Exosomes from Human Adipose Tissue-Derived Mesenchymal Stem Cells Promote Epidermal Barrier Repair by Inducing de Novo Synthesis of Ceramides in Atopic Dermatitis.

Atopic dermatitis (AD) is a multifactorial, heterogeneous disease associated with epidermal barrier disruption and intense systemic inflammation. Previously, we showed that exosomes derived from human adipose tissue-derived mesenchymal stem cells (ASC-exosomes) attenuate AD-like symptoms by reducing multiple inflammatory cytokine levels. Here, we investigated ASC-exosomes' effects on skin barrier restoration by analyzing protein and lipid contents. We found that subcutaneous injection of ASC-exosomes in an oxazolone-induced dermatitis model remarkably reduced trans-epidermal water loss, while enhancing stratum corneum (SC) hydration and markedly decreasing the levels of inflammatory cytokines such as IL-4, IL-5, IL-13, TNF-α, IFN-γ, IL-17, and TSLP, all in a dose-dependent manner. Interestingly, ASC-exosomes induced the production of ceramides and dihydroceramides. Electron microscopic analysis revealed enhanced epidermal lamellar bodies and formation of lamellar layer at the interface of the SC and stratum granulosum with ASC-exosomes treatment. Deep RNA sequencing analysis of skin lesions demonstrated that ASC-exosomes restores the expression of genes involved in skin barrier, lipid metabolism, cell cycle, and inflammatory response in the diseased area. Collectively, our results suggest that ASC-exosomes effectively restore epidermal barrier functions in AD by facilitating the de novo synthesis of ceramides, resulting in a promising cell-free therapeutic option for treating AD

DFT‐basierte Entdeckung von Ethynyl‐Triazolyl‐Phosphinaten als modulare Elektrophile für die chemoselektive Cystein‐Biokonjugation und Profilierung

Wir berichten über eine Dichtefunktionaltheorie (DFT)-basierte Entdeckung von Ethinyl-Triazolyl-Phosphinaten (ETP) als eine neue Klasse elektrophiler Verbindungen für die selektive Biokonjugation von Cystein. Mit Hilfe der CuI-katalysierten Azid-Alkin-Cycloaddition (CuAAC) in wässrigem Puffer konnten wir eine Vielzahl funktioneller elektrophiler Bausteine, darunter auch Proteine, aus Diethynylphosphinat herstellen. Wir verwendeten diese ETP-Reagenzien, um fluoreszierende Peptid-Konjugate für die Markierung von Rezeptoren auf lebenden Zellen sowie ein stabiles und biologisch aktives Antikörper-Wirkstoff-Konjugat zu erhalten. Darüber hinaus konnten wir ETP-Elektrophile unter nativen Bedingungen in ein Azid-haltiges Ubiquitin einbauen und ihr Potenzial für die Protein-Protein-Konjugation demonstrieren. Schließlich zeigen wir die exzellente Cystein-Selektivität dieser neuen Klasse von Elektrophilen in Massenspektrometrie basierten, proteomweiten Reaktivitätsstudien und unterstreichen damit die generelle Anwendbarkeit in homogenen Biokonjugationsstrategien zur Verknüpfung zweier komplexer Biomoleküle.Deutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/501100001659Leibniz-Gemeinschaft http://dx.doi.org/10.13039/501100001664Studienstiftung des Deutschen Volkes http://dx.doi.org/10.13039/501100004350Alexander von Humboldt-Stiftung http://dx.doi.org/10.13039/100005156Institute for Basic Science in KoreaPeer Reviewe

DFT‐Guided Discovery of Ethynyl‐Triazolyl‐Phosphinates as Modular Electrophiles for Chemoselective Cysteine Bioconjugation and Profiling

We report the density functional theory (DFT) guided discovery of ethynyl‐triazolyl‐phosphinates (ETPs) as a new class of electrophilic warheads for cysteine selective bioconjugation. By using CuI‐catalysed azide alkyne cycloaddition (CuAAC) in aqueous buffer, we were able to access a variety of functional electrophilic building blocks, including proteins, from diethynyl‐phosphinate. ETP‐reagents were used to obtain fluorescent peptide‐conjugates for receptor labelling on live cells and a stable and a biologically active antibody‐drug‐conjugate. Moreover, we were able to incorporate ETP‐electrophiles into an azide‐containing ubiquitin under native conditions and demonstrate their potential in protein–protein conjugation. Finally, we showcase the excellent cysteine‐selectivity of this new class of electrophile in mass spectrometry based, proteome‐wide cysteine profiling, underscoring the applicability in homogeneous bioconjugation strategies to connect two complex biomolecules.By means of density functional theory calculations, ethynyl‐triazolyl‐phosphinates (ETPs) were discovered as modular and cysteine‐selective electrophiles for bioconjugation. Using CuI‐click chemistry in aqueous buffers, this functional group can be easily introduced into azide‐containing (bio‐)molecules. These reagents can be used for proteome‐wide cysteine profiling and to obtain functional peptide‐ and protein conjugates, as well as protein–protein conjugates . imageDeutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/501100001659Leibniz-Gemeinschaft http://dx.doi.org/10.13039/501100001664Studienstiftung des Deutschen Volkes http://dx.doi.org/10.13039/501100004350Alexander von Humboldt-Stiftung http://dx.doi.org/10.13039/100005156Institute for Basic Science in KoreaPeer Reviewe

The impact of comorbid anxiety on quantitative EEG heterogeneity in children with attention-deficit/hyperactivity disorder

ObjectiveThe objective of this study was to compare quantitative electroencephalography (Q-EEG) characteristics of children with Attention-deficit/hyperactivity disorder (ADHD), taking into account the presence of a comorbidity for anxiety disorder. It also sought to investigate the impact of comorbid anxiety on the Q-EEG heterogeneity of children with ADHD.MethodA total of 141 children with ADHD but without comorbid anxiety (ADHD-Only), 25 children with a comorbidity for anxiety disorder (ADHD-ANX) and 43 children in the control group were assessed. To compare Q-EEG characteristics between groups, we performed ANCOVA (Analysis of Covariance) on relative power and theta/beta ratio (TBR) controlling for covariates such as age, sex, and FSIQ. Relative power values from 19 electrodes were averaged for three regions (frontal, central and posterior). Furthermore, cluster analysis (Ward’s method) using the squared Euclidian distance was conducted on participants with ADHD to explore the impact of anxiety on the heterogeneity of Q-EEG characteristics in ADHD.ResultsThere were no significant group differences in cognitive and behavioral measures. However, significant differences between groups were observed in the theta values in the central region, and the beta values in the frontal, central and posterior regions. In post hoc analyses, It was found that the ADHD-ANX group has significantly higher beta power values than the ADHD-Only group in all regions. For the theta/beta ratio, the ADHD-Only group had significantly higher values than the ADHD-ANX group in frontal, central and posterior regions. However, the control group did not show significant differences compared to both the ADHD-Only and ADHD-ANX group. Through clustering analysis, the participants in the ADHD-Only and ADHD-ANX groups were classified into four clusters. The ratios of children with comorbidities for anxiety disorder within each cluster were significantly different (χ2 = 10.018, p = 0.019).ConclusionAttention-deficit/hyperactivity disorder children with comorbid anxiety disorder showed lower theta power in the central region, higher beta power in all regions and lower TBR in all regions compared to those without comorbid anxiety disorder. The ratios of children with comorbidities for anxiety disorder within each cluster were significantly different

Effects of interval and sprint training under hypobaric hypoxia on aerobic, anaerobic, and time trial performance in elite Korean national male mountain bike cyclists—a pilot study

The purpose of our study to determine the effects of interval hypoxic training (IHT) and repeated sprint training in hypoxia (RSH) on metabolic and cardiac function during submaximal exercise, aerobic and anaerobic performance, and time trial performance in elite Korean national male mountain bike (MTB) cyclists. The participants included elite Korean national male MTB cyclists (n = 4) preparing for the 19th Asian Games in Hangzhou 2022. The hypoxic training frequency was 90 min (3 days per week for 4 weeks). Before and after hypoxic training, metabolic and cardiac functions during submaximal exercise, aerobic performance, anaerobic performance and time trial performance were measured. Oxygen uptake, carbon dioxide excretion, and heart rate tended to decrease, and stroke volume, end-diastolic volume and cardiac output tended to increase. In aerobic, anaerobic and time trial performances, the peak torque in aerobic performance significantly increased (p = 0.046). Maximal oxygen uptake and exercise time in aerobic performance, relative peak power, relative mean power, post-exercise blood lactate level, fatigue index in anaerobic performance, and time trial performance showed an improved tendency (all p = 0.068). Our pilot study confirmed that although the sample size was small, IHT and RSH can potentially improve athletic performance in elite Korean national male MTB cyclists

Comparative and experimental studies on the relationship between body size and countershading in caterpillars

Countershading is a gradient of colouration in which the illuminated dorsal surfaces are darker than the unilluminated ventral surface. It is widespread in the animal kingdom and endows the body with a more uniform colour to decrease the chance of detection by predators. Although recent empirical studies support the theory of survival advantage conferred by countershading, this camouflage strategy has evolved only in some of the cryptic animals, and our understanding of the factors that affect the evolution of countershading is limited. This study examined the association between body size and countershading using lepidopteran larvae (caterpillars) as a model system. Specifically, we predicted that countershading may have selectively evolved in large-sized species among cryptic caterpillars if (1) large size constrains camouflage which facilitates the evolution of a trait reinforcing their crypsis and (2) the survival advantage of countershading is size-dependent. Phylogenetic analyses of four different lepidopteran families (Saturniidae, Sphingidae, Erebidae, and Geometridae) suggest equivocal results: countershading was more likely to be found in larger species in Saturniidae but not in the other families. The field predation experiment assuming avian predators did not support size-dependent predation in countershaded prey. Collectively, we found only weak evidence that body size is associated with countershading in caterpillars. Our results suggest that body size is not a universal factor that has shaped the interspecific variation in countershading observed in caterpillars.N

Control of the Biodegradability of Piezoelectric Peptide Nanotubes Integrated with Hydrophobic Porphyrin

Diphenylalanine (FF) is a piezoelectric material that is widely known for its high piezoelectric constant, self-assembly characteristics, and ease of manufacture. Because of its biocompatible nature, it is useful for implantable applications. However, its use in real applications is challenging because it degrades too easily in the body due to its solubility in water (0.76 g/mL). Upon incorporation of hydrophobic and biocompatible porphyrins into the FF, the degradability of the piezoelectric FF and their piezoelectric nanogenerators (PENGs) is controlled. Porphyrin-incorporated FFs are also formed as piezoelectric nanostructures well aligned on the substrate through self-assembly, and their piezoelectric properties are comparable to those of FF. The FF-based PENG degrades in only 5 min, whereas the FF-porphyrin-based PENG produces a stable output for >15 min in phosphatebuffered saline. This strategy for realizing biodegradable functional materials and devices with tunable degradation rates in the body can be applied to many implantable electronics.FALS

What Motivates Users to Keep Using Social Mobile Payments?

Due to the rapid diffusion of social mobile payment (SMP), the current research explores the post-adoption behavior of SMP users. It proposes a research model to determine the core predictors of users’ continuance intentions to use SMPs. Through the analysis of survey data from South Korea, it indicates that satisfaction strongly and positively affects users’ continuance intentions. Moreover, satisfaction is influenced by perceived usefulness (PU), security, and enjoyment. Interestingly, although perceived ease of use (PEU) does not directly affect satisfaction, it can indirectly influence satisfaction via users’ PU and perceived enjoyment. Furthermore, perceived ubiquity has strong effects on users’ PU and PEU. The study also discusses meaningful implications, and provides suggestions for future studies