Formulative Study and Intracellular Fate Evaluation of Ethosomes and Transethosomes for Vitamin D3 Delivery

In this pilot study, ethosomes and transethosomes were investigated as potential delivery systems for cholecalciferol (vitamin D3), whose deficiency has been correlated to many disorders such as dermatological diseases, systemic infections, cancer and sarcopenia. A formulative study on the influence of pharmaceutically acceptable ionic and non-ionic surfactants allowed the preparation of different transethosomes. In vitro cytotoxicity was evaluated in different cell types representative of epithelial, connective and muscle tissue. Then, the selected nanocarriers were further investigated at light and transmission electron microscopy to evaluate their uptake and intracellular fate. Both ethosomes and transethosomes proven to have physicochemical properties optimal for transdermal penetration and efficient vitamin D3 loading; moreover, nanocarriers were easily internalized by all cell types, although they followed distinct intracellular fates: ethosomes persisted for long times inside the cytoplasm, without inducing subcellular alteration, while transethosomes underwent rapid degradation giving rise to an intracellular accumulation of lipids. These basic results provide a solid scientific background to in vivo investigations aimed at exploring the efficacy of vitamin D3 transdermal administration in different experimental and pathological conditions.     

Age-Related Changes in the Matrisome of the Mouse Skeletal Muscle

Aging is characterized by a progressive decline of skeletal muscle (SM) mass and strength which may lead to sarcopenia in older persons. To date, a limited number of studies have been performed in the old SM looking at the whole, complex network of the extracellular matrix (i.e., matrisome) and its aging-associated changes. In this study, skeletal muscle proteins were isolated from whole gastrocnemius muscles of adult (12 mo.) and old (24 mo.) mice using three sequential extractions, each one analyzed by liquid chromatography with tandem mass spectrometry. Muscle sections were investigated using fluorescence- and transmission electron microscopy. This study provided the first characterization of the matrisome in the old SM demonstrating several statistically significantly increased matrisome proteins in the old vs. adult SM. Several proteomic findings were confirmed and expanded by morphological data. The current findings shed new light on the mutually cooperative interplay between cells and the extracellular environment in the aging SM. These data open the door for a better understanding of the mechanisms modulating myocellular behavior in aging (e.g., by altering mechano-sensing stimuli as well as signaling pathways) and their contribution to age-dependent muscle dysfunction.     

Identification of Rare LRP5 Variants in a Cohort of Males with Impaired Bone Mass

Osteoporosis is the most common bone disease characterized by reduced bone mass and increased bone fragility. Genetic contribution is one of the main causes of primary osteoporosis; therefore, both genders are affected by this skeletal disorder. Nonetheless, osteoporosis in men has received little attention, thus being underestimated and undertreated. The aim of this study was to identify novel genetic variants in a cohort of 128 males with idiopathic low bone mass using a next-generation sequencing (NGS) panel including genes whose mutations could result in reduced bone mineral density (BMD). Genetic analysis detected in eleven patients ten rare heterozygous variants within the LRP5 gene, which were categorized as VUS (variant of uncertain significance), likely pathogenic and benign variants according to American College of Medical Genetics and Genomics (ACMG) guidelines. Protein structural and Bayesian analysis performed on identified LRP5 variants pointed out p.R1036Q and p.R1135C as pathogenic, therefore suggesting the likely association of these two variants with the low bone mass phenotype. In conclusion, this study expands our understanding on the importance of a functional LRP5 protein in bone formation and highlights the necessity to sequence this gene in subjects with idiopathic low BMD.     

Lipofilling in Breast Oncological Surgery: A Safe Opportunity or Risk for Cancer Recurrence?

Lipofilling (LF) is a largely employed technique in reconstructive and esthetic breast surgery. Over the years, it has demonstrated to be extremely useful for treatment of soft tissue defects after demolitive or conservative breast cancer surgery and different procedures have been developed to improve the survival of transplanted fat graft. The regenerative potential of LF is attributed to the multipotent stem cells found in large quantity in adipose tissue. However, a growing body of pre-clinical evidence shows that adipocytes and adipose-derived stromal cells may have pro-tumorigenic potential. Despite no clear indication from clinical studies has demonstrated an increased risk of cancer recurrence upon LF, these observations challenge the oncologic safety of the procedure. This review aims to provide an updated overview of both the clinical and the pre-clinical indications to the suitability and safety of LF in breast oncological surgery. Cellular and molecular players in the crosstalk between adipose tissue and cancer are described, and heterogeneous contradictory results are discussed, highlighting that important issues still remain to be solved to get a clear understanding of LF safety in breast cancer patients.     

Study on silicon surface oxidation of post-implant resist cleaning

Minimum substrate loss is required for resist strip of high dose, ultra shallow junction implant for source/drain extensions. Silicon surface oxidation of downstream plasma resist strip results in silicon recess of the source/drain extension regions. This paper reports the study of silicon surface oxidation for different resist strip plasma chemistries and the effect of plasma strip process parameters such as power, pressure and temperature on silicon surface oxidation. A good agreement was found between optical ellipsometry, XPS (X-ray photoelectron spectroscopy) and TEM (transmission electron spectroscopy) for thickness measurement of very thin (<20 Å) oxide grown on silicon surface due to plasma exposure. Selectivity of crust breakthrough and resist removal over silicon oxidation was also discussed in this paper along with dopant loss.     

Efficient inclusion for a class of XML types with interleaving and counting

Inclusion between XML types is important but expensive, and is much more expensive when unordered types are considered. We prove here that inclusion for XML types with interleaving and counting can be decided in polynomial time in the presence of two important restrictions: no element appears twice in the same content model, and Kleene star is only applied to disjunctions of single elements.     

Study of Evaporative Convection in an Open Cavity under Shear Stress Flow

When a layer of volatile liquid is exposed to a shear flow of inert gas, thermal patterns, in the form of interfacial ripples and bulk plumes, are created by the combined action of evaporative, shear-driven and surface-tension-driven instabilities. The topology of the interfacial thermal patterns is mainly influenced by the geometry of the evaporating surface, the thickness of the evaporating layer, the intensity of the shear flow and by the physic-chemical properties of the working fluid. In this paper, by means of numerical simulations, we focused our attention on the dynamics of the interfacial thermal patterns for different working fluids and thicknesses of the volatile liquid layer. This study has been performed in the frame of the ESA sponsored Space Program on heat and mass transfer CIMEX-1. The choice of the fluids—ethyl alcohol and FC72 (n-perfluorohexane)—the reference values for the inert gas flow rate, the thickness of the liquid layer as well as the geometrical features of the computational domain correspond exactly to the ones foreseen for the CIMEX-1 experiment. However, the main conclusions can be considered of more general validity.     

Alkali-free glass as a high energy density dielectric material

One of the greatest challenges in the development of new high energy density materials is to increase dielectric permittivity while maintaining high breakdown strength. The dielectric breakdown behavior of an alkali-free barium boroaluminosilicate glass is shown to have remarkably high DC dielectric breakdown strength (12 MV/cm) and reasonably high permittivity (~ 6), equating to energy densities in excess of 35 J/cm³. This behavior is attributed to highly polarizable Ba ions enhancing the real part of complex permittivity, the low loss due to the alkali-free composition, and the substantially defect-free quality of the glass and its surfaces. To our knowledge, this is the highest breakdown strength reported for a bulk glass, and rivals the breakdown strength more typically observed in pristine thin films of SiO₂. These findings indicate that alkali-free multicomponent glasses may be strong candidates for next-generation high energy density storage capacitors for portable or pulsed power applications.     

On the asymptotic behaviour of shells of revolution in free vibration

We consider the free vibration problem of thin shells of revolution of constant type of geometry, focusing on the asymptotic behaviour of the lowest eigenfrequency, as the thickness tends to zero. Numerical experiments are computed using two discretization methods, collocation and finite elements, each corresponding to a different shell model. Our results are in agreement with theoretical results obtained using interpolation theory and cited in literature.