A Synonymous Genetic Alteration of LMX1B in a Family with Nail-Patella Syndrome

The gene responsible for nail-patella syndrome, LMX1B, has recently been identified on chromosome 9q. Here we present a patient with nail-patella syndrome and an autosomal dominant pattern of inheritance. A 17-year-old girl visited our clinic for the evaluation and treatment of proteinuria. She had dystrophic nails, palpable iliac horns, and hypoplastic patellae. Electron microscopy of a renal biopsy showed irregular thickening of the glomerular basement membrane. A family history over three generations revealed five affected family members. Genetic analysis found a change of TCG to TCC, resulting in a synonymous alteration at codon 219 in exon 4 of the LMX1B gene in two affected family members. The same alteration was not detected in an unaffected family member. This is the first report of familial nail-patella syndrome associated with an LMX1B in Korea mutation, However, we can not completely rule out the possibility that the G-to-C change may be a single nucleotide polymorphism as this genetic mutation cause no alteration in amino acid sequence of LMX1B

Pyruvate Dehydrogenase Kinase Is a Metabolic Checkpoint for Polarization of Macrophages to the M1 Phenotype

Metabolic reprogramming during macrophage polarization supports the effector functions of these cells in health and disease. Here, we demonstrate that pyruvate dehydrogenase kinase (PDK), which inhibits the pyruvate dehydrogenase-mediated conversion of cytosolic pyruvate to mitochondrial acetyl-CoA, functions as a metabolic checkpoint in M1 macrophages. Polarization was not prevented by PDK2 or PDK4 deletion but was fully prevented by the combined deletion of PDK2 and PDK4; this lack of polarization was correlated with improved mitochondrial respiration and rewiring of metabolic breaks that are characterized by increased glycolytic intermediates and reduced metabolites in the TCA cycle. Genetic deletion or pharmacological inhibition of PDK2/4 prevents polarization of macrophages to the M1 phenotype in response to inflammatory stimuli (lipopolysaccharide plus IFN-γ). Transplantation of PDK2/4-deficient bone marrow into irradiated wild-type mice to produce mice with PDK2/4-deficient myeloid cells prevented M1 polarization, reduced obesity-associated insulin resistance, and ameliorated adipose tissue inflammation. A novel, pharmacological PDK inhibitor, KPLH1130, improved high-fat diet-induced insulin resistance; this was correlated with a reduction in the levels of pro-inflammatory markers and improved mitochondrial function. These studies identify PDK2/4 as a metabolic checkpoint for M1 phenotype polarization of macrophages, which could potentially be exploited as a novel therapeutic target for obesity-associated metabolic disorders and other inflammatory conditions

Effects of d-α-tocopherol supplements on lipid metabolism in a high-fat diet-fed animal model.

High-fat diet up-regulates either insulin resistance or triglycerides, which is assumed to be related to the expression of peroxisome proliferator-activated receptor (PPAR)-α and PPAR-γ. The beneficial effects of vitamin E on insulin resistance are well known; however, it is not clear if vitamin E with a high-fat diet alters the expression of PPAR-α and PPAR-γ. We investigated the effects of d-α-tocopherol supplementation on insulin sensitivity, blood lipid profiles, lipid peroxidation, and the expression of PPAR-α and PPAR-γ in a high-fat (HF) diet-fed male C57BL/6J model of insulin resistance. The animals were given a regular diet (CON; 10% fat), a HF diet containing 45% fat, or a HF diet plus d-α-tocopherol (HF-E) for a period of 20 weeks. The results showed that the HF diet induced insulin resistance and altered the lipid profile, specifically the triglyceride (TG) and total cholesterol (TC) levels (P < 0.05). In this animal model, supplementation with d-α-tocopherol improved insulin resistance as well as the serum levels of TG and very-low-density lipoprotein-cholesterol (VLDL-C) (P < 0.05). Moreover, the treatment decreased the levels of malondialdehyde (MDA) in the serum and liver while increasing hepatic PPAR-α expression and decreasing PPAR-γ expression. In conclusion, the oral administration of d-α-tocopherol with a high-fat diet had positive effects on insulin resistance, lipid profiles, and oxidative stress through the expression of PPAR-α and PPAR-γ in a high-fat diet-fed male mice

Effects of d-α-tocopherol supplements on lipid metabolism in a high-fat diet-fed animal model.

High-fat diet up-regulates either insulin resistance or triglycerides, which is assumed to be related to the expression of peroxisome proliferator-activated receptor (PPAR)-α and PPAR-γ. The beneficial effects of vitamin E on insulin resistance are well known; however, it is not clear if vitamin E with a high-fat diet alters the expression of PPAR-α and PPAR-γ. We investigated the effects of d-α-tocopherol supplementation on insulin sensitivity, blood lipid profiles, lipid peroxidation, and the expression of PPAR-α and PPAR-γ in a high-fat (HF) diet-fed male C57BL/6J model of insulin resistance. The animals were given a regular diet (CON; 10% fat), a HF diet containing 45% fat, or a HF diet plus d-α-tocopherol (HF-E) for a period of 20 weeks. The results showed that the HF diet induced insulin resistance and altered the lipid profile, specifically the triglyceride (TG) and total cholesterol (TC) levels (P < 0.05). In this animal model, supplementation with d-α-tocopherol improved insulin resistance as well as the serum levels of TG and very-low-density lipoprotein-cholesterol (VLDL-C) (P < 0.05). Moreover, the treatment decreased the levels of malondialdehyde (MDA) in the serum and liver while increasing hepatic PPAR-α expression and decreasing PPAR-γ expression. In conclusion, the oral administration of d-α-tocopherol with a high-fat diet had positive effects on insulin resistance, lipid profiles, and oxidative stress through the expression of PPAR-α and PPAR-γ in a high-fat diet-fed male mice

The Development of Regional Vessel Traffic Congestion Forecasts Using Hybrid Data from an Automatic Identification System and a Port Management Information System

The present study proposes a new method that forecasts congestion in the area near a port by combining the automatic identification systems of ships and port management information data. The proposed method achieves 85% accuracy for one-day-long ship congestion forecasts. This accuracy level is high enough to act as a reference value for both manned and unmanned operation situations for autonomous vessels in port areas. The proposed forecast algorithm achieves 95% accuracy when used for a one-hour ship congestion forecast. However, the accuracy of the algorithm is degraded to almost half when the automatic identification system or the port management system is used independently

Enhancing Container Vessel Arrival Time Prediction through Past Voyage Route Modeling: A Case Study of Busan New Port

Container terminals are at the center of global logistics, and are highly dependent on the schedule of vessels arriving. Conventional ETA records from ships, utilized for terminal berth planning, lack sufficient accuracy for effective plan implementation. Thus, there is a pressing need for improved ETA prediction methods. In this research, we propose a novel approach that leverages past voyage route patterns to predict the ETA of container vessels arriving at a container terminal at Busan New Port, South Korea. By modeling representative paths based on previous ports of call, the method employs real-time position and speed data from the Automatic Identification System (AIS) to predict vessel arrival times. By inputting AIS data into segmented representative routes, optimal parameters yielding minimal ETA errors for each vessel are determined. The algorithm’s performance evaluation during the modeling period demonstrates its effectiveness, achieving an average Mean Absolute Error (MAE) of approximately 3 h and 14 min. These results surpass the accuracy of existing ETA data, such as ETA in the Terminal Operating System and ETA in the AIS of a vessel, indicating the algorithm’s superiority in ETA estimation. Furthermore, the algorithm consistently outperforms the existing ETA benchmarks during the evaluation period, confirming its enhanced accuracy

Political Ideologies, Government Trust, and COVID-19 Vaccine Hesitancy in South Korea: A Cross-Sectional Survey

This study aimed to assess the correlation between political ideologies, government trust, and COVID-19 vaccine hesitancy in South Korea during the COVID-19 pandemic. A cross-sectional survey was conducted among South Korea’s general population and 1000 respondents (aged 18 years and older) were included. We used multivariate logistic regression models to identify the factors associated with vaccine hesitancy. Respondents who self-identified as liberal or held “no political opinion” had higher rates of vaccine hesitancy than conservative respondents. People’s trust in the government’s countermeasures was associated with vaccination. Respondents who had risk perceptions (affective and cognitive) of COVID-19 had lower rates of vaccine hesitancy. Perceptions that the vaccine was not safe and being aged 18–29, 30–39, or 40–49 were associated with a higher probability of vaccine hesitancy. This study found that even if vaccine safety and risk perceptions toward COVID-19 were adjusted, self-rated political ideologies and government trust was associated with COVID-19 vaccine hesitancy. More effort to communicate with those who are *liberal or “no political opinion”, younger, and have lower level of trust in the government are required to dissolve vaccine hesitancy. Further studies should analyze the mechanism of COVID-19 vaccine uptake for effective herd immunity

HVC1 ameliorates hyperlipidemia and inflammation in LDLR−/− mice

Abstract Background HVC1 consists of Coptidis Rhizoma (dried rhizome of Coptischinensis), Scutellariae Radix (root of Scutellariabaicalensis), Rhei Rhizoma (rhizome of Rheum officinale), and Pruni Cortex (cortex of Prunusyedoensis Matsum). Although the components are known to be effective in various conditions such as inflammation, hypertension, and hypercholesterolemia, there are no reports of the molecular mechanism of its hypolipidemic effects. Methods We investigated the hypolipidemic effect of HVC1 in low-density lipoprotein receptor-deficient (LDLR−/−) mice fed a high-cholesterol diet for 13 weeks. Mice were randomized in to 6 groups: ND (normal diet) group, HCD (high-cholesterol diet) group, and treatment groups fed HCD and treated with simvastatin (10 mg/kg, p.o.) or HVC1 (10, 50, or 250 mg/kg, p.o.). Results HVC1 regulated the levels of total cholesterol, triglyceride (TG), low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol in mouse serum. In addition, it regulated the transcription level of the peroxisome proliferator-activated receptors (PPARs), sterol regulatory element-binding proteins (SREBP)-2, 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase, lipoprotein lipase (LPL), apolipoprotein B (apo B), liver X receptor (LXR), and inflammatory cytokines (IL-1β, IL-6, and TNF-α). Furthermore, HVC1 activated 5′ adenosine monophosphate-activated protein kinase (AMPK). Conclusion Our results suggest that HVC1 might be effective in preventing high-cholesterol diet-induced hyperlipidemia by regulating the genes involved in cholesterol and lipid metabolism, and inflammatory responses

Astaxanthin Ameliorates Lipopolysaccharide-Induced Neuroinflammation, Oxidative Stress and Memory Dysfunction through Inactivation of the Signal Transducer and Activator of Transcription 3 Pathway

Astaxanthin (AXT), a xanthophyll carotenoid compound, has potent antioxidant, anti-inflammatory and neuroprotective properties. Neuroinflammation and oxidative stress are significant in the pathogenesis and development of Alzheimer’s disease (AD). Here, we studied whether AXT could alleviate neuroinflammation, oxidative stress and memory loss in lipopolysaccharide (LPS) administered mice model. Additionally, we investigated the anti-oxidant activity and the anti-neuroinflammatory response of AXT in LPS-treated BV-2 microglial cells. The AXT administration ameliorated LPS-induced memory loss. This effect was associated with the reduction of LPS-induced expression of inflammatory proteins, as well as the production of reactive oxygen species (ROS), nitric oxide (NO), cytokines and chemokines both in vivo and in vitro. AXT also reduced LPS-induced β-secretase and Aβ1⁻42 generation through the down-regulation of amyloidogenic proteins both in vivo and in vitro. Furthermore, AXT suppressed the DNA binding activities of the signal transducer and activator of transcription 3 (STAT3). We found that AXT directly bound to the DNA- binding domain (DBD) and linker domain (LD) domains of STAT3 using docking studies. The oxidative stress and inflammatory responses were not downregulated in BV-2 cells transfected with DBD-null STAT3 and LD-null STAT3. These results indicated AXT inhibits LPS-induced oxidant activity, neuroinflammatory response and amyloidogenesis via the blocking of STAT3 activity through direct binding