Oncolytic ImmunoViroTherapy : A long history of crosstalk between viruses and immune system for cancer treatment

Cancer Immunotherapy relies on harnessing a patient's immune system to fine-tune specific anti-tumor responses and ultimately eradicate cancer. Among diverse therapeutic approaches, oncolytic viruses (OVs) have emerged as a novel form of cancer immunotherapy. OVs are a naturally occurring or genetically modified class of viruses able to selectively kill cancer cells, leaving healthy cells unharmed; in the last two decades, the role of OVs has been redefined to act beyond their oncolytic activity. Indeed, the immunogenic cancer cell death mediated by OVs induces the release of tumor antigens that in turn induces anti-tumor immunity, allowing OVs to act as in situ therapeutic cancer vaccines. Additionally, OVs can be engineered for intratumoral delivery of immunostimulatory molecules such as tumor antigens or cytokines to further enhance anti-tumor response. Moreover, OVs can be used in combination with other cancer immunotherapeutic approaches such as Immune Checkpoint Inhibitors and CAR-T cells. The current review first defines the three main mechanisms of action (MOA) of OVs currently used in cancer therapy that are: i) Oncolysis, ii) OV-induced cancer-specific immune activation, and iii) Exploiting preexisting anti-viral immunity to enhance cancer therapy. Secondly, we focus on how OVs can induce and/or improve anti-cancer immunity in a specific or unspecific fashion, highlighting the importance of these approaches. Finally, the last part of the review analyses OVs combined with other cancer immunotherapies, revising present and future clinical applications. (c) 2021 Published by Elsevier Inc.Peer reviewe

A Critical Review of the Recent Improvements in Minimizing Nuclear Waste by Innovative Gas-Cooled Reactors

This paper presents a critical review of the recent improvements in minimizing nuclear waste in terms of quantities, long-term activities, and radiotoxicities by innovative GCRs, with particular emphasis to the results obtained at the University of Pisa. Regarding these last items, in the frame of some EU projects (GCFR, PUMA, and RAPHAEL), we analyzed symbiotic fuel cycles coupling current LWRs with HTRs, finally closing the cycle by GCFRs. Particularly, we analyzed fertile-free and Pu-Th-based fuel in HTR: we improved plutonium exploitation also by optimizing Pu/Th ratios in the fuel loaded in an HTR. Then, we chose GCFRs to burn residual MA. We have started the calculations on simplified models, but we ended them using more "realistic" models of the reactors. In addition, we have added the GCFR multiple recycling option usingkeffcalculations for all the reactors. As a conclusion, we can state that, coupling HTR with GCFR, the geological disposal issues concerning high-level radiotoxicity of MA can be considerably reduced

Laser-driven quantum magnonics and THz dynamics of the order parameter in antiferromagnets

The impulsive generation of two-magnon modes in antiferromagnets by femtosecond optical pulses, so-called femto-nanomagnons, leads to coherent longitudinal oscillations of the antiferromagnetic order parameter that cannot be described by a thermodynamic Landau-Lifshitz approach. We argue that this dynamics is triggered as a result of a laser-induced modification of the exchange interaction. In order to describe the oscillations we have formulated a quantum mechanical description in terms of magnon pair operators and coherent states. Such an approach allowed us to} derive an effective macroscopic equation of motion for the temporal evolution of the antiferromagnetic order parameter. An implication of the latter is that the photo-induced spin dynamics represents a macroscopic entanglement of pairs of magnons with femtosecond period and nanometer wavelength. By performing magneto-optical pump-probe experiments with 10 femtosecond resolution in the cubic KNiF$_3$ and the uniaxial K$_2$NiF$_4$ collinear Heisenberg antiferromagnets, we observed coherent oscillations at the frequency of 22 THz and 16 THz, respectively. The detected frequencies as a function of the temperature ideally fit the two-magnon excitation up to the N\'eel point. The experimental signals are described as dynamics of magnetic linear dichroism due to longitudinal oscillations of the antiferromagnetic vector.Comment: 25 pages, 10 figure

Widefield phototransient imaging for visualizing 3D motion of resonant particles in scattering environments

: Identifying, visualising and ultimately tracking dynamically moving non-fluorescent nanoparticles in the presence of non-specific scattering is a long-standing challenge across the nano- and life-sciences. In this work we demonstrate that our recently developed ultrafast holographic transient (UHT) microscope is ideally suited for meeting this challenge. We show that UHT microscopy allows reliably distinguishing off-resonant, dielectric, from resonant, metallic, nanoparticles, based on the phototransient signal: a pre-requisite for single-particle tracking in scattering environments. We then demonstrate the capability of UHT microscopy to holographically localize in 3D single particles over large volumes of view. Ultimately, we combine the two concepts to simultaneously track several tens of freely diffusing gold nanoparticles, within a 110 × 110 × 110 μm volume of view at an integration time of 10 ms per frame, while simultaneously recording their phototransient signals. The combined experimental concepts outlined and validated in this work lay the foundation for background-free 3D single-particle tracking applications or spectroscopy in scattering environments and are immediately applicable to systems as diverse as live cells and tissues or supported heterogeneous catalysts

Diamagnetism of real-space pairs above Tc in hole doped cuprates

The nonlinear normal state diamagnetism reported by Lu Li et al. [Phys. Rev. B 81, 054510 (2010)] is shown to be incompatible with an acclaimed Cooper pairing and vortex liquid above the resistive critical temperature. Instead it is perfectly compatible with the normal state Landau diamagnetism of real-space composed bosons, which describes the nonlinear magnetization curves in less anisotropic cuprates La-Sr-Cu-O (LSCO) and Y-Ba-Cu-O (YBCO) as well as in strongly anisotropic bismuth-based cuprates in the whole range of available magnetic fields.Comment: 4 pages, 4 figure

Tailoring the specificity of the type C feruloyl esterase FoFaeC from Fusarium oxysporum towards methyl sinapate by rational redesign based on small molecule docking simulations

The type C feruloyl esterase FoFaeC from Fusarium oxysporum is a newly discovered enzyme with high potential for use in the hydrolysis of lignocellulosic biomass but it shows low activity towards sinapates. In this work, small molecule docking simulations were employed in order to identify important residues for the binding of the four model methyl esters of hydroxycinnamic acids, methyl ferulate/caffeate/sinapate/p-coumarate, to the predicted structure of FoFaeC. Subsequently rational redesign was applied to the enzyme’ active site in order to improve its specificity towards methyl sinapate. A double mutation (F230H/T202V) was considered to provide hydrophobic environment for stabilization of the methoxy substitution on sinapate and a larger binding pocket. Five mutant clones and the wild type were produced in Pichia pastoris and biochemically characterized. All clones showed improved activity, substrate affinity, catalytic efficiency and turnover rate compared to the wild type against methyl sinapate, with clone P13 showing a 5-fold improvement in catalytic efficiency. Although the affinity of all mutant clones was improved against the four model substrates, the catalytic efficiency and turnover rate decreased for the substrates containing a hydroxyl substitution

Macrospin dynamics in antiferromagnets triggered by sub-20 femtosecond injection of nanomagnons

The understanding of how the sub-nanoscale exchange interaction evolves in macroscale correlations and ordered phases of matter, such as magnetism and superconductivity, requires to bridging the quantum and classical worlds. This monumental challenge has so far only been achieved for systems close to their thermodynamical equilibrium. Here we follow in real time the ultrafast dynamics of the macroscale magnetic order parameter in the Heisenberg antiferromagnet KNiF 3 triggered by the impulsive optical generation of spin excitations with the shortest possible nanometre wavelength and femtosecond period. Our magneto-optical pump-probe experiments also demonstrate the coherent manipulation of the phase and amplitude of these femtosecond nanomagnons, whose frequencies are defined by the exchange energy. These findings open up opportunities for fundamental research on the role of short-wavelength spin excitations in magnetism and strongly correlated materials; they also suggest that nanospintronics and nanomagnonics can employ coherently controllable spin waves with frequencies in the 20 THz domain

Effects of Probiotics Supplementation on Risk and Severity of Infections in Athletes: A Systematic Review

The aim of this review was to appraise the literature on the effects of probiotics supplementation on gastrointestinal (GI) and upper respiratory tract infection (URTI) risk and prognosis in athletes. The search was conducted using the following electronic databases: MEDLINE (PubMed); Web of Science; Scopus; and SPORTDiscus (EBSCO). According to the PRISMA guidelines, randomized controlled studies performed on healthy athletes with a note dose of probiotics supplementation were considered. From the 2304 articles found, after eliminating reviews and studies on animals and unhealthy subjects and after screening of titles and abstracts, 403 studies were considered eligible. From these, in accordance with the inclusion and exclusion criteria, 16 studies were selected, ten of which concerned endurance athletes. The majority of the studies reported beneficial effects of probiotics in reducing the risk of developing the examined infections or the severity of related symptoms. However, due to the differences in formulations used and populations analyzed in the available studies, further research is needed in this field to achieve stronger and more specific evidence