The use of ALD and PVD coatings as defect sealants to increase the corrosion resistance of thermal spray coatings

Thermal spray coatings are widely used to improve the surface properties of materials, in particular the wear and oxidation resistance. Nevertheless, the corrosion resistance is slightly increased due to the fact that this type of coatings present some internal defects (pores, cracks) that allow the corrosive media to penetrate up to the substrate, that undergoes to corrosion degradation. The amount of these defects is strongly influenced by both the deposition technique and the material deposited. The aim of this work is to seal the internal porosities of the thermal spray coatings by the use of both PVD and ALD coatings or the combination of the two. The thermal spray coating analysed in this work is a pure alumina coating, deposited by Air Plasma Spray (APS) technique, that has been sealed with CrN coating, deposited by PVD (Physical Vapour Deposition) technique, and/or TiO2 coatings, deposited by ALD (Atomic Layer Deposition). The substrate used is a common medium C steel. The samples were then characterized in order to determine the microstructure (SEM+EDXS, light microscope) and the chemical composition (Rf-GDOES elemental profiling), that is important to determine the depth of penetration of the PVD and/or ALD coating inside the thermal spray deposit. Afterwards, a detailed electrochemical characterization in 3,5wt% NaCl aqueous solution was performed to verify the efficiency of the sealant treatment. In detail, a monitor in function of the time of the OCP potential was performed up to 24h of immersion time. In addition, potentiodynamic tests were performed using a 3 electrode electrochemical cell (CE: Pt wire, RE: Ag/AgCl). The same tests were then performed on the same samples that present an artificial defect produced by Rf-GDOES. The main goal of these tests is to determine the maximum depth of a defect that can allow the corrosive media to penetrate the thermal spray coating. Preliminary results showed that the use of PVD and ALD coatings as sealants can reduce the permeation of the corrosive media on the substrate

The Use of Thin Films as Defect Sealants to Increase the Corrosion Resistance of Thermal Spray Coatings

Thermal spray-coated components are widely used as wear-resistant coatings in many applications. However, these coatings have high levels of discontinuities that affect the corrosion resistance of the coated system. To reduce this problem, these coatings are usually sealed with liquid sealants (metals, organic or inorganic). The aim of this work is to seal the surface discontinuities of thermal-sprayed coatings using PVD and/or ALD coatings. To this end, CrN (arc deposition PVD) and TiO2 (ALD) coatings were deposited on thermal-sprayed alumina coatings. The samples produced were then analysed in both cross-sectional and planar views to detect the possible permeation of the thin film coatings into the thermal spray defects. Rf-GDOES measurements were performed to detect the very thin ALD deposit on the surface. The corrosion resistance of the sealed coatings was verified with immersion tests, wherein the OCP was monitored for 24 h, and potentiodynamic tests were performed after 15 min and 24 h immersions. The results showed that the thin films were not able to block the permeation of corrosive media, but they could reduce the permeation of corrosive media with a beneficial behaviour on corrosion resistance

Integración de sistemas ERP para el monitoreo de planes y detección de eventos disruptivos en cadenas de suministros

Los sistemas de Planificación de Recursos Empresariales (ERP Enterprise Resource Planning) se definen como un conjunto de aplicaciones que permiten gestionar de manera integrada los procesos de negocio de las empresas. En la actualidad, los sistemas ERP carecen de flexibilidad suficiente para generar Cadenas de Suministros (CS) flexibles capaces de reaccionar rápidamente a eventos disruptivo. Es por ello, en este trabajo se propone un servicio MASM-ERP que integra los planes de abastecimiento, producción y distribución definidos en los ERP de las empresas involucradas en una CS. También permite monitorear la ejecución de estos planes y notificar la ocurrencia de eventos disruptivos a los actores pertinentes. El monitoreo durante la ejecución de planes permite anticiparse a los cambios que podrían tener lugar en el horizonte de tiempo considerado y mejorar los procesos de toma de decisión.IX Workshop Innovación en Sistemas de Software (WISS).Red de Universidades con Carreras en Informática (RedUNCI

Biomarkers of aging in frailty and age-associated disorders: State of the art and future perspective

According to the Geroscience concept that organismal aging and age-associated diseases share the same basic molecular mechanisms, the identification of biomarkers of age that can efficiently classify people as biologically older (or younger) than their chronological (i.e. calendar) age is becoming of paramount importance. These people will be in fact at higher (or lower) risk for many different age-associated diseases, including cardiovascular diseases, neurodegeneration, cancer, etc. In turn, patients suffering from these diseases are biologically older than healthy age-matched individuals. Many biomarkers that correlate with age have been described so far. The aim of the present review is to discuss the usefulness of some of these biomarkers (especially soluble, circulating ones) in order to identify frail patients, possibly before the appearance of clinical symptoms, as well as patients at risk for age-associated diseases. An overview of selected biomarkers will be discussed in this regard, in particular we will focus on biomarkers related to metabolic stress response, inflammation, and cell death (in particular in neurodegeneration), all phenomena connected to inflammaging (chronic, low-grade, age-associated inflammation). In the second part of the review, next-generation markers such as extracellular vesicles and their cargos, epigenetic markers and gut microbiota composition, will be discussed. Since recent progresses in omics techniques have allowed an exponential increase in the production of laboratory data also in the field of biomarkers of age, making it difficult to extract biological meaning from the huge mass of available data, Artificial Intelligence (AI) approaches will be discussed as an increasingly important strategy for extracting knowledge from raw data and providing practitioners with actionable information to treat patients

Autophagy as a new therapeutic target in Duchenne muscular dystrophy

A resolutive therapy for Duchene muscular dystrophy, a severe degenerative disease of the skeletal muscle, is still lacking. Because autophagy has been shown to be crucial in clearing dysfunctional organelles and in preventing tissue damage, we investigated its pathogenic role and its suitability as a target for new therapeutic interventions in Duchenne muscular dystrophy (DMD). Here we demonstrate that autophagy is severely impaired in muscles from patients affected by DMD and mdx mice, a model of the disease, with accumulation of damaged organelles. The defect in autophagy was accompanied by persistent activation via phosphorylation of Akt, mammalian target of rapamycin (mTOR) and of the autophagy-inhibiting pathways dependent on them, including the translation-initiation factor 4E-binding protein 1 and the ribosomal protein S6, and downregulation of the autophagy-inducing genes LC3, Atg12, Gabarapl1 and Bnip3. The defective autophagy was rescued in mdx mice by long-term exposure to a low-protein diet. The treatment led to normalisation of Akt and mTOR signalling; it also reduced significantly muscle inflammation, fibrosis and myofibre damage, leading to recovery of muscle function. This study highlights novel pathogenic aspects of DMD and suggests autophagy as a new effective therapeutic target. The treatment we propose can be safely applied and immediately tested for efficacy in humans

PTX3 Intercepts Vascular Inflammation in Systemic Immune-Mediated Diseases

PTX3 is a prototypic soluble pattern recognition receptor, expressed at sites of inflammation and involved in regulation of the tissue homeostasis. PTX3 systemic levels increase in many (but not all) immune-mediated inflammatory conditions. Research on PTX3 as a biomarker has so far focused on single diseases. Here, we performed a multi-group comparative study with the aim of identifying clinical and pathophysiological phenotypes associated with PTX3 release. PTX3 concentration was measured by ELISA in the plasma of 366 subjects, including 96 patients with giant cell arteritis (GCA), 42 with Takayasu's arteritis (TA), 10 with polymyalgia rheumatica (PMR), 63 with ANCA-associated systemic small vessel vasculitides (AAV), 55 with systemic lupus erythematosus (SLE), 21 with rheumatoid arthritis (RA) and 79 healthy controls (HC). Patients with SLE, AAV, TA and GCA, but not patients with RA and PMR, had higher PTX3 levels than HC. PTX3 concentration correlated with disease activity, acute phase reactants and prednisone dose. It was higher in females, in patients with recent-onset disease and in those with previous or current active vasculitis at univariate analysis. Active small- or large- vessel vasculitis were the main independent variables influencing PTX3 levels at multivariate analysis. High levels of PTX3 in the blood can contribute to identify an increased risk of vascular involvement in patients with systemic immune-mediated diseases

Nitric oxide confers therapeutic activity to dendritic cells in a mouse model of melanoma

Susceptibility of dendritic cells (DCs) to tumor-induced apoptosis reduces their efficacy in cancer therapy. Here we show that delivery within exponentially growing B16 melanomas of DCs treated ex vivo with nitric oxide (NO), released by the NO donor (z)-1-[2-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA-NO), significantly reduced tumor growth, with cure of 37% of animals. DETA-NO-treated DCs became resistant to tumor-induced apoptosis because DETA-NO prevented tumor-induced changes in the expression of Bcl-2, Bax, and Bcl-xL; activation of caspase-9; and a reduction in the mitochondrial membrane potential. DETA-NO also increased DC cytotoxic activity against tumor cells and DC ability to trigger T-lymphocyte proliferation. All of the effects of DETA-NO were mediated through cGMP generation. NO and NO-generating drugs may therefore be used to increase the anticancer efficacy of DCs

Monoclonal antibodies against SARS-CoV-2 to prevent COVID-19 worsening in a large multicenter cohort

Objective: Monoclonal antibodies (mAbs) against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) reduced Coronavirus Disease 2019 (COVID-19) hospitalizations in people at risk of clinical worsening. Real-world descriptions are limited. Methods: CONDIVIDIAMO, a two-year multicenter observational study, consecutively enrolled SARS-CoV-2 outpatients with ≥1 risk factor for COVID-19 progression receiving mAbs. Demographic data, underlying medical condition, type of mAbs combination received, duration of symptoms before mAbs administration, COVID-19 vaccination history, were collected upon enrolment and centrally recorded. Data on outcomes (hospitalizations, reasons of hospitalization, deaths) were prospectively collected. The primary endpoint was the rate of hospitalization or death in a 28-day follow-up, whichever occurred first; subjects were censored at the day of last follow-up or up to 28 days. The Kaplan-Meier method was used to estimate the incidence rate curve in time. The Cox regression model was used to assess potential risk factors for unfavorable outcome. Results were shown as hazard ratio (HR) along with the corresponding 95 % Confidence Interval (95%CI). Results: Among 1534 subjects (median [interquartile range, IQR] age 66.5 [52.4-74.9] years, 693 [45.2 %] women), 632 (41.2 %) received bamlanivimab ± etesevimab, 209 (13.6 %) casirivimab/imdevimab, 586 (38.2 %) sotrovimab, 107 (7.0 %) tixagevimab/cilgavimab. After 28-day follow-up, 87/1534 (5.6 %, 95%CI: 4.4%-6.8 %) met the primary outcome (85 hospitalizations, 2 deaths). Hospitalizations for COVID-19 (52, 3.4 %) occurred earlier than for other reasons (33, 2.1 %), after a median (IQR) of 3.5 (1-7) versus 8 (3-15) days (p = 0.006) from mAbs administration.In a multivariable Cox regression model, factors independently associated with increased hospitalization risk were age (hazard ratio [HR] 1.02, 95%CI 1.00-1.03, p = 0.021), immunodeficiency (HR 1.78, 95%CI 1.11-2.85, p = 0.017), pre-Omicron calendar period (HR 1.66, 95%CI 1.02-2.69, p = 0.041). Conclusions: MAbs real-world data over a 2-year changing pandemic landscape showed the feasibility of the intervention, although the hospitalization rate was not negligible. Immunosuppressed subjects remain more at risk of clinical worsening

Oxidation of HMGB1 Causes Attenuation of Its Pro-Inflammatory Activity and Occurs during Liver Ischemia and Reperfusion

High mobility group box 1 (HMGB1) is a nuclear transcription factor. Once HMGB1 is released by damaged cells or activated immune cells, it acts as danger molecule and triggers the inflammatory signaling cascade. Currently, evidence is accumulating that posttranslational modifications such as oxidation may modulate the pro-inflammatory potential of danger signals. We hypothesized that oxidation of HMGB1 may reduce its pro-inflammatory potential and could take place during prolonged ischemia and upon reperfusion