Quantum Conductance Probing of Oxygen Vacancies in SrTiO3 Epitaxial Thin Film Using Graphene

The quantum Hall conductance in monolayer graphene on an epitaxial SrTiO3 (STO) thin film is studied to understand the role of oxygen vacancies in determining the dielectric properties of STO. As the gate voltage sweep range is gradually increased in our device, we observe systematic generation and annihilation of oxygen vacancies evidenced from the hysteretic conductance behavior in graphene. Furthermore, based on the experimentally observed linear scaling relation between the effective capacitance and the voltage sweep range, a simple model is constructed to manifest the relationship among the dielectric properties of STO with oxygen vacancies. The inherent quantum Hall conductance in graphene can be considered as a sensitive, robust, and non-invasive probe for understanding the electronic and ionic phenomena in complex transition metal oxides without impairing the oxide layer underneath.Comment: 21 pages, 4 figures, 2 supp. figure

Appropriateness of the anxiety subscale of the Hospital Anxiety and Depression Scale for Koreans to measure preoperative anxiety and the effect of preoperative anxiety on postoperative quality of recovery

Background The reliability and validity of the anxiety subscale of the Hospital Anxiety and Depression Scale for Koreans (K-HADS-A) has not been studied in Korean surgical patients. This study aimed to validate the usefulness of K-HADS-A for measuring preoperative anxiety in Korean surgical patients. Additionally, the effect of preoperative anxiety on postoperative quality of recovery was evaluated. Methods Preoperative anxiety in 126 inpatients with planned elective surgery was measured using the K-HADS-A. The postoperative quality of recovery was measured using the Korean version of the Quality of Recovery-15. The validity and reliability of the K-HADS-A were evaluated. The differences in quality of recovery on the first and seventh day postoperatively were then compared between the anxious and non-anxious groups. Results There was a statistical correlation between the K-HADS-A and Anxiety Likert Scale. The goodness-of-fit indices of the structural equation model showed how well the data from the K-HADS-A match their concept. The Kaiser-Meyer-Olkin value was 0.848, and the P value of Bartlett’s test of sphericity was < 0.001. Cronbach’s alpha was high at 0.872. The K-HADS-A had an acceptable level of validity and reliability. Postoperative quality of recovery was significantly lower in the anxious group (postoperative day 1: t = 2.058, P = 0.042; postoperative day 7: t = 3.430, P = 0.002). Conclusions The K-HADS-A is an acceptable tool for appropriately assessing preoperative anxiety in Korean surgical patients. Assessing preoperative anxiety is valuable, because preoperative anxiety affects the postoperative quality of mental and physical recovery

The Effect of Electrical Muscle Stimulation and In-bed Cycling on Muscle Strength and Mass of Mechanically Ventilated Patients: A Pilot Study

Background Critically ill patients experience muscle weakness, which leads to functional disability. Both functional electrical stimulation (FES) and in-bed cycling can be an alternative measure for intensive care unit (ICU) patients who are not feasible for active exercise. The aim of this study was to examine whether FES and in-bed cycling have a positive effect on muscle mass in ICU patients. Methods Critically ill patients who received mechanical ventilation for at least 24 hours were included. After passive range of motion exercise, in-bed cycling was applied for 20 minutes, and FES was applied for 20 minutes on the left leg. The right leg received in-bed cycling and the left leg received both FES and in-bed cycling. Thigh circumferences and rectus femoris cross-sectional area (CSA) were assessed with ultrasonography before and after the intervention. Muscle strength was assessed by Medical Research Council scale. Results A total of 10 patients were enrolled in this study as a pilot study. Before and after the intervention, the CSA of right rectus femoris increased from 5.08 ± 1.51 cm2 to 6.01 ± 2.21 cm2 , which was statistically significant (P = 0.003). The thigh circumference was also increased and statistically significant (P = 0.006). There was no difference between left and right in regard to FES application. There is no significant change in muscle strength before and after the intervention (right and left, P = 0.317 and P = 0.368, respectively). Conclusions In-bed cycling increased thigh circumferences rectus femoris CSA. Adding FES did not show differences

GSK-3β inhibition by curcumin mitigates amyloidogenesis via TFEB activation and anti-oxidative activity in human neuroblastoma cells

© 2020 Informa UK Limited, trading as Taylor & Francis Group.The translocation of transcription factor EB (TFEB) to the nucleus plays a pivotal role in the regulation of basic cellular processes, such as lysosome biogenesis and autophagy. Autophagy is an intracellular degradation system that delivers cytoplasmic constituents to the lysosome, which is important in maintaining cellular homeostasis during environmental stress. Furthermore, oxidative stress is a critical cause for the progression of neurodegenerative diseases. Curcumin has anti-oxidative and anti-inflammatory activities, and is expected to have potential therapeutic effects in various diseases. In this study, we demonstrated that curcumin regulated TFEB export signalling via inhibition of glycogen synthase kinase-3β (GSK-3β); GSK-3β was inactivated by curcumin, leading to reduced phosphorylation of TFEB. We further showed that H2O2-induced oxidative stress was reduced by curcumin via the Nrf2/HO-1 pathway in human neuroblastoma cells. In addition, we showed that curcumin induced the degradation of amyloidogenic proteins, including amyloid-β precursor protein and α-synuclein, through the TFEB-autophagy/lysosomal pathway. In conclusion, curcumin regulates autophagy by controlling TFEB through the inhibition of GSK-3β, and increases antioxidant gene expression in human neuroblastoma cells. These results contribute to the development of novel cellular therapies for neurodegenerative diseases.

CO ameliorates cellular senescence and aging by modulating the miR-34a/Sirt1 pathway

Oxidative stress is recognised as a key factor that can lead to cellular senescence and aging. Carbon monoxide (CO) is produced by haemoxygenase-1 (HO-1), which exerts cytoprotective effects in aging-related diseases, whereas the effect of CO on cellular senescence and aging has not been elucidated. In the current study, we clearly demonstrated that CO delays the process of cellular senescence and aging through regulation of miR-34a and Sirt1 expression. CO reduced H2O2-induced premature senescence in human diploid fibroblast WI-38 cells measured with SA-beta-Gal-staining. Furthermore, CO significantly decreased the expression of senescence-associated secretory phenotype (SASP), including TNF-alpha IL-6, and PAI-1 and increased the transcriptional levels of antioxidant genes, such as HO-1 and NQO1. Moreover, CO apparently enhanced the expression of Sirt1 through down-regulation of miR-34a. Next, to determine whether Sirt1 mediates the inhibitory effect of CO on cellular senescence, we pre-treated WI-38 cells with the Sirt1 inhibitor Ex527 and a miR-34a mimic followed by the administration of H2O2 and evaluated the expression of SASP and antioxidant genes as well as ROS production. According to our results, Sirt1 is crucial for the antiaging and antioxidant effects of CO. Finally, CO prolonged the lifespan of Caenorhabditis elegans and delayed high-fat diet-induced liver aging. Taken together, these findings demonstrate that CO reduces cellular senescence and liver aging through the regulation of miR-34a and Sirt1.

Upregulated Glucose Metabolism Correlates Inversely with CD8(+) T-cell Infiltration and Survival in Squamous Cell Carcinoma

Antibodies that block T-cell–regulatory checkpoints have recently emerged as a transformative approach to cancer treatment. However, the clinical efficacy of checkpoint blockade depends upon inherent tumor immunogenicity, with variation in infiltrating T cells contributing to differences in objective response rates. Here, we sought to understand the molecular correlates of tumor-infiltrating T lymphocytes (TIL) in squamous cell carcinoma (SCC), using a systems biologic approach to integrate publicly available omics datasets with histopathologic features. We provide evidence that links TIL abundance and therapeutic outcome to the regulation of tumor glycolysis by EGFR and HIF, both of which are attractive molecular targets for use in combination with immunotherapeutics

HPV, tumour metabolism and novel target identification in head and neck squamous cell carcinoma

Background Metabolic changes in tumour cells are used in clinical imaging and may provide potential therapeutic targets. Human papillomavirus (HPV) status is important in classifying head and neck cancers (HNSCC), identifying a distinct clinical phenotype; metabolic differences between these HNSCC subtypes remain poorly understood. Methods We used RNA sequencing to classify the metabolic expression profiles of HPV+ve and HPV−ve HNSCC, performed a meta-analysis on FDG-PET imaging characteristics and correlated results with in vitro extracellular flux analysis of HPV−ve and HPV+ve HNSCC cell lines. The monocarboxylic acid transporter-1 (MCT1) was identified as a potential metabolic target and tested in functional assays. Results Specific metabolic profiles were associated with HPV status, not limited to carbohydrate metabolism. There was dominance of all energy pathways in HPV-negative disease, with elevated expression of genes associated with glycolysis and oxidative phosphorylation. In vitro analysis confirmed comparative increased rates of oxidative phosphorylation and glycolysis in HPV-negative cell lines. PET SUV(max) scores however were unable to reliably differentiate between HPV-positive and HPV-negative tumours. MCT1 expression was significantly increased in HPV-negative tumours, and inhibition suppressed tumour cell invasion, colony formation and promoted radiosensitivity. Conclusion HPV-positive and negative HNSCC have different metabolic profiles which may have potential therapeutic applications

Group A streptococcus induces CD1a-autoreactive T cells and promotes psoriatic inflammation

Group A Streptococcus (GAS) infection is associated with multiple clinical sequelae, including different subtypes of psoriasis. Such post-streptococcal disorders have been long known but are largely unexplained. CD1a is expressed at constitutively high levels by Langerhans cells and presents lipid antigens to T cells, but the potential relevance to GAS infection has not been studied. Here, we investigated whether GAS-responsive CD1a-restricted T cells contribute to the pathogenesis of psoriasis. Healthy individuals had high frequencies of circulating and cutaneous GAS-responsive CD4+ and CD8+ T cells with rapid effector functions, including the production of interleukin-22 (IL-22). Human skin and blood single-cell CITE-seq analyses of IL-22-producing T cells showed a type 17 signature with proliferative potential, whereas IFN-γ-producing T cells displayed cytotoxic T lymphocyte characteristics. Furthermore, individuals with psoriasis had significantly higher frequencies of circulating GAS-reactive T cells, enriched for markers of activation, cytolytic potential, and tissue association. In addition to responding to GAS, subsets of expanded GAS-reactive T cell clones/lines were found to be autoreactive, which included the recognition of the self-lipid antigen lysophosphatidylcholine. CD8+ T cell clones/lines produced cytolytic mediators and lysed infected CD1a-expressing cells. Furthermore, we established cutaneous models of GAS infection in a humanized CD1a transgenic mouse model and identified enhanced and prolonged local and systemic inflammation, with resolution through a psoriasis-like phenotype. Together, these findings link GAS infection to the CD1a pathway and show that GAS infection promotes the proliferation and activation of CD1a-autoreactive T cells, with relevance to post-streptococcal disease, including the pathogenesis and treatment of psoriasis