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Abstract Prebiotics are defined as non-digestible dietary components that promote the growth of beneficial gut microorganisms. In many cases, however, this capability is not systematically evaluated. Here, we develop a methodology for determining prebiotic-responsive bacteria using the popular dietary supplement inulin. We first identify microbes with a capacity to bind inulin using mesoporous silica nanoparticles functionalized with inulin. 16S rRNA gene amplicon sequencing of sorted cells revealed that the ability to bind inulin was widespread in the microbiota. We further evaluate which taxa are metabolically stimulated by inulin and find that diverse taxa from the phyla Firmicutes and Actinobacteria respond to inulin, and several isolates of these taxa can degrade inulin. Incubation with another prebiotic, xylooligosaccharides (XOS), in contrast, shows a more robust bifidogenic effect. Interestingly, the Coriobacteriia Eggerthella lenta and Gordonibacter urolithinfaciens are indirectly stimulated by the inulin degradation process, expanding our knowledge of inulin-responsive bacteria.

Summary: Studies indicate that the radiotracer 2-[18F]fluoro-2-deoxy-D-glucose (2-[18F]FDG) can be metabolized beyond 2-[18F]FDG-6-phosphate (2-[18F]FDG-6-P), but its metabolism is incompletely understood. Most importantly, it remains unclear whether downstream metabolism affects tracer accumulation in vivo. Here we present a fingerprint of 2-[18F]FDG radiometabolites over time in cancer cells, corresponding tumor xenografts and murine organs. Strikingly, radiometabolites representing glycogen metabolism or the oxPPP correlated inversely with tracer accumulation across all examined tissues. Recent studies suggest that not only hexokinase, but also hexose-6-phosphate dehydrogenase (H6PD), an enzyme of the oxidative pentose phosphate pathway (oxPPP), determines 2-[18F]FDG accumulation. However, little is known about the corresponding enzyme glucose-6-phosphate dehydrogenase (G6PD). Our mechanistic in vitro experiments on the role of the oxPPP propose that 2-[18F]FDG can be metabolized via both G6PD and H6PD, but data from separate enzyme knockdown suggest diverging roles in downstream tracer metabolism. Overall, we propose that tissue-specific metabolism beyond 2-[18F]FDG-6-P could matter for imaging.

Strain engineering can enhance oxygen transport in cathodes in solid oxide fuel cells. Here, atomic scale imaging is used to probe local structures in tensile- and compressive-strained La0.6Sr0.4CoO3-δ films, revealing higher oxygen vacancy concentration in tensile films, and vacancy ordering.

Opuntia joconostle is a semi-wild cactus cultivated for its fruit. However, the cladodes are often discarded, wasting the potentially useful mucilage in them. The mucilage is composed primarily of heteropolysaccharides, characterized by their molar mass distribution, monosaccharide composition, structural features (by vibrational spectroscopy, FT IR, and atomic force microscopy, AFM), and fermentability by known saccharolytic commensal members of the gut microbiota. After fractionation with ion exchange chromatography, four polysaccharides were found: one neutral (composed mainly of galactose, arabinose, and xylose) and three acidic, with a galacturonic acid content from 10 to 35%mol. Their average molar masses ranged from 1.8 × 105 to 2.8 × 105 g·mol−1. Distinct structural features such as galactan, arabinan, xylan, and galacturonan motifs were present in the FT IR spectra. The intra- and intermolecular interactions of the polysaccharides, and their effect on the aggregation behavior, were shown by AFM. The composition and structural features of these polysaccharides were reflected in their prebiotic potential. Lactobacilli and Bifidobacteria were not able to utilize them, whereas members of Bacteroidetes showed utilization capacity. The obtained data suggest a high economic potential for this Opuntia species, with potential uses such as animal feed in arid areas, precise prebiotic, and symbiotic formulations, or as the carbon skeleton source in a green refinery. Our methodology can be used to evaluate the saccharides as the phenotype of interest, helping to guide the breeding strategy.

A new state parameter-based user-subroutine for finite-element software packages, which can be used to simulate microstructure-dependent stress–strain relations, is presented. Well-established precipitation kinetics, strain hardening and strengthening models are brought into a condensed form to optimise computational efficiency, without losing their predictive capabilities. The framework includes main strengthening mechanisms, such as, precipitation strengthening, solid solution strengthening, the cross-core diffusion effect and work hardening. With the novel user-subroutine, the microstructure evolution of various thermo-mechanical treatments on the full integration point grid of the finite element (FE) mesh can be calculated. The validation of the simulations is carried out by mechanical testing as well as microstructure characterisation of an Al-6082 alloy, including transmission electron microscopy (TEM) investigations after various annealing times at 180 °C.

Of many defining characteristics for a flood resilient city and its infrastructure networks, mitigating flooding impacts and recovering quickly to a pre-flood state are to be considered of high importance. With a likely increase in the frequency and intensity of future heavy precipitation and flooding events in Europe, the vulnerability of the electrical distribution network of Maxvorstadt, Munich will also increase. These facts justify the need for quantifying how the electrical distribution network would respond to flooding, and more so, how stakeholders can better prepare for such an event. For a synthetic electrical distribution network of Maxvorstadt, the timing and location of network components failure due to flooding and affected persons without power have been computed for a combination of realistic future flooding events via the Electrical Network Flood Resilience Model developed in this study. It has been learned that most buildings, and therefore their inhabitants, lose power due to the failure of a specific component, Medium Voltage—Low Voltage transformer buses, and that flood risk solutions should focus on protecting network components from inundation to ensure its functionality through flooding events. Solutions like dry proofing such components before severe flooding occurs is recommended for several neighborhoods analyzed in this study.

The glucose derivative 2-[18F]fluoro-2-deoxy-D-glucose (2-[18F]FDG) is still the most used radiotracer for positron emission tomography, as it visualizes glucose utilization and energy demand. In general, 2-[18F]FDG is said to be trapped intracellularly as 2-[18F]FDG-6-phosphate, which cannot be further metabolized. However, increasingly, this dogma is being questioned because of publications showing metabolism beyond 2-[18F]FDG-6-phosphate and even postulating 2-[18F]FDG imaging to depend on the enzyme hexose-6-phosphate dehydrogenase in the endoplasmic reticulum. Therefore, we aimed to study 2-[18F]FDG metabolism in the human cancer cell lines HT1080, HT29 and Huh7 applying HPLC. We then compared 2-[18F]FDG metabolism with intracellular tracer accumulation, efflux and the cells’ metabolic state and used a graphical Gaussian model to visualize metabolic patterns. The extent of 2-[18F]FDG metabolism varied considerably, dependent on the cell line, and was significantly enhanced by glucose withdrawal. However, the metabolic pattern was quite conserved. The most important radiometabolites beyond 2-[18F]FDG-6-phosphate were 2-[18F]FDMannose-6-phosphate, 2-[18F]FDG-1,6-bisphosphate and 2-[18F]FD-phosphogluconolactone. Enhanced radiometabolite formation under glucose reduction was accompanied by reduced efflux and mirrored the cells’ metabolic switch as assessed via extracellular lactate levels. We conclude that there can be considerable metabolism beyond 2-[18F]FDG-6-phosphate in cancer cell lines and a comprehensive understanding of 2-[18F]FDG metabolism might help to improve cancer research and tumor diagnosis.

Context: Inflammation and cell differentiation lead to a number of severe diseases. In the recent years, various studies focused on the anti-inflammatory and anticancer activity of essential oils (EOs) of numerous plants, including different Pinus species. Objective: The phytochemical composition, anti-inflammatory and cytotoxic activity of EOs from needles and twigs of Pinus heldreichii Christ (Pinaceae) and P. peuce Griseb., and from needles, twigs and cones of P. mugo Turra were determined. Materials and methods: For separation and identification of the EOs, gas chromatography/flame ion detector (GC/FID) and GC/mass spectrometry were performed. The amount of secreted IL-6 in a lipopolysaccharide (LPS)-stimulated macrophage model was quantified (concentration of oils: 0.0001–0.2%, 3 h incubation). Cytotoxicity on the cancer cell lines HeLa, CaCo-2 and MCF-7 were determined using a MTT (Thiazolyl Blue Tetrazolium Bromide) assay (concentration of oils: 0.001–0.1%, 24 h incubation). Results: The most prominent members in the oils include: δ-3-carene, α-pinene and linalool-acetate (P. mugo); α-pinene, β-phellandrene and β-pinene (P. peuce); limonene, α-pinene and (E)-caryophyllene (P. heldreichii). EOs showed significant cytotoxic effects on cancer cell lines (IC50 0.007 to >0.1%), with a reduction in cell viability with up to 90% at a concentration of 0.1%, and anti-inflammatory activity (IC50 0.0008–0.02%) with a reduction of IL-6 secretion with up to 60% at a concentration of 0.01%. Discussion and conclusion: The EOs of needles and twigs from P. peuce and P. heldreichii as well as of needles, twigs and cones of P. mugo can be considered as promising agents for anticancer and anti-inflammatory drugs.

[11C]SNAP-7941 and its radiofluorinated, fluoro-ethyl derivative [18F]FE@SNAP have been developed as the first positron emission tomography tracers for melanin-concentrating hormone receptor 1 (MCHR1) imaging. Accumulation of these MCHR1 PET-tracers in rat brown adipose tissue (BAT) in vivo provided first indication of MCHR1 expression in rodent BAT. To rule out off-target binding, affinity of both MCHR1 ligands toward adrenergic beta-3 receptors (ADRB3) was examined. Further, specific binding of [11C]SNAP-7941 to brown adipocytes and effects of MCHR1 ligands on brown adipocyte activation were investigated. SNAP-7941 and FE@SNAP evinced to be highly selective toward MCHR1. [11C]SNAP-7941 binding to brown adipocytes was shown to be mainly MCHR1-specific. This data strongly indicates MCHR1 expression in rodent BAT and moreover, a peripheral, anti-obesity effect of MCHR1 antagonists directly exerted in BAT is proposed. Moreover, MCHR1 expression in murine brown adipocytes was confirmed by protein and mRNA analysis. We conclude that MCHR1 PET imaging contributes to basic research in endocrinology by elucidating the involvement of the MCH system in peripheral tissues, such as BAT.

The aim of the study was to investigate the solubility of piroxicam (Prx) depending on the inclusion complexation with various cyclodextrins (CDs) and on ethanol as a co-solvent. The phase-solubility method was applied to determine drug solubility in binary and ternary systems. The results showed that in systems consisting of the drug dissolved in ethanol–water mixtures, the drug solubility increased exponentially with a rising concentration of ethanol. The phase solubility measurements of the drug in aqueous solutions of CDs, β-CD and γ-CD exhibited diagrams of AL-type, whereas 2,6-dimethyl-β-CD revealed AP-type. The destabilizing effect of ethanol as a co-solvent was observed for all complexes regardless of the CD type, as a consequence of it the lowering of the complex formation constants. In systems with a higher concentration of ethanol, the drug solubility was increased in opposition to the decreasing complex formation constants. According to this study, the type of CDs played a more important role on the solubility of Prx, and the use of ethanol as a co-solvent exhibited no synergistic effect on the improvement of Prx solubility. The Prx solubility was increased again due to the better solubility in ethanol.

Fructans as prebiotics are an important factor in the functional food industry due to their beneficial effect on health. However, the influence of structure and degree of polymerization (dp) on their prebiotic effect is not fully elucidated so far. Unbranched inulin-type (β-2,1 linked) fructans from chicory and branched mixed-type (β-2,1 and β-2,6 linked) fructans from agaves were separated into fractions with different dps using preparative size exclusion chromatography, and the growth curves of selected probiotic strains were determined. All fructans exerted a significant growth enhancement, being higher with lower dp and with branching. Lactobacillus acidophilus and L. paracasei CRL431 quickly used fractions independent of the dp, whereas other strains (i.e. L. reuteri) did not use or only slowly used high dp fractions. Most strains cleaved fructans into smaller units before uptake into the cells. Our findings may contribute significantly to the development of improved prebiotic formulations.

The aim of this work is to improve physical properties and biological activities of the two flavanones hesperetin and naringenin by complexation with β-cyclodextrin (β-CD) and its methylated derivatives (2,6-di-O-methyl-β-cyclodextrin, DM-β-CD and randomly methylated-β-CD, RAMEB). The free energies of inclusion complexes between hesperetin with cyclodextrins (β-CD and DM-β-CD) were theoretically investigated by molecular dynamics simulation. The free energy values obtained suggested a more stable inclusion complex with DM-β-CD. The vdW force is the main guest–host interaction when hesperetin binds with CDs. The phase solubility diagram showed the formation of a soluble complex of AL type, with higher increase in solubility and stability when hesperetin and naringenin were complexed with RAMEB. Solid complexes were prepared by freeze-drying, and the data from differential scanning calorimetry (DSC) confirmed the formation of inclusion complexes. The data obtained by the dissolution method showed that complexation with RAMEB resulted in a better release of both flavanones to aqueous solution. The flavanones-β-CD/DM-β-CD complexes demonstrated a similar or a slight increase in anti-inflammatory activity and cytotoxicity towards three different cancer cell lines. The overall results suggested that solubilities and bioactivities of both flavanones were increased by complexation with methylated β-CDs.

The dry, powdered cladodes of Opuntia ficus-indica are often-used in over-the-counter (OTC) pharmaceutical formulations. Gentle drying techniques, such as lyophilization and vacuum drying are compared with convection drying for the cladodes and also compared with another species of economic importance, Opuntia joconostle. The heteropolysaccharide purified from the mucilage extracted from the dried powders were investigated in their monosaccharide composition (HPAEC-PAD, TLC), mineral and protein content, molecular dimensions (SEC) and fermentability by probiotic bacteria (Bioscreen technique) for evaluation of the prebiotic potential of the mucilage. The heteropolysaccharide is composed of galactose, arabinose, xylose, galacturonic acid and rhamnose. O. ficus-indica includes an additional 13% of glucose coming from an α-glucan. The content of Ca (0.3%) and Mg (0.4%) is relatively low in both species; the content of protein adds up to 1.5% in O. ficus-indica but is significantly lower in O. joconostle with 0.8%. The average molecular mass Mw of the extracted mucilage ranges from 3.7 to 4.7 × 105 g∙mol−1 for both species; only the mucilage from long-time convection drying (C2) delivers a lower average Mw of 2.6 × 105 g∙mol−1, due to partial breakdown of the mucilage matrix. All tested probiotic strains utilized the mucilage to some extent; C2 being the most active, and thus confirms the prebiotic potential of cladode’s powder and its derived products. In general, the molecular dimensions and prebiotic potential are not extremely sensitive to the drying treatment, yet temperature and drying time can modify the cladode’s powder to a profile with better prebiotic characteristics.

An integrated framework for deformation modeling has been developed, which combines a physical state parameter-based formulation for microstructure evolution during plastic deformation processes with constitutive creep models of polycrystalline materials. The implementations of power law, Coble, Nabarro–Herring and Harper–Dorn creep and grain boundary sliding are described and their contributions to the entire stress response at a virtual applied strain rate are discussed. The present framework simultaneously allows calculating the plastic deformation under prescribed strain rate or constant stress, as well as stress relaxation after preceding stress or strain loading. The framework is successfully applied for the construction of deformation mechanism maps.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The aim of this study was to develop green robusta coffee beans extract loaded nanostructured lipid carriers (NLCs) for enhancing dermal application and its efficiency. The green robusta coffee beans extract cultivated in Chumphon (CP) exhibited the highest antioxidant activity in the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay with IC50 of 34.1 ± 0.9 µg/ml, lipid peroxidation inhibition with percentage inhibition of 38.8 ± 1.7, and ferric reducing antioxidant power (FRAP) assay with a FRAP value of 234.5 ± 12.3 mM FeSO4/g. The extract contained caffeine, chlorogenic acid, and caffeic acid as major compounds. The anti-inflammatory test indicated that CP could decrease the secretion of IL-6 in macrophage cells and caused no irritation to blood vessels on the irritation test by hen’s egg test chorioallantoic membrane (HET-CAM) assay. The particle size of CP-loaded NLCs was 158.1 ± 0.2 nm with a narrow polydispersity index and showed no noticeable difference after the stability test. Entrapment efficacy of CP-loaded NLCs was found to be over 60%. Caffeine and chlorogenic acid in CP-loaded NLCs were released sustainably and penetrated deeper into the skin than the extract in a conventional emulsion. In conclusion, the CP-loaded NLCs can be further used in cosmetics for dermal applications due to good efficacy and safety.