Azaaurones as Potent Antimycobacterial Agents Active against MDR- and XDR-TB

Herein we report the screening of a small library of aurones and their isosteric counterparts, azaaurones and N-acetylazaaurones, against Mycobacterium tuberculosis. Aurones were found to be inactive at 20 μm , whereas azaaurones and N-acetylazaaurones emerged as the most potent compounds, with nine derivatives displaying MIC₉₉ values ranging from 0.4 to 2.0 μm . In addition, several N-acetylazaaurones were found to be active against multidrug-resistant (MDR) and extensively drug-resistant (XDR) clinical M. tuberculosis isolates. The antimycobacterial mechanism of action of these compounds remains to be determined; however, a preliminary mechanistic study confirmed that they do not inhibit the mycobacterial cytochrome bc1 complex. Additionally, microsomal metabolic stability and metabolite identification studies revealed that N-acetylazaaurones are deacetylated to their azaaurone counterparts. Overall, these results demonstrate that azaaurones and their N-acetyl counterparts represent a new entry in the toolbox of chemotypes capable of inhibiting M. tuberculosis growth.     

Low-cost and high-performance 3D printed YBCO superconductors

High-performance YBCO 123 (YBa₂Cu₃O_7-x) bulk superconductor samples were produced using the 3D printing paste-extrusion technique. The YBCO powder obtained after sintering a pre-mixture of Y₂O₃, BaCO₃ and CuO powders at 950 °C was used in the formulation of pastes for extrusion in a 3D freeform printer. The 3D samples printed from pastes containing the pre-mixture powders were sintered, while those produced using the YBCO powder were not. X-ray diffraction (XRD), energy dispersive spectroscopy (EDS) and Raman analysis all confirmed the YBCO phase after sintering, both in the powder and in the samples made with the pre-mixture. Scanning electron microscopy (SEM) images revealed powder grains of heterogeneous size and geometry, as well as grain aggregation, in the sintered samples. Superconducting quantum interference device (SQUID) measurements taken within a fixed magnetic range revealed that the printed pieces have a typical magnetization temperature of 92 K, reaching ?1.43 emu/g and ?1.59 emu/g respectively a zero-field-cooled magnetization (ZFC) for sintered and non-sintered printed samples.     

Development of a Topical Insulin Polymeric Nanoformulation for Skin Burn Regeneration: An Experimental Approach

Insulin is a peptide hormone with many physiological functions, besides its use in diabetes treatment. An important role of insulin is related to the wound healing process—however, insulin itself is too sensitive to the external environment requiring the protective of a nanocarrier. Polymer-based nanoparticles can protect, deliver, and retain the protein in the target area. This study aims to produce and characterize a topical treatment for wound healing consisting of insulin-loaded poly-DL-lactide/glycolide (PLGA) nanoparticles. Insulin-loaded nanoparticles present a mean size of approximately 500 nm and neutral surface charge. Spherical shaped nanoparticles are observed by scanning electron microscopy and confirmed by atomic force microscopy. SDS-PAGE and circular dichroism analysis demonstrated that insulin preserved its integrity and secondary structure after the encapsulation process. In vitro release studies suggested a controlled release profile. Safety of the formulation was confirmed using cell lines, and cell viability was concentration and time-dependent. Preliminary safety in vivo assays also revealed promising results.     

Characterization of LDH (phyllosilicate/carbonate) type compounds formed in the pozzolanic reaction of phyllosilicate-rich industrial waste

Reutilization of industrial waste products as cement additives yields a number of secondary materials, yet their identification is not always trivial. Confirmation of the formation of a LDH-type (phyllosilicate/carbonate) material is the main purpose of this study. Mineralogically, organic and inorganic compounds form some industrial wastes, among which the phyllosilicates are prominent. Crystalline and amorphous hydrated phases appeared during the pozzolanic reaction in a dehydroxylated phyllosilicate/lime system, whose controlled activation yielded dehydroxylated products with high pozzolanic properties. The LDH-type (phyllosilicate/carbonate) material was one of the reaction products; this material could be considered as the superposition type 1:1 of tetrahedral layers of silicon and aluminum and octahedral layers of aluminum (dehydroxylated kaolinite), generating a positive charge in the interlaminar region compensated by carbonate anions with a basal spacing (001) measured by XRD at 7.57Å. Therefore, several techniques were used to determine whether they could be included in the structural group named Layered Double Hydroxides (LDHs), as they are, too, laminar layers of oxides and hydroxides with a positive laminar charge in the interlayer region compensated by the presence of anions with similar basal spacing. In this research, the effects of activation temperature and calcite proportion were analyzed on the hydrated phases formed after 28 days of pozzolanic reaction in a metakaolin (MK)/lime system. The MK was obtained from a mix of 1:1; 2:1 and 3:1 kaolinite:calcite mixture, thermally activated at 750°C for 2 hours, comparing it with kaolinite activated at 600°C for 2 hours. As the most LDH-rich sample, the 1:1 LDH-type (phyllosilicate/carbonate) phase was characterized using XRD, SEM-EDX, HRTEM-EDX, FTIR, NMR-MAS, and Raman spectroscopy.     

Schnelle lokale Raman‐Messung zur Untersuchung von Konzentrationsprofilen bei Mischvorgängen in Mikrokanälen

For the evaluation of mixing processes in microreactors, it is necessary to be able to investigate them in detail. For this purpose, a novel optical measuring system is presented, which allows the visualization of mixing and diffusion‐limited processes as well as concentration differences in fluid films. It consists of focusing optics with a microscope objective. In combination with a Raman spectrometer, various processes such as diffusion in the microreactor can be measured and investigated non‐invasively.     

Modulation of rumen pH by sodium bicarbonate and a blend of different sources of magnesium oxide in lactating dairy cows submitted to a concentrate challenge

With the objective of evaluating the potential effects of sodium bicarbonate or a magnesium-based product on rumen pH and milk performance of dairy cattle exposed to a dietary challenge, 30 lactating Holstein cows (648 ± 67 kg of body weight; 44.4 ± 9.9 kg/d of milk yield; 155 ± 75 d in milk) were blocked by parity (9 primiparous and 21 multiparous) and randomly distributed to 3 treatment groups. One group received a total mixed ration (TMR) that acted as a control (CTR), a second group (SB) received the same TMR but with an additional supplementation of 0.8% of sodium bicarbonate, and a third group (MG) received the same TMR as CTR but an additional supplementation of 0.4% of a magnesium-based product (pHix-Up, Timab, Dinard, France). After 1 wk of exposure to this TMR, all 3 rations were supplemented with 1 kg/d of barley, which was then increased 1 kg/wk until reaching 3 kg/d of barley during wk 4 of the study. Every kilogram of barley replaced 1 kg of forage in the diet. Individual feed intake and behavior were monitored using electronic feed bins. Seven cows per treatment were equipped with an intraruminal bolus that recorded pH every 15 min. As the severity of the barley challenge increased, dry matter intake decreased, but this decrease was more pronounced in SB cows than in MG cows, with an intermediate response for CTR cows. The MG cows produced more milk when challenged with 2 or 3 kg/d of additional barley than when challenged with 1 kg/d, whereas CTR cows produced less milk with the 3 kg/d challenge compared with 1 or 2 kg/d, and the SB cows maintained milk production. Milk fat content decreased with barley challenges, with CTR cows experiencing a more severe decrease than SB cows, which maintained stable butterfat values throughout the study, and MG cows showed a decline in milk fat content only with the 3 kg/d of additional barley. Meal size was also reduced as the severity of barley challenge increased, and this reduction was more modest in MG cows than in SB cows. The number of daily meals consumed by SB and MG cows was more constant than that recorded in CTR cows. Cows on the CTR and SB treatments showed a marked decrease in rumen pH with the 3 kg/d of additional barley, whereas MG cows maintained stable rumen pH during the barley challenges and had greater average rumen pH (5.93 ± 0.04) than CTR cows (5.83 ± 0.04) with the 3 kg/d of additional barley; SB cows showed intermediate values (5.85 ± 0.04). Last, MG cows spent less time (32.3 ± 6.1%) with rumen pH ≤5.8 when exposed to the 3 kg/d of barley challenge than CTR and SB cows (50.7 ± 5.02%). In conclusion, supplementation with MG prevents the decline in dry matter intake and milk production induced by a rumen challenge, whereas supplementation with SB prevents the decay in milk production but does not prevent the decrease in feed intake. These changes were probably due to the ability of the MG treatment to prevent a reduction in rumen pH when challenging cows with 3 kg/d of additional barley in the ration.