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Tumor heterogeneity represents a possible cause of error in detecting predictive genetic alterations on tumor tissue and can be overcome by testing alterations in circulating tumor DNA (ctDNA) using liquid biopsy. We assessed 72 consecutive patients with a diagnosis of metastatic colorectal cancer (mCRC) using Idylla™ Biocartis, a fully automated platform that evaluates the most frequent mutations of KRAS, NRAS and BRAF genes. We correlated the results of liquid biopsy and standard tissue-based next generation sequencing (NGS) analyses to patient clinical features. The overall agreement was 81.94%. Concordance was 85.71% and 96.15% in treatment-naïve patients and in the patient subgroup with liver metastases, respectively. In liver metastases positive, treatment-naïve patients, sensitivity, specificity and positive predictive value (PPV) were 92.31%, 100% and 100%, respectively. Circulating mutational fraction (CMF) was significantly higher in patients with liver metastases and high carcinoembryonic antigen (CEA) levels. In a subgroup of patients pre-treated with anti-Epidermal Growth Factor Receptor (EGFR) agents, emerging KRAS mutations were evidenced in 33% of cases. Testing RAS/BRAF mutations on plasma using the Idylla™ Biocartis platform is feasible and reliable in mCRC patients in clinical practice.

Molybdenum carbides have emerged as an optimal alternative to noble expensive materials for hydrogen evolution reaction (HER). Most reported synthesis methods involve prolonged operations at high temperatures in reactive gases environments. In this study, we introduce nanosecond Pulsed Laser Ablation in Liquid (PLAL) as a viable and environmental friendly approach for synthesizing molybdenum carbide by ablating a molybdenum (Mo) target in ethanol. Structural and compositional characterizations on the nanoparticles (NPs) reveal no oxidation and the absence of a graphitic shell, confirming the formation of hexagonal Mo 2 C and cubic MoC. The NPs loaded on nickel foam exhibit significant HER activity in an aqueous 1 M KOH electrolyte, with a potential of 136 mV vs. RHE at 10 mA cm − 2 and 240 mV at 50 mA cm − 2 . The calculated mass activity (0.05 A/cm 2 ) highlights the high intrinsic activity of this material compared to conventional and non-green synthesis methods reported in literature.

How nice would it be to obtain the size distribution of a nanoparticle dispersion fast and without electron microscope measurements? UV-Vis-NIR spectrophotometry offers a very rapid solution; however, the spectra interpretation can be very challenging and needs to take into account the size distribution of the nanoparticles and agglomeration. This work suggests a Monte Carlo method for rapid fitting UV-Vis-NIR spectra using one or two size distributions starting from a dataset of precomputed spectra based on Mie theory. The proposed algorithm is tested on copper nanoparticles produced with Pulsed Laser Ablation in Liquid and on gold nanoparticles from the literature. The fitted distribution results are comparable with Transmission Electron Microscope results and, in some cases, reflect the presence of agglomeration.

One important risk factor for the development of asthma is allergen sensitization. Recent increasing evidence suggests a prominent role of mast cells in asthma pathophysiology. Since Palmitoylethanolamide (PEA), an endogenous lipid mediator chemically related to - and co-released with- the endocannabinoid anandamide, behaves as a local autacoid down-regulator of mast cell activation and inflammation, we explored the possible contribution of PEA in allergic sensitization, by using ovalbumin (OVA) as sensitizing agent in the mouse. PEA levels were dramatically reduced in the bronchi of OVA-treated animals. This effect was coupled to a significant up-regulation of CB and GPR55 receptors, two of the proposed molecular PEA targets, in bronchi harvested from allergen-sensitized mice. PEA supplementation (10 mg/kg, 15 min before each allergen exposure) prevented OVA-induced bronchial hyperreactivity, but it did not affect IgE plasma increase. On the other hand, PEA abrogated allergen-induced cell recruitment as well as pulmonary inflammation. Evaluation of pulmonary sections evidenced a significant inhibitory action of PEA on pulmonary mast cell recruitment and degranulation, an effect coupled to a reduction of leukotriene C production. These findings demonstrate that allergen sensitization negatively affects PEA bronchial levels and suggest that its supplementation has the potential to prevent the development of asthma-like features.

Non-enzymatic electrochemical glucose sensors are of great importance in biomedical applications, for the realization of portable diabetic testing kits and continuous glucose monitoring systems. Nanostructured materials show a number of advantages in the applications of analytical electrochemistry, compared to macroscopic electrodes, such as great sensitivity and little dependence on analyte diffusion close to the electrode–solution interface. Obtaining electrodes based on nanomaterials without using expensive lithographic techniques represents a great added value. In this paper, we modeled the chronoamperometric response towards glucose determination by four electrodes consisting of nanostructured gold onto graphene paper (GP). The nanostructures were obtained by electrochemical etch, thermal and laser processes of thin gold layer. We addressed experiments obtaining different size and shape of gold nanostructures. Electrodes have been characterized by field emission scanning electron microscopy (FE-SEM), X-ray photoelectron spectroscopy (XPS), cyclic voltammetry, and chronoamperometry. We modeled the current-time response at the potential corresponding to two-electrons oxidation process of glucose by the different nanostructured gold systems. The finest nanostructures of 10–200 nm were obtained by laser dewetting of 17 nm thin and 300 °C thermal dewetting of 8 nm thin gold layers, and they show that semi-infinite linear diffusion mechanism predominates over radial diffusion. Electrochemical etching and 17 nm thin gold layer dewetted at 400 °C consist of larger gold islands up to 1 μm. In the latter case, the current-time curves can be fitted by a two-phase exponential decay function that relies on the mixed second-order formation of adsorbed glucose intermediate followed by its first-order decay to gluconolactone.

Recently, hydrogen evolution reaction (HER) in alkaline media has received a renewed interest both in the fundamental research as well as in practical applications. Pulsed Laser Ablation in Liquid (PLAL) has been demonstrated as a very useful technique for the unconventional preparation of nanomaterials with amazing electro-catalyst properties toward HER, compared to those of nanomaterials prepared by conventional methods. In this paper, we compared the electro-sorption properties of hydrogen in alkaline media by Pt, Pd, Pt80Pd20, and Cu(OH)2 nanoparticles (NPs) prepared by PLAL. The NPs were placed onto graphene paper (GP). Noble metal particles have an almost spherical shape, whereas Cu(OH)2 presents a flower-bud-like shape, formed by very thin nanowalls. XPS analyses of Cu(OH)2 are compatible with a high co-ordination of Cu(II) centers by OH and H2O. A thin layer of perfluorosulfone ionomer placed onto the surface of nanoparticles (NPs) enhances their distribution on the surface of graphene paper (GP), thereby improving their electro-catalytic properties. The proposed mechanisms for hydrogen evolution reaction (HER) on noble metals and Cu(OH)2 are in line with the adsorption energies of H, OH, and H2O on the surfaces of Pt, Pd, and oxidized copper. A significant spillover mechanism was observed for the noble metals when supported by graphene paper. Cu(OH)2 prepared by PLAL shows a competitive efficiency toward HER that is attributed to its high hydrophilicity which, in turn, is due to the high co-ordination of Cu(II) centers in very thin Cu(OH)2 layers by OH- and H2O. We propose the formation of an intermediate complex with water which can reduce the barrier energy of water adsorption and dissociation.

Sphingosine-1-phosphate (S1P) has been widely associated with inflammation-based lung pathologies. Because B cells play a critical role as antigen-presenting and/or Ig-producing cells during asthmatic conditions, we wanted to dissect the role of these cells in S1P-dependent airway hyperreactivity and inflammation. Mice were sensitized to ovalbumin or exposed to S1P. Ovalbumin sensitization caused airway hyperreactivity coupled to an increased lung infiltration of B cells, which was significantly reduced after the inhibition of sphingosine kinases I/II. Similarly, the sole administration of S1P increased bronchial reactivity compared with vehicle and was accompanied by a higher influx of B cells in a time-dependent manner. This effect was associated with higher levels of IL-13, transforming growth factor-β, IL-10, and T regulatory cells. In addition, isolated S1P-derived lung B cells increased CD4+ and CD8+ T cell proliferation in vitro, and their suppressive nature at Day 14 was associated with the higher release of transforming growth factor-β and IL-10 when they were cocultured. Therefore, to prove the role of B cells in S1P-mediated airway inflammation, and because CD20 expression, contrary to major hystocompatibility complex I and major hystocompatibility complex II, was up-regulated at Day 14, CD20+ B cells were depleted by means of a specific monoclonal antibody. The absence of CD20+ B cells increased airway reactivity and inflammation in S1P-treated mice compared with control mice. These data imply that sphingosine kinase/S1P–mediated airway inflammation is countered by B cells via the induction of an immune-suppressive environment to reduce asthma-like outcomes in mice.

Sphingosine-1-phosphate (S1P) levels significantly increase in bronchoalveolar lavage (BAL) of asthmatic patients following segmental allergen challenge and this increase well correlates with pulmonary inflammation. Epidemiological, genetic, clinical, and experimental data indicate a potential for the toll-like receptor 4 (TLR4) to initiate and exacerbate allergic airway diseases. The aim of this study was to evaluate the contribution of TLR4 in S1P-dependent asthma-like disease in mice. BALB/c or TLR4 defective (C3H/HeJ) mice received S1P (10 ng/mouse), LPS (0.1 μg/mouse) or S1P + LPS. Furthermore, S1P-treated BALB/c mice were injected with the purified rabbit anti-TLR4 antibody (10 μg/mouse). S1P administration induced airway hyperreactivity and pulmonary inflammation associated to an increase in the percentage of dendritic cells (DCs) and macrophages into the lung of BALB/c mice. These effects were coupled to a reduction of DCs in the mediastinic lymph node. All these S1P-mediated effects were absent in TLR4 defective mice or reversed by treatment with a purified rabbit anti-TLR4 antibody. Confocal analysis of pulmonary sections showed a significant increase in TLR4 cells and a similar presence of S1P and TLR4 following S1P challenge. Accordingly, the immunoprecipitation evidenced an increased S1P /TLR4 interaction. In conclusion, our findings suggest that a functional interaction between S1P and TLR4 leads to an enhanced allergic inflammatory response. Thus, S1P pathway contributes to the sentinel role played by innate immunity providing new targets for prevention and treatment of allergic airway diseases.

Introduction Several studies have suggested that chronic kidney disease (CKD) may be associated with olfactory impairment. However, to date, the impact of renal replacement therapies has only been partly defined. Methods We tested the olfactory function of 235 participants [50 kidney transplant recipients (KT), 49 hemodialyzed patients (HD), 30 peritoneal dialysis patients (PD), 51 patients with CKD not on dialysis (ND-CKD) and 55 healthy subjects (HS)] by the Sniffin’ Sticks test (Burghardt®, Wedel, Germany), including the sub-tests for the determination of odor threshold ( T ), odor discrimination ( D ), odor identification ( I ). Each subtest result was then summed up to a composite score, known as the TDI score. The Sino-Nasal Outcome Test-22 (SNOT22), Montreal Cognitive Assessment (MoCA) test and olfactory function Visual Analogue Scale (ofVAS) were also performed. Results The mean TDI score was significantly lower (and consistent with hyposmia), in HD, PD and ND-CKD compared to HS and KT (ANOVA p < 0.001). Similar results were observed in the I and D tests, and with the T score, though with regard to the latter, only in PD and ND-CKD patients. Multiple comparisons among groups demonstrated no significant differences between KT and HS. After adjustments for confounding factors, a significant linear association was found between both urea (β − 0.03, p < 0.003) and eGFR (β 0.08, p < 0.001) with TDI score. No significant association was observed between the TDI score and the ofVAS score (p = 0.293). Conclusions Olfactory impairment affects a large number of CKD patients in the pre-dialysis phase as well as those on dialysis. Kidney transplantation may reverse this condition with a possible positive impact on the quality of life and social behaviors/relationships. Graphic abstract

Cu nanoparticles were produced by using solid-state dewetting (dry) of a 1.3 nm Cu layer or laser ablation of a Cu solid target (wet) in acetone and methanol. The morphology and chemical composition of the nanoparticles were investigated as a function of the synthesis methods and their key parameters of the annealing temperature (200–500 °C) and the liquid environment during the ablation. Cu nanoparticles were then embedded in transparent conductive oxide (TCO) films as aluminum-doped zinc oxide (AZO) or zirconium-doped indium oxide (IZrO); the TCObott/Cu nanoparticle/TCOtop structures were synthesized with all combinations of AZO and IZrO as the top and bottom layers. The goal was to achieve a plasmonic and conductive structure for photovoltaic applications via a comparison of the involved methods and all fabricated structures. In particular, solid-state dewetting produced faceted or spherical (depending on the annealing temperature) nanoparticles with an average size below 150 nm while laser ablation produced spherical nanoparticles below 250 nm. Dry and wet plasmonic conductive structures as a function of the TCOs employed and the temperature of annealing could reach a sheet resistance of 86 Ω/sq. The energy band-gap Egap, absorbance, transmittance, and reflectance of the plasmonic conductive structures were investigated in the UV–vis–NIR range. They showed a dependence on the sequence of the top and bottom TCO, with best transmittances of 89.4% for the dry plasmonic conductive structure and 84.7% for the wet plasmonic conductive structure. The latter showed a higher diffused transmittance of between 10–20% in the visible range.