Porous structures printed by fused deposition of granules processed from a novel polyamide/alumina-based system

Alumina ceramic porous structures were shaped by the fused deposition of alumina/polyamide 612 composite granules using an FDM 3D printer with a modified extruder to process granulated powder instead of a filament. The composite granules were prepared via thermally induced phase separation (TIPS). Firstly, in order to determine the proportion of polymer/solvent to be used in the TIPS process, different volume fractions of PA612 in dimethyl sulfoxide (DMSO) were studied (0.01 to 0.20), and the granules obtained were characterized by SEM, DSC, and Raman spectroscopy. Secondly, the addition of different ceramic loadings to the PA612/DMSO solution was studied with the aim of determining the amount to be used for preparing the composite granules by TIPS. In particular, the effect of the alumina content on the morphology and size of the obtained composite granules was studied. In addition, rheological properties (oscillatory and rotational tests) of the feed materials were studied. Finally, the printing conditions, including the nozzle temperature and nozzle diameter, and the extrusion process, were optimized in order to obtain porous structures with good quality. Alumina porous structures were successfully printed, debinded, and sintered. Adequate bonding between layers was achieved, and no defects at interfaces were detected.     

Cyclic Nigerosyl-Nigerose as Oxygen Nanocarrier to Protect Cellular Models from Hypoxia/Reoxygenation Injury: Implications from an In Vitro Model

Heart failure (HF) prevalence is increasing among the aging population, and the mortality rate remains unacceptably high despite improvements in therapy. Myocardial ischemia (MI) and, consequently, ischemia/reperfusion injury (IRI), are frequently the basis of HF development. Therefore, cardioprotective strategies to limit IRI are mandatory. Nanocarriers have been proposed as alternative therapy for cardiovascular disease. Controlled reoxygenation may be a promising strategy. Novel nanocarriers, such as cyclic nigerosyl-nigerose (CNN), can be innovative tools for oxygen delivery in a controlled manner. In this study we analyzed new CNN-based formulations as oxygen nanocarriers (O₂-CNN), and compared them with nitrogen CNN (N₂-CNN). These different CNN-based formulations were tested using two cellular models, namely, cardiomyoblasts (H9c2), and endothelial (HMEC) cell lines, at different concentrations. The effects on the growth curve during normoxia (21% O₂, 5% CO₂ and 74% N₂) and their protective effects during hypoxia (1% O₂, 5% CO₂ and 94% N₂) and reoxygenation (21% O₂, 5% CO₂ and 74% N₂) were studied. Neither O₂-CNN nor N₂-CNN has any effect on the growth curve during normoxia. However, O₂-CNN applied before hypoxia induces a 15–30% reduction in cell mortality after hypoxia/re-oxygenation when compared to N₂-CNN. O₂-CNN showed a marked efficacy in controlled oxygenation, which suggests an interesting potential for the future medical application of soluble nanocarrier systems for MI treatment.     

In Silico Analysis of the Molecular-Level Impact of SMPD1 Variants on Niemann-Pick Disease Severity

Sphingomyelin phosphodiesterase (SMPD1) is a key enzyme in the sphingolipid metabolism. Genetic SMPD1 variants have been related to the Niemann-Pick lysosomal storage disorder, which has different degrees of phenotypic severity ranging from severe symptomatology involving the central nervous system (type A) to milder ones (type B). They have also been linked to neurodegenerative disorders such as Parkinson and Alzheimer. In this paper, we leveraged structural, evolutionary and stability information on SMPD1 to predict and analyze the impact of variants at the molecular level. We developed the SMPD1-ZooM algorithm, which is able to predict with good accuracy whether variants cause Niemann-Pick disease and its phenotypic severity; the predictor is freely available for download. We performed a large-scale analysis of all possible SMPD1 variants, which led us to identify protein regions that are either robust or fragile with respect to amino acid variations, and show the importance of aromatic-involving interactions in SMPD1 function and stability. Our study also revealed a good correlation between SMPD1-ZooM scores and in vitro loss of SMPD1 activity. The understanding of the molecular effects of SMPD1 variants is of crucial importance to improve genetic screening of SMPD1-related disorders and to develop personalized treatments that restore SMPD1 functionality.     

Back to the Origins: Background and Perspectives of Grapevine Domestication

Domestication is a process of selection driven by humans, transforming wild progenitors into domesticated crops. The grapevine (Vitis vinifera L.), besides being one of the most extensively cultivated fruit trees in the world, is also a fascinating subject for evolutionary studies. The domestication process started in the Near East and the varieties obtained were successively spread and cultivated in different areas. Whether the domestication occurred only once, or whether successive domestication events occurred independently, is a highly debated mystery. Moreover, introgression events, breeding and intense trade in the Mediterranean basin have followed, in the last thousands of years, obfuscating the genetic relationships. Although a succession of studies has been carried out to explore grapevine origin and different evolution models are proposed, an overview of the topic remains pending. We review here the findings obtained in the main phylogenetic and genomic studies proposed in the last two decades, to clarify the fundamental questions regarding where, when and how many times grapevine domestication took place. Finally, we argue that the realization of the pan-genome of grapes could be a useful resource to discover and track the changes which have occurred in the genomes and to improve our understanding about the domestication.     

Evidence for a Negative Correlation between Human Reactive Enamine-Imine Intermediate Deaminase A (RIDA) Activity and Cell Proliferation Rate: Role of Lysine Succinylation of RIDA

Reactive intermediate deaminase (Rid) proteins are enzymes conserved in all domains of life. UK114, a mammalian member of RidA subfamily, has been firstly identified as a component of liver perchloric acid-soluble proteins (L-PSP). Although still poorly defined, several functions have been attributed to the mammalian protein UK114/RIDA, including the reactive intermediate deamination activity. The expression of UK114/RIDA has been observed in some tumors, arousing interest in this protein as an evaluable tumor marker. However, other studies reported a negative correlation between UK114/RIDA expression, tumor differentiation degree and cell proliferation. This work addressed the question of UK114/RIDA expression in human non-tumor HEK293 cell lines and in some human tumor cell lines. Here we reported that human RIDA (hRIDA) was expressed in all the analyzed cell line and subjected to lysine (K-)succinylation. In HEK293, hRIDA K-succinylation was negatively correlated to the cell proliferation rate and was under the control of SIRT5. Moreover, K-succinylation clearly altered hRIDA quantification by immunoblotting, explaining, at least in part, some discrepancies about RIDA expression reported in previous studies. We found that hRIDA was able to deaminate reactive enamine-imine intermediates and that K-succinylation drastically reduced deaminase activity. As predicted by in silico analysis, the observed reduction of deaminase activity has been related to the drastic alterations of hRIDA structure inferred by K-succinylation. The role of hRIDA and the importance of its K-succinylation in cell metabolism, especially in cancer biology, have been discussed.     

Molecular Biomarkers in Idiopathic Pulmonary Fibrosis: State of the Art and Future Directions

Idiopathic pulmonary fibrosis (IPF), the most lethal form of interstitial pneumonia of unknown cause, is associated with a specific radiological and histopathological pattern (the so-called “usual interstitial pneumonia” pattern) and has a median survival estimated to be between 3 and 5 years after diagnosis. However, evidence shows that IPF has different clinical phenotypes, which are characterized by a variable disease course over time. At present, the natural history of IPF is unpredictable for individual patients, although some genetic factors and circulating biomarkers have been associated with different prognoses. Since in its early stages, IPF may be asymptomatic, leading to a delayed diagnosis. Two drugs, pirfenidone and nintedanib, have been shown to modify the disease course by slowing down the decline in lung function. It is also known that 5–10% of the IPF patients may be affected by episodes of acute and often fatal decline. The acute worsening of disease is sometimes attributed to identifiable conditions, such as pneumonia or heart failure; but many of these events occur without an identifiable cause. These idiopathic acute worsenings are termed acute exacerbations of IPF. To date, clinical biomarkers, diagnostic, prognostic, and theranostic, are not well characterized. However, they could become useful tools helping facilitate diagnoses, monitoring disease progression and treatment efficacy. The aim of this review is to cover molecular mechanisms underlying IPF and research into new clinical biomarkers, to be utilized in diagnosis and prognosis, even in patients treated with antifibrotic drugs.     

Percutaneous Coronary Intervention (PCI) Reprograms Circulating Extracellular Vesicles from ACS Patients Impairing Their Cardio-Protective Properties

Extracellular vesicles (EVs) are promising therapeutic tools in the treatment of cardiovascular disorders. We have recently shown that EVs from patients with Acute Coronary Syndrome (ACS) undergoing sham pre-conditioning, before percutaneous coronary intervention (PCI) were cardio-protective, while EVs from patients experiencing remote ischemic pre-conditioning (RIPC) failed to induce protection against ischemia/reperfusion Injury (IRI). No data on EVs from ACS patients recovered after PCI are currently available. Therefore, we herein investigated the cardio-protective properties of EVs, collected after PCI from the same patients. EVs recovered from 30 patients randomly assigned (1:1) to RIPC (EV-RIPC) or sham procedures (EV-naive) ({"type":"clinical-trial","attrs":{"text":"NCT02195726","term_id":"NCT02195726"}}NCT02195726) were characterized by TEM, FACS and Western blot analysis and evaluated for their mRNA content. The impact of EVs on hypoxia/reoxygenation damage and IRI, as well as the cardio-protective signaling pathways, were investigated in vitro (HMEC-1 + H9c2 co-culture) and ex vivo (isolated rat heart). Both EV-naive and EV-RIPC failed to drive cardio-protection both in vitro and ex vivo. Consistently, EV treatment failed to activate the canonical cardio-protective pathways. Specifically, PCI reduced the EV-naive Dusp6 mRNA content, found to be crucial for their cardio-protective action, and upregulated some stress- and cell-cycle-related genes in EV-RIPC. We provide the first evidence that in ACS patients, PCI reprograms the EV cargo, impairing EV-naive cardio-protective properties without improving EV-RIPC functional capability.     

Design of Lu2O3-reinforced Cf/SiC-ZrB2-ZrC ultra-high temperature ceramic matrix composites: Wetting and interfacial reactivity by ZrSi2 based alloys

The wettability and infiltration of molten ZrSi₂ and ZrSi₂-Lu₂O₃ alloys into C_f/SiC and B₄C-infiltrated C_f/SiC composites were investigated to understand the interfacial interactions that occur during the development of C_f/SiC-ZrC and C_f/SiC-ZrB₂-ZrC-Lu₂O₃ materials. A significant evaporation of Si from the liquid affected the wetting behaviour of the alloy when tested in a vacuum at 1670 °C. The better wetting and spreading of the alloy over the surface was observed for the composites with lower overall porosity (12 %). On the other hand, the formation of an outer dense layer, followed up by the uniform infiltrated region up to ～ 1 mm was observed for the C_f/SiC with higher porosity (21 %). The infiltrated alloy reacted with SiC matrix to form ZrC or with B₄C-infiltrated SiC matrix to form ZrB₂-ZrC-SiC. The Lu₂O₃ particles were not wetted by the melt, and were pushed away of the reaction zone by the solidification front.     

Short-term maternal psychological stress in the post-conception period in ewes affects fetal growth and gestation length

Fetal development can be influenced by maternal environment in the peri-conceptional period. This study investigated the effect of maternal feed intake and psychological stress within the first 6 days after conception on embryo development and fetal growth. Superovulated ewes (n=40) were artificially inseminated with semen from one ram. Ewes were then divided into four groups (n=10): group 1 (control) was fed at maintenance level, group 2 (high) at 2x maintenance, and group 3 (low) at 0.5x maintenance on days 2-6 after conception. Group 4 (stress) was fed at maintenance level and then an intense physical and psychological stress challenge was applied for 1 h only on days 2 and 3 after conception. Embryos were recovered at day 6. A total of 113 transferable grade embryos were transferred singly into synchronized untreated recipients, while the remaining embryos (n=165) were fixed and stained for cell counts. Post-conception maternal stress or feed intake did not alter the cell count or grade of day 6 embryos. Fetuses from the stress group had longer crown-rump lengths at day 30 and longer femur length at day 58. Fetuses from the stressed and high feed groups had greater abdominal circumferences at day 85. Subsequent birth weights were not significantly different. Ewes carrying lambs from the stress treatment had shorter gestation lengths. These results show that short-term perturbations of the post-conception maternal environment have measurable effects on fetal development and gestation length.     

Biobased surfactant-like molecules from organic wastes: the effect of waste composition and composting process on surfactant properties and on the ability to solubilize Tetrachloroethene (PCE)

In this work, four surfactant-like humic acids (HAs) obtained from garden lignocellulose wastes and kitchen food wastes mixed with garden-lignocellulose wastes, both before and after composting, were tested for surfactant properties and the ability to solubilize tetrachloroethene (PCE). The waste-derived HAs showed good surfactant properties, lowering the water surface tension from 74 mN m(-1) to 45.4 +/- 4.4 mN m(-1), with a critical micelle concentration (CMC) of 1.54 +/- 1.68 g L(-1), which is lower than many synthetic ionic surfactants. CMC was affected by both waste origin and composting processes. The addition of food waste and composting reduced CMC by adding alkyl-C (measured by CP MAS 13C NMR) and N- and S-HA contents (amide molecules), so that a multistep regression was found [CMC = 24.6 - 0.189 alkyl C - 2.64 (N + S); R2 = 0.77, P < 0.10, n = 6]. The four HAs solubilized PCE at the rate of 0.18-0.47 g PCE/g aqueous biosurfactant. These results were much higher than those reported in the literature for a commercial HA (0.026 g/g), but they were in line with those measured in this work for nonionic surfactants such as Tween-80 (0.69 g/g) and Triton X-100 (1.08 g/g).