A strategy for grouping of nanomaterials based on key physico-chemical descriptors as a basis for safer-by-design NMs

SummaryThere is an urgent need to establish a fundamental understanding of the mechanisms of nanomaterial (NM) interaction with living systems and the environment, in order for regulation of NMs to keep pace with their increasing industrial application. Identification of critical properties (physicochemical descriptors) that confer the ability to induce harm in biological systems is crucial, enabling both prediction of impacts from related NMs (via quantitative nanostructure–activity relationships (QNARs) and read-across approaches) and development of strategies to ensure these features are avoided or minimised in NM production in the future (“safety by design”). A number of challenges to successful implementation of such a strategy exist, including: (i) the lack of widely available systematically varied libraries of NMs to enable generation of sufficiently robust datasets for development and validation of QNARs; (ii) the fact that many physicochemical properties of pristine NMs are inter-related and thus cannot be varied systematically in isolation from others (e.g. increasing surface charge may impact on hydrophobicity, or changing the shape of a NM may introduce defects or alter the atomic configuration of the surface); and (iii) the effect of ageing, transformation and biomolecule coating of NMs under environmental or biological conditions.A novel approach to identify interlinked physicochemical properties, and on this basis identify overarching descriptors (axes or principle components) which can be used to correlate with toxicity is proposed. An example of the approach is provided, using three principle components which we suggest can be utilised to fully describe each NM, these being the intrinsic (inherent) properties of the NM, composition (which we propose as a separate parameter) and extrinsic properties (interaction with media, molecular coronas etc.)

A lambda=3 mm molecular line survey of NGC1068. Chemical signatures of an AGN environment

We aimed to study the molecular composition of the interstellar medium (ISM) surrounding an Active Galactic Nucleus (AGN), by making an inventory of molecular species and their abundances, as well as to establish a chemical differentiation between starburst galaxies and AGN. We used the IRAM-30 m telescope to observe the central 1.5-2 kpc region of NGC1068, covering the frequencies between 86.2 GHz and 115.6 GHz. Using Boltzmann diagrams, we calculated the column densities of the detected molecules. We used a chemical model to reproduce the abundances found in the AGN, to determine the origin of each detected species, and to test the influence of UV fields, cosmic rays, and shocks on the ISM. We identified 24 different molecular species and isotopologues, among which HC3N, SO, N2H+, CH3CN, NS, 13CN, and HN13C are detected for the first time in NGC1068. We obtained the upper limits to the isotopic ratios 12C/13C=49, 16O/18O=177 and 32S/34S=5. Our chemical models suggest that the chemistry in the nucleus of NGC1068 is strongly influenced by cosmic rays, although high values of both cosmic rays and far ultraviolet (FUV) radiation fields also explain well the observations. The gas in the nucleus of NGC1068 has a different chemical composition as compared to starburst galaxies. The distinct physical processes dominating galaxy nuclei (e.g. C-shocks, UV fields, X-rays, cosmic rays) leave clear imprints in the chemistry of the gas, which allow to characterise the nucleus activity by its molecular abundances.Comment: 16 pages, 6 figures, 7 tables. Accepted for publication in Astronomy and Astrophysic

Lambda = 3 mm line survey of nearby active galaxies

We used the IRAM 30m telescope to observe the frequency range [86-116]GHz towards the central regions of the starburst galaxies M83, M82, and NGC253, the AGNs M51, NGC1068, and NGC7469, and the ULIRGs Arp220 and Mrk231. Assuming LTE conditions, we calculated the column densities of 27 molecules and 10 isotopologues. Among others, we report the first tentative detections of CH3CHO, HNCO, and NS in M82 and, for the first time in the extragalactic medium, HC5N in NGC253. Halpha recombination lines were only found in M82 and NGC253. Vibrationally excited lines of HC3N were only detected in Arp220. CH3CCH emission is only seen in the starburst-dominated galaxies. By comparison of the fractional abundances among the galaxies, we looked for the molecules that are best suited to characterise the chemistry of starbursts, AGNs and ULIRGs, as well as the differences among galaxies within the same group.Comment: 24 pages, 6 figures, 12 tables. Accepted for publication in Astronomy and Astrophysic

Anti-Inflammatory Characteristics of Local Anesthetics: Inhibition of TNF-α Secretion of Lipopolysaccharide-Stimulated Leucocytes in Human Blood Samples

Background. Local anesthetics (LAs) have potent anti-inflammatory properties. Inflammatory down-regulation is crucial in diseases with overactive immune reactions, such as acute respiratory distress syndrome (ARDS) and chronic inflammation. We investigated the influence of four LAs, procaine, lidocaine, mepivacaine, and bupivacaine, on the reduction of tumor necrosis factor-alpha (TNF-α) secretion in lipopolysaccharide (LPS)-activated human leucocytes. Methods. Blood samples of 28 individuals were stimulated with LPS. The reduction of TNF-α production by each of the four LAs added (0.5 mg/mL) was measured and correlated with biometric variables. A response was defined as reduction to <85% of initial levels. Results. All four LAs down-regulated the TNF-α secretion in 44–61%: Bupivacaine (44.4%), lidocaine (61.5%), mepivacaine (44.4%), and procaine (50% of the individuals, “responders”). The TNF-α secretion was reduced to 67.4, 68.0, 63.6, and 67.1% of the initial values in responders. The effects in both patients and healthy persons were the same. Interindividual responses to LAs were not correlated with the duration or type of complaints, basal TNF-α serum level, sex, BMI, or age of responders. Conclusions. Four clinically relevant LAs (amid-LA and ester-LA) attenuate the inflammatory response provoked by LPS. They are potential candidates for drug repositioning in treating overactive immune reactions and chronic inflammation

UBC®Rapid Test for detection of carcinoma in situ for bladder cancer

UBC®Rapid Test is a test that detects fragments of cytokeratins 8 and 18 in urine. We present results of a multicentre study measuring UBC®Rapid Test in bladder cancer patients and healthy controls with focus on carcinoma in situ (CIS) and high-grade bladder cancer. From our study with N = 452 patients, we made a stratified sub-analysis for carcinoma in situ of the urinary bladder. Clinical urine samples were used from 87 patients with tumours of the urinary bladder (23 carcinoma in situ, 23 non-muscle-invasive low-grade tumours, 21 non-muscle-invasive high-grade tumours and 20 muscle-invasive high-grade tumours) and from 22 healthy controls. The cut-off value was defined at 10.0 µg/L. Urine samples were analysed by the UBC®Rapid Test point-of-care system (concile Omega 100 POC reader). Pathological levels of UBC Rapid Test in urine are higher in patients with bladder cancer in comparison to the control group (p < 0.001). Sensitivity was calculated at 86.9% for carcinoma in situ, 30.4% for non-muscle-invasive low-grade bladder cancer, 71.4% for nonmuscle-invasive high grade bladder cancer and 60% for muscle-invasive high-grade bladder cancer, and specificity was 90.9%. The area under the curve of the quantitative UBC®Rapid Test using the optimal threshold obtained by receiveroperated curve analysis was 0.75. Pathological values of UBC®Rapid Test in urine are higher in patients with high-grade bladder cancer in comparison to low-grade tumours and the healthy control group. UBC®Rapid Test has potential to be more sensitive and specific urinary protein biomarker for accurate detection of high-grade patients and could be added especially in the diagnostics for carcinoma in situ and non-muscle-invasive high-grade tumours of urinary bladder cancer

Regulation of the arachidonic acid mobilization in macrophages by combustion-derived particles

<p>Abstract</p> <p>Background</p> <p>Acute exposure to elevated levels of environmental particulate matter (PM) is associated with increasing morbidity and mortality rates. These adverse health effects, e.g. culminating in respiratory and cardiovascular diseases, have been demonstrated by a multitude of epidemiological studies. However, the underlying mechanisms relevant for toxicity are not completely understood. Especially the role of particle-induced reactive oxygen species (ROS), oxidative stress and inflammatory responses is of particular interest.</p> <p>In this <it>in vitro </it>study we examined the influence of particle-generated ROS on signalling pathways leading to activation of the arachidonic acid (AA) cascade. Incinerator fly ash particles (MAF02) were used as a model for real-life combustion-derived particulate matter. As macrophages, besides epithelial cells, are the major targets of particle actions in the lung murine RAW264.7 macrophages and primary human macrophages were investigated.</p> <p>Results</p> <p>The interaction of fly ash particles with macrophages induced both the generation of ROS and as part of the cellular inflammatory responses a dose- and time-dependent increase of free AA, prostaglandin E₂/thromboxane B₂(PGE₂/TXB₂), and 8-isoprostane, a non-enzymatically formed oxidation product of AA. Additionally, increased phosphorylation of the mitogen-activated protein kinases (MAPK) JNK1/2, p38 and ERK1/2 was observed, the latter of which was shown to be involved in MAF02-generated AA mobilization and phosphorylation of the cytosolic phospolipase A₂. Using specific inhibitors for the different phospolipase A₂isoforms the MAF02-induced AA liberation was shown to be dependent on the cytosolic phospholipase A₂, but not on the secretory and calcium-independent phospholipase A₂. The initiation of the AA pathway due to MAF02 particle exposure was demonstrated to depend on the formation of ROS since the presence of the antioxidant N-acetyl-cysteine (NAC) prevented the MAF02-mediated enhancement of free AA, the subsequent conversion to PGE₂/TXB₂via the induction of COX-2 and the ERK1/2 and JNK1/2 phosphorylation. Finally we showed that the particle-induced formation of ROS, liberation of AA and PGE₂/TXB₂together with the phosphorylation of ERK1/2 and JNK1/2 proteins was decreased after pre-treatment of macrophages with the metal chelator deferoxamine mesylate (DFO).</p> <p>Conclusions</p> <p>These results indicate that one of the primary mechanism initiating inflammatory processes by incinerator fly ash particles seems to be the metal-mediated generation of ROS, which triggers via the MAPK cascade the activation of AA signalling pathway.</p

Inverse Design of All-dielectric Metasurfaces with Bound States in the Continuum

Metasurfaces with bound states in the continuum (BICs) have proven to be a powerful platform for drastically enhancing light-matter interactions, improving biosensing, and precisely manipulating near- and far-fields. However, engineering metasurfaces to provide an on-demand spectral and angular position for a BIC remains a prime challenge. A conventional solution involves a fine adjustment of geometrical parameters, requiring multiple time-consuming calculations. In this work, to circumvent such tedious processes, we develop a physics-inspired, inverse design method on all-dielectric metasurfaces for an on-demand spectral and angular position of a BIC. Our suggested method predicts the core-shell particles that constitute the unit cell of the metasurface, while considering practical limitations on geometry and available materials. Our method is based on a smart combination of a semi-analytical solution, for predicting the required dipolar Mie coefficients of the meta-atom, and a machine learning algorithm, for finding a practical design of the meta-atom that provides these Mie coefficients. Although our approach is exemplified in designing a metasurface sustaining a BIC, it can, also, be applied to many more objective functions. With that, we pave the way toward a general framework for the inverse design of metasurfaces in specific and nanophotonic structures in general.Comment: 20 pages, 5 figures, Supplementary Materia

Inverse design of all-dielectric metasurfaces with accidental bound states in the continuum

Metasurfaces with bound states in the continuum (BICs) have proven to be a powerful platform for drastically enhancing light–matter interactions, improving biosensing, and precisely manipulating near- and far-fields. However, engineering metasurfaces to provide an on-demand spectral and angular position for a BIC remains a prime challenge. A conventional solution involves a fine adjustment of geometrical parameters, requiring multiple time-consuming calculations. In this work, to circumvent such tedious processes, we develop a physics-inspired, inverse design method on all-dielectric metasurfaces for an on-demand spectral and angular position of a BIC. Our suggested method predicts the core–shell particles that constitute the unit cell of the metasurface, while considering practical limitations on geometry and available materials. Our method is based on a smart combination of a semi-analytical solution, for predicting the required dipolar Mie coefficients of the meta-atom, and a machine learning algorithm, for finding a practical design of the meta-atom that provides these Mie coefficients. Although our approach is exemplified in designing a metasurface sustaining a BIC, it can, also, be applied to many more objective functions. With that, we pave the way toward a general framework for the inverse design of metasurfaces in specific and nanophotonic structures in general