Biochemical and Cellular Characterization of New Radio-Resistant Cell Lines Reveals a Role of Natural Flavonoids to Bypass Senescence

Cancer is one of the main causes of death worldwide, and, among the most frequent cancer types, osteosarcoma accounts for 56% of bone neoplasms observed in children and colorectal cancer for 10.2% of tumors diagnosed in the adult population. A common and frequent hurdle in cancer treatment is the emergence of resistance to chemo- and radiotherapy whose biological causes are largely unknown. In the present work, human osteosarcoma (SAOS) and colorectal adenocarcinoma (HT29) cell lines were γ-irradiated at doses mimicking the sub-lethal irradiation in clinical settings to obtain two radio-resistant cellular sub-populations named SAOS400 and HT500, respectively. Since “therapy-induced senescence” (TIS) is often associated with tumor response to radiotherapy in cancer cells, we measured specific cellular and biochemical markers of senescence in SAOS400 and HT500 cells. In detail, both cell lines were characterized by a higher level of expression of cyclin-dependent kinase inhibitors p16^INK4 and p21^CIP1 and increased positivity to SAβ-gal (senescence-associated β-galactosidase) with respect to parental cells. Moreover, the intracellular levels of reactive oxygen species in the resistant cells were significantly lower compared to the parental counterparts. Subsequently, we demonstrated that senolytic agents were able to sensitize SAOS400 and HT500 to cell death induced by γ-irradiation. Employing two natural flavonoids, fisetin and quercetin, and a BH3-mimetic, ABT-263/navitoclax, we observed that their association with γ-irradiation significantly reduced the expression of p16^INK4, p21^CIP1 and synergistically (combination index < 1) increased cell death compared to radiation mono-alone treatments. The present results reinforce the potential role of senolytics as adjuvant agents in cancer therapy.     

Storage of chicken breast meat in paper coated with different types of hydrophobic agents

Chicken meat is well known for its high nutritional value. Its shelf life is short, due to the pronounced perishability, even under refrigeration. Paper bags are usually used as packaging materials, due to their biodegradability. The main negative aspect concerning paper is its high porosity and low moisture barrier. In this regard, it has to be coated/modified with efficient moisture barrier materials. The storage of chicken breast meat wrapped in four types of paper-based materials currently in use in Romania (RO), Italy (IT), Spain (SP) and Slovenia (SLO) is reported. RO and IT are paper coated with polyethylene (PE) film, SP is waxed paper, and SLO is paper modified with hydrophobized starch. The influence of the coating film on the organoleptical, biochemical and microbiological characteristics of the chicken breast meat stored at 4°C was the aim of the study. The mathematical modelling revealed two aspects: (1) the stability period in which the meat safe for consumption is in the range 1.92–2.18 days in the case of all paper types, and (2) cadaverine, the amine generated by protein degradation, is a less sensitive indicator of the meat alteration than microbial growth. The papers coated with PE (RO and IT samples) and with hydrophobized starch (SLO paper) were packaging materials more efficient that the waxed paper (SP sample). The polyethylene film reduced the conversion of putrescine into spermidine in a higher extent than wax.     

The Impact of X-Ray Radiation on Chemical and Optical Properties of Triple-Cation Lead Halide Perovskite: from the Surface to the Bulk

Understanding the effects of X-rays on halide perovskite thin films is critical for accurate and reliable characterization of this class of materials, as well as their use in detection systems. In this study, advanced optical imaging techniques are employed, both spectrally and temporally resolved, coupled with chemical characterizations to obtain a comprehensive picture of the degradation mechanism occurring in the material during photoemission spectroscopy measurements. Two main degradation pathways are identified through the use of local correlative physico-chemical analysis. The first one, at low X-Ray fluence, shows minor changes of the surface chemistry and composition associated with the formation of electronic defects. Moreover, a second degradation route occurring at higher fluence leads to the evaporation of the organic cations and the formation of an iodine-poor perovskite. Based on the local variation of the optoelectronic properties, a kinetic model describing the different mechanisms is proposed. These findings provide valuable insight on the impact of X-rays on the perovskite layers during investigations using X-ray based techniques. More generally, a deep understanding of the interaction mechanism of X-rays with perovskite thin films is essential for the development of perovskite-based X-ray detectors and solar for space applications.     

Improving Néel Domain Walls Dynamics and Skyrmion Stability Using He Ion Irradiation

Ion irradiation with light ions is an appealing way to finely tune the magnetic properties of thin magnetic films and in particular the perpendicular magnetic anisotropy (PMA). In this work, the effect of He⁺ irradiation on the magnetization reversal and on the domain wall dynamics  of Pt/Co/AlOx trilayers is illustrated. Fluences up to 1.5 × 10¹⁵ ions cm⁻² strongly decrease the PMA, without affecting neither the spontaneous magnetization nor the strength of the interfacial Dzyaloshinskii–Moriya interaction (DMI). This confirms experimentally the robustness of the DMI interaction against interfacial chemical intermixing, already predicted by theory. In parallel with the decrease of the PMA, a strong decrease of the domain wall depinning field is observed after irradiation. This allows the domain walls to reach large maximum velocities with a lower magnetic field compared to that needed for the pristine films. Decoupling PMA from DMI can, therefore, be beneficial for the design of low energy devices based on domain wall dynamics. When the samples are irradiated with larger He⁺ fluences, the magnetization gets close to the out-of-plane/in-plane reorientation transition, where ≈100nm size magnetic skyrmions are stabilized. It is observed that as the He⁺ fluence increases, the skyrmion size decreases while these magnetic textures become more stable against the application of an external magnetic field, as predicted by theoretical models developed for ultrathin films with labyrinthine domains.     

Trapped Pore Waters in the Open Proton Channel HV1

The voltage-gated proton channel, H_V1, is crucial for innate immune responses. According to alternative hypotheses, protons either hop on top of an uninterrupted water wire or bypass titratable amino acids, interrupting the water wire halfway across the membrane. To distinguish between both hypotheses, the water mobility for the putative case of an uninterrupted wire is estimated. The predicted single-channel water permeability 2.3 × 10⁻¹² cm³ s⁻¹ reflects the permeability-governing number of hydrogen bonds between water molecules in single-file configuration and pore residues. However, the measured unitary water permeability does not confirm the predicted value. Osmotic deflation of reconstituted lipid vesicles reveals negligible water permeability of the H_V1 wild-type channel and the D174A mutant open at 0 mV. The conductance of 1400 H⁺ s⁻¹ per wild-type channel agrees with the calculated diffusion limit for a ≈2 Å capture radius for protons. Removal of a charged amino acid (D174) at the pore mouth decreases H⁺ conductance by reducing the capture radius. At least one intervening amino acid contributes to H⁺ conductance while interrupting the water wire across the membrane.     

Boronic Acid Moieties Stabilize Adhesion of Microalgal Biofilms on Glassy Substrates: A Chemical Tool for Environmental Applications

Photosynthetic organisms such as diatoms microalgae provide innovative routes to eco-friendly technologies for environmental pollution bioremediation. Living diatoms are capable to incorporate in vivo a wide variety of chemical species dispersed in seawater, thus being promising candidates for eco-friendly removal of toxic contaminants. However, their exploitation requires immobilization methods that allow to confine microalgae during water treatment. Here we demonstrate that a biofilm of Phaeodactylum tricornutum diatom cells grown on the surface of a glassy substrate bearing boronic acid protruding moieties is stably anchored to the substrate resisting mechanical stress and it is suitable for removal of up to 80 % metal ions (As, Cr, Cu, Zn, Sn, Pb, Sb) in a model polluted water sample. Control experiments also suggest that stabilization of the biofilm adhesion occurs by interaction of boronic acid surface groups of the substrate with the hydroxyl groups of diatoms extracellular polysaccharides.