High-Fat Diet Aggravates Cerebral Infarct,Hemorrhagic Transformation and Neuroinflammation in a Mouse Stroke Model

Background: Stroke in context of type 2 diabetes (T2D) is associated with a poorer outcome than in non-diabetic conditions. We aimed at creating a new reproducible mouse model of stroke in impaired glucose tolerance conditions induced by high-fat diet. Methods: Adult C57BL6 mice were fed for 2 months with either normal diet (ND) or high-fat diet (HFD). We used a model of Middle Cerebral Artery Occlusion (MCAO) for 90 min. Oral Glucose Tolerance Test (OGTT) and Insulin Tolerance Test (ITT) were used to assess pre-diabetic status. Brain infarct volume, hemorrhagic transformation (HT) as well as systemic and cerebral inflammatory markers were evaluated. Results: HFD was associated with an increased body weight and glycemia following OGTT. The HFD group presented a significant increase in brain infarct volume (38.7 (IQR 30–46.7%) vs. 28.45 (IQR 21–30%); p = 0.016) and HT (HFD: 2 (IQR 1–5) vs. ND: 0 (IQR 0–1); p = 0.012) and higher levels of IL-6 and MCP-1 in infarcted hemisphere compared to the ND group. Conclusion: Two months of HFD in adult mice were sufficient to alter the lipid profile and the control of hyperglycemia. These metabolic perturbations were significantly associated with increased infarct volume and hemorrhagic complications.     

Corrosion and mechanical properties of plasma electrolytic oxidation‐coated AZ80 magnesium alloy

Plasma electrolytic oxidation (PEO) coatings were produced on AZ80 magnesium alloy in a solution containing silicates and phosphates and working at high current densities with short treatment times. The effect of a sealing treatment in boiling water on corrosion and mechanical properties of the coatings were investigated. Moreover, the corrosion mechanism of the samples with and without the sealing treatment was evaluated. The microstructure of the coatings was characterized with scanning electron microscope observation and X‐ray diffraction analysis. The mechanical properties were evaluated with nanoindentation tests and the corrosion resistance was studied by potentiodynamic polarization, electrochemical impedance spectroscopy, and scanning vibrating electrode technique. The results showed that the sealing did not influence the microstructure and the mechanical properties of the samples and instead produced a remarkable increase in the corrosion resistance. The crevice corrosion, present in the sample without the sealing, was avoided with the treatment in boiling water.     

In situ observation of synthesized nanoparticles in ultra-dilute aerosols via X-ray scattering

In-air epitaxy of nanostructures (Aerotaxy) has recently emerged as a viable route for fast, large-scale production. In this study, we use small-angle X-ray scattering to perform direct in-flight characterizations of the first step of this process, i.e., the engineered formation of Au and Pt aerosol nanoparticles by spark generation in a flow of N₂ gas. This represents a particular challenge for characterization because the particle density can be extremely low in controlled production. The particles produced are examined during production at operational pressures close to atmospheric conditions and exhibit a lognormal size distribution ranging from 5–100 nm. The Au and Pt particle production and detection are compared. We observe and characterize the nanoparticles at different stages of synthesis and extract the corresponding dominant physical properties, including the average particle diameter and sphericity, as influenced by particle sintering and the presence of aggregates. We observe highly sorted and sintered spherical Au nanoparticles at ultra-dilute concentrations (< 5 × 10⁵ particles/cm³) corresponding to a volume fraction below 3 × 10^–10, which is orders of magnitude below that of previously measured aerosols. We independently confirm an average particle radius of 25 nm via Guinier and Kratky plot analysis. Our study indicates that with high-intensity synchrotron beams and careful consideration of background removal, size and shape information can be obtained for extremely low particle concentrations with industrially relevant narrow size distributions.

     

Nitroxide Radicals with Cucurbit[n]urils and Other Cavitands

The interface of nitroxide radicals with cucurbit[n]urils (CB[n]) is covered in this review. Either used as spin probes, spin labels, or stoppers for paramagnetic rotaxanes, nitroxides offer new opportunities to investigate CB[n] and their inclusion complexes, especially thanks to EPR spectroscopy. On the other hand, CB[n] also offer interesting opportunities to modulate nitroxide properties such as protection or structuring. The multiple back and forth between the two well-established areas where nitroxides bring information about CB[n], and CB[n] modulate nitroxide properties, have enabled to shed some light at this new interesting interface.     

The structure solution of the F-type i-ZnMgHf from the X-ray diffraction

ABSTRACT

We report a successful growth of the ZnMgHf F-type icosahedral quasicrystal in the form of faceted single grains. By varying the heat treatment parameters we were able to obtain single crystals with a quality suitable for a single crystal X-ray diffraction which was conducted in a synchrotron facility. Ab initio structure solution by a charge flipping algorithm manifests the existence of two types of Bergman clusters. Clusters are differentiated by the preferential occupation of the high-symmetry positions by hafnium in a rhombic triacontahedron, being the outer shell of the atomic cluster.

This paper is part of a Thematic Issue on The Crystallographic Aspects of Metallic Alloys.     

Structural and Functional Characterization of 4-Hydroxyphenylacetate 3-Hydroxylase from Escherichia coli

The hydroxylation of phenols into polyphenols, which are valuable chemicals and pharmaceutical products, is a challenging reaction. The search for green synthetic processes has led to considering microorganisms and pure hydroxylases as catalysts for phenol hydroxylation. Herein, we report the structural and functional characterization of the flavin adenine dinucleotide (FAD)-dependent 4-hydroxyphenylacetate 3-monooxygenase from Escherichia coli, named HpaB. It is shown that this enzyme enjoys a relatively broad substrate specificity, which allows the conversion of a number of non-natural phenolic compounds, such as tyrosol, hydroxymandelic acid, coumaric acid, hydroxybenzoic acid and its methyl ester, and phenol, into the corresponding catechols. The reaction can be performed by using a simple chemical assay based on formate as the electron donor and the organometallic complex [Rh(bpy)Cp*(H₂O)]²⁺ (Cp*: 1,2,3,4,5-pentamethylcyclopentadiene, bpy: 2,2′-bipyridyl) as the catalyst for FAD reduction. The availability of a crystal structure of HpaB in complex with FAD at 1.8 Å resolution opens up the possibility of the rational tuning of the substrate specificity and activity of this interesting class of phenol hydroxylases.     

Modified Galacto- or Fuco-Clusters Exploiting the Siderophore Pathway to Inhibit the LecA- or LecB-Associated Virulence of Pseudomonas aeruginosa

Galacto- and fuco-clusters conjugated with one to three catechol or hydroxamate motifs were synthesised to target LecA and LecB lectins of Pseudomonas aeruginosa (PA) localised in the outer membrane and inside the bacterium. The resulting glycocluster–pseudosiderophore conjugates were evaluated as Trojan horses to cross the outer membrane of PA by iron transport. The data suggest that glycoclusters with catechol moieties are able to hijack the iron transport, whereas those with hydroxamates showed strong nonspecific interactions. Mono- and tricatechol galactoclusters ( G1C and G3C ) were evaluated as inhibitors of infection by PA in comparison with the free galactocluster ( G0 ). All of them exhibited an inhibitory effect between 46 to 75 % at 100 μM, with a higher potency than G0 . This result shows that LecA localised in the outer membrane of PA is involved in the infection mechanism.     

Involvement of GPx-3 in the Reciprocal Control of Redox Metabolism in the Leukemic Niche

The bone marrow (BM) microenvironment plays a crucial role in the development and progression of leukemia (AML). Intracellular reactive oxygen species (ROS) are involved in the regulation of the biology of leukemia-initiating cells, where the antioxidant enzyme GPx-3 could be involved as a determinant of cellular self-renewal. Little is known however about the role of the microenvironment in the control of the oxidative metabolism of AML cells. In the present study, a coculture model of BM mesenchymal stromal cells (MSCs) and AML cells (KG1a cell-line and primary BM blasts) was used to explore this metabolic pathway. MSC-contact, rather than culture with MSC-conditioned medium, decreases ROS levels and inhibits the Nrf-2 pathway through overexpression of GPx3 in AML cells. The decrease of ROS levels also inactivates p38MAPK and reduces the proliferation of AML cells. Conversely, contact with AML cells modifies MSCs in that they display an increased oxidative stress and Nrf-2 activation, together with a concomitant lowered expression of GPx-3. Altogether, these experiments suggest that a reciprocal control of oxidative metabolism is initiated by direct cell–cell contact between MSCs and AML cells. GPx-3 expression appears to play a crucial role in this cross-talk and could be involved in the regulation of leukemogenesis.