Mthfr gene ablation enhances susceptibility to arsenic prenatal toxicity

Background

In utero exposure to arsenic is known to adversely affect reproductive outcomes. Evidence of arsenic teratogenicity varies widely and depends on individual genotypic differences in sensitivity to As. In this study, we investigated the potential interaction between 5,10-methylenetetrahydrofolate reductase (Mthfr) genotype and arsenic embryotoxicity using the Mthfr knockout mouse model.

Methods

Pregnant dams were treated with sodium arsenate, and reproductive outcomes including: implantation, resorption, congenital malformation and fetal birth weight were recorded at E18.5.

Results

When the dams in Mthfr^+/− × Mthfr^+/− matings were treated with 7.2 mg/kg As, the resorption rate increased to 43.4%, from a background frequency of 7.2%. The As treatment also induced external malformations (40.9%) and significantly lowered the average fetal birth weight among fetuses, without any obvious toxic effect on the dam. When comparing the pregnancy outcomes resulting from different mating scenarios (Mthfr^+/+ × Mthfr^+/−, Mthfr^+/− × Mthfr^+/− and Mthfr^−/− × ^Mthfr+/−) and arsenic exposure; the resorption rate showed a linear relationship with the number of null alleles (0, 1 or 2) in the Mthfr dams. Fetuses from nullizygous dams had the highest rate of external malformations (43%) and lowest average birth weight. When comparing the outcomes of reciprocal matings (nullizygote × wild-type versus wild-type × nullizygote) after As treatment, the null dams showed significantly higher rates of resorptions and malformations, along with lower fetal birth weights.

Conclusions

Maternal genotype contributes to the sensitivity of As embryotoxicity in the Mthfr mouse model. The fetal genotype, however, does not appear to affect the reproductive outcome after in utero As exposure.     

Synthesis and characterization of a novel controlled release zinc oxide/gentamicin–chitosan composite with potential applications in wounds care

Freshly prepared ZnO nanoparticles were incorporated into a chitosan solution in weight ratios ranging from 1:1 to 12:1. Starting from the ratio of 3:1 the chitosan solution was transformed into a gel with a high consistency, which incorporates 15 mL water for only 0.1 g solid substance. The powders obtained after drying the gel were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM) and thermal analysis (TG-DSC). The electronic (UV–vis), infrared (FTIR) and photoluminescence (PL) spectra were also recorded. ZnO particles were coated with gentamicin and incorporated into the chitosan matrix, to yield a ZnO/gentamicin–chitosan gel. The release rate of gentamicin was monitored photometrically. This ZnO/gentamicin–chitosan gel proved great antimicrobial properties, inhibiting Staphylococcus aureus and Pseudomonas aeruginosa growth in both planktonic and surface-attached conditions. The results indicate that the obtained composite can be used in cutaneous healing for developing improved wound dressings, which combine the antibacterial activity of all three components with the controlled release of the antibiotic. This wound dressing maintains a moist environment at the wound interface, providing a cooling sensation and soothing effect, while slowly releasing the antibiotic. The system is fully scalable to any other soluble drug, as the entire solution remains trapped in the ZnO–chitosan gel.     

New silica nanostructure for the improved delivery of topical antibiotics used in the treatment of staphylococcal cutaneous infections

In this paper, we report the synthesis, characterization (FT-IR, XRD, BET, HR-TEM) and bioevaluation of a novel γ-aminobutiric acid/silica (noted GABA-SiO₂ or γ-SiO₂) hybrid nanostructure, for the improved release of topical antibiotics, used in the treatment of Staphylococcus aureus infections. GABA-SiO₂ showed IR bands which were assigned to Si–O–Si (stretch mode). The XRD pattern showed a broad peak in the range of 18–30° (2θ), indicating an amorphous structure. Based on the BET analysis, estimations about surface area (438.14 m²/g) and pore diameters (4.76 nm) were done. TEM observation reveals that the prepared structure presented homogeneity and an average size of particles not exceeding 10 nm. The prepared nanostructure has significantly improved the anti-staphylococcal activity of bacitracin and kanamycin sulfate, as demonstrated by the drastic decrease of the minimal inhibitory concentration of the respective antibiotics loaded in the GABA-SiO₂ nanostructure. These results, correlated with the high biocompatibility of this porous structure, are highlighting the possibility of using this carrier for the local delivery of the antimicrobial substances in lower active doses, thus reducing their cytotoxicity and side-effects.     

Surface Finish Analysis in Single Point Incremental Sheet Forming of Rib-Stiffened 2024-T3 and 7075-T6 Alclad Aluminium Alloy Panels

The article presents the results of the analysis of the interactions between the single point incremental forming (SPIF) process parameters and the main roughness parameters of stiffened ribs fabricated in Alclad aluminium alloy panels. EN AW-7075-T6 and EN AW-2024-T3 Alclad aluminium alloy sheets were used as the research material. Panels with longitudinal ribs were produced with different values of incremental vertical step size and tool rotational speed. Alclad is formed of high-purity aluminium surface layers metallurgically bonded to aluminium alloy core material. The quality of the surface roughness and unbroken Alclad are key problems in SPIF of Alclad sheets destined for aerospace applications. The interactions between the SPIF process parameters and the main roughness parameters of the stiffened ribs were determined. The influence of forming parameters on average roughness Sa and the 10-point peak–valley surface roughness Sz was determined using artificial neural networks. The greater the value of the incremental vertical step size, the more prominent the ridges found in the inner surface of stiffened ribs, especially in the case of both Alclad aluminium alloy sheets. The predictive models of ANNs for the Sa and the Sz were characterised by performance measures with R² values lying between 0.657 and 0.979. A different character of change in surface roughness was found for sheets covered with and not covered with a soft layer of technically pure aluminium. In the case of Alclad sheets, increasing the value of the incremental vertical step size increases the value of the surface roughness parameters Sa and Sz. In the case of the sheets not covered by Alclad, reduction of the tool rotational speed increases the Sz parameter and decreases the Sa parameter. An obvious increase in the Sz parameter was observed with an increase in the incremental vertical step size.     

ZnO Nanoparticles-Modified Dressings to Inhibit Wound Pathogens

Zinc oxide (ZnO) nanoparticles (NPs) have been investigated for various skin therapies in recent years. These NPs can improve the healing and modulate inflammation in the wounds, but the mechanisms involved in such changes are yet to be known. In this study, we have designed a facile ZnO nano-coated dressing with improved antimicrobial efficiency against typical wound pathogens involved in biofilm and chronic infections. ZnO NPs were obtained by hydrothermal method and characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and Fourier-transform infrared spectroscopy. Antibacterial and antibiofilm effects were evaluated against laboratory and clinical isolates of significant Gram-negative (Pseudomonas aeruginosa and Escherichia coli) and Gram-positive (Staphylococcus aureus and Enterococcus faecalis) opportunistic pathogens, by quantitative methods. Our results have shown that the developed dressings have a high antibacterial efficiency after 6–24 h of contact when containing 0.6 and 0.9% ZnO NPs and this effect is similar against reference and clinical isolates. Moreover, biofilm development is significantly impaired for up to three days of contact, depending on the NPs load and microbial species. These results show that ZnO-coated dressings prevent biofilm development of main wound pathogens and represent efficient candidates for developing bioactive dressings to fight chronic wounds.     

The Effects of Low Doses of Two Fusarium Toxins,Zearalenone and Deoxynivalenol,on the Pig Jejunum. A Light and Electron Microscopic Study

Immature gilts were administered per os with zearalenone (ZEN) at 40 μg/kg BW (group Z, n = 9), deoxynivalenol (DON) at 12 μg/kg BW (group D, n = 9), a mixture of ZEN and DON (group M, n = 9) or a placebo (group C, n = 9) over a period of six weeks. The pigs were sacrificed after one, three, or six weeks of the treatment (12 pigs per each time-point). Histological investigations revealed an increase in the mucosal thickness and the crypt depth as well as a decrease in the ratio of the villus height to the crypt depth in groups D and M after six weeks of exposure to the mycotoxins. The number of goblet cells in the villus epithelium was elevated in groups Z and M after one week and in group D after three weeks. The administration of ZEN increased the lymphocyte number in the villus epithelium after 1 week and the plasma cell quantity in the lamina propria after one, three, and six weeks of the experiment. DON treatment resulted in an increase in the lymphocyte number in the villus epithelium and the lamina propria after six weeks, and in the plasma cell quantity in the lamina propria after one, three, and six weeks of exposure. In group M, lymphocyte counts in the epithelium and the lamina propria increased significantly after six weeks. Neither mycotoxin induced significant adverse changes in the ultrastructure of the mucosal epithelium and the lamina propria or in the intestinal barrier permeability. Our results indicate that immune cells are the principal target of low doses of ZEN and DON.     

Critical Raw Materials Saving by Protective Coatings under Extreme Conditions: A Review of Last Trends in Alloys and Coatings for Aerospace Engine Applications

Several applications, where extreme conditions occur, require the use of alloys often containing many critical elements. Due to the ever increasing prices of critical raw materials (CRMs) linked to their high supply risk, and because of their fundamental and large utilization in high tech products and applications, it is extremely important to find viable solutions to save CRMs usage. Apart from increasing processes’ efficiency, substitution, and recycling, one of the alternatives to preserve an alloy and increase its operating lifetime, thus saving the CRMs needed for its manufacturing, is to protect it by a suitable coating or a surface treatment. This review presents the most recent trends in coatings for application in high temperature alloys for aerospace engines. CRMs’ current and future saving scenarios in the alloys and coatings for the aerospace engine are also discussed. The overarching aim of this paper is to raise awareness on the CRMs issue related to the alloys and coating for aerospace, suggesting some mitigation measures without having the ambition nor to give a complete overview of the topic nor a turnkey solution.     

Semi-Hybrid CO2 Laser Metal Deposition Method with Inter Substrate Buffer Zone

This article presents the results of the metal deposition process using additive materials in the form of filler wire and metal powder. An important problem in wire deposition using a CO₂ laser was overcome by using a combination of the abovementioned methods. The deposition of a multicomponent alloy—Inconel 625—on a basic substrate such as structural steel is presented. The authors propose a new approach for stopping carbon and iron diffusion from the substrate, by using the Semi-Hybrid Deposition Method (S-HDM) developed by team members. The proposed semi-hybrid method was compared with alternative wire and powder deposition using laser beam. Differences of S-HDM and classic wire deposition and powder deposition methods are presented using metallographic analysis, within optic and electron microscopy. Significant differences in the obtained results reveal advantages of the developed method compared to traditional deposition methods. A comparison of the aforementioned methods performed using nickel based super alloy Inconel 625 deposited on low carbon steel substrate is presented. An alternative prototyping approach for an advanced high alloy materials deposition using CO₂ laser, without the requirement of using the same substrate was presented in this article. This study confirmed the established assumption of reducing selected components diffusion from a substrate via buffer layer. Results of metallographic analysis confirm the advantages and application potential of using the new semi-hybrid method for prototyping high alloy materials on low alloy structural steel substrate.     

Assessment of Technological Capabilities for Forming Al-C-B System Coatings on Steel Surfaces by Electrospark Alloying Method

In this paper, the possibility of applying the electrospark alloying (ESA) method to obtain boron-containing coatings characterised by increased hardness and wear resistance is considered. A new method for producing such coatings is proposed. The method consists in applying grease containing aluminium powder and amorphous boron to the surface to be treated and subsequently processing the obtained surface using the ESA method by a graphite electrode. The microstructural analysis of the Al-C-B coatings on steel C40 showed that the surface layer consists of several zones, the number and parameters of which are determined by the energy conditions of the ESA process. Durametric studies showed that with an increase in the discharge energy influence, the microhardness values of both the upper strengthened layer and the diffusion zone increased to W_p = 0.13 J, Hµ = 6487 MPa, and W_p = 4.9 J, Hµ = 12350 MPa, respectively. The results of X-ray diffraction analysis indicate that at the discharge energies of 0.13 and 0.55 J, the phase composition of the coating is represented by solid solutions of body-centred cubic lattice (BCC) and face-centred cubic lattice (FCC). The coatings obtained at W_p = 4.9 J were characterised by the presence of intermetallics Fe₄Al₁₃ and borocementite Fe₃ (CB) in addition to the solid solutions. The X-ray spectral analysis of the obtained coatings indicated that during the electrospark alloying process, the surface layers were saturated with aluminium, boron, and carbon. With increasing discharge energy, the diffusion zone increases; during the ESA process with the use of the discharge energy of 0.13 J for steel C40, the diffusion zone is 10–15 μm. When replacing a substrate made of steel C40 with the same one material but of steel C22, an increase in the thickness of the surface layer accompanied by a slight decrease in microhardness is observed as a result of processing with the use of the ESA method. There were simulated phase portraits of the Al-C-B coatings. It is shown that near the stationary points in the phase portraits, one can see either a slowing down of the evolution or a spiral twisting of the diffusion-process particle.