Effect of geometry and green density on the anisotropic sintering shrinkage of axisymmetric iron parts

Sintering shrinkage of prior cold compacted iron rings with different geometry (height to wall thickness ratio) and green density in the 6.5–7.3?g/cm³ range was investigated. It displays a minimum at an intermediate green density. Axial, tangential and radial shrinkages are different, due to the gradients of green density along the axial and the radial directions. Therefore, the effect of height on shrinkage and its anisotropy is the result of their effect on the stress distribution in the green parts during cold compaction, and the resulting green density and deformation experienced by the powder. Anisotropy decreases on increasing shrinkage.     

From experimental data,the mechanics relationships describing the behaviour of four different low alloyed steel powders during uniaxial cold compaction

This work aims at determining the constitutive model of four commercial water atomised low alloyed steel powders during cold compaction. Single-action experiments were performed, obtaining cylindrical specimens with different H/D ratios. The distribution of axial and radial stresses was investigated, and the relationships describing both the radial stress transmission coefficient and the flow stress as functions of the relative density were determined. The radial stress transmission coefficient also confirmed the hypothesised value of Poisson’s coefficient. The friction coefficient between the powder column and the die wall was determined, also highlighting the influence of the H/D ratio. Measuring the axial and radial strains due to spring-back, the axial and radial elastic moduli were determined, as functions of the relative density. The results obtained for the four materials were compared, also highlighting both differences and similarities.     

Design,Synthesis, Radiosynthesis and Biological Evaluation of Fenretinide Analogues as Anticancer and Metabolic Syndrome-Preventive Agents

Fenretinide (4-HPR) is a synthetic derivative of all-trans-retinoic acid (ATRA) characterised by improved therapeutic properties and toxicological profile relative to ATRA. 4-HPR has been mostly investigated as an anti-cancer agent, but recent studies showed its promising therapeutic potential for preventing metabolic syndrome. Several biological targets are involved in 4-HPR's activity, leading to the potential use of this molecule for treating different pathologies. However, although 4-HPR displays quite well-understood multitarget promiscuity with regards to pharmacology, interpreting its precise physiological role remains challenging. In addition, despite promising results in vitro, the clinical efficacy of 4-HPR as a chemotherapeutic agent has not been satisfactory so far. Herein, we describe the preparation of a library of 4-HPR analogues, followed by the biological evaluation of their anti-cancer and anti-obesity/diabetic properties. The click-type analogue 3 b showed good capacity to reduce the amount of lipid accumulation in 3T3-L1 adipocytes during differentiation. Furthermore, it showed an IC₅₀ of 0.53±0.8 μM in cell viability tests on breast cancer cell line MCF-7, together with a good selectivity (SI=121) over noncancerous HEK293 cells. Thus, 3 b was selected as a potential PET tracer to study retinoids in vivo, and the radiosynthesis of [¹⁸F] 3b was successfully developed. Unfortunately, the stability of [¹⁸F] 3b turned out to be insufficient to pursue imaging studies.     

Unpatterned Bioactive Poly(Butylene 1,4-Cyclohexanedicarboxylate)-Based Film Fast Induced Neuronal-Like Differentiation of Human Bone Marrow-Mesenchymal Stem Cells

Herein, we present poly(butylene 1,4-cyclohexanedicarboxylate) (PBCE) films characterized by an unpatterned microstructure and a specific hydrophobicity, capable of boosting a drastic cytoskeleton architecture remodeling, culminating with the neuronal-like differentiation of human bone marrow-mesenchymal stem cells (hBM-MSCs). We have used two different filming procedures to prepare the films, solvent casting (PBCE) and compression-moulding (PBCE*). PBCE film had a rough and porous surface with spherulite-like aggregations (Ø = 10–20 μm) and was characterized by a water contact angle = 100°. PBCE* showed a smooth and continuous surface without voids and visible spherulite-like aggregations and was more hydrophobic (WCA = 110°). Both surface characteristics were modulated through the copolymerization of different amounts of ether-oxygen-containing co-units into PBCE chemical structure. We showed that only the surface characteristics of PBCE-solvent-casted films steered hBM-MSCs toward a neuronal-like differentiation. hBM-MSCs lost their canonical mesenchymal morphology, acquired a neuronal polarized shape with a long cell protrusion (≥150 μm), expressed neuron-specific class III β-tubulin and microtubule-associated protein 2 neuronal markers, while nestin, a marker of uncommitted stem cells, was drastically silenced. These events were observed as early as 2-days after cell seeding. Of note, the phenomenon was totally absent on PBCE* film, as hBM-MSCs maintained the mesenchymal shape and behavior and did not express neuronal/glial markers.     

Serenoa repens and Urtica dioica Fixed Combination: In-Vitro Validation of a Therapy for Benign Prostatic Hyperplasia (BPH)

Benign prostatic hyperplasia (BPH) is an age-related chronic disorder, characterized by the hyperproliferation of prostatic epithelial and stromal cells, which drives prostate enlargement. Since BPH aetiology and progression have been associated with the persistence of an inflammatory stimulus, induced both by Nuclear Factor-kappa B (NF-κB) activation and reactive oxygen species (ROS) production, the inhibition of these pathways could result in a good tool for its clinical treatment. This study aimed to evaluate the antioxidant and anti-inflammatory activity of a combined formulation of Serenoa repens and Urtica dioica (SR/UD) in an in vitro human model of BPH. The results confirmed both the antioxidant and the anti-inflammatory effects of SR/UD. In fact, SR/UD simultaneously reduced ROS production, NF-κB translocation inside the nucleus, and, consequently, interleukin 6 (IL-6) and interleukin 8 (IL-8) production. Furthermore, the effect of SR/UD was also tested in a human androgen-independent prostate cell model, PC3. SR/UD did not show any significant antioxidant and anti-inflammatory effect, but was able to reduce NF-κB translocation. Taken together, these results suggested a promising role of SR/UD in BPH and BPH-linked disorder prevention.     

A2B Adenosine Receptors: When Outsiders May Become an Attractive Target to Treat Brain Ischemia or Demyelination

Adenosine is a signaling molecule, which, by activating its receptors, acts as an important player after cerebral ischemia. Here, we review data in the literature describing A_2BR-mediated effects in models of cerebral ischemia obtained in vivo by the occlusion of the middle cerebral artery (MCAo) or in vitro by oxygen-glucose deprivation (OGD) in hippocampal slices. Adenosine plays an apparently contradictory role in this receptor subtype depending on whether it is activated on neuro-glial cells or peripheral blood vessels and/or inflammatory cells after ischemia. Indeed, A_2BRs participate in the early glutamate-mediated excitotoxicity responsible for neuronal and synaptic loss in the CA1 hippocampus. On the contrary, later after ischemia, the same receptors have a protective role in tissue damage and functional impairments, reducing inflammatory cell infiltration and neuroinflammation by central and/or peripheral mechanisms. Of note, demyelination following brain ischemia, or autoimmune neuroinflammatory reactions, are also profoundly affected by A_2BRs since they are expressed by oligodendroglia where their activation inhibits cell maturation and expression of myelin-related proteins. In conclusion, data in the literature indicate the A_2BRs as putative therapeutic targets for the still unmet treatment of stroke or demyelinating diseases.     

Assessing the Potential Content of Ethyl Carbamate in White,Red, and Rosé Wines as a Key Factor for Pursuing Urea Degradation by Purified Acid Urease

The ethyl carbamate (EC) content of a wine after a given temperature‐time storage was theoretically predicted from the potential concentration of ethyl carbamate (PEC), as determined via an accelerated EC formation test. Such information was used to decide whether an enzymatic treatment was needed to reduce the wine urea level before bottling/aging. To this end, 6 white, red, and rosé wines, manufactured in Italy as such or enriched with urea, were tested for their PEC content either before or after enzymatic treatment using a purified acid urease preparation derived from Lactobacillus fermentum. The treatment was severely affected by the total phenolic content (TP) of the wine, the estimated pseudo‐first‐order kinetic rate constant for NH₃ formation reducing by a factor of approximately 2000 as the TP increased from 0 to 1.64 g L^‐1. Such a sensitivity to TP was by far greater than that pertaining to a killed cell‐based enzyme preparation used previously. Urea hydrolysis was successful at reducing EC concentration in wines with low levels of TP and other EC precursors.     

Functional Properties of Plasticized Bio-Based Poly(Lactic Acid)_Poly(Hydroxybutyrate) (PLA_PHB) Films for Active Food Packaging

Fully bio-based and biodegradable active films based on poly(lactic acid) (PLA) blended with poly(3-hydroxybutyrate) (PHB) and incorporating lactic acid oligomers (OLA) as plasticizers and carvacrol as active agent were extruded and fully characterized in their functional properties for antimicrobial active packaging. PLA_PHB films showed good barrier to water vapor, while the resistance to oxygen diffusion decreased with the addition of OLA and carvacrol. Their overall migration in aqueous food simulant was determined and no significant changes were observed by the addition of carvacrol and OLA to the PLA_PHB formulations. However, the effect of both additives in fatty food simulant can be considered a positive feature for the potential protection of foodstuff with high fat content. Moreover, the antioxidant and antimicrobial activities of the proposed formulations increased by the presence of carvacrol, with enhanced activity against Staphylococcus aureus if compared to Escherichia coli at short and long incubation times. These results underlined the specific antimicrobial properties of these bio-films suggesting their applicability in active food packaging.