial science. With the need to substitute toxic solvents in nanofabrication processes becoming more pressing, the search for alternative solvents has taken on a crucial role in this field. Additionally, the use of toxic, non-economical organic solvents, such as N-methyl-2 pyrrolidone and dimethylformamide, is not suitable for all biomedical applications, even though these solvents are often considered as the best exfoliating agents for nanomaterial fabrication. In this context, the success of producing two-dimensional transition metal dichalcogenides (2D TMDs), such as MoS2 and WS2, with excellent captivating properties is due to the ease of synthesis based on environment-friendly, benign methods with fewer toxic chemicals involved. Herein, we report for the first time on the use of cyrene as an exfoliating agent to fabricate monolayer and few-layered 2D TMDs with a versatile, less time-consuming liquid-phase exfoliation technique. This bio-derived, aprotic, green and eco-friendly solvent produced a stable, surfactant-free, concentrated 2D TMD dispersion with very interesting features, as characterized by UV–visible and Raman spectroscopies. The surface charge and morphology of the fabricated nanoflakes were analyzed using ς-potential and scanning electron microscopy. The study demonstrates that cyrene is a promising green solvent for the exfoliation of 2D TMD nanosheets with potential advantages over traditional organic solvents. The ability to produce smaller-sized—especially in the case of WS2 as compared to MoS2—and mono/few-layered nanostructures with higher negative surface charge values makes cyrene a promising candidate for various biomedical and electronic applications. Overall, the study contributes to the development of sustainable and environmentally friendly methods for the production of 2D nanomaterials for various applications

Electron spin polarization in realistic trajectories around the magnetic node of two counter-propagating, circularly polarized, ultra-intense lasers

It has recently been suggested that two counter-propagating, circularly polarized, ultra-intense lasers can induce a strong electron spin polarization at the magnetic node of the electromagnetic field that they setup (Del Sorbo et al 2017 Phys. Rev. A 96 043407). We confirm these results by considering a more sophisticated description that integrates over realistic trajectories. The electron dynamics is weakly affected by the variation of power radiated due to the spin polarization. The degree of spin polarization differs by approximately 5% if considering electrons initially at rest or already in a circular orbit. The instability of trajectories at the magnetic node induces a spin precession associated with the electron migration that establishes an upper temporal limit to the polarization of the electron population of about one laser period

Signatures of quantum effects on radiation reaction in laser-electron-beam collisions

Two signatures of quantum effects on radiation reaction in the collision of a GeV electron beam with a high intensity (>3×1020Wcm-2]]>) laser pulse have been considered. We show that the decrease in the average energy of the electron beam may be used to measure the Gaunt factor for synchrotron emission. We derive an equation for the evolution of the variance in the energy of the electron beam in the quantum regime, i.e. quantum efficiency parameter . We show that the evolution of the variance may be used as a direct measure of the quantum stochasticity of the radiation reaction and determine the parameter regime where this is observable. For example, stochastic emission results in a 25% increase in the standard deviation of the energy spectrum of a GeV electron beam, 1 fs after it collides with a laser pulse of intensity 1021W cm-2. This effect should therefore be measurable using current high-intensity laser systems

Prediction of SARS-CoV-2-Related Lung Inflammation Spreading by V:ERITAS (Vanvitelli Early Recognition of Inflamed Thoracic Areas Spreading)

Background Coronavirus disease 2019 (COVID-19) can be complicated by interstitial pneu-monia, possibly leading to severe acute respiratory failure and death. Because of variable evolution ranging from asymptomatic cases to the need for invasive ventilation, COVID-19 outcomes cannot be precisely predicted on admission. The aim of this study was to provide a simple tool able to predict the outcome of COVID-19 pneumonia on admission to a low-intensity ward in order to better plan management strategies for these patients. Methods The clinical records of 123 eligible patients were reviewed. The following variables were analyzed on admission: chest computed tomography severity score (CTSS), PaO2/FiO2 ratio, lactate dehydrogenase (LDH), neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio, C-reactive protein (CRP), fibrinogen, D-dimer, aspartate aminotransferase (AST), alanine aminotransferase, alkaline phosphatase, and albumin. The main outcome was the intensity of respiratory support (RS). To simplify the statistical analysis, patients were split into two main groups: those requiring no or low/moderate oxygen support (group 1); and those needing subintensive/intensive RS up to mechanical ventilation (group 2). Results The RS intensity was significantly associated with higher CTSS and NLR scores; lower PaO2/FiO2 ratios; and higher serum levels of LDH, CRP, D-dimer, and AST. After multivariate logistic regression and ROC curve analysis, CTSS and LDH were shown to be the best predictors of respiratory function worsening. Conclusions Two easy-to-obtain parameters (CTSS and LDH) were able to reliably predict a worse evolution of COVID-19 pneumonia with values of >7 and >328 U/L, respectively

Efficient ion acceleration and dense electron-positron plasma creation in ultra-high intensity laser-solid interactions

The radiation pressure of next generation ultra-high intensity ($>10^{23}$ W/cm$^{2}$) lasers could efficiently accelerate ions to GeV energies. However, nonlinear quantum-electrodynamic effects play an important role in the interaction of these laser pulses with matter. Here we show that these effects may lead to the production of an extremely dense ($\sim10^{24}$ cm$^{-3}$) pair-plasma which absorbs the laser pulse consequently reducing the accelerated ion energy and energy conversion efficiency by up to 30-50\%

Tocilizumab in Hospitalized Patients with Severe Covid-19 Pneumonia

BACKGROUND Coronavirus disease 2019 (Covid-19) is associated with immune dysregulation and hyperinflammation, including elevated interleukin-6 levels. The use of tocilizu- mab, a monoclonal antibody against the interleukin-6 receptor, has resulted in better outcomes in patients with severe Covid-19 pneumonia in case reports and retrospective observational cohort studies. Data are needed from randomized, placebo-controlled trials. METHODS In this phase 3 trial, we randomly assigned patients who were hospitalized with severe Covid-19 pneumonia in a 2:1 ratio receive a single intravenous infusion of tocilizumab (at a dose of 8 mg per kilogram of body weight) or placebo. Approxi- mately one quarter of the participants received a second dose of tocilizumab or placebo 8 to 24 hours after the first dose. The primary outcome was clinical status at day 28 on an ordinal scale ranging from 1 (discharged or ready for discharge) to 7 (death) in the modified intention-to-treat population, which included all the patients who had received at least one dose of tocilizumab or placebo. RESULTS Of the 452 patients who underwent randomization, 438 (294 in the tocilizumab group and 144 in the placebo group) were included in the primary and secondary analyses. The median value for clinical status on the ordinal scale at day 28 was 1.0 (95% confidence interval [CI], 1.0 to 1.0) in the tocilizumab group and 2.0 (non-ICU hospitalization without supplemental oxygen) (95% CI, 1.0 to 4.0) in the placebo group (between-group difference, −1.0; 95% CI, −2.5 to 0; P=0.31 by the van Elteren test). In the safety population, serious adverse events occurred in 103 of 295 patients (34.9%) in the tocilizumab group and in 55 of 143 patients (38.5%) in the placebo group. Mortality at day 28 was 19.7% in the tocilizumab group and 19.4% in the placebo group (weighted difference, 0.3 percentage points (95% CI, –7.6 to 8.2; nominal P=0.94). CONCLUSIONS In this randomized trial involving hospitalized patients with severe Covid-19 pneu- monia, the use of tocilizumab did not result in significantly better clinical status or lower mortality than placebo at 28 days. (Funded by F. Hoffmann–La Roche and the Department of Health and Human Services; COVACTA ClinicalTrials.gov num- ber, NCT04320615.