Targeting E3 ubiquitin ligases and their adaptors as a therapeutic strategy for metabolic diseases.

Posttranslational modification of proteins via ubiquitination determines their activation, translocation, dysregulation, or degradation. This process targets a large number of cellular proteins, affecting all biological pathways involved in the cell cycle, development, growth, and differentiation. Thus, aberrant regulation of ubiquitination is likely associated with several diseases, including various types of metabolic diseases. Among the ubiquitin enzymes, E3 ubiquitin ligases are regarded as the most influential ubiquitin enzymes due to their ability to selectively bind and recruit target substrates for ubiquitination. Continued research on the regulatory mechanisms of E3 ligases and their adaptors in metabolic diseases will further stimulate the discovery of new targets and accelerate the development of therapeutic options for metabolic diseases. In this review, based on recent discoveries, we summarize new insights into the roles of E3 ubiquitin ligases and their adaptors in the pathogenesis of metabolic diseases by highlighting recent evidence obtained in both human and animal model studies.

Patterned Sandwich-Type Silver Nanowire-Based Flexible Electrode by Photolithography.

Silver nanowires (AgNWs) are one of the important flexible electrode material candidates that can replace brittle indium tin oxide (ITO). In this work, we demonstrated novel patterned sandwich-type AgNW-based transparent electrodes easily prepared using the photolithography method for application in flexible devices. A cross-linked underlayer was introduced to increase the adhesion properties between a poly(ethylene terephthalate) substrate and AgNWs, and as a result, a uniform AgNW layer was easily deposited. Finally, the AgNW layer could be easily patterned by introducing a photocross-linkable upper layer without lift-off, dry transfer, and removal methods. A mixture of poly(sodium-4-styrene sulfonate) (PSS-Na+) and 2,4-hexadiyne-1,6-diol (HDD), which is a component of the upper layer, exhibited good cross-linking properties as well as excellent adhesion to the AgNW layer. Through the above method, it was possible to easily fabricate a patterned electrode with smooth surface morphology. Moreover, AgNW-based patterned electrodes exhibit good optical and electrical properties (Rs = 29.8 Ω/□, T550 nm = 94.6%), making them suitable for optoelectronic devices. Flexible polymer solar cells (PSCs) using patterned AgNW electrodes showed a high power conversion efficiency of over 10%, which is comparable to that of PSCs using rigid ITO electrodes. In addition, the high mechanical stability of AgNW-based PSCs was confirmed by bending experiments.

Improved Stability of All-Polymer Solar Cells Using Crosslinkable Donor and Acceptor Polymers Bearing Vinyl Moieties in the Side-Chains.

Crosslinkable polymers have attracted tremendous attention in various fields of science and technology, owing to their potential utilization in applications requiring dimensional and morphological stability under thermal and mechanical stress. In this study, random terpolymers were successfully synthesized by introducing thiophene-based monomers bearing vinyl functional groups in the side-chain of the polymer donor (PBDBT-BV20) and polymer acceptor (N2200-TV10) structures. The physical properties of the blend films of PBDBT-BV20 and N2200-TV10 before and after thermal crosslinking were extensively investigated and compared to those of the homogeneous individual polymer films. The results revealed that a network polymer with donor and acceptor polymer chains, which can lock the internal morphology, could be achieved by inducing crosslinking between the vinyl groups in the mixed state of PBDBT-BV20 and N2200-TV10. In addition, the power conversion efficiency (PCE) of the polymer solar cells (PSCs) containing the blend films that were crosslinked by a two-step thermal annealing process was improved. The enhanced PCE could be attributed to the individual crystallization of PBDBT-BV20 and N2200-TV10 in the blend phase at 120 °C and then thermal crosslinking at 140 °C. In addition, the PSCs with the crosslinked blend film exhibited an excellent shelf-life of over 1200 h and a thermally stable PCE. Furthermore, the crosslinked blend film exhibited excellent mechanical stability under bending stress in flexible PSCs using plastic substrates.

The Effect of Cognitive Training in a Day Care Center in Patients with Early Alzheimer's Disease Dementia: A Retrospective Study.

OBJECTIVE: This study aimed to evaluate the effect of cognitive training programs on the progression of dementia in patients with early stage Alzheimer's disease dementia (ADD) at the day care center. METHODS: From January 2015 to December 2018, a total of 119 patients with early ADD were evaluated. All subjects were classified into two groups according to participate in cognitive training program in addition to usual standard clinical care. Changes in scores for minimental status examination-dementia screening (MMSE-DS) and clinical dementia rating-sum of boxes (CDR-SOB) during the 12 months were compared between two groups. Multivariable logistic regression analyses were performed. RESULTS: As compared to case-subjects (n=43), the MMSE-DS and CDR-SOB scores were significantly worse at 12 months in the control-subjects (n=76). A statistically significant difference between the two groups was observed due to changes in MMSE-DS (p=0.012) and CDR-SOB (p<0.001) scores. Multivariable logistic regression analysis showed that the cognitive training program (odds ratio and 95% confidence interval: 0.225, 0.070-0.725) was independently associated with less progression of ADD. CONCLUSION: The cognitive training program was associated with benefits in maintaining cognitive function for patients with earlystage ADD that were receiving medical treatment.

The Effects of Fabric Containing Chamaecyparis obtusa Essential Oil on Atopic Dermatitis-Like Lesions: A Functional Clothing Possibility.

BACKGROUND: Essential oil derived from Chamaecyparis obtusa (EOCO) has been used as an alternative treatment for allergy-related diseases due to its immune-modulating characteristics. Clothing has the longest and most intense contact with human skin, and functional fabrics with intrinsic properties have been increasingly implemented in medical applications. Specially designed fabrics may support atopic dermatitis (AD) treatment. In this study, the effects of fabric containing EOCO on AD were investigated using an NC/Nga mouse model. METHODS: The fabric was applied for 6 h per day for 14 days. The therapeutic effects were evaluated according to measurements of skin lesion severity (modified SCORAD score), transepidermal water loss (TEWL), serum IgE and inflammatory cytokine levels, lesion thickness measured after hematoxylin and eosin staining, and immunohistochemical and Western blot analysis for skin epidermal differentiation protein. RESULTS: The EOCO group exhibited significantly reduced modified SCORAD score, TEWL, and serum IgE levels. Among the inflammatory cytokines analyzed, only the mean values of regulated on activation, normal T cell expressed and secreted were observed to be decreased compared with other control groups. The histological analysis of the skin also revealed that the EOCO group expressed reduced epidermal hyperplasia and recovered filaggrin, involucrin, and loricrin expression. CONCLUSIONS: It was confirmed that fabric containing EOCO has anti-atopic and anti-inflammatory properties. The study data show that fabric containing EOCO can be implemented as an alternative functional clothing for people suffering from AD.

Protein Extraction from Porcine Myocardium Using Ultrasonication.

Porcine myocardium is regarded as a byproduct in slaughterhouses and is rarely used as a food source due to its unsuitability for processing and consumption. In this study, we sought to develop an efficient ultrasonication method to extract protein from porcine myocardium. Comparisons of protein yield using various ultrasonication conditions with porcine myocardium revealed that treatment with 0.2 M NaCl, with pH 8.0, at an extraction temperature of less than 40 °C and an amplitude of 60% to 80% was optimal, yielding an extraction rate of 90%. In addition, SDS-PAGE analysis showed that increasing the time interval for ultrasonication increased the presence of myosin heavy chain and actin protein content. Functional analysis of the physiological properties of the isolated proteins using an ATPase assay showed that Ca and Mg ATPase activity was virtually undetectable in the early stages of ultrasonic treatment and that the proteins denatured rapidly. An analysis of protein digestion also showed that the digestive capacity of proteins treated by ultrasonication methods was greater. These results demonstrate that the ultrasonication method is effective for high-yield protein extraction from cardiac myofibrils of porcine myocardium with low salt concentrations, low Ca and Mg ATPase activities, and high digestive capacities.