Small-angle neutron scattering (SANS) characterization of 13.5 Cr oxide dispersion strengthened ferritic steel for fusion applications

Small-angle neutron scattering (SANS) has been utilized for micro-structural investigation on laboratory heats of oxide dispersion strengthened (ODS) 13.5 Cr wt % ferritic steel, with 0.3 wt% Y$_{2}$O$_{3}$ and with variable Ti and W contents. The results show that increasing the Ti content from 0.2 to 0.4 wt% a distribution of nano-clusters develops, tentatively identified as Y$_{2}$Ti$_{2}$O$_{7}$, with average radii as small as 6.5 Å and volume fractions increasing from 0.021 to 0.032. The measured SANS cross-sections show also the growth of much larger defects, possibly Cr oxides. Furthermore, the ratio of magnetic to nuclear SANS components shows that the defect composition varies both with their size and with the Ti and the W content. These results are in qualitative agreement with transmission electron microscopy (TEM) observations, showing a striking influence of Ti addition on particle size refinement. However, while TEM is limited in statistics and minimum observable size of the Ti-rich nano-clusters, the defect distributions obtained by these SANS measurements provide complementary information useful for morphological characterization of the micro-structure in the investigated material

Nanostructures by Self-assembling Peptide Amphiphile as Potential Selective Drug Carriers

The self-assembling behaviour, at physiological pH, of the amphiphile peptide (C18)(2)L5CCK8 in nanostructures is reported. Stable aggregates presenting a critical micellar concentration of 2 X 10(-6) mol kg(-1), and characterized by water exposed CCK8 peptide in P-sheet conformation, are obtained. Small angle neutron scattering experiments are indicative for a 3D structure with dimensions >= 100 nm. AFM images confirm the presence of nanostructures. Fluorescence experiments indicating the sequestration of pyrene, chosen as drug model, and the anticancer Doxorubicin within the nanostructures are reported

Progressive fibrosing interstitial lung diseases: A current perspective

Interstitial lung diseases (ILDs) are a large and diverse group of rare and chronic respiratory disorders, with idiopathic pulmonary fibrosis (IPF) being the most common and best-studied member. Increasing interest in fibrosis as a therapeutic target and the appreciation that fibrotic mechanisms may be a treatable target of IPF prompted the development and subsequent approval of the antifibrotics, pirfenidone and nintedanib. The management of ILDs has changed considerably following an understanding that IPF and some ILDs share similar disease behavior of progressive fibrosis, termed “progressive fibrosing phenotype”. Indeed, antifibrotic treatment has shown to be beneficial in ILDs characterized by the progressive fibrosing phenotype. This narrative review summarizes current knowledge in the field of progressive fibrosing ILDs. Here, we discuss the clinical characteristics and pathogenesis of lung fibrosis and highlight relevant literature concerning the mechanisms underlying progressive fibrosing ILDs. We also summarize current diagnostic approaches and the available treatments of progressive fibrosing ILDs and address the optimization of treating progressive fibrosing ILDs with antifibrotics in clinical practice

Peptide-containing aggregates as selective nanocarriers for therapeutics

New nanocarriers are obtained by assembling two amphiphilic monomers: one containing the bioactive peptide CCK8 spaced, by a polydisperse poly(ethylene glycol), from two hydrophobic tails ((C18)2PEG2000CCK8), and the other containing a chelating agent able to give stable radiolabeled indium-111 complexes linked to the same hydrophobic moiety ((C18)2DTPAGlu). The size and shape of the supramolecular aggregates were structurally characterized by dynamic light scattering, small-angle neutron scattering, and cryogenic transmission electronic microscopy. Under the experimental conditions we investigated (pH 7.4 and molar ratio between monomers 30:70), there is the presence of high polydisperse aggregates: rod-like micelles with a radius of 40 Å and length >700 Å, open bilayer fragments with thickness 65 Å, and probably vesicles. The presence of the bioactive peptide well exposed on the external surface of the aggregate allows selective targeting of nanocarriers towards the cholecystokinin receptors overexpressed by the cancerous cells. In vitro binding assays and in vivo biodistribution studies by nuclear medicine experiments using indium-111 are reported. Moreover, preliminary data concerning the drug loading capability of the aggregates and their drug efficiency on the target cells is reported by using the cytotoxic drug doxorubicin. Incubation of receptor-positive and control cells with peptide-containing aggregates filled with doxorubicin shows significantly lower cell survival in receptor-expressing cells relative to the control, for samples incubated in the presence of doxorubicin

Toxicity of antioxidant supplements in patients with male factor infertility: A systematic review and meta-analysis of randomized controlled trials

Treating oxidative stress through antioxidant therapy has been considered an appealing strategy in the management of male infertility. However, evidence regarding the toxicity of an-tioxidant therapy is controversial. We summarized the available clinical evidence on the toxicity associated with the use of antioxidants in infertile males. A systematic review was performed in March 2021. We included randomized controlled trials evaluating the incidence of adverse events in male patients with infertility receiving antioxidant therapy. Thirteen studies involving 1999 male patients were identified. Antioxidant supplementation in patients with male factor infertility was associated with a statistically significantly increased risk of nausea (Odds Ratio: 2.16, 95% Confidence Interval: 1.05–4.43, p = 0.036), headache (Odds Ratio: 3.05, 95% Confidence Interval: 1.59– 5.85 p = 0.001), and dyspepsia (Odds Ratio: 4.12, 95% Confidence Interval: 1.43–11.85, p = 0.009) compared to a placebo. Treatment discontinuation due to adverse events was not significantly higher in patients taking antioxidants compared to a placebo (Odds Ratio: 2.29, 95% Confidence Interval: 0.76–6.88, p = 0.139). When antioxidant supplementation is considered, a more accurate risk/benefit analysis is warranted

Impact of Circadian Desynchrony on Spermatogenesis: A Mini Review

The purpose of this mini review is to provide data about pre-clinical and clinical evidence exploring the impact of circadian desynchrony on spermatogenesis. Several lines of evidence exist demonstrating that disruption of circadian rhythms may interfere with male fertility. Experimental knock-out or knock-down of clock genes, physiologically involved in the regulation of circadian rhythms, are associated with impairments of fertility pathways in both animal and human models. Moreover, disruption of circadian rhythms, due to reduction of sleep duration and/or alteration of its architecture can negatively interfere in humans with circulating levels of male sexual hormones as well as with semen parameters. Unfortunately, current evidence remains low due to study heterogeneity

Mixed micelles composed of Peptides and Gadolinium complexes as tumor-specific contrast agents in MRI: a SANS study

A detailed structural investigation on mixed micelle aggregates as target-specific contrast agents for magnetic resonance imaging technique has been carried out by way of small angle neutron scattering measurements. These mixed micelles are formed by two new amphiphilic molecules formed by a bioactive peptide and a claw moiety. The first molecule, C18H37CONH(AdOO)(x)-G-CCK8 (C18LxCCK8, x = 2, 5), contains an 18-carbon-atom alkylic chain bound to the C-terminal of the cholecystokinin octapeptide amide (CCK 26-33 or CCK8) and is able to bind to the overexpressed CCK receptor of some tumor cells. The second molecule, C(18)H(37)CONHLys(DTPAGlu)CONH25- (C18DTPAGlu) or its gadolinium complex [C(18)H(37)CONHLys(DTPAGlu)CONH2Gd](2-), C18DTPAGlu(Gd),contains the same 18-carbon-atom alkylic chain bound, through a lysine residue, to the DTPAGlu chelating agent. Small angle neutron scattering measurements have been performed on ternary systems at different total concentrations and at various ratios of the two molecules. The effect of the concentration on the aggregation number as well as on the shape of the micelle has been investigated. Furthermore in order to optimize the exposure of the peptide on the micelle surface, C18LxCCK8 having the spacer L of different length has been used. The pure binary systems of the synthesized molecules are also presented

Cubosomes for Ruthenium complex delivery: formulation and characterization

An amphiphilic ruthenium-based molecule (DOPURu) with potential antineoplastic activity has been synthesized, and its aggregation behavior in the presence of phospholipids has been investigated. A very rich variety of aggregates has been found, spanning from vesicles to cubic bicontinuous phases. Cubosomes here presented represent one of the first systems with potential use for medical therapy

Mutual and intradiffusion coefficients for the binary system n-decyl dimethyl phosphine oxide + water at 25 °C

Diffusion coefficients for the binary system n-decyl dimethyl phosphine oxide + water have been studied at 25 °C, with the aim to quantitatively describe the surfactant micellization process in aqueous medium. Accurate mutual diffusion coefficients have been measured by the Taylor dispersion technique. Intradiffusion coefficients of both components have been measured by the pulsed gradient spin echo (PGSE)-FT NMR technique. The data have been compared and interpreted in the framework of the equilibrium model of surfactant self-aggregation. Interpolation of the mutual diffusion coefficients has allowed us to estimate reliable values of the average number of surfactant molecules involved in the formation of a micellar aggregate and the constant of the equilibrium between these aggregates and surfactant unimers. Interpolation of water intradiffusion coefficients has allowed us to estimate the number of water molecules involved in the hydration of surfactants in unimeric and micellized form