Seed‐Free Solid‐State Growth of Large Lead‐Free Piezoelectric Single Crystals: (Na1/2K1/2)NbO3

Large Na_0.5K_0.5NbO₃ (NKN) piezoelectric single crystals were obtained by seed‐free solid‐state crystal growth method, which is a traditional sintering grain growth process, with LiBiO₃ used as a sintering aid. The largest dimension of the single crystals obtained was 11 mm × 9 mm × 3 mm. In addition to the LiBiO₃ doping content, temperature, and time effect of the crystal growth process was systematically investigated and considered from the kinetics point of view. With the assistance of Avrami analysis, parameters relevant to the crystal growth process were determined. Laue diffraction and transmission electron microscopy suggested an orthorhombic symmetry for the single crystalline structure. Dielectric‐frequency‐temperature measurements revealed an orthorhombic‐tetragonal and tetragonal‐cubic phase transition at 155°C and 405°C, respectively, both of which are typical of first‐order transitions, and have a well‐defined thermal hysteresis. Rayleigh analysis was performed regarding to the extrinsic reversible and nonreversible piezoelectric properties, and the result suggested a dominant intrinsic reversible piezoelectric contribution of 91.5% under E₀ = 1 kV/cm AC amplitude. Such a single crystal growth process route is low cost and a relative simple preparation process.     

Influence of Salmonella in pigs preharvest and during pork processing on human health costs and risks from pork

Salmonellosis in humans is a costly disease traditionally assumed to be associated with exposure to contaminated food. We have developed a farm-to-fork model that allows estimation of the human health costs and risks associated with Salmonella in pork. This analysis focuses on the stages of the pork production chain up to the point of producing a chilled pork carcass. The model predicts the number of human cases of salmonellosis associated with pork (mean, 99,430; 90% confidence interval, 20,970 to 245,560) and the corresponding social costs (mean, $81.53 million; 90% confidence interval, $18.75 million to $197.44 million). Sensitivity and scenario analyses suggest that changes in Salmonella status during processing are more important for human health risk and have a higher benefit:cost ratio when compared with on-farm strategies for Salmonella control. Specifically, benefit:cost ratios are less than 1 (indicating they are not likely to be profitable from a social economic perspective) for the on-farm strategies of vaccination and meal feeding, whereas rinsing carcasses at various temperatures with and without sanitizer all have benefit:cost ratios greater than 1 (indicating they are profitable from a social economic perspective). This type of modeling is useful for evaluation of the relative cost effectiveness of interventions at different points in the food chain when allocating limited food safety dollars and is best used for examining trends and alternative strategies rather than for providing definitive dollar value estimates of risk. The dollar value estimates must be considered in the context of the wide confidence intervals.     

The Sedentary Lifestyle and Masticatory Dysfunction: Time to Review the Contribution to Age-Associated Cognitive Decline and Astrocyte Morphotypes in the Dentate Gyrus

As aging and cognitive decline progresses, the impact of a sedentary lifestyle on the appearance of environment-dependent cellular morphologies in the brain becomes more apparent. Sedentary living is also associated with poor oral health, which is known to correlate with the rate of cognitive decline. Here, we will review the evidence for the interplay between mastication and environmental enrichment and assess the impact of each on the structure of the brain. In previous studies, we explored the relationship between behavior and the morphological features of dentate gyrus glial fibrillary acidic protein (GFAP)-positive astrocytes during aging in contrasting environments and in the context of induced masticatory dysfunction. Hierarchical cluster and discriminant analysis of GFAP-positive astrocytes from the dentate gyrus molecular layer revealed that the proportion of AST1 (astrocyte arbors with greater complexity phenotype) and AST2 (lower complexity) are differentially affected by environment, aging and masticatory dysfunction, but the relationship is not straightforward. Here we re-evaluated our previous reconstructions by comparing dorsal and ventral astrocyte morphologies in the dentate gyrus, and we found that morphological complexity was the variable that contributed most to cluster formation across the experimental groups. In general, reducing masticatory activity increases astrocyte morphological complexity, and the effect is most marked in the ventral dentate gyrus, whereas the effect of environment was more marked in the dorsal dentate gyrus. All morphotypes retained their basic structural organization in intact tissue, suggesting that they are subtypes with a non-proliferative astrocyte profile. In summary, the increased complexity of astrocytes in situations where neuronal loss and behavioral deficits are present is counterintuitive, but highlights the need to better understand the role of the astrocyte in these conditions.     

Proteomic Tools for the Quantitative Analysis of Artificial Peptide Libraries: Detection and Characterization of Target-Amplified PD-1 Inhibitors

We report a quantitative proteomics data analysis pipeline, which coupled to protein-directed dynamic combinatorial chemistry (DDC) experiments, enables the rapid discovery and direct characterization of protein-protein interaction (PPI) modulators. A low-affinity PD-1 binder was incubated with a library of >100 D-peptides under thiol-exchange favoring conditions, in the presence of the target protein PD-1, and we determined the S-linked dimeric species that resulted, amplified in the protein samples versus the controls. We chemically synthesized the target dimer candidates and validated them by thermophoresis binding and protein-protein interaction assays. The results provide a proof-of-concept for using this strategy in the high-throughput search of improved drug-like peptide binders that block therapeutically relevant protein-protein interactions.     

Functional Graphene for Peritumoral Brain Microenvironment Modulation Therapy in Glioblastoma

Peritumoral brain invasion is the main target to cure glioblastoma. Chemoradiotherapy and targeted therapies fail to combat peritumoral relapse. Brain inaccessibility and tumor heterogeneity explain this failure, combined with overlooking the peritumor microenvironment. Reduce graphene oxide (rGO) provides a unique opportunity to modulate the local brain microenvironment. Multimodal graphene impacts are reported on glioblastoma cells in vitro but fail when translated in vivo because of low diffusion. This issue is solved by developing a new rGO formulation involving ultramixing during the functionalization with polyethyleneimine (PEI) leading to the formation of highly water-stable rGO-PEI. Wide mice brain diffusion and biocompatibility are demonstrated. Using an invasive GL261 model, an anti-invasive effect is observed. A major unexpected modification of the peritumoral area is also observed with the neutralization of gliosis. In vitro, mechanistic investigations are performed using primary astrocytes and cytokine array. The result suggests that direct contact of rGO-PEI_UT neutralizes astrogliosis, decreasing several proinflammatory cytokines that would explain a bystander tumor anti-invasive effect. rGO also significantly downregulates several proinvasive/protumoral cytokines at the tumor cell level. The results open the way to a new microenvironment anti-invasive nanotherapy using a new graphene nanomaterial that is optimized for in vivo brain delivery.     

Surface Reduced Manganese States as a Source of Oxygen Reduction Activity in BaMnO3

In relation to perovskites, tweaking the oxidation state of the B-site cation is fundamental to controlling the catalytic activity of these materials, thus necessitating a complete characterization of surface oxidation states. Herein, using a combination of atomic-scale imaging and spectroscopic techniques, structure-property correlation in barium manganese oxide (BaMnO₃) is established for the oxygen reduction reaction (ORR). Electron energy loss spectroscopy (EELS) on the synthesized BaMnO₃ find the rods to contain an amorphous surface layer with reduced Mn³⁺ states compared to Mn⁴⁺ states in the bulk. Consequently, the BaMnO₃ rods show electrocatalytic activity for the ORR, which originates from the presence of Mn³⁺ at the rod surface. Furthermore, heating of the samples in air at 300 and 800 °C results in a decrease in the number of Mn³⁺ states, and thus lowering of the ORR activity. This study represents a step-stone study in understanding the mechanism of ORR activity and its association to the Mn³⁺ state at the perovskite's surface, opening up possibilities for further surface engineering and tuning catalytic properties.