Internal Magnetic Field Gradients in Heterogeneous Porous Systems: Comparison Between Spin-Echo and Diffusion Decay Internal Field (DDIF) Method

Two techniques used for evaluating internal magnetic field gradient (G _i), spin-echo (SE) and diffusion decay internal field (DDIF), were investigated at 9.4 T and compared in porous systems characterized by different pores size ranging from 4 to 96 μm with magnetic susceptibility difference between solid and liquid phase, \(\Delta \chi\)  ≈ 1.6 ppm. Since diffusion of a fluid in a solid porous matrix plays a role in both SE and DDIF methods, we investigated these two different methods by highlighting their dependence on characteristic parameters and length scales used to describe diffusion behavior of fluids in porous systems. Therefore, G _i behavior as a function of the dephasing length (l _g), diffusion length (l _d) and pores size (l _s) was obtained. Moreover G _i was evaluated by using both free diffusion and measured apparent diffusion coefficient of water, to quantify diffusion effect in different porous samples. This study gives more insight into the physical dynamics process to explain contrast mechanisms recently exploited by DDIF and SE applications for cancellous bone quality measurements.     

W^+W^-, WZ and ZZ production in the POWHEG-BOX-V2

We present an implementation of the vector boson pair production processes $ZZ$ , $W^+W^-$ and $WZ$ within the POWHEG-BOX-V2. This implementation, derived from the POWHEG BOX version, has several improvements over the old one, among which the inclusion of all decay modes of the vector bosons, the possibility to generate different decay modes in the same run, speed optimization and phase space improvements in the handling of interference and singly resonant contributions.     

Insights into the Reactivity of Gold–Dithiocarbamato Anticancer Agents toward Model Biomolecules by Using Multinuclear NMR Spectroscopy

Some gold(III)–dithiocarbamato derivatives of either single amino acids or oligopeptides have shown promise as potential anticancer agents, but their capability to interact with biologically relevant macromolecules is still poorly understood. We investigated the affinity of the representative complex [Au^IIIBr₂(dtc‐Sar‐OCH₃)] (dtc: dithiocarbamate; Sar: sarcosine (N‐methylglycine)) with selected model molecules for histidine‐, methionine‐, and cysteine‐rich proteins (that is, 1‐methylimidazole, dimethylsulfide, and N‐acetyl‐L ‐cysteine, respectively). In particular, detailed mono‐ and multinuclear NMR studies, in combination with multiple ¹³C/¹⁵N enrichments, allowed interactions to be followed over time and indicated somewhat unexpected reaction pathways. Whereas dimethylsulfide proved to be unreactive, a sudden multistep redox reaction occurred in the presence of the other potential sulfur donor, N‐acetyl‐L ‐cysteine (confirmed if glutathione was used instead). On the other hand, 1‐methylimidazole underwent an unprecedented acid–base reaction with the gold(III) complex, rather than the expected coordination to the metal center by replacing, for instance, a bromide. Our results are discussed herein and compared with the data available in the literature on related complexes; our findings confirm that the peculiar reactivity of gold(III)–dithiocarbamato complexes can lead to novel reaction pathways and, therefore, to new cytotoxic mechanisms in cancer cells.     

Assessing the Functional and Structural Stability of the Met80Ala Mutant of Cytochrome c in Dimethylsulfoxide

The Met80Ala variant of yeast cytochrome c is known to possess electrocatalytic properties that are absent in the wild type form and that make it a promising candidate for biocatalysis and biosensing. The versatility of an enzyme is enhanced by the stability in mixed aqueous/organic solvents that would allow poorly water-soluble substrates to be targeted. In this work, we have evaluated the effect of dimethylsulfoxide (DMSO) on the functionality of the Met80Ala cytochrome c mutant, by investigating the thermodynamics and kinetics of electron transfer in mixed water/DMSO solutions up to 50% DMSO v/v. In parallel, we have monitored spectroscopically the retention of the main structural features in the same medium, focusing on both the overall protein structure and the heme center. We found that the organic solvent exerts only minor effects on the redox and structural properties of the mutant mostly as a result of the modification of the dielectric constant of the solvent. This would warrant proper functionality of this variant also under these potentially hostile experimental conditions, that differ from the physiological milieu of cytochrome c.     

Promising Nanocarriers to Enhance Solubility and Bioavailability of Cannabidiol for a Plethora of Therapeutic Opportunities

In recent years, the interest in cannabidiol (CBD) has increased because of the lack of psychoactive properties. However, CBD has low solubility and bioavailability, variable pharmacokinetics profiles, poor stability, and a pronounced presystemic metabolism. CBD nanoformulations include nanosuspensions, polymeric micelles and nanoparticles, hybrid nanoparticles jelled in cross-linked chitosan, and numerous nanosized lipid formulations, including nanostructured lipid carriers, vesicles, SNEEDS, nanoemulsions, and microemulsions. Nanoformulations have resulted in high CBD solubility, encapsulation efficiency, and stability, and sustained CBD release. Some studies assessed the increased C_max and AUC and decreased T_max. A rational evaluation of the studies reported in this review evidences how some of them are very preliminary and should be completed before performing clinical trials. Almost all the developed nanoparticles have simple architectures, are well-known and safe nanocarriers, or are even simple nanosuspensions. In addition, the conventional routes of administration are generally investigated. As a consequence, many of these studies are almost ready for forthcoming clinical translations. Some of the developed nanosystems are very promising for a plethora of therapeutic opportunities because of the versatility in terms of the release, the crossing of physiological barriers, and the number of possible routes of administration.     

First Evidence of Anti-Steatotic Action of Macrotympanain A1, an Amphibian Skin Peptide from Odorrana macrotympana

Many different amphibian skin peptides have been characterized and proven to exert various biological actions, such as wound-healing, immunomodulatory, anti-oxidant, anti-inflammatory and anti-diabetic effects. In this work, the possible anti-steatotic effect of macrotympanain A1 (MA1) (FLPGLECVW), a skin peptide isolated from the Chinese odorous frog Odorrana macrotympana, was investigated. We used a well-established in vitro model of hepatic steatosis, consisting of lipid-loaded rat hepatoma FaO cells. In this model, a 24 h treatment with 10 µg/mL MA1 exerted a significant anti-steatotic action, being able to reduce intracellular triglyceride content. Accordingly, the number and diameter of cytosolic lipid droplets (LDs) were reduced by peptide treatment. The expression of key genes of hepatic lipid metabolism, such as PPARs and PLINs, was measured by real-time qPCR. MA1 counteracted the fatty acid-induced upregulation of PPARγ expression and increased PLIN3 expression, suggesting a role in promoting lipophagy. The present data demonstrate for the first time a direct anti-steatotic effect of a peptide from amphibian skin secretion and pave the way to further studies on the use of amphibian peptides for beneficial actions against metabolic diseases.     

The effect of operating conditions on the physicochemical characteristics of whey protein–based systems

The uptake of proteins is highly recommended, mainly for athletes, elderly people and patients with serious diseases like dysphagia. In this work, whey proteins were used for producing two kinds of aqueous materials: suspensions of proteins, in the native form, and gels, obtained by protein denaturation. In the first system, proteins are used as interfacial active ingredients or as thickening agents of the aqueous phase, whereas in the second one they are used as structuring agents. These protein-based materials show very different rheological and microstructural behaviour even at the same concentration. In the case of an undenatured system, a growing protein fraction resulted in an increased dimension of their aggregates and all investigated systems exhibited a liquid-like behaviour with a viscosity independent of shear rate and well described by a Krieger-Dougherty model. In the case of thermally denatured systems, it has been observed that, at increasing protein content, aggregates evolve towards a continuous gel network with a fractal behaviour. Both systems have been modelled, according to their specific behaviour, with the aim of proposing equations suitable to relate macroscopic properties and microstructure, useful for designing new food products with predictable properties for different industrial uses.

.