Back to the roots, desiccation and radiation resistances are ancestral characters in bdelloid rotifers.

BACKGROUND: Bdelloid rotifers are micro-invertebrates distributed worldwide, from temperate latitudes to the most extreme areas of the planet like Antarctica or the Atacama Desert. They have colonized any habitat where liquid water is temporarily available, including terrestrial environments such as soils, mosses, and lichens, tolerating desiccation and other types of stress such as high doses of ionizing radiation (IR). It was hypothesized that bdelloid desiccation and radiation resistance may be attributed to their potential ability to repair DNA double-strand breaks (DSBs). Here, these properties are investigated and compared among nine bdelloid species collected from both mild and harsh habitats, addressing the correlation between the ability of bdelloid rotifers to survive desiccation and their capacity to repair massive DNA breakage in a phylogenetically explicit context. Our research includes both specimens isolated from habitats that experience frequent desiccation (at least 1 time per generation), and individuals sampled from habitats that rarely or never experienced desiccation. RESULTS: Our analysis reveals that DNA repair prevails in somatic cells of both desiccation-tolerant and desiccation-sensitive bdelloid species after exposure to X-ray radiation. Species belonging to both categories are able to withstand high doses of ionizing radiation, up to 1000 Gy, without experiencing any negative effects on their survival. However, the fertility of two desiccation-sensitive species, Rotaria macrura and Rotaria rotatoria, was more severely impacted by low doses of radiation than that of desiccation-resistant species. Surprisingly, the radioresistance of desiccation-resistant species is not related to features of their original habitat. Indeed, bdelloids isolated from Atacama Desert or Antarctica were not characterized by a higher radioresistance than species found in more temperate environments. CONCLUSIONS: Tolerance to desiccation and radiation are supported as ancestral features of bdelloid rotifers, with a group of species of the genus Rotaria having lost this trait after colonizing permanent water habitats. Together, our results provide a comprehensive overview of the evolution of desiccation and radiation resistance among bdelloid rotifers.

Indacaterol inhibits collective cell migration and IGDQ-mediated single cell migration in metastatic breast cancer MDA-MB-231 cells.

Metastasis is the main cause of deaths related to breast cancer. This is particular the case for triple negative breast cancer. No targeted therapies are reported as efficient until now. The extracellular matrix, in particular the fibronectin type I motif IGDQ, plays a major role in regulating cell migration prior metastasis formation. This motif interacts with specific integrins inducing their activation and the migratory signal transduction.Here, we characterized the migratory phenotype of MDA-MB-231 cells, using functionalized IGDQ-exposing surfaces, and compared it to integrin A5 and integrin B3 knock-down cells. A multiomic analysis was developed that highlighted the splicing factor SRSF6 as a putative master regulator of cell migration and of integrin intracellular trafficking. Indacaterol-induced inhibition of SRSF6 provoked: i) the inhibition of collective and IGDQ-mediated cell migration and ii) ITGA5 sequestration into endosomes and lysosomes. Upon further studies, indacaterol may be a potential therapy to prevent cell migration and reduce metastasis formation in breast cancer. Video Abstract.

Investigation of the Antibacterial Properties of Silver-Doped Amorphous Carbon Coatings Produced by Low Pressure Magnetron Assisted Acetylene Discharges.

Hospital-acquired infections are responsible for a significant part of morbidity and mortality. Among the possible modes of transmission, this study focuses on environmental surfaces by developing innovative antibacterial coatings that can be applied on interior fittings in hospitals. This work aims to optimize a coating made of an amorphous carbon matrix doped with silver (a-C:H:Ag) produced by a hybrid PVD/PECVD process and to evaluate its antibacterial activity. We present a coating characterization (chemical composition and morphology) as well as its stability in an ageing process and after multiple exposures to bacteria. The antibacterial activity of the coatings is demonstrated against Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive) bacteria through several bioassays. Moreover, the data suggest a crucial role of silver diffusion towards the surface and nanoparticle formation to explain the very promising anti-bacterial activities reported in this work.

High performance of 3D silicon nanowires array@CrN for electrochemical capacitors.

Silicon nanowire (SiNW) arrays were coated with chromium nitride (CrN) for use as supercapacitor electrodes. The CrN layer of different thicknesses was deposited onto SiNWs using bipolar magnetron sputtering method. The areal capacitance of the SiNWs-CrN, as measured in 0.5 M H2SO4 electrolyte, was as high as 180 mF cm-2 at a scan rate of 5 mV s-1 (equivalent to 31.8 mF cm-2 at 1.6 mA cm-2) with an excellent electrochemical retention of 92% over 15 000 cycles. This work paves the way toward using CrN modified 3D SiNWs arrays for micro-supercapacitor application.

Is aggregated synthetic amorphous silica toxicologically relevant?

BACKGROUND: The regulatory definition(s) of nanomaterials (NMs) frequently uses the term 'agglomerates and aggregates' (AA) despite the paucity of evidence that AA are significantly relevant from a nanotoxicological perspective. This knowledge gap greatly affects the safety assessment and regulation of NMs, such as synthetic amorphous silica (SAS). SAS is used in a large panel of industrial applications. They are primarily produced as nano-sized particles (1-100 nm in diameter) and considered safe as they form large aggregates (> 100 nm) during the production process. So far, it is indeed believed that large aggregates represent a weaker hazard compared to their nano counterpart. Thus, we assessed the impact of SAS aggregation on in vitro cytotoxicity/biological activity to address the toxicological relevance of aggregates of different sizes. RESULTS: We used a precipitated SAS dispersed by different methods, generating 4 ad-hoc suspensions with different aggregate size distributions. Their effect on cell metabolic activity, cell viability, epithelial barrier integrity, total glutathione content and, IL-8 and IL-6 secretion were investigated after 24 h exposure in human bronchial epithelial (HBE), colon epithelial (Caco2) and monocytic cells (THP-1). We observed that the de-aggregated suspension (DE-AGGR), predominantly composed of nano-sized aggregates, induced stronger effects in all the cell lines than the aggregated suspension (AGGR). We then compared DE-AGGR with 2 suspensions fractionated from AGGR: the precipitated fraction (PREC) and the supernatant fraction (SuperN). Very large aggregates in PREC were found to be the least cytotoxic/biologically active compared to other suspensions. SuperN, which contains aggregates larger in size (> 100 nm) than in DE-AGGR but smaller than PREC, exhibited similar activity as DE-AGGR. CONCLUSION: Overall, aggregation resulted in reduced toxicological activity of SAS. However, when comparing aggregates of different sizes, it appeared that aggregates > 100 nm were not necessarily less cytotoxic than their nano-sized counterparts. This study suggests that aggregates of SAS are toxicologically relevant for the definition of NMs.

Correlation of structural and optical properties using virtual materials analysis.

Thin film growth of ${\textrm{TiO}}_2$TiO2 by physical vapor deposition processes is simulated in the Virtual Coater framework resulting in virtual thin films. The simulations are carried out for artificial, simplified deposition conditions as well as for conditions representing a real coating process. The study focuses on porous films which exhibit a significant anisotropy regarding the atomistic structure and consequently, to the index of refraction. A method how to determine the effective anisotropic index of refraction of virtual thin films by the effective medium theory is developed. The simulation applies both, classical molecular dynamics as well as kinetic Monte Carlo calculations, and finally the properties of the virtual films are compared to experimentally grown films especially analyzing the birefringence in the evaluation.

HIF-1α is a key mediator of the lung inflammatory potential of lithium-ion battery particles.

BACKGROUND: Li-ion batteries (LIB) are increasingly used worldwide. They are made of low solubility micrometric particles, implying a potential for inhalation toxicity in occupational settings and possibly for consumers. LiCoO2 (LCO), one of the most used cathode material, induces inflammatory and fibrotic lung responses in mice. LCO also stabilizes hypoxia-inducible factor (HIF) -1α, a factor implicated in inflammation, fibrosis and carcinogenicity. Here, we investigated the role of cobalt, nickel and HIF-1α as determinants of toxicity, and evaluated their predictive value for the lung toxicity of LIB particles in in vitro assays. RESULTS: By testing a set of 5 selected LIB particles (LCO, LiNiMnCoO2, LiNiCoAlO2) with different cobalt and nickel contents, we found a positive correlation between their in vivo lung inflammatory activity, and (i) Co and Ni particle content and their bioaccessibility and (ii) the stabilization of HIF-1α in the lung. Inhibition of HIF-1α with chetomin or PX-478 blunted the lung inflammatory response to LCO in mice. In IL-1ß deficient mice, HIF-1α was the upstream signal of the inflammatory lung response to LCO. In vitro, the level of HIF-1α stabilization induced by LIB particles in BEAS-2B cells correlated with the intensity of lung inflammation induced by the same particles in vivo. CONCLUSIONS: We conclude that HIF-1α, stabilized in lung cells by released Co and Ni ions, is a mechanism-based biomarker of lung inflammatory responses induced by LIB particles containing Co/Ni. Documenting the Co/Ni content of LIB particles, their bioaccessibility and their capacity to stabilize HIF-1α in vitro can be used to predict the lung inflammatory potential of LIB particles.

Subchronic exposure to titanium dioxide nanoparticles modifies cardiac structure and performance in spontaneously hypertensive rats.

BACKGROUND: Non-communicable diseases, intended as the results of a combination of inherited, environmental and biological factors, kill 40 million people each year, equivalent to roughly 70% of all premature deaths globally. The possibility that manufactured nanoparticles (NPs) may affect cardiac performance, has led to recognize NPs-exposure not only as a major Public Health concern, but also as an occupational hazard. In volunteers, NPs-exposure is problematic to quantify. We recently found that inhaled titanium dioxide NPs, one of the most produced engineered nanomaterials, acutely increased cardiac excitability and promoted arrhythmogenesis in normotensive rats by a direct interaction with cardiac cells. We hypothesized that such scenario can be exacerbated by latent cardiovascular disorders such as hypertension. RESULTS: We monitored cardiac electromechanical performance in spontaneously hypertensive rats (SHRs) exposed to titanium dioxide NPs for 6 weeks using a combination of cardiac functional measurements associated with toxicological, immunological, physical and genetic assays. Longitudinal radio-telemetry ECG recordings and multiple-lead epicardial potential mapping revealed that atrial activation times significantly increased as well as proneness to arrhythmia. At the third week of nanoparticles administration, the lung and cardiac tissue encountered a maladaptive irreversible structural remodelling starting with increased pro-inflammatory cytokines levels and lipid peroxidation, resulting in upregulation of the main pro-fibrotic cardiac genes. At the end of the exposure, the majority of spontaneous arrhythmic events terminated, while cardiac hemodynamic deteriorated and a significant accumulation of fibrotic tissue occurred as compared to control untreated SHRs. Titanium dioxide nanoparticles were quantified in the heart tissue although without definite accumulation as revealed by particle-induced X-ray emission and ultrastructural analysis. CONCLUSIONS: The co-morbidity of hypertension and inhaled nanoparticles induces irreversible hemodynamic impairment associated with cardiac structural damage potentially leading to heart failure. The time-dependence of exposure indicates a non-return point that needs to be taken into account in hypertensive subjects daily exposed to nanoparticles.

Vapor sensing with a natural photonic cell.

Photonic structures encased by a permeable envelope give rise to iridescent blue color in the scales covering the male Hoplia coerulea beetle. This structure comprises a periodic porous multilayer. The color of these scales is known for changing from blue to green upon contact with water despite the presence of the envelope. This optical system has been referred to as a photonic cell due to the role of the envelope that mediates fluid exchanges with the surrounding environment. Following from previously studied liquid-induced changes in the color appearance of H. coerulea, we measured vapor-induced color changes in its appearance. This response to vapor exposure was marked by reflectance redshift and an increase in peak reflectance intensity. Different physico-chemical processes were investigated to explain the increase in reflectance intensity, a property not usually associated with vapor-induced optical signature changes. These simulations indicated the optical response arose from physisorption of a liquid film on the beetle scales followed by liquid penetration through the envelope and the filling of micropores within the body of the photonic structure.

LET-dependent radiosensitization effects of gold nanoparticles for proton irradiation.

The development of new modalities and protocols is of major interest to improve the outcome of cancer treatment. Given the appealing physical properties of protons and the emerging evidence of biological relevance of the use of gold nanoparticles (GNPs), the radiosensitization effects of GNPs (5 or 10 nm) have been investigated in vitro in combination with a proton beam of different linear energy transfer (LET). After the incubation with GNPs for 24 h, nanoparticles were observed in the cytoplasm of A431 cells exposed to 10 nm GNPs, and in the cytoplasm as well as the nucleus of cells exposed to 5 nm GNPs. Cell uptake of 0.05 mg ml-1 of GNPs led to 0.78 pg Au/cell and 0.30 pg Au/cell after 24 h incubation for 10 and 5 nm GNPs respectively. A marked radiosensitization effect of GNPs was observed with 25 keV µm-1 protons, but not with 10 keV µm-1 protons. This effect was more pronounced for 10 nm GNPs than for 5 nm GNPs. By using a radical scavenger, a major role of reactive oxygen species in the amplification of the death of irradiated cell was identified. All together, these results open up novel perspectives for using high-Z metallic NPs in protontherapy.

Physicochemical and toxicological evaluation of silica nanoparticles suitable for food and consumer products collected by following the EC recommendation.

Specific information about the particle size distribution, agglomeration state, morphology, and chemical composition of four silica samples, used as additives in food and in personal care products, were achieved with a combination of analytical techniques. The combined use of differential centrifugal sedimentation (DCS), sedimentation field flow fractionation (SdFFF), and scanning and transmission electron microscopy (SEM and TEM) allows to classify the water dispersed samples as "nanomaterials" according to the EC definition. The mechanical stirring and the ultrasound treatment were compared as dispersion methods. The particle surface chemical composition, determined by particle-induced X-ray emission (PIXE) and X-ray photoelectron spectroscopy (XPS), assessed the different levels of purity between the pyrogenic and the precipitated silica and highlighted particle surface chemical composition modifications in the outer shell when dispersed by mechanical stirring. The potential toxic effects of silica on intestinal Caco-2 cells were investigated using MTS assay and by measuring lactate dehydrogenase (LDH) release and caspases 3/7 activity after 24 h of incubation. No or limited decrease of cell viability was observed for all particles regardless of dispersion procedure, suggesting a relative innocuity of these silica samples.

Synergistic Effect of He for the Fabrication of Ne and Ar Gas-Charged Silicon Thin Films as Solid Targets for Spectroscopic Studies.

Sputtering of silicon in a He magnetron discharge (MS) has been reported as a bottom-up procedure to obtain He-charged silicon films (i.e., He nanobubbles encapsulated in a silicon matrix). The incorporation of heavier noble gases is demonstrated in this work with a synergistic effect, producing increased Ne and Ar incorporations when using He-Ne and He-Ar gas mixtures in the MS process. Microstructural and chemical characterizations are reported using ion beam analysis (IBA) and scanning and transmission electron microscopies (SEM and TEM). In addition to gas incorporation, He promotes the formation of larger nanobubbles. In the case of Ne, high-resolution X-ray photoelectron and absorption spectroscopies (XPS and XAS) are reported, with remarkable dependence of the Ne 1s photoemission and the Ne K-edge absorption on the nanobubble's size and composition. The gas (He, Ne and Ar)-charged thin films are proposed as "solid" targets for the characterization of spectroscopic properties of noble gases in a confined state without the need for cryogenics or high-pressure anvils devices. Also, their use as targets for nuclear reaction studies is foreseen.

Advances in the Mechanistic Understanding of Iron Oxide Nanoparticles' Radiosensitizing Properties.

Among the plethora of nanosystems used in the field of theranostics, iron oxide nanoparticles (IONPs) occupy a central place because of their biocompatibility and magnetic properties. In this study, we highlight the radiosensitizing effect of two IONPs formulations (namely 7 nm carboxylated IONPs and PEG5000-IONPs) on A549 lung carcinoma cells when exposed to 225 kV X-rays after 6 h, 24 h and 48 h incubation. The hypothesis that nanoparticles exhibit their radiosensitizing effect by weakening cells through the inhibition of detoxification enzymes was evidenced by thioredoxin reductase activity monitoring. In particular, a good correlation between the amplification effect at 2 Gy and the residual activity of thioredoxin reductase was observed, which is consistent with previous observations made for gold nanoparticles (NPs). This emphasizes that NP-induced radiosensitization does not result solely from physical phenomena but also results from biological events.

Effects of SiC nanoparticles orally administered in a rat model: biodistribution, toxicity and elemental composition changes in feces and organs.

BACKGROUND: Silicon carbide (SiC) presents noteworthy properties as a material such as high hardness, thermal stability, and photoluminescent properties as a nanocrystal. However, there are very few studies in regard to the toxicological potential of SiC NPs. OBJECTIVES: To study the toxicity and biodistribution of silicon carbide (SiC) nanoparticles in an in vivo rat model after acute (24h) and subacute (28days) oral administrations. The acute doses were 0.5, 5, 50, 300 and 600mg·kg(-1), while the subacute doses were 0.5 and 50mg·kg(-1). RESULTS: SiC biodistribution and elemental composition of feces and organs (liver, kidneys, and spleen) have been studied by Particle-Induced X-ray Emission (PIXE). SiC and other elements in feces excretion increased by the end of the subacute assessment. SiC did not accumulate in organs but some elemental composition modifications were observed after the acute assessment. Histopathological sections from organs (stomach, intestines, liver, and kidneys) indicate the absence of damage at all applied doses, in both assessments. A decrease in the concentration of urea in blood was found in the 50mg·kg(-1) group from the subacute assessment. No alterations in the urine parameters (sodium, potassium, osmolarity) were found. CONCLUSION: This is the first study that assesses the toxicity, biodistribution, and composition changes in feces and organs of SiC nanoparticles in an in vivo rat model. SiC was excreted mostly in feces and low traces were retrieved in urine, indicating that SiC can cross the intestinal barrier. No sign of toxicity was however found after oral administration.

Quantification of nanoparticles in aqueous food matrices using Particle-Induced X-ray Emission.

Nanoparticles (NPs) of SiO(2) (15 nm) or Ag (20 - 40 nm) were dispersed in water, coffee and milk at several aqueous dilutions. The NPs dispersions concentrations were quantified with an ion beam technique: Particle-Induced X-ray Emission. Additional measurements in relation to the state of the NPs dispersions were done: particle size distribution by centrifuge liquid sedimentation and the extreme surface composition by X-ray photoelectron spectroscopy. The particle size distribution of SiO(2) and Ag NPs dispersions in water and Ag NPs in coffee remained mostly as primary particles with hydrodynamic diameters close to the reported pristine NPs diameter. SiO(2) NPs agglomerated in coffee. In milk, both NPs presented an adsorption with milk lipids. Extreme surface composition corroborated adsorption in milk and showed that SiO(2) agglomerates adsorb some coffee components. A linear tendency in the measurement of the concentration dilutions of all dispersions was measured, and a lack of media influence in the slope of each curve was found. Limits of detection with the current setup were estimated at 0.5 and 0.3 mg/ml for SiO(2) and Ag NPs, respectively.

Taking Advantage of the Senescence-Promoting Effect of Olaparib after X-ray and Proton Irradiation Using the Senolytic Drug, ABT-263.

Radiotherapy (RT) is a key component of cancer treatment. Although improvements have been made over the years, radioresistance remains a challenge. For this reason, a better understanding of cell fates in response to RT could improve therapeutic options to enhance cell death and reduce adverse effects. Here, we showed that combining RT (photons and protons) to noncytotoxic concentration of PARP inhibitor, Olaparib, induced a cell line-dependent senescence-like phenotype. The senescent cells were characterized by morphological changes, an increase in p21 mRNA expression as well as an increase in senescence-associated ß-galactosidase activity. We demonstrated that these senescent cells could be specifically targeted by Navitoclax (ABT-263), a Bcl-2 family inhibitor. This senolytic drug led to significant cell death when combined with RT and Olaparib, while limited cytotoxicity was observed when used alone. These results demonstrate that a combination of RT with PARP inhibition and senolytics could be a promising therapeutic approach for cancer patients.

IGDQ motogenic peptide gradient induces directional cell migration through integrin (αv)ß3 activation in MDA-MB-231 metastatic breast cancer cells.

In the context of breast cancer metastasis study, we have shown in an in vitro model of cell migration that IGDQ-exposing (IsoLeu-Gly-Asp-Glutamine type I Fibronectin motif) monolayers (SAMs) on gold sustain the adhesion of breast cancer MDA-MB-231 cells by triggering Focal Adhesion Kinase and integrin activation. Such tunable scaffolds are used to mimic the tumor extracellular environment, inducing and controlling cell migration. The observed migratory behavior induced by the IGDQ-bearing peptide gradient along the surface allows to separate cell subpopulations with a "stationary" or "migratory" phenotype. In this work, we knocked down the integrins α5(ß1) and (αv)ß since they are already known to be implicated in cell migration. To this aim, a whole proteomic analysis was performed in beta 3 integrin (ITGB3) or alpha 5 integrin (ITGA5) knock-down MDA-MB-231 cells, in order to highlight the pathways implied in the integrin-dependent cell migration. Our results showed that i) ITGB3 depletion influenced ITGA5 mRNA expression, ii) ITGB3 and ITGA5 were both necessary for IGDQ-mediated directional single cell migration and iii) integrin (αv)ß3 was activated by IGDQ fibronectin type I motif. Finally, the proteomic analysis suggested that co-regulation of recycling transport of ITGB3 by ITGA5 is potentially necessary for directional IGDQ-mediated cell migration.

Growth mechanisms involved in the synthesis of smooth and microtextured films by acetylene magnetron discharges.

The growth of hydrogenated amorphous carbons (a-C:H) produced by continuous or pulsed discharges of acetylene (C(2)H(2)) in an unbalanced magnetron setup was investigated. At 5 × 10(-3) Torr, only smooth films are obtained, whereas at 5 × 10(-1) Torr using a pulsed discharge some microtextured films are formed if the duty cycle is low. The morphology of these microtextured films consists of nanoparticles, filamentary particles, and particular agglomerates ("microflowers"). This paper presents a study of acetylene gas phase polymerization by mass spectrometry, and a detailed analysis of bulk structure of films by combining three techniques which include IR spectroscopy, Raman spectroscopy, and laser desorption/ionization Fourier transform mass spectrometry (LDI-FTMS). Finally, based on the study of gas phase and film structure, we propose a model for the growth of both smooth and microtextured films.

Surface properties and cell adhesion onto allylamine-plasma and amine-plasma coated glass coverslips.

Surface properties of nanoparticles to be used for radioimmunotherapy need to be optimized to allow antibody conjugation while ensuring biocompatibility. We aimed to investigate cell adhesion and proliferation onto different coatings to be used for nanoparticles. C, CH(x) or SiO(x) coatings deposited onto glass coverslips by magnetron deposition as well as nitrogen functionalized materials synthetized using different reactive sputtering conditions and PPAA (plasma polymerized allylamine) coating, were compared. Amine functionalization did increase hydrophilicity in all the materials tested. Biocompatibility was assessed by measuring cell viability, morphology, attachment, spreading, and pro-inflammatory cytokine secretion. The results show that C and CN(x) were the most biocompatible substrates while SiO(x) and SiO(x)N(y) were the most toxic materials. PPAA coatings displayed unexpectedly an intermediate biocompatibility. A correlation could be observed between wettability and cell proliferation except for C coated surface, indicating that more complex processes than hydrophilicity alone are taking place that affect cell functions.

Gold nanoparticles meet medical radionuclides.

Thanks to their unique optical and physicochemical properties, gold nanoparticles have gained increased interest as radiosensitizing, photothermal therapy and optical imaging agents to enhance the effectiveness of cancer detection and therapy. Furthermore, their ability to carry multiple medically relevant radionuclides broadens their use to nuclear medicine SPECT and PET imaging as well as targeted radionuclide therapy. In this review, we discuss the radiolabeling process of gold nanoparticles and their use in (multimodal) nuclear medicine imaging to better understand their specific distribution, uptake and retention in different in vivo cancer models. In addition, radiolabeled gold nanoparticles enable image-guided therapy is reviewed as well as the enhancement of targeted radionuclide therapy and nanobrachytherapy through an increased dose deposition and radiosensitization, as demonstrated by multiple Monte Carlo studies and experimental in vitro and in vivo studies.