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BackgroundEzetimibe, which lowers cholesterol by blocking the intestinal cholesterol transporter Niemann-Pick C1 like 1, is reported to reduce hepatic steatosis in humans and animals. Here, we demonstrate the changes in hepatic metabolites and lipids and explain the underlying mechanism of ezetimibe in hepatic steatosis.MethodsWe fed Otsuka Long-Evans Tokushima Fatty (OLETF) rats a high-fat diet (60 kcal % fat) with or vehicle (control) or ezetimibe (10 mg kg-1) via stomach gavage for 12 weeks and performed comprehensive metabolomic and lipidomic profiling of liver tissue. We used rat liver tissues, HepG2 hepatoma cell lines, and siRNA to explore the underlying mechanism.ResultsIn OLETF rats on a high-fat diet, ezetimibe showed improvements in metabolic parameters and reduction in hepatic fat accumulation. The comprehensive metabolomic and lipidomic profiling revealed significant changes in phospholipids, particularly phosphatidylcholines (PC), and alterations in the fatty acyl-chain composition in hepatic PCs. Further analyses involving gene expression and triglyceride assessments in rat liver tissues, HepG2 hepatoma cell lines, and siRNA experiments unveiled that ezetimibe’s mechanism involves the upregulation of key phospholipid biosynthesis genes, CTP:phosphocholine cytidylyltransferase alpha and phosphatidylethanolamine N-methyl-transferase, and the phospholipid remodeling gene lysophosphatidylcholine acyltransferase 3.ConclusionThis study demonstrate that ezetimibe improves metabolic parameters and reduces hepatic fat accumulation by influencing the composition and levels of phospholipids, specifically phosphatidylcholines, and by upregulating genes related to phospholipid biosynthesis and remodeling. These findings provide valuable insights into the molecular pathways through which ezetimibe mitigates hepatic fat accumulation, emphasizing the role of phospholipid metabolism. more...

Postural orthostatic tachycardia syndrome (POTS) is a complex condition marked by an atypical autonomic response to standing, leading to orthostatic intolerance and significant tachycardia without accompanying hypotension. In recent studies, a considerable number of individuals recovering from COVID-19 have been reported to experience POTS within 6 to 8 months post-infection. Key symptoms of POTS include fatigue, difficulty with orthostatic tolerance, tachycardia, and cognitive challenges. The underlying causes of POTS following COVID-19 remain unknown, with various theories proposed such as renin–angiotensin–aldosterone system (RAAS) dysregulation, hyperadrenergic reaction, and direct viral infection. Healthcare professionals should be vigilant for POTS in patients who have recovered from COVID-19 and are experiencing signs of autonomic dysfunction and use diagnostic procedures such as the tilt-up table test for confirmation. COVID-19-related POTS should be approached with a holistic strategy. Although many patients show improvement with initial non-drug treatments, for subjects who do not respond and exhibit more severe symptoms, medication-based therapies may be necessary. The current understanding of COVID-19-related POTS is limited, underscoring the need for more research to increase knowledge and enhance treatment approaches. more...

Objective: Abnormal autophagic function and activated inflammasomes are typical features in the liver of patients with non-alcoholic steatohepatitis (NASH). Here, we explored whether gemigliptin, a dipeptidyl peptidase 4 (DPP4) inhibitor for treatment of type 2 diabetes, can induce autophagy and regulate inflammasome activation as a potential NASH treatment independent of its anti-diabetic effect. Methods: Expression analysis was performed using human liver samples obtained from 18 subjects who underwent hepatectomy. We explored the function and mechanism of gemigliptin using a methionine- and choline-deficient diet (MCD)-induced NASH mouse model and HepG2 cells cultured in MCD-mimicking medium. Results: Autophagy was suppressed by marked decreases in the expression of ULK1 and LC3II/LC3I ratio in human NAFLD/NASH patients, a NASH mouse model, and HepG2 cells cultured with MCD-mimicking media. Surprisingly, we found that the expression of p-AMPK decreased in liver tissues from patients with steatosis but was restored in NASH patients. The expression of p-AMPK in the NASH mouse model was similar to that of the control group. Hence, these results indicate that autophagy was reduced in NASH via an AMPK-independent pathway. However, gemigliptin treatment attenuated lipid accumulation, inflammation, and fibrosis in the liver of MCD diet–fed mice with restoration of ULK1 expression and autophagy induction. In vitro, gemigliptin alleviated inflammasome activation through induction of ULK1-dependent autophagy. Furthermore, gemigliptin treatment upregulated ULK1 expression and activated AMPK even after siRNA-mediated knockdown of AMPKα1/2 and ULK1, respectively. Conclusions: Collectively, these results suggest that gemigliptin ameliorated NASH via AMPK-independent, ULK1-mediated effects on autophagy. more...

Atmospheric processes involve both space and time. Thus, humans looking at atmospheric imagery can often spot important signals in an animated loop of an image sequence not apparent in an individual (static) image. Utilizing such signals with automated algorithms requires the ability to identify complex spatiotemporal patterns in image sequences. That is a very challenging task due to the endless possibilities of patterns in both space and time. Here, we review different concepts and techniques that are useful to extract spatiotemporal signals from meteorological image sequences to expand the effectiveness of AI algorithms for classification and prediction tasks. We first present two applications that motivate the need for these approaches in meteorology, namely the detection of convection from satellite imagery and solar forecasting. Then we provide an overview of concepts and techniques that are helpful for the interpretation of meteorological image sequences, such as (a) feature engineering methods using (i) meteorological knowledge, (ii) classic image processing, (iii) harmonic analysis, and (iv) topological data analysis; (b) ways to use convolutional neural networks for this purpose with emphasis on discussing different convolution filters (2D/3D/LSTM-convolution); and (c) a brief survey of several other concepts, including the concept of “attention” in neural networks and its utility for the interpretation of image sequences and strategies from self-supervised and transfer learning to reduce the need for large labeled datasets. We hope that presenting an overview of these tools—many of which are not new but underutilized in this context—will accelerate progress in this area. more...

In-storage processing technology allows applications to run on embedded processors and accelerators inside solid-state drives (SSDs) for efficient computing distribution. Especially, in pattern matching applications, in-storage computing can be processed quickly due to low data access latency, and the number of I/Os can be reduced by returning only a small amount of results to the host system after processing. Previously proposed in-storage processing is separated into three phases: command decoding, data access, and data processing. In this case, data processing is strictly isolated from data access, and the isolation constraints the utilization of storage. Merging data access and data processing among the phases can enhance the utilization of storage. To efficiently merge them, we propose two-stage in-storage processing and scheduling, especially for the pattern matching application. The first stage processing during data access reduces the second stage processing latency. Also, leveraging the pattern matching results of the first stage processing, our scheduler prioritizes key requests that should return the results to the host system so that they are completed earlier than non-key requests. The proposed scheduling reduces the response time of in-storage processing requests by 52.6 % on average. more...

Complex regional pain syndrome (CRPS) is a condition associated with neuropathic pain that causes significant impairment of daily activities and functioning. Nuclear factor kappa B (NFκB) is thought to play an important role in the mechanism of CRPS. Recently, exosomes loaded with super-repressor inhibitory kappa B (Exo-srIκB, IκB; inhibitor of NFκB) have been shown to have potential anti-inflammatory effects in various inflammatory disease models. We investigated the therapeutic effect of Exo-srIκB on a rodent model with chronic post-ischemia pain (CPIP), a representative animal model of Type I CRPS. After intraperitoneal injection of a vehicle, Exo-srIκB, and pregabalin, the paw withdrawal threshold (PWT) was evaluated up to 48 h. Administration of Exo-srIκB increased PWT compared to the vehicle and pregabalin, and the relative densities of p-IκB and IκB showed significant changes compared to the vehicle 24 h after Exo-srIκB injection. The levels of several cytokines and chemokines were reduced by the administration of Exo-srIκB in mice with CPIP. In conclusion, our results showed more specifically the role of NFκB in the pathogenesis of CRPS and provided a theoretical background for novel treatment options for CRPS. more...

While multiple previous studies have proposed utilizing an ambient display for providing real-time posture feedback to seated computer workers, it is not well understood how effective ambient feedback is in supporting the users' dual task of computer work and posture monitoring/rectification. The objective of the current study was to evaluate an ambient display for real-time posture feedback in comparison with typical conditions, an on-screen display and no display condition, in terms of the dual task performance. The ambient and the on-screen display were also compared in terms of perceived detection efficiency and user acceptance measures. A total of 24 participants performed the dual task in each of the three display conditions (the ambient, on-screen and no display conditions). The dependent measures for the dual task performance were the number of typed answers and the occurrence rate of high-risk postures; and, for the subjective evaluation, two detection efficiency measures (visibility and understandability) and four user acceptance measures (performance expectancy, effort expectancy, attitude toward using technology and social influence) were employed. The study demonstrated that both the ambient and the on-screen displays enhanced the dual task performance with respect to the no-display condition and the ambient display was superior to the on-screen display in the subjective experience measures. more...

In October 1946, mathematicians and physicists founded the Korean Society of Mathematics and Physics, which was relaunched as the Korean Mathematical Society (KMS) in March 1952. This article presents the history of three journals published by the KMS. Volume 1 of the first journal, Mathematics Education, was published in 1955, but it was discontinued after publication of volume 3. After that, as the KMS was reorganized in the 1960s, it began once more to publish a journal in 1964, with the title Mathematics. Later, Mathematics was divided into the Journal of the Korean Mathematical Society and the Bulletin of the Korean Mathematical Society. A third journal, Communications of the Korean Mathematical Society, was first published in 1986. Since then, a total of three journals have been published by the KMS. We can conceive of the years before 1980 as an era focused on education, while the subsequent years have constituted a research era. In this period, mathematics in Korea achieved remarkable growth through extensive international collaboration in research and the internationalization of journals of the KMS. In particular, the Journal of the Korean Mathematical Society and Bulletin of the Korean Mathematical Society achieved being indexed in SCIE, while Communications of the Korean Mathematical Society achieved being indexed in ESCI, a stage that precedes being indexed in SCIE. The journals published by the KMS will continue to serve as a venue for outstanding research results from throughout the world to be published and contribute greatly to the international growth of Korean mathematical capabilities. more...

Abstract Background Agastache rugosa (Fisch. & C.A.Mey.) Kuntze (Korean mint) is used to treat diverse types of human disorders in traditional medicine. In recent years, its non-fermented leaf extract (ARE) has been shown to possess protective properties against ultraviolet-B (UV-B) radiation-induced photooxidative stress. The present work aimed to examine whether probiotic bacterial fermentation would potentiate the skin anti-photoaging activity of ARE or not, by comparing the protective properties of ARE and corresponding fermented extract (ARE-F) against UV-B radiation-induced photooxidative stress in HaCaT keratinocytes. Methods ARE-F was produced from ARE by the fermentation with Lactobacillus rhamnosus HK-9, a type of Gram-positive probiotic bacterial strain. Anti-photoaging activities were evaluated by analyzing reactive oxygen species (ROS), promatrix metalloproteinases (proMMPs), total glutathione (GSH) and total superoxide dismutase (SOD) in UV-B-irradiated HaCaT keratinocytes. Antiradical activity was determined using 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging assay. Results ARE-F contained higher attenuating activity on the UV-B-induced ROS generation than ARE. Similarly, ARE-F was able to diminish the UV-B-induced proMMP-9 and -2 more effectively than ARE. ARE-F displayed higher tendencies to augment the UV-B-reduced total GSH content and SOD activity than ARE. However, there were no significant difference between ARE and ARE-F in ABTS radical scavenging activities. Conclusions The findings suggest that the UV-B radiation-protective activity of ARE is enhanced by probiotic bacterial fermentation, which might improve the therapeutic and cosmetic values of A. rugosa leaves. more...

Context: Geniposide (genipin-1-O-β-d-glucoside) is a major bioactive ingredient in the fruits of gardenia [Gardenia jasminoides J. Ellis (Rubiaceae)], a traditional herbal medicine in Asian countries. Objective: This work assesses the skin anti-photoaging potential of geniposide in human dermal fibroblasts under UV-B irradiation. Materials and methods: The anti-photoaging property of geniposide, at varying concentrations (5, 12 and 30 μM) treated for 30 min prior to UV-B irradiation, was evaluated by analysing reactive oxygen species (ROS), promatrix metalloproteinase-2 (proMMP-2), glutathione (GSH), superoxide dismutase (SOD), nuclear factor erythroid 2-related factor 2 (Nrf2) and cellular viability. Results: Geniposide suppressed the ROS elevation under UV-B irradiation, which was revealed using three ROS-sensitive fluorescent dyes. The use of 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA), dihydroethidium (DHE) and dihydrorhodamine 123 (DHR-123) elicited the IC50 values of 10.5, 9.8 and 21.0 μM, respectively. Geniposide attenuated proMMP-2 at activity and protein levels that were elevated under UV-B-irradiation. Geniposide at 5, 12 and 30 μM augmented the UV-B-reduced total GSH content to 1.9 ± 0.1-, 2.2 ± 0.2- and 4.1 ± 0.2-fold, respectively. Geniposide at 5, 12 and 30 μM upregulated total SOD activity to 2.3 ± 0.1-, 2.5 ± 0.3- and 3.3 ± 0.3-fold, respectively, under UV-B irradiation. The UV-B-reduced Nrf2 levels were also upregulated by geniposide treatment. Geniposide, at the concentrations used, was unable to interfere with cellular viabilities under UV-B irradiation. Discussion and conclusions: After the skin anti-photoaging potential of geniposide may be further verified, it can be utilized as a safer resource in the manufacture of effective anti-aging cosmetics. more...

It is an important issue to search for self-orthogonal codes for construction of quantum codes by CSS construction (Calderbank-Sho-Steane codes); in quantum error correction, CSS codes are a special type of stabilizer codes constructed from classical codes with some special properties, and the CSS construction of quantum codes is a well-known construction. First, we employ hierarchical posets with two levels for construction of binary linear codes. Second, we find some necessary and sufficient conditions for these linear codes constructed using posets to be self-orthogonal, and we use these self-orthogonal codes for obtaining binary quantum codes. Finally, we obtain four infinite families of binary quantum codes for which the minimum distances are three or four by CSS construction, which include binary quantum Hamming codes with length n≥7. We also find some (almost) “optimal” quantum codes according to the current database of Grassl. Furthermore, we explicitly determine the weight distributions of these linear codes constructed using posets, and we present two infinite families of some optimal binary linear codes with respect to the Griesmer bound and a class of binary Hamming codes. more...

Toxin peptides derived from the skin secretions of amphibians possess unique hypoglycemic activities. Many of these peptides share cationic and amphipathic structural similarities and appear to possess cell-penetrating abilities. The mechanism of their insulinotropic action is yet not elucidated, but they have shown great potential in regulating the blood glucose levels in animal models. Therefore, they have emerged as potential drug candidates as therapeutics for type 2 diabetes. Despite their anti-diabetic activity, there remain pharmaceutical challenges to be addressed for their clinical applications. Here, we present an overview of recent studies related to the toxin-derived anti-diabetic peptides derived from the skin secretions of amphibians. In the latter part, we introduce the bottleneck challenges for their delivery in vivo and general drug delivery strategies that may be applicable to extend their blood circulation time. We focus our research on the strategies that have been successfully applied to improve the plasma half-life of exendin-4, a clinically available toxin-derived anti-diabetic peptide drug. more...

As a posterior ocular disease, wet age-related macular degeneration (WAMD) has been known to be related to vision loss, accompanying ocular complications. The intravitreous injection of VEGF antibodies has been reported to be an effective treatment to relieve symptoms of WAMD. However, the limitations of this treatment are high costs and invasiveness. For this reason, oral delivery route can be considered as a cost-effective way and the safest method to deliver drug molecules to the eyes. Accordingly, ursodeoxycholic acid (UDCA) was included in the oral formulation as the potential substance for the cure of WAMD in the animal model. Various pharmacological activities, such as antioxidant or anti-inflammatory effects, have been reported for UDCA and recent reports support the effects of UDCA in ocular treatment. However, due to poor water solubility and low pKa (around 5.0), it has been challenging to formulate aqueous solution of UDCA in the neutral pH range. In the present study, we confirmed the aqueous solubility of the oral UDCA formulation and performed a preclinical study, including pharmacokinetic profiling and WAMD model efficacy study in mice after oral administration of the drug solution. The results demonstrated that the formulation improved bioavailability of UDCA and efficiently delivered UDCA to the eye tissues after oral absorption. UDCA formulation was found to have inhibitory effects of choroidal neovascularization with a functional recovery in mice retinas. Taken together, our results suggest that the oral UDCA formulation could be used as a potent supplement for the cure of WAMD and related retinal diseases. more...