Formation of mesoglobules in aqueous media from thermo-sensitive poly(ethoxytriethyleneglycol acrylate)

A series of six poly(ethoxytriethyleneglycol acrylate) (PETEGA) homopolymers were synthesized by atom transfer radical polymerization, reversible addition-fragmentation transfer polymerization, and anionic polymerization in order to cover a molecular weight range from 7,000 to 40,000 Da. The polymers exhibited a lower critical solution temperature (LCST) behavior in water, which was observed by the occurrence of a cloud point (CP) at around 35 °C. The transmittance of visible light versus temperature dependence overlapped during the cooling and the heating cycles, showing almost a complete lack of hysteresis. Moreover, instead of the occurrence of an uncontrolled macroscopic phase separation, stable colloidal aggregates (mesoglobules) of narrow distribution in particle size were formed in water at temperatures above the LCST of PETEGA at 1 g L⁻¹ solutions. The dimensions of the mesoglobules ranged from 91 to 235 nm, and particle size was not influenced by the molecular weight of PETEGA. Temperature changes caused considerable variations of the mesoglobules dimensions, which were smaller at higher temperatures. The addition of an anionic surfactant simultaneously increased the CP values by 4–6 °C and lowered the dimensions of the mesoglobules.     

Improvement of Major Depression is Associated with Increased Erythrocyte DHA

The aim of this study was to determine if changes in omega‐3 polyunsaturated fatty acid status following tuna oil supplementation correlated with changes in scores of depression. A total of 95 volunteers receiving treatment for major depression were randomised to consume 8 × 1 g capsules per day of HiDHA (2 g DHA, 0.6 g EPA and 10 mg Vitamin E) or olive oil (placebo) for 16 weeks, whilst undergoing weekly counseling sessions by trained clinical psychologists using a standard empirically validated psychotherapy. Depression status was assessed using the 17 item Hamilton rating scale for depression and the Beck Depression Inventory by a psychodiagnostician who was blind to the treatment. Blood was taken at baseline and 16 weeks (n = 48) for measurement of erythrocyte fatty acids. With HiDHA supplementation, erythrocyte DHA content rose from 4.1 ± 0.2 to 7.9 ± 0.4 % (mean ± SEM, p < 0.001) of total fatty acids but did not change (4.0 ± 0.2 to 4.1 ± 0.2 %) in the olive oil group. The mean changes in scores of depression did not differ significantly between the two groups (?12.2 ± 2.1 for tuna oil and ?14.4 ± 2.3 for olive oil). However, analysis of covariance showed that in the fish oil group there was a significant correlation (r = ?0.51) between the change in erythrocyte DHA and the change in scores of depression (p < 0.05). Further study of the relationship between DHA and depression is warranted.     

Dietary Intake and Food Sources of EPA, DPA and DHA in Australian Children

Secondary analysis of the 2007 Australian National Children’s Nutrition and Physical Activity survey was undertaken to assess the intake and food sources of EPA, DPA and DHA (excluding supplements) in 4,487 children aged 2–16 years. An average of two 24-h dietary recalls was analysed for each child and food sources of EPA, DPA and DHA were assessed using the Australian nutrient composition database called AUSNUT 2007. Median (inter quartile range, IQR) for EPA, DPA and DHA intakes (mg/day) for 2–3, 4–8, 9–13, 14–16 year were: EPA 5.3 (1.5–14), 6.7 (1.8–18), 8.7 (2.6–23), 9.8 (2.7–28) respectively; DPA 6.2 (2.2–14), 8.2 (3.3–18), 10.8 (4.3–24), 12.2 (5–29) respectively; and DHA 3.9 (0.6–24), 5.1 (0.9–26), 6.8 (1.1–27), 7.8 (1.5–33) respectively. Energy-adjusted intakes of EPA, DPA and DHA in children who ate fish were 7.5, 2 and 16-fold higher, respectively (P < 0.001) compared to those who did not eat fish during the 2 days of the survey. Intake of total long chain n-3 PUFA was compared to the energy adjusted suggested dietary target (SDT) for Australian children and 20 % of children who ate fish during the 2 days of the survey met the SDT. Fish and seafood products were the largest contributors to DHA (76 %) and EPA (59 %) intake, while meat, poultry and game contributed to 56 % DPA. Meat consumption was 8.5 times greater than that for fish/seafood. Australian children do not consume the recommended amounts of long chain omega-3 fatty acids, especially DHA, which could be explained by low fish consumption.     

The introduction of alkyl,ester, carboxylate,amino, hydroxyl,and phosphate functional groups to the surface of polyethylene

The surface of polyethylene was derivatized with ester, carboxylate, amino, hydroxyl, and phosphate functional groups. α, ω bifunctional alkanes, containing on one end a primary amine, were coupled to oxidized polyethylene through an amide linkage. Polyethylene was first oxidized with chromic acid, the carboxylate groups were converted to the acyl chloride with phosphorus pentachloride, and then reacted with a primary amine to give the covalently bound amide. The copposing ends of the bifunctional alkanes were the methyl, tertiary amine, ester, and hydroxyl groups. The ester was converted to the carboxylate by acid cleavage and the hydroxyl group converted to the phosphate by treatment first with phosphorus oxychloride and then aqueous base. Attenuated total reflection FTIR, XPS, and pH-dependent contact angle wetting were used to characterize the surfaces. The FTIR data were used to confirm the formation of the amide and to detect an undesired carboxylate/ammonium ion complex formed in the presence of trace amounts of water. XPS data were used to confirm expected changes in elemental composition and to provide quantitative estimates of the yields. Oxidation of the polyethylene introduced 5 × 10¹⁴ carboxylate groups/cm² in the 25 Å XPS sampling depth. Of these, up to 98% could be converted to the amide. The advancing contact angle data confirmed the acid/base behavior of the functional groups.     

Antimicrobial Efficacy of a Novel Eucalyptus Oil,Chlorhexidine Digluconate and Isopropyl Alcohol Biocide Formulation

Effective surface disinfection is a fundamental infection control strategy within healthcare. This study assessed the antimicrobial efficacy of novel biocide formulations comprising 5% and 2% eucalyptus oil (EO) combined with 2% chlorhexidine digluconate (CHG) and 70% isopropyl alcohol (IPA) contained within a wipe. The efficacy of this novel antimicrobial formulation to remove and eliminate methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli and Candida albicans from steel surfaces was investigated. Adpression studies of pre-contaminated wipes were also utilised to assess their potential to induce cross-contamination between hard surfaces. Furthermore, the bactericidal nature of the EO-formulation was established in addition to time-kill. The EO-containing formulations demonstrated bactericidal antimicrobial efficacy against all microorganisms and did not induce surface cross-contamination. There was no significant difference (p < 0.05) between the 5% and 2% EO formulations in their ability to remove microorganisms from steel surfaces, however both significantly (p < 0.05) removed more than the control formulations. Microbial biofilms were eliminated within 10 min (p < 0.05) when exposed to the EO formulations. Our novel EO-formulation demonstrated rapid antimicrobial efficacy for potential disinfection and elimination of microbial biofilms from hard surfaces and may therefore be a useful adjunct to current infection control strategies currently employed within healthcare facilities.     

Tailoring Encodable Lanthanide‐Binding Tags as MRI Contrast Agents

Lanthanide‐binding tags (LBTs), peptide‐based coexpression tags with high affinity for lanthanide ions, have previously been applied as luminescent probes to provide phasing for structure determination in X‐ray crystallography and to provide restraints for structural refinement and distance information in NMR. The native affinity of LBTs for Gd³⁺ indicates their potential as the basis for engineering of peptide‐based MRI agents. However, the lanthanide coordination state that enhances luminescence and affords tightest binding would not be ideal for applications of LBTs as contrast agents, due to the exclusion of water from the inner coordination sphere. Herein, we use structurally defined LBTs as the starting point for re‐engineering the first coordination shell of the lanthanide ion to provide for high contrast through direct coordination of water to Gd³⁺ (resulting in the single LBT peptide, m‐sLBT). The effectiveness of LBTs as MRI contrast agents was examined in vitro through measurement of binding affinity and proton relaxivity. For imaging applications that require targeted observation, fusion to specific protein partners is desirable. However, a fusion protein comprising a concatenated double LBT (dLBT) as an N‐terminal tag for the model protein ubiquitin had reduced relaxivity compared with the free dLBT peptide. This limitation was overcome by the use of a construct based on the m‐sLBT sequence (q‐dLBT–ubiquitin). The structural basis for the enhanced contrast was examined by comparison of the X‐ray crystal structure of xq‐dLBT–ubiquitin (wherein two tryptophan residues are replaced with serine), to that of dLBT‐ubiquitin. The structure shows that the backbone conformational dynamics of the MRI variant may allow enhanced water exchange. This engineered LBT represents a first step in expanding the current base of specificity‐targeted agents available.     

Evolutionary Imprint of Catalytic Domains in Fungal PKS–NRPS Hybrids

Fungal hybrid enzymes consisting of a polyketide synthase (PKS) and a nonribosomal peptide synthetase (NRPS) module are involved in the biosynthesis of a vast array of ecologically and medicinally relevant natural products. Whereas a dozen gene clusters could be assigned to the requisite PKS–NRPS pathways, the programming of the multifunctional enzymes is still enigmatic. Through engineering and heterologously expressing a chimera of PKS (lovastatin synthase, LovB) and NRPS (cytochalasin synthase, CheA) in Aspergillus terreus, we noted the potential incompatibility of a fungal highly reducing PKS (hrPKS) with the NRPS component of fungal PKS–NRPS hybrids. To rationalize the unexpected outcome of the gene fusion experiments, we conducted extensive bioinformatic analyses of fungal PKS–NRPS hybrids and LovB‐type PKS. From motif studies and the function of the engineered chimeras, a noncanonical function of C‐terminal condensation (C) domains in truncated PKS–NRPS homologues was inferred. More importantly, sequence alignments and phylogenetic trees revealed an evolutionary imprint of the PKS–NRPS domains, which reflect the evolutionary history of the entire megasynthase. Furthermore, a detailed investigation of C and adenylation (A) domains provides support for a scenario in which not only the A domain but also the C domain participates in amino acid selection. These findings shed new light on the complex code of this emerging class of multifunctional enzymes and will greatly facilitate future combinatorial biosynthesis and pathway engineering approaches towards natural product analogues.     

Aromatic Linkers Unleash the Antiproliferative Potential of 3-Chloropiperidines Against Pancreatic Cancer Cells

In this study, we describe the synthesis and biological evaluation of a set of bis-3-chloropiperidines (B−CePs) containing rigid aromatic linker structures. A modification of the synthetic strategy also enabled the synthesis of a pilot tris-3-chloropiperidine (Tri-CeP) bearing three reactive meta-chloropiperidine moieties on the aromatic scaffold. A structure–reactivity relationship analysis of B−CePs suggests that the arrangement of the reactive units affects the DNA alkylating activity, while also revealing correlations between the electron density of the aromatic system and the reactivity with biologically relevant nucleophiles, both on isolated DNA and in cancer cells. Interestingly, all aromatic 3-chloropiperidines exhibited a marked cytotoxicity and tropism for 2D and 3D cultures of pancreatic cancer cells. Therefore, the new aromatic 3-chloropiperidines appear to be promising contenders for further development of mustard-based anticancer agents aimed at pancreatic cancers.     

Experimental study of bubble formation in a glass-forming liquid doped with cerium oxide

This work aims to study the mechanisms of oxygen bubble formation coming from redox reaction of a polyvalent element incorporated in a glass melt. Borosilicate glass composition is selected for its use as a glass matrix for nuclear waste conditioning. Cerium is selected as a polyvalent element as it may be found in nuclear waste. The chosen material is characterized in terms of physical properties which influence bubble formation and growth. A postmortem optical microscope approach is used to observe bubbles in the investigated material after thermal treatment for varying temperatures (900°C-1100°C) and durations. To support the understanding of oxygen bubble formation, cerium speciation by X-ray absorption near-edge structure (XANES) and bubble gas composition are experimentally evaluated. In this article, we indicate how bubbles are formed in the investigated glass melt system. It is also demonstrated that the mechanisms that govern bubble evolution are fundamentally the same and that the plot's optimum points are strongly influenced by the temperature. These last statements are confirmed by considering some bubble features, such as bubble mean density and bubble mean diameter evolutions, and normalizing the experimental time using a characteristic residence time (t_η) obtaining thereafter a dimensionless time, which is a function of the glass melt properties obtained by the physical characterizations. The impact of temperature and time on bubble formation is described.     

Optimized production of a high-performance hybrid biomaterial: biomineralized spider silk for bone tissue engineering

Silks have been widely used as biomaterials due to their biocompatibility, biodegradability, and excellent mechanical properties. In the present work, native spider silk was used as organic template for controlled nucleation of hydroxyapatite (HA) nano-coating that can act as biomimetic interface. Different bio-inspired neutralization methods and process parameters were evaluated to optimize the silk functionalization. The morphology and chemical composition were investigated by scanning electron microscopy, energy-dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, and X-ray diffraction analysis and mechanical properties were studied through tensile tests. Results showed that the optimized protocol enabled a controlled and homogeneous nucleation of apatite nano-crystals while maintaining silk mechanical performances after mineralization. This study reports the optimization of a simple and effective bio-inspired nucleation process for precise nucleation of HA onto spider silk templates, suitable to develop high-performance hybrid interfaces for bone tissue engineering. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48739.