Molecular mechanisms driving the microgels behaviour: a Raman spectroscopy and Dynamic Light Scattering study

Responsive microgels based on poly(N-isopropylacrylamide) (PNIPAM) exhibit peculiar behaviours due to the competition between the hydrophilic and hydrophobic interactions of the constituent networks. The interpenetration of poly-acrilic acid (PAAc), a pH-sensitive polymer, within the PNIPAM network, to form Interpenetrated Polymer Network (IPN) microgels, affects this delicate balance and the typical Volume-Phase Transition (VPT) leading to complex behaviours whose molecular nature is still completely unexplored. Here we investigate the molecular mechanism driving the VPT and its influence on particle aggregation for PNIPAM/PAAc IPN microgels by the joint use of Dynamic Light Scattering and Raman Spectroscopy. Our results highlight that PNIPAM hydrophobicity is enhanced by the interpenetration of PAAc promoting interparticle interactions, a crossover concentration is found above which aggregation phenomena become relevant. Moreover we find that, at variance with PNIPAM, for IPN microgels a double-step molecular mechanisms occurs upon crossing the VPT, the first involving the coil-to-globule transition typical of PNIPAM and the latter associated to PAAc steric hindrance.Comment: preprint versio

Divergences in insulin resistance between the different phenotypes of the polycystic ovary syndrome

Context/Objective: Current diagnostic criteria for polycystic ovary syndrome (PCOS) have generated distinct PCOS phenotypes, based on the different combinations of diagnostic features found in each patient. Our aim was to assess whether either each single diagnostic feature or their combinations into the PCOS phenotypes may predict insulin resistance in these women. Patients/Design: A total of 137 consecutive Caucasian women with PCOS, diagnosed by the Rotterdam criteria, underwent accurate assessment of diagnostic and metabolic features. Insulin sensitivity was measured by the glucose clamp technique. Results: Among women with PCOS, 84.7% had hyperandrogenism, 84.7% had chronic oligoanovulation, and 89% had polycystic ovaries. According to the individual combinations of these features, 69.4% of women had the classic phenotype, 15.3% had the ovulatory phenotype, and 15.3% had the normoandrogenic phenotype. Most subjects (71.4%) were insulin resistant. However, insulin resistance frequency differed among phenotypes, being 80.4%, 65.0%, and 38.1%, respectively, in the 3 subgroups (P < .001). Although none of the PCOS diagnostic features per se was associated with the impairment in insulin action, after adjustment for covariates, the classic phenotype and, to a lesser extent, the ovulatory phenotype were independently associated with insulin resistance, whereas the normoandrogenic phenotype was not. Metabolic syndrome frequency was also different among phenotypes (P = .030). Conclusions: There is a scale of metabolic risk among women with PCOS. Although no single diagnostic features of PCOS are independently associated with insulin resistance, their combinations, which define PCOS phenotypes, may allow physicians to establish which women should undergo metabolic screening. In metabolic terms, women belonging to the normoandrogenic phenotype behave as a separate group

Microglia-derived microvesicles affect microglia phenotype in glioma

Extracellular-released vesicles (EVs), such as microvesicles (MV) and exosomes (Exo) provide a new type of inter-cellular communication, directly transferring a ready to use box of information, consisting of proteins, lipids and nucleic acids. In the nervous system, EVs participate to neuron-glial cross-talk, a bidirectional communication important to preserve brain homeostasis and, when dysfunctional, involved in several CNS diseases. We investigated whether microglia-derived EVs could be used to transfer a protective phenotype to dysfunctional microglia in the context of a brain tumor. When MV, isolated from microglia stimulated with LPS/IFNg were brain injected in glioma-bearing mice, we observed a phenotype switch of tumor associated myeloid cells (TAMs) and a reduction of tumor size. Our findings indicate that the MV cargo, which contains upregulated transcripts for several inflammation-related genes, can transfer information in the brain of glioma bearing mice modifying microglial gene expression, reducing neuronal death and glioma invasion, thus promoting the recovery of brain homeostasis

Influence of drug/lipid interaction on the entrapment efficiency of isoniazid in liposomes for antitubercular therapy: a multi-faced investigation

Hypothesis. Isoniazid is one of the primary drugs used in tuberculosis treatment. Isoniazid encapsulation in liposomal vesicles can improve drug therapeutic index and minimize toxic and side effects. In this work, we consider mixtures of hydrogenated soy phosphatidylcholine/phosphatidylglycerol (HSPC/DPPG) to get novel biocompatible liposomes for isoniazid pulmonary delivery. Our goal is to understand if the entrapped drug affects bilayer structure. Experiments. HSPC-DPPG unilamellar liposomes are prepared and characterized by dynamic light scattering, $\zeta$-potential, fluorescence anisotropy and Transmission Electron Microscopy. Isoniazid encapsulation is determined by UV and Laser Transmission Spectroscopy. Calorimetry, light scattering and Surface Pressure measurements are used to get insight on adsorption and thermodynamic properties of lipid bilayers in the presence of the drug. Findings. We find that INH-lipid interaction can increase the entrapment capability of the carrier due to isoniazid adsorption. The preferential INH-HSPC dipole-dipole interaction promotes modification of lipid packing and ordering and favors the condensation of a HSPC-richer phase in molar excess of DPPG. Our findings highlight the importance of fundamental investigations of drug-lipid interactions for the optimal design of liposomal nanocarriers.Comment: 28 pages (main manuscript + supplementary information

Solid–electrolyte interface formation on Si nanowires in Li-Ion batteries: the impact of electrolyte additives

The morphological changes of Si nanowires (Si NWs) cycled in 1:1 ethylene–carbonate (EC)/diethyl–carbonate (DEC) with or without different additives, fluoroethylene carbonate (FEC) or vinylene carbonate (VC), as well as the composition of the deposited solid–electrolyte interphase layer, are investigated by a combination of experimental microscopic and spectroscopic techniques. Scanning electron microscopy and optical spectroscopy highlight that the NW morphology is better preserved in samples cycled in the presence of FEC and VC additives compared to the additive-free electrolyte. However, only the use of FEC is capable of slightly mitigating the amorphization of silicon upon cycling. The solid electrolyte interphase (SEI) formed over the Si NWs cycled in the additive-free electrolyte is richer in organic and inorganic carbonates compared to the SEI grown in the presence of the VC and FEC additives. Furthermore, both additives are able to remarkably limit the degradation of the LiPF6 salt. Overall, the use of the FEC-additive in the carbonate-based electrolyte promotes both morphological and structural resilience of the Si NWs upon cycling thanks to the optimal composition of the SEI layer

On the dynamics of internal waves in a nonlinear, weakly nonhydrostatic three-layer ocean

Aspects of the dynamics of internal solitary waves evolving in a three-layer ocean are investigated using a new numerical multilayer model that solves the nonlinear, weakly nonhydrostatic Boussinesq equations and uses high-resolution in situ data. The model applications refer to two different phenomena frequently observed in the real ocean, which can be described using a three-layer model rather than a two-layer model. In the first application the influence of the strength of a shallow seasonal thermocline superimposed on a two-layer permanent stratification on the structure of internal solitary waves is studied. It is found that while for small to medium wave amplitudes a decrease in the strength of the thermocline yields an increase in the simulated wavelengths, for large wave amplitudes this dependence is no longer monotonic. In particular, in the limiting case of a vanishing thermocline, first-mode internal solitary wave solutions of the three-layer numerical model tend to the analytical internal solitary wave solutions of the Miyata equations, a two-layer model, in which the full nonlinearity of the shallow-water theory up to first-order phase dispersion is retained. In the second application that refers particularly to high-resolution observations made north and south of the Strait of Messina in the Eurafrican Mediterranean basin the generation of internal solitary waves by the evolution of surface and subsurface water jets is investigated. The analysis of the in situ data shows in fact that from very energetic surface and subsurface jet-like disturbances subject to strong turbulent mixing internal solitary waves emerge as robust, quasi-nondissipative oceanic features. Idealized flow conditions aimed at approximating possible initial stages of the observed water jets are imposed to force our numerical model. In general, good agreement is found between characteristics of observed and simulated wave fields. Our investigation identifies the observed water jets as peculiar features of the complex ocean dynamics and suggests that layered numerical models can represent helpful tools in understanding fundamental processes inherent in their intricate dynamics

The Imaging X-ray Polarimetry Explorer (IXPE): Technical Overview

The Imaging X-ray Polarimetry Explorer (IXPE) will expand the information space for study of cosmic sources, by adding linear polarization to the properties (time, energy, and position) observed in x-ray astronomy. Selected in 2017 January as a NASA Astrophysics Small Explorer (SMEX) mission, IXPE will be launched into an equatorial orbit in 2021. The IXPE mission will provide scientifically meaningful measurements of the x-ray polarization of a few dozen sources in the 2-8 keV band, including polarization maps of several x-ray-bright extended sources and phase-resolved polarimetry of many bright pulsating x-ray sources

Solid&ndash;Electrolyte Interface Formation on Si Nanowires in Li-Ion Batteries: The Impact of Electrolyte Additives

The morphological changes of Si nanowires (Si NWs) cycled in 1:1 ethylene&ndash;carbonate (EC)/diethyl&ndash;carbonate (DEC) with or without different additives, fluoroethylene carbonate (FEC) or vinylene carbonate (VC), as well as the composition of the deposited solid&ndash;electrolyte interphase layer, are investigated by a combination of experimental microscopic and spectroscopic techniques. Scanning electron microscopy and optical spectroscopy highlight that the NW morphology is better preserved in samples cycled in the presence of FEC and VC additives compared to the additive-free electrolyte. However, only the use of FEC is capable of slightly mitigating the amorphization of silicon upon cycling. The solid electrolyte interphase (SEI) formed over the Si NWs cycled in the additive-free electrolyte is richer in organic and inorganic carbonates compared to the SEI grown in the presence of the VC and FEC additives. Furthermore, both additives are able to remarkably limit the degradation of the LiPF6 salt. Overall, the use of the FEC-additive in the carbonate-based electrolyte promotes both morphological and structural resilience of the Si NWs upon cycling thanks to the optimal composition of the SEI layer

Blueberry-Derived Exosome-Like Nanoparticles Counter the Response to TNF-α-Induced Change on Gene Expression in EA.hy926 Cells

Exosome-like nanoparticles (ELNs) are attracting interest as important vehicles of intercellular communication, both in prokaryotes and eukaryotes. Recently, dietary nanoparticles similar to mammalian exosomes have attracted attention for these features. In particular they appear to be relevant in the modulation of several cellular processes as well as candidate carriers of bioactive molecules (proteins, lipids, and nucleic acids, including miRNAs) with therapeutic value. Herein, we investigated the cellular uptake of blueberry-derived ELNs (B-ELNs) by a human stabilized endothelial cell line (EA.hy926) and the ability of B-ELNs to modulate the expression of inflammatory genes as the response of tumor necrosis factor-α (TNF-α). Our results indicate that 1) EA.hy926 cells internalize B-ELNs in a dose-dependent manner; 2) pretreatment with B-ELNs counters TNF-α-induced reactive oxygen species (ROS) generation and loss of cell viability and modulates the differential expression of 29 genes (fold change &gt; 1.5) induced by TNF-α compared to control; 3) pathway analysis reveals their involvement in a total of 340 canonical pathways, 121 KEGG pathways, and 121 GO Biological processes; and 4) the intersection between differentially expressed (DE) genes and miRNAs contained in B-ELNs unveils a set of candidate target genes, such as prostaglandin I2 synthase (PTGIS), mitogen-activated protein kinase 14 (MAPK14), and phosphodiesterase 7A (PDE7A), for ELNs-contained cargo. In conclusion, our study indicates that B-ELNs can be considered candidate therapeutic carriers of bioactive compounds potentially able to protect vascular system against various stressors