Ratiometric Detection of Glutathione Based on Disulfide Linkage Rupture between a FRET Coumarin Donor and a Rhodamine Acceptor

Abnormal levels of glutathione, a cellular antioxidant, can lead to a variety of diseases. We have constructed a near-infrared ratiometric fluorescent probe to detect glutathione concentrations in biological samples. The probe consists of a coumarin donor, which is connected through a disulfide-tethered linker to a rhodamine acceptor. Under the excitation of the coumarin donor at 405 nm, the probe shows weak visible fluorescence of the coumarin donor at 470 nm and strong near-infrared fluorescence of the rhodamine acceptor at 652 nm due to efficient Forster resonance energy transfer (FRET) from the donor to the acceptor. Glutathione breaks the disulfide bond through reduction, which results in a dramatic increase in coumarin fluorescence and a corresponding decrease in rhodamine fluorescence. The probe possesses excellent cell permeability, biocompatibility, and good ratiometric fluorescence responses to glutathione and cysteine with a self-calibration capability. The probe was utilized to ratiometrically visualize glutathione concentration alterations in HeLa cells and Drosophila melanogaster larvae.     

Intergenerational Metabolomic Analysis of Mothers with a History of Gestational Diabetes Mellitus and Their Offspring

Shared metabolomic patterns at delivery have been suggested to underlie the mother-to-child transmission of adverse metabolic health. This study aimed to investigate whether mothers with gestational diabetes mellitus (GDM) and their offspring show similar metabolomic patterns several years postpartum. Targeted metabolomics (including 137 metabolites) was performed in plasma samples obtained during an oral glucose tolerance test from 48 mothers with GDM and their offspring at a cross-sectional study visit 8 years after delivery. Partial Pearson’s correlations between the area under the curve (AUC) of maternal and offspring metabolites were calculated, yielding so-called Gaussian graphical models. Spearman’s correlations were applied to investigate correlations of body mass index (BMI), Matsuda insulin sensitivity index (ISI-M), dietary intake, and physical activity between generations, and correlations of metabolite AUCs with lifestyle variables. This study revealed that BMI, ISI-M, and the AUC of six metabolites (carnitine, taurine, proline, SM(-OH) C14:1, creatinine, and PC ae C34:3) were significantly correlated between mothers and offspring several years postpartum. Intergenerational metabolite correlations were independent of shared BMI, ISI-M, age, sex, and all other metabolites. Furthermore, creatinine was correlated with physical activity in mothers. This study suggests that there is long-term metabolic programming in the offspring of mothers with GDM and informs us about targets that could be addressed by future intervention studies.     

Evaluation of the pore morphology formation of the Freeze Foaming process by in situ computed tomography

The so-called Freeze Foaming method aims at manufacturing ceramic cellular scaffolds for diverse applications. One application is dedicated to potential bone replacement material featuring open, micro and interconnected porosity. However, the main challenges of this foaming method is to achieve a homogeneous pore morphology. In a current project, the authors throw light on the bubble/pore and strut formation of this process by in situ computed tomography. This allows for evaluating varying process parameter’s effects on the growth of the ceramic foam during the foaming process. As first result and basis for CT analysis, a stable and reproducible model suspension was developed which resulted in reproducible foam structures. In dependence of selected process parameters like pressure reduction rate or air content in the ceramic suspension resulting Freeze Foams became adjustable with regard to their pore morphology. Pore size and distribution data as well as the porosity were characterized and evaluated accordingly.     

Thermo-physical properties of as deposited and aged thermal barrier coatings (TBC) for gas turbines: State-of-the art and advanced TBCs

In the perspective of fuelling the future generations of gas turbines by hydrogen rich syngas, the evaluation of the effect of a higher water vapour content into the flue gases on the TBC used, or potentially usable, is a need. For this purpose YPSZ APS TBC with two different microstructures have been exposed for 500?h at different temperatures in the range 1000?°C–1250?°C either in air and air +20% vol. H₂O. The comparison between the different testing conditions has been performed in terms of sintering kinetics and phase stability, as evaluated by thermal diffusivity measurements and Synchrotron X-Rays diffraction, respectively. Furthermore the characterisation of thermal properties of two innovative TBCs (GZO-YPSZ and YAG) potentially able to withstand the CMAS attack and erosive environments, respectively, has been carried out.No clear evidence of a different behaviour of TBC has been observed, at least in the considered aging time and temperature range.     

Genetic Deficiency and Pharmacological Stabilization of Mast Cells Ameliorate Pressure Overload-Induced Maladaptive Right Ventricular Remodeling in Mice

Although the response of the right ventricle (RV) to the increased afterload is an important determinant of the patient outcome, very little is known about the underlying mechanisms. Mast cells have been implicated in the pathogenesis of left ventricular maladaptive remodeling and failure. However, the role of mast cells in RV remodeling remains unexplored. We subjected mast cell-deficient WBB6F1-KitW/W-v (Kit^W/Kit^W-v) mice and their mast cell-sufficient littermate controls (MC^+/+) to pulmonary artery banding (PAB). PAB led to RV dilatation, extensive myocardial fibrosis, and RV dysfunction in MC^+/+ mice. In PAB Kit^W/Kit^W-v mice, RV remodeling was characterized by minimal RV chamber dilatation and preserved RV function. We further administered to C57Bl/6J mice either placebo or cromolyn treatment starting from day 1 or 7 days after PAB surgery to test whether mast cells stabilizing drugs can prevent or reverse maladaptive RV remodeling. Both preventive and therapeutic cromolyn applications significantly attenuated RV dilatation and improved RV function. Our study establishes a previously undescribed role of mast cells in pressure overload-induced adverse RV remodeling. Mast cells may thus represent an interesting target for the development of a new therapeutic approach directed specifically at the heart.     

C/C-SiC component for metallic phase change materials

Thanks to their high energy density and thermal conductivity, metallic Phase Change Materials (mPCM) have shown great potential to improve the performance of thermal energy storage systems. However, the commercial application of mPCM is still limited due to their corrosion behavior with conventional container materials. This work first addresses on a fundamental level, whether carbon-based composite-ceramics are suitable for corrosion critical components in a thermal storage system. The compatibility between the mPCM AlSi₁₂ and the Liquid Silicon Infiltration (LSI)-based carbon fiber reinforced silicon carbide (C/C-SiC) composite is then investigated via contact angle measurements, microstructure analysis, and mechanical testing after exposure. The results reveal that the C/C-SiC composite maintains its mechanical properties and microstructure after exposure in the strongly corrosive mPCM. Based on these results, efforts were made to design and manufacture a container out of C/C-SiC for the housing of mPCM in vehicle application. The stability of the component filled with mPCM was proven nondestructively via computer tomography (CT). Successful thermal input- and output as well as thermal storage ability were demonstrated using a system calorimeter under conditions similar to the application. The investigated C/C-SiC composite has significant application potential as a structural material for thermal energy storage systems with mPCM.     

Current Status on Stem Cells and Cancers of the Gastric Epithelium

Gastric cancer is still a leading cause of cancer-related mortality worldwide in spite of declining incidence. Gastric cancers are, essentially, adenocarcinomas and one of the strongest risk factors is still infection with Helicobacter pylori. Within the last years, it became clear that gastric self-renewal and carcinogenesis are intimately linked, particularly during chronic inflammatory conditions. Generally, gastric cancer is now regarded as a disease resulting from dysregulated differentiation of stem and progenitor cells, mainly due to an inflammatory environment. However, the situation in the stomach is rather complex, consisting of two types of gastric units which show bidirectional self-renewal from an unexpectedly large variety of progenitor/stem cell populations. As in many other tumors, cancer stem cells have also been characterized for gastric cancer. This review focuses on the various gastric epithelial stem cells, how they contribute to self-renewal and which routes are known to gastric adenocarcinomas, including their stem cells.