Assessment of free-radical scavenging and anti-bacterial potential of Thymol conjugated with Gum Acacia-Chitosan copolymeric nanoformulation

This study details with thymol loaded on anionic copolymeric (Gum Acacia-Chitosan) nanoformulation prepared using ionic gelation to further enhance its therapeutic effectiveness. Optimized nanoparticles of 10:1 ratio (Gum Acacia:Chitosan) having entrapmentefficiency of 97% and mean hydrodynamic diameter of 172 nm (obtained using DLS) were characterized and in vitro examined for drug release effect, antioxidant potential and antibacterial activity. Zeta potential reading (-31.4 mV) confirmed optimized nanoformulation as stable and Electron-microscopy affirmed spherical morphology. FTIR analysis revealed entrapment as well as chemical-conjugation of thymol in polymer matrices. Thymol availability lasting more than 24 hours was verified in vitro by drug release experiments. Synthesized nanoformulation demonstrated superior antioxidant and antibacterial activity which may be attributable to its anionic charge, slow sustained release and synergistic effect provided by copolymers. Hence this investigation suggests control-release strategy using these copolymers for further utilization of thymol as natural therapeutic molecule by overcoming its solubility, stability and oxidation problems.

Exploring Gunnera tinctoria: From Nutritional and Anti-Tumoral Properties to Phytosome Development Following Structural Arrangement Based on Molecular Docking

Gunnera tinctoria, an underexplored invasive plant found in Azores, Portugal, was studied regarding its nutritional, antioxidant, and antitumoral properties. Higher antioxidant activity was found in baby leaves, followed by adult leaves and inflorescences. A phenolic fraction of the plant was enriched using adsorbent resin column chromatography (DiaionTM HP20LX, and Relite EXA90). Antitumoral effects were observed with the enriched fractions in breast (MCF-7) and pancreatic (AsPC-1) cancer cell lines, being more pronounced in the latter. To improve protection and membrane absorption rates of phenolic compounds, nano-phytosomes and cholesterol-conjugated phytosomes coated with natural polymers were loaded with the enriched fraction. The particles were characterized, and their physiochemical properties were evaluated and compared. All samples presented anionic charge and nanometer size in relation to the inner layer and micrometer size regarding the external layers. In addition, the molecular arrangement of phenolics within both types of phytosomes were studied for the first time by molecular docking. Polarity and molecular size were key factors on the molecular arrangement of the lipid bilayer. In conclusion, G. tinctoria showed to be an interesting source of nutrients and phenolic compounds with anti-tumoral potential. Moreover, phytosome loading with these compounds can increase their stability and bioavailability having in view future applications.

Use of Multi-Anionic Sodium Tripolyphosphate to Enhance Dispersion of Concentrated Kaolin Slurries in Seawater

This research aims to analyze the impact of sodium tripolyphosphate (STPP) as a rheological modifier of concentrated kaolin slurries in seawater at pH 8, which is characteristic of copper sulfide processing operations. The dispersion phenomenon was analyzed through chord length measurements using the focused beam reflectance measurement (FBRM) technique, complementing size distributions in unweighted and square-weighted modes. The reduction of the rheological properties was significant, decreasing from 231 Pa in a reagent-free environment to 80 Pa after the application of STPP. A frequency sweep in a linear viscoelastic regime indicated that by applying a characteristic dosage of 0.53 kg/t of STPP, the pulp before yielding increases its phase angle, which increases its liquid-like character. Measurements of the chord length verified the dispersion of particles, which showed an apparent increase in the proportion of fine particles and a reduction of the coarser aggregates when STPP was applied. Measurements of the zeta potential suggested that the high anionic charge of the reagent (pentavalent) increases the electrostatic repulsions between particles, overcoming the effect of cations in seawater. The results are relevant for the mining industry, especially when the deposits have high contents of complex gangues, such as clays, that increase the rheological properties. This increases the energy costs and water consumption needed for pumping the tailings from thickeners to the tailing storages facilities. The strategies that allow for the improvement of the fluidity and deformation of the tailings generate slack in order to maximize water recovery in the thickening stages.

On the Lithium Distribution in Halide Superionic Argyrodites by Halide Incorporation in Li7−xPS6−xClx

<p>Superionic lithium argyrodites are attractive as solid electrolytes for all-solid-state-batteries. These materials of composition Li₆PS₅X (X = Cl, Br, and I) exhibit structural disorder between the X⁻/S²⁻ positions, with higher disorder realizing better Li⁺ transport. Further replacement of the sulfide by chloride anions (for the series Li₇_−xPS₆_−xCl_x) has been shown to increase the ionic conductivity. However, the underlying changes to the lithium substructure are still relatively unknown. Here we explore a larger range of nominal halide compositions in this material from x = 0.25 to x = 1.5 and explore the changes with neutron diffraction and impedance spectroscopy. The replacement of S²⁻ by Cl⁻causes a lowered average charge in the center of the prevalent Li⁺ “cages”, which in turn causes weaker interactions with Li⁺ ions. Analysis of neutron diffraction data reveals that the increased Cl⁻ content causes these clustered Li⁺ “cages” to become more interconnected, thereby increasing Li⁺ conductivity through the structure. This study explores the understanding of the fundamental structure–transport correlations in the argyrodites, specifically structural changes withinthe Li⁺ ion substructure upon changing anionic charge distribution.</p>

On the Lithium Distribution in Halide Superionic Argyrodites by Halide Incorporation in Li7−xPS6−xClx

<p>Superionic lithium argyrodites are attractive as solid electrolytes for all-solid-state-batteries. These materials of composition Li₆PS₅X (X = Cl, Br, and I) exhibit structural disorder between the X⁻/S²⁻ positions, with higher disorder realizing better Li⁺ transport. Further replacement of the sulfide by chloride anions (for the series Li₇_−xPS₆_−xCl_x) has been shown to increase the ionic conductivity. However, the underlying changes to the lithium substructure are still relatively unknown. Here we explore a larger range of nominal halide compositions in this material from x = 0.25 to x = 1.5 and explore the changes with neutron diffraction and impedance spectroscopy. The replacement of S²⁻ by Cl⁻causes a lowered average charge in the center of the prevalent Li⁺ “cages”, which in turn causes weaker interactions with Li⁺ ions. Analysis of neutron diffraction data reveals that the increased Cl⁻ content causes these clustered Li⁺ “cages” to become more interconnected, thereby increasing Li⁺ conductivity through the structure. This study explores the understanding of the fundamental structure–transport correlations in the argyrodites, specifically structural changes withinthe Li⁺ ion substructure upon changing anionic charge distribution.</p>

How Teichoic Acids Could Support a Periplasm in Gram-Positive Bacteria, and Let Cell Division Cheat Turgor Pressure

The cytoplasm of bacteria is maintained at a higher osmolality than the growth medium, which generates a turgor pressure. The cell membrane (CM) cannot support a large turgor, so there are two possibilities for transferring the pressure to the peptidoglycan cell wall (PGW): (1) the CM could be pressed directly against the PGW, or (2) the CM could be separated from the PGW by a periplasmic space that is isoosmotic with the cytoplasm. There is strong evidence for gram-negative bacteria that a periplasm exists and is isoosmotic with the cytoplasm. No comparable studies have been done for gram-positive bacteria. Here I suggest that a periplasmic space is probably essential in order for the periplasmic proteins to function, including especially the PBPs that remodel the peptidoglycan wall. I then present a semi-quantitative analysis of how teichoic acids could support a periplasm that is isoosmotic with the cytoplasm. The fixed anionic charge density of teichoic acids in the periplasm is ∼0.5 M, which would bring in ∼0.5 M Na+ neutralizing ions. This approximately balances the excess osmolality of the cytoplasm that would produce a turgor pressure of 19 atm. The 0.5 M fixed charge density is similar to that of proteoglycans in articular cartilage, suggesting a comparability ability to support pressure. An isoosmotic periplasm would be especially important for cell division, since it would allow CM constriction and PGW synthesis to avoid turgor pressure.

Mast Cell β-Tryptase Is Enzymatically Stabilized by DNA

Tryptase is a tetrameric serine protease located within the secretory granules of mast cells. In the secretory granules, tryptase is stored in complex with negatively charged heparin proteoglycans and it is known that heparin is essential for stabilizing the enzymatic activity of tryptase. However, recent findings suggest that enzymatically active tryptase also can be found in the nucleus of murine mast cells, but it is not known how the enzmatic activity of tryptase is maintained in the nuclear milieu. Here we hypothesized that tryptase, as well as being stabilized by heparin, can be stabilized by DNA, the rationale being that the anionic charge of DNA could potentially substitute for that of heparin to execute this function. Indeed, we showed that double-stranded DNA preserved the enzymatic activity of human β-tryptase with a similar efficiency as heparin. In contrast, single-stranded DNA did not have this capacity. We also demonstrated that DNA fragments down to 400 base pairs have tryptase-stabilizing effects equal to that of intact DNA. Further, we showed that DNA-stabilized tryptase was more efficient in degrading nuclear core histones than heparin-stabilized enzyme. Finally, we demonstrated that tryptase, similar to its nuclear localization in murine mast cells, is found within the nucleus of primary human skin mast cells. Altogether, these finding reveal a hitherto unknown mechanism for the stabilization of mast cell tryptase, and these findings can have an important impact on our understanding of how tryptase regulates nuclear events.

Fibrillation and characterization of lignin-containing neutral sulphite (NS) pulps rich in hemicelluloses and anionic charge

The potential of neutral sulphite pulps from softwood with different yields (c. 58–84%) and high residual lignin contents (c. 10–25 wt%) was investigated as a raw material for lignin-containing cellulose nanofibrils (LCNFs) by following their fibrillation during grinding. It was found that the lower yield (58–65%) pulps needed two grinding cycles to produce fibrillated fibers with water retention values (WRV) as high as 400 g/g (at the energy consumption level of 1400 kWh/t). In contrast, the high yield (77–84%) pulps fibrillated more slowly, requiring five grinding cycles to reach comparable WRV values. Apparently, higher crosslinking degrees of lignin in the high yield pulps are hampering the fibrillation, although the high hemicellulose contents (21–24 wt%) and the high charge densities (200–350 µmol/g, originating from carboxylic and sulphonic acid groups) of the pulps were expected to enhance the fibrillation. Nevertheless, regardless of the different fibrillation behaviour, most of the pulps formed c. 10–15% of nanosized material below 30 nm and significant amounts of fibrils with size under 100 nm based on the centrifugation method and FE-SEM images. As the pulps were of moderate to high yield and fibrillated easily without any chemical or enzymatic pretreatments, they show promise for cost-efficient production of LCNFs. The nanopapers prepared from the fibrillated pulps showed tensile strengths (73–125 MPa) comparable with the nanopapers from high yield mechanical pulps, whereas the water contact angles (41°–58°) were closer the those of chemical pulps.

Molecular Analysis of Membrane Targeting by the C2 Domain of the E3 Ubiquitin Ligase Smurf1

SMAD ubiquitination regulatory factor 1 (Smurf1) is a Nedd4 family E3 ubiquitin ligase that regulates cell motility, polarity and TGF&beta; signaling. Smurf1 contains an N-terminal protein kinase C conserved 2 (C2) domain that targets cell membranes and is required for interactions with membrane-localized substrates such as RhoA. Here we investigated the lipid-binding mechanism of Smurf1 C2, revealing a general affinity for anionic membranes in addition to a selective affinity for phosphoinositides (PIPs). We found that Smurf1 C2 localizes not only to the plasma membrane but also to negatively charged intracellular sites, acting as an anionic charge sensor and selective PIP-binding domain. Site-directed mutagenesis combined with docking/molecular dynamics simulations revealed that the Smurf1 C2 domain loop region primarily interacts with PIPs and cell membranes, as opposed to the &beta;-surface cationic patch employed by other C2 domains. By depleting PIPs from the inner leaflet of the plasma membrane, we found that PIP binding is necessary for plasma membrane localization. Finally, we used a Smurf1 cellular ubiquitination assay to show that the amount of ubiquitin at the plasma membrane interface depends on the lipid-binding properties of Smurf1. This study shows the mechanism by which Smurf1 C2 targets membrane-based substrates and reveals a novel interaction based on PI(4,5)P2 and PIP3 selectivity.