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Extensive studies have been performed on the role of 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) in metabolic diseases. Our previous study reported glucose could directly regulate hexose-6-phosphate dehydrogenase (H6PDH) and 11β-HSD1. Recently, we further investigated the interplay of H6PDH and 11β-HSD1 and their roles in hepatic gluconeogenesis and insulin resistance to elucidate the importance of H6PDH and 11β-HSD1 in pathogenesis of type 2 diabetes mellitus (T2DM). T2DM rats model and H6PDH or 11β-HSD1 siRNA transfected in CBRH-7919 cells were used to explore the effect of H6PDH and 11β-HSD1 in T2DM. The results showed that the expression and activity of H6PDH and 11β-HSD1 in livers of diabetic rats were increased, with the expressions of PEPCK and G6Pase or liver corticosterone increased apparently. It also showed that H6PDH siRNA and 11β-HSD1 siRNA could inhibit the protein expression and enzyme activity by each other. With H6PDH siRNA, the enhancement of gluconeogenesis was blocked and insulin resistance stimulated by corticosterone was reduced. H6PDH and 11β-HSD1 might be the effective and prospective targets for T2DM and metabolic syndromes, based on the interplay between these two enzymes.

It is well established that diabetes mellitus accelerates atherosclerotic vascular disease. Endothelial injury has been proposed to be the initial event in the pathogenesis of atherosclerosis. Endothelium not only acts as a semi-selective barrier but also serves physiological and metabolic functions. Diabetes or high glucose in circulation triggers a series of intracellular responses and organ damage such as endothelial dysfunction and apoptosis. One such response is high glucose-induced chronic endoplasmic reticulum stress in the endothelium. The unfolded protein response is an acute reaction that enables cells to overcome endoplasmic reticulum stress. However, when chronically persistent, endoplasmic reticulum stress response could ultimately lead to endothelial dysfunction and atherosclerosis. Herein, we discuss the scientific advances in understanding endoplasmic reticulum stress-induced endothelial dysfunction, the pathogenesis of diabetes-accelerated atherosclerosis and endoplasmic reticulum stress as a potential target in therapies for diabetic atherosclerosis.

The retina is a light sensitive tissue that contains specialized photoreceptor cells called rods and cones which process visual signals. These signals are relayed to the brain through interneurons and the fibers of the optic nerve. The retina is susceptible to a variety of degenerative diseases, including age-related macular degeneration (AMD), diabetic retinopathy (DR), retinitis pigmentosa (RP) and other inherited retinal degenerations. In order to reveal the mechanism underlying these diseases and to find methods for the prevention/treatment of retinal degeneration, animal models have been generated to mimic human eye diseases. In this paper, several well-characterized and commonly used animal models are reviewed. Of particular interest are the contributions of these models to our understanding of the mechanisms of retinal degeneration and thereby providing novel treatment options including gene therapy, stem cell therapy, nanomedicine, and CRISPR/Cas9 genome editing. Role of newly-identified adaptor protein epsins from our laboratory is discussed in retinal angiogenesis and VEGFR2 signaling.

Alzheimer's disease (AD) is the world's most common form of dementia, in which aggregation of amyloid-β (Aβ) is the hallmark. Unfortunately, few medicines have succeeded to completely cure AD. Yangxue Qingnao (YXQN) is a Chinese traditional medicine, and its pharmacological effect is improving cerebral blood flow. In this study, we firstly demonstrated that YXQN reduced AD-like pathology and cognitive impairment in APPswePS1dE9 (APP/PS1) mice with 2 months administration. Our data showed that YXQN substantially ameliorated behavioral defects in 10-month old APP/PS1 mice using Morris Water Maze and Y-maze tests, in which the cognitive ability of YXQN high-dose group approaches to wild type mice. Next, we focused on the brain pathological alterations in the YXQN group by three experiments, including thioflavin-S, congo-red, and Aβ-immunohistochemistry staining. The results demonstrated that the high-dose of YXQN dramatically suppressed amyloid plaques in the hippocampus and cortex of APP/PS1 mice, which showed a 47-72% reduction in plaque deposits, relative to the vehicle group. In addition, our data verified that YXQN decreased the cerebral amyloid load by attenuating β-secretase BACE1 and γ-secretase PS1 in the pathological processing of APP, and promoting the level of α-secretase ADAM10 in the physiological processing of APP to generate more sAPPα, which combats amyloidosis formation, and also carries out neurotropic and neuroprotective effect. Taken together, our results strongly suggest that YXQN could be a potential medicine for AD, and provide new evidence for further AD drug research and development.

Purpose: A group of 10 prelingually deafened children with cochlear implants (CIs) formed a choir and received 21 months of formal music training. The purpose of this study was to evaluate the singing proficiency of these children. Method: The participants included all choir members (7 girls and 3 boys, mean age of 9.5 years old) who were unilateral CI users. Meanwhile, 8 age-matched children with normal hearing were recruited as controls and were trained on 1 song for 2 weeks. Individual singing samples without instrument accompaniment were recorded from all participants. The singing samples were subject to acoustic analysis in which the fundamental frequency (F0) of each note was extracted and the duration was measured. Five metrics were developed and computed to quantify the accuracy of their pitch and rhythm performance. The 5 metrics included (a) percent correct of F0 contour direction of adjacent notes, (b) mean deviation of the normalized F0 across the notes, (c) mean deviation of the pitch intervals, (d) mean deviation of adjacent note duration ratio, and (e) mean absolute deviation of note duration. Results: The choir members with CIs demonstrated high accuracy in both pitch and tempo measures and performed on par with the children with normal hearing. Early start of music training after implantation and use of bimodal hearing contributed to the development of better music ability in these children with CIs. Conclusion: These findings indicated that rigorous music training could facilitate high singing proficiency in prelingually deafened children with CIs.

AbstractWe give a generic description of the non-defining primes l, for which the Steinberg character lies in the principal l-block of a finite reductive group. [ABSTRACT FROM AUTHOR]

Aim/Introduction: Type 2 diabetes mellitus (T2DM) is one of the most frequent and widespread disease in the world.Obesity is the most significant predictor of T2DM, but the exact mechanism how obesity promotes T2DM remains unknown. Finding specific biomarkers to assist in diagnosing and treating patients with obese and T2DM is critical. Materials and Methods: We collected liver tissues from obesity patients with and without T2DM for proteomic sequencing and immunohistochemistry assay. Analysis Gene Ontology(GO) enrichment, Kyoto Encyclopedia of Genes and Genomes(KEGG), and protein interaction network (PPI) were performed on the parameters and data derived from the Tandem Mass Tags(TMT)-based proteomics analysis of liver tissues. Transcriptome data were downloaded from the Gene Expression Omnibus(GEO)website and genes that are deferentially expressed in both transcriptome and proteome were selected. Results: We identified 140 deferentially expressed proteins from proteomic sequencing. Six biomarkers were deferentially expressed in both proteome and transcriptome with consistent changes in direction. The protein–protein interaction (PPI) analysis suggested CMPK1, the expression with greatest difference, was the core protein among the six biomarkers. Immunohistochemistry validated CMPK1 was upregulated significantly in the liver tissues of T2DM patients. The correlation analysis revealed that the expression of CMPK1 was significantly associated with key molecules in T2DM-related pathways at both protein and transcriptome levels. Conclusion and Novelty: Our study showed CMPK1 was upregulated in the liver of T2DM patients and provides a possible new target for screening and diagnosing T2DM in patients with obese and a novel theoretical basis for the pathophysiological mechanism of obesity-related metabolic diseases. [ABSTRACT FROM AUTHOR]

Customer mistreatment as a common workplace stressor in the service industry has detrimental effects on service employees. Drawing on cognitive theories of rumination, the current study examined the effect of daily customer mistreatment experience on employee recovery outcomes (sleep quality and next‐morning vigor) through affective rumination. Further, we investigated the moderating role of trait mindfulness on the relationship between customer mistreatment and employee affective rumination. With 390 matched time‐lagged daily observations collected from 107 fulltime in‐patient nurses across five working days, our multilevel analyses revealed that daily customer mistreatment experience at work was negatively related to employee sleep quality on the same night and vigor in the next morning via affective rumination and that employee's affective rumination at the end of work and sleep quality at night sequentially mediated the relationship between daily experience of customer mistreatment and morning vigor. Besides, trait mindfulness buffered the relationship between daily customer mistreatment and affective rumination. These findings shed light on the understanding of the mechanisms between customer mistreatment and employee recovery states and potentially malleable individual characteristics that might mitigate the negative effects of customer mistreatment. [ABSTRACT FROM AUTHOR]

Charge transfer is vital in determining the optoelectronic properties of atomically thin materials, yet remains elusive in type I heterostructures. Here, distinct two‐step charge transfer processes in a type I MoS2/PtSe2 heterostructure are reported. By exclusively exciting the smaller bandgap PtSe2, strong exciton photobleaching peaks of the larger bandgap MoS2 are observed, indicating primary hot carrier transfer from PtSe2 to MoS2 within 70 fs. More importantly, the amplitude of the exciton peaks shows a secondary increase after the initial rapid decay. These dynamics are distinctly different from the monotonic decrease in monolayer MoS2 and indicate a secondary charge transfer process that is attributed to hot carriers re‐generated in PtSe2 by intralayer Auger recombination. Concurrently, the exciton energy blue shifts within 100 ps, probing the dynamic buildup of a charge‐transfer induced electric field across the heterostructure interface, which displaces electron and hole wavefunctions of MoS2 excitons and reduces the exciton binding energy. The results are corroborated by carrier dynamics and transient absorption spectra simulations by considering the two‐step charge transfer processes. The work reveals Auger‐assisted hot carrier transfer processes in type I heterostructures and suggests the possibility for optoelectronic and photocatalytic applications by optical sub‐bandgap excitation. [ABSTRACT FROM AUTHOR]

The integration of wave energy converters (WECs) into floating offshore wind turbine (FOWT) can effectively reduce costs and increase power generation. When WECs are integrated into FOWT, the hydrodynamic interference, motion coupling, and other factors contribute to the high spatial dimension of the coupled optimization, making it difficult to find the globally optimal solution. Therefore, this study proposes an optimization method based on a wind‐wave coupling model, and takes a new wind‐wave hybrid system as an example for verification and analysis. First, the experimental design is completed through random sampling, and the corresponding WECs and wind turbine power of each sample point are calculated using full coupling simulation. And then according to the design input and simulation results, the wind‐wave coupling model is obtained by training the elliptical basis functions neural network (EBFNN). At last, based on this model, the non‐dominated sorting genetic algorithm II (NSGA‐II) is used to optimize the WECs microarray. The results show that the prediction model established in this paper has high accuracy and is used with the NSGA‐II to effectively improve the wind‐wave coupling energy harvesting. This method can effectively solve the problem of high coupling dimensions in the process of hybrid system design. [ABSTRACT FROM AUTHOR]