the incidence of dementia, a clinical symptom characterized by severe cognitive decline, is increasing worldwide. Predictive biomarkers are therefore required for early identification and management. D-amino acids in the brain contribute to cognitive function and are suggested as useful biomarkers for diagnosing dementia risk. to clarify their relationship with human cognitive decline, we developed an identification method of chiral metabolomics for detecting slight differences in chiral amino acid amounts. chiral tandem liquid chromatography-tandem mass spectrometry systems were applied for sensitive and selective amino acid species along with chiral species determination based on anion and zwitterion exchange mechanisms. in a comprehensive health cohort (cross-sectional study), we measured blood chiral amino acid levels from 305 women (65-80 years old) classified into Control, Mild-cognitive-impairment (Mci), and Dementia groups using the Mini-Mental State examination. Mci exhibited higher D-pro (D-pro/(D-pro + L-pro)) proportion vs the control group, suggesting this proportion as a useful biomarker for Mci. Biomarker accuracy was improved in combination with D-Ser proportion. Receiver operating characteristics analysis of the control vs. Mci proportion obtained area under the curve (0.80) with 70% sensitivity and 84% specificity at the optimal cutoff value (0.30). Thus, dementia monitoring can be improved by including trace D-amino acids measurements. Dementia is a clinical symptom indicating a type of cognitive dysfunction that, when severe, leads to increasing dependence on others in aspects of daily living. Various types of dementia include Alzheimer (AD), cerebrovascular, Lewy body, and frontotemporal dementia. The detailed cause of onset has not yet been elucidated and no effective biomarkers are available for the early diagnosis of dementia or selection of therapeutic agents 1. The prodromal stage of dementia and mild cognitive impairment (MCI) have attracted attention in recent years as early stages of cognitive decline. It has been reported that approximately 10% of MCI converts to AD annually 2. Moreover, 14-44% of patients with MCI improve to the status of healthy elderly individuals through early interventions 3. Therefore, the early diagnosis of dementia risk and timely interventions, such as nutrition, exercise, and sleep, are desired to prevent cognitive decline in the at-risk elderly population. Current methods of diagnosis require a wide range of clinical tests including cognitive performance assessment, genetic screening, measurement of amyloid beta and tau proteins in the liquor cerebrosinalis, brain imaging, and behavioural assessments 4. Especially in recent years, numerous researchers have aimed to identify appropriate markers measurable in the blood for the early identification and management of dementia. For example, quantitative measurements of amyloid beta and its sequester protein in the blood have been developed 5-9. However, these biomarkers are difficult to apply toward practical d...

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Blocking characteristics of 2.2 kV and 3.3 kV -class 4H-SiC MOSFETs with various doping conditions for the edge termination region have been investigated. By optimizing the implanted dose into the edge termination structure consisting of junction termination extension (JTE) and field limiting ring (FLR), a breakdown voltage of 3,850 V for 3.3 kV -class MOSFET has been attained. This result corresponds to about 95% of the approximate parallel-plane breakdown voltage estimated from the doping concentration and the thickness of the epitaxial layer. Implanted doping for the JFET region is effective in reducing JFET resistance, resulting in the specific on-resistance of 14.2 mΩcm2 for 3.3 kV SiC MOSFETs. Switching characteristics at the high drain voltage of 2.0 kV are also discussed.

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