Hippocampal glucose uptake as a surrogate of metabolic change of microglia in Alzheimers disease

Abstract Background Dynamically altered microglia play an important role in the progression of Alzheimers disease (AD). Here, we found a close association of the metabolic reconfiguration of microglia with increased hippocampal glucose uptake on [18F]fluorodeoxyglucose (FDG) PET. Methods We used an AD animal model, 5xFAD, to analyze hippocampal glucose metabolism using both animal FDG PET and ex vivo FDG uptake test. Cells of the hippocampus were isolated to perform single-cell RNA-sequencing (scRNA-seq). The molecular features of cells associated with glucose metabolism were analyzed at a single-cell level. In order to apply our findings to human brain imaging study, brain FDG PET data obtained from the Alzheimers Disease Neuroimaging Initiative were analyzed. FDG uptake in the hippocampus was compared according to the diagnosis, AD, mild cognitive impairment, and controls. The correlation analysis between hippocampal FDG uptake and soluble TREM2 in cerebrospinal fluid was performed. Results In the animal study, 8- and 12-month-old 5xFAD mice showed higher FDG uptake in the hippocampus than wild-type mice. Cellular FDG uptake tests showed that FDG activity in hippocampal microglia was increased in the AD model, while FDG activity in non-microglial cells of the hippocampus was not different between the AD model and wild-type. scRNA-seq data showed that changes in glucose metabolism signatures including glucose transporters, glycolysis and oxidative phosphorylation, mainly occurred in microglia. A subset of microglia with higher glucose transporters with defective glycolysis and oxidative phosphorylation was increased according to disease progression. In the human imaging study, we found a positive association between soluble TREM2 and hippocampal FDG uptake. FDG uptake in the hippocampus at the baseline scan predicted mild cognitive impairment conversion to AD. Conclusions We identified the reconfiguration of microglial glucose metabolism in the hippocampus of AD, which could be evaluated by FDG PET as a feasible surrogate imaging biomarker for microglia-mediated inflammation

c-Jun N-terminal kinase activation has a prognostic implication and is negatively associated with FOXO1 activation in gastric cancer

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Abstract Background Since the biological function of c-Jun N-terminal kinase (JNK) in gastric cancer remains unclear, we investigated the clinical significance of JNK activation and its association with FOXO1 activation. Methods Immunohistochemical tissue array analysis of 483 human gastric cancer specimens was performed, and the results of the immunostaining were quantified. The correlation between JNK activation (nuclear staining for pJNK) and clinicopathological features, the proliferation index, prognosis or FOXO1 inactivation (cytoplasmic staining for pFOXO1) was analyzed. The SNU-638 gastric cancer cell line was used for in vitro analysis. Results Nuclear staining of pJNK was found in 38 % of the gastric carcinomas and was higher in the early stages of pTNM (P < 0.001). pJNK staining negatively correlated with lymphatic invasion (P = 0.034) and positively correlated with intestinal type by Laurens classification (P = 0.037), Ki-67-labeling index (P < 0.001), cyclin D1 (P = 0.045), cyclin E (P < 0.001) and pFOXO1 (P < 0.001). JNK activation correlated with a longer patients survival (P =0.008) and patients with a JNK-active and FOXO1-inactive tumor had a higher survival rate than the remainder of the population (P = 0.004). In vitro analysis showed that JNK inhibition by SP600125 in SNU-638 cells decreased cyclin D1 protein expression and increased FOXO1 activation. Further, JNK inhibition markedly suppressed colony formation, which was partially restored by FOXO1 shRNA expression. Conclusions Our results indicate that JNK activation may serve as a valuable prognostic factor in gastric cancer, and that it is implicated in gastric tumorigenesis, at least in part, through FOXO1 inhibition

Effects of a safflower tea supplement on antioxidative status and bone markers in postmenopausal women

We conducted this study to examine the effects of safflower seed granular tea containing physiologically active polyphenols on antioxidative activities and bone metabolism. Forty postmenopausal women ages 49 to 64-years were recruited from Daegu and Gyeongbuk and were randomly assigned to either a safflower tea supplement (Saf-tea) group (n = 27) or a placebo group (n = 13). The Saf-tea group received 20 g of safflower seed granule tea per day containing a 13% ethanol extract of defatted safflower seeds, whereas the placebo group received a similar type of tea that lacked the ethanol extract. No significant changes in nutrient intake for either the placebo or Saf-tea groups were observed before or after the study period, except vitamin A intake increased after 6 months in the Saf-tea group. Dietary phytoestrogen intakes were similar in the Saf-tea group (60.3 mg) and placebo group (52.5 mg). Significant increases in plasma genistein and enterolactone were observed in the Saf-tea group. After 6 months of supplementation, serum levels of antioxidant vitamins such as α-tocopherol and ascorbic acid increased significantly, and TBARS levels decreased in the Saf-tea group compared to the placebo group. Serum osteocalcin levels were reduced (P < 0.05) in the Saf-tea group after 6 months, whereas serum osteocalcin did not change in the placebo group. Urinary deoxypyridinoline/creatinine excretion was not different between the two groups at baseline, and did not change in either group after 6 months. Bone mineral density decreased significantly in the placebo group (P < 0.01) but not in the supplemented group. It was concluded that polyphenols (72 mg/day), including serotonin derivatives, in the Saf-tea had both antioxidant and potential bone protecting effects in postmenopausal women without liver toxicity

A Comparability Study of Two Standardized English as a Foreign Language Tests

This study investigates the degree of comparability between TEPS and TOEIC regarding test content and construct considering that these elements are important since they are frequently utilized as official English tests in Korea. The New TEPS, an updated version of the original TEPS that reflects the needs analysis, and TOEIC, which was revised in 2016, were analyzed based on the following theoretical frameworks that focus on language elements. This study systematically analyzed test attributes based on: 1) Test Task Characteristics (type, length, speed, etc.) of each test section and item distribution based on the type and content category, 2) Various corpus indices of the test content, and 3) Test Usefulness (construct validity, authenticity, and interactiveness), comparing the overall test comparability between the New TEPS and TOEIC. Results indicate that although the tests objectives and development foundations differ, there were similarities in content and construct. Nevertheless, a handful of discrepancies were also identified, necessitating the thorough examination of the tests compatibility when interpreting test results. In addition, based on the theoretical framework of Test Usefulness, the strengths and weaknesses of each tests content and construct were examined. This study also postulates a suitable direction to develop a valid communicative proficiency test

Greenhouse Gas Emissions from Incineration of Municipal Solid Waste in Seoul, South Korea

Greenhouse gas (GHG) emissions from the incineration of municipal solid waste (MSW) have become a concern in the solid waste community from the perspective of climate change mitigation and response. In this study, we aimed to estimate the GHG emissions from the incineration of MSW in Seoul, with a population of about 10 million, by using the IPCC (Intergovernmental Panel on Climate Change) 2006 guideline and scenario analysis for 2030 and 2040. In 2021, Seoul generated 2899 kt of MSW/yr. Approximately 40% (1163 kt/yr) of Seoul’s MSW was disposable (or non-recyclable) waste. Out of the disposable waste, about 741 kt/yr of combustible waste was treated by incineration, resulting in 545 kt CO2 eq emissions, which was about 7.5 times higher than the 74 kt CO2 eq in 2000. The dominant contributor to the GHG emissions was plastic waste, accounting for the largest fraction of 92% (501 kt CO2 eq/yr in 2021). Scenario analysis showed that if the current situation (BAU scenario) is considered, with the assumption of no reduction in MSW generation, the capacity of Seoul’s four incineration facilities will be exceeded in 2029. All other scenarios (S1, S2, and S3) showed reduced amounts of MSW incineration and GHG emissions compared to the BAU scenario. Especially, S3 (waste reduction and increased recycling rate) revealed a 53% reduction when compared to the BAU scenario. Based on the results of our scenario analysis, it is expected that in 2040, the GHG emissions from incineration will be in a range of from about 389 kt CO2 eq to 832 kt CO2 eq, depending on the waste minimization policy and recycling efforts in the future. Strengthened regulations on and efforts towards plastic waste reduction and the recycling of MSW will be crucial with the perspectives of GHG emissions by incineration and resource recovery

Association of the Vitamin D Level and Quality of School Life in Adolescents with Irritable Bowel Syndrome

There is no treatment of choice for irritable bowel syndrome, which affects up to 20% of school-aged children. This cross-sectional study evaluated the difference in the average vitamin D level between subtypes of irritable bowel syndrome, and the relationship between the vitamin D level as well as the severity of irritable bowel syndrome symptoms. We included 124 adolescents aged 10&#8315;17 years (68 boys, 56 girls; mean age 12.29 &#177; 1.92 years) from 2014 to 2016. Patients with irritable bowel syndrome were diagnosed by Rome III criteria and classified by clinical manifestation: irritable bowel syndrome with constipation (n = 29), irritable bowel syndrome with diarrhea (n = 63), and irritable bowel syndrome with constipation and diarrhea (n = 32). The severity of irritable bowel syndrome symptoms and school absence were evaluated. Vitamin D levels were measured by serum 25-hydroxyvitamin D. The chi-square test and analysis of variance were used. The patients&#8217; average vitamin D level was 16.25 &#177; 6.58 ng/mL. There was a significant negative association of the 25-hydroxyvitamin D level with symptom severity and school absence (p = 0.022 and p &lt; 0.001, respectively). Vitamin D supplementation could be considered as a choice of therapeutic method

Classification of Research Papers on Radio Frequency Electromagnetic Field (RF-EMF) Using Graph Neural Networks (GNN)

This study compares the performance of graph convolutional neural network (GCN) models with conventional natural language processing (NLP) models for classifying scientific literature related to radio frequency electromagnetic field (RF-EMF). Specifically, the study examines two GCN models: BertGCN and the citation-based GCN. The study concludes that the model achieves consistently good performance when the input text is long enough, based on the attention mechanism of BERT. When the input sequence is short, the composition parameter λ, which combines output values of the two subnetworks of BertGCN, plays a crucial role in achieving high classification accuracy. As the value of λ increases, the classification accuracy also increases. The study also proposes and tests a simplified variant of BertGCN, revealing performance differences among the models under two different data conditions by the existence of keywords. This study has two main contributions: (1) the implementation and testing of a variant of BertGCN and citation-based GCN for document classification tasks related to radio frequency electromagnetic fields publications, and (2) the confirmation of the impact of model conditions, such as the existence of keywords and input sequence length, in the original BertGCN. Although this study focused on a specific domain, our approaches have broader implications that extend beyond scientific publications to general text classification