Comparative Phylogenetic Analysis of Ancient Korean Tea "Hadong Cheon-Nyeon Cha (Camellia sinensis var. sinensis)" Using Complete Chloroplast Genome Sequences.

Wild teas are valuable genetic resources for studying evolution and breeding. Here, we report the complete chloroplast genome of the ancient Korean tea 'Hadong Cheon-nyeon Cha' (C. sinensis var. sinensis), which is known as the oldest tea tree in Korea. This study determined seven Camellia sinensis var. sinenesis, including Hadong Cheon-nyeon Cha (HCNC) chloroplast genome sequences, using Illumina sequencing technology via de novo assembly. The chloroplast genome sizes ranged from 157,019 to 157,114 bp and were organized into quadripartite regions with the typical chloroplast genomes. Further, differences in SNPs and InDels were detected across the seven chloroplast genomes through variance analysis. Principal component and phylogenetic analysis suggested that regional constraints, rather than functional constraints, strongly affected the sequence evolution of the cp genomes in this study. These genomic resources provide evolutionary insight into Korean tea plant cultivars and lay the foundation for a better understanding of the ancient Korean tea plant HCNC.

Artificial Intelligence-Based Anomaly Detection Technology over Encrypted Traffic: A Systematic Literature Review.

As cyber-attacks increase in unencrypted communication environments such as the traditional Internet, protected communication channels based on cryptographic protocols, such as transport layer security (TLS), have been introduced to the Internet. Accordingly, attackers have been carrying out cyber-attacks by hiding themselves in protected communication channels. However, the nature of channels protected by cryptographic protocols makes it difficult to distinguish between normal and malicious network traffic behaviors. This means that traditional anomaly detection models with features from packets extracted a deep packet inspection (DPI) have been neutralized. Recently, studies on anomaly detection using artificial intelligence (AI) and statistical characteristics of traffic have been proposed as an alternative. In this review, we provide a systematic review for AI-based anomaly detection techniques over encrypted traffic. We set several research questions on the review topic and collected research according to eligibility criteria. Through the screening process and quality assessment, 30 research articles were selected with high suitability to be included in the review from the collected literature. We reviewed the selected research in terms of dataset, feature extraction, feature selection, preprocessing, anomaly detection algorithm, and performance indicators. As a result of the literature review, it was confirmed that various techniques used for AI-based anomaly detection over encrypted traffic were used. Some techniques are similar to those used for AI-based anomaly detection over unencrypted traffic, but some technologies are different from those used for unencrypted traffic.

Dextran sodium sulfate (DSS)-induced colitis is alleviated in mice after administration of flavone-derived NRF2-activating molecules.

Inflammatory Bowel Disease (IBD) is a chronic and relapsing inflammatory condition characterized by severe symptoms such as diarrhea, fatigue, and weight loss. Growing evidence underscores the direct involvement of the nuclear factor-erythroid 2-related factor 2 (NRF2) in the development and progression of IBD, along with its associated complications, including colorectal cancer. The NRF2 pathway plays a crucial role in cellular responses to oxidative stress, and dysregulation of this pathway has been implicated in IBD. Flavones, a significant subclass of flavonoids, have shown pharmacological impacts in various diseases including IBD, through the NRF2 signaling pathway. In this study, we conducted a screening of compounds with a flavone structure and identified NJK15003 as a promising NRF2 activator. NJK15003 demonstrated potent NRF2 activation, as evidenced by the upregulation of downstream proteins, promoter activation, and NRF2 nuclear translocation in IBD cellular models. Treatment with NJK15003 effectively restored the protein levels of tight junctions in cells treated with dextran sodium sulfate (DSS) and in DSS-treated mice, suggesting its potential to protect cells from barrier integrity disruption in IBD. In DSS-treated mice, the administration of NJK15003 resulted in the prevention of body weight loss, a reduction in colon length shortening, and a decrease in the disease activity index. Furthermore, NJK15003 treatment substantially alleviated inflammatory responses and apoptotic cell death in the colon of DSS-treated mice. Taken together, this study proposes the potential utility of NRF2-activating flavone compounds, exemplified by NJK15003, for the treatment of IBD.

Survivin enhances hippocampal neurogenesis and cognitive function in Alzheimer's disease mouse model.

AIMS: Cognitive impairment is associated with reduced hippocampal neurogenesis; however, the causes of decreased hippocampal neurogenesis remain highly controversial. Here, we investigated the role of survivin in the modulation of hippocampal neurogenesis in AD. METHODS: To investigate the effect of survivin on neurogenesis in neural stem cells (NSCs), we treated mouse embryonic NSCs with a survivin inhibitor (YM155) and adeno-associated viral survivin (AAV-Survivin). To explore the potential role of survivin expression in AD, AAV9-Survivin or AAV9-GFP were injected into the dentate gyrus (DG) of hippocampus of 7-month-old wild-type and 5XFAD mice. Cognitive function was measured by the Y maze and Morris water maze. Neurogenesis was investigated by BrdU staining, immature, and mature neuron markers. RESULTS: Our results indicate that suppression of survivin expression resulted in decreased neurogenesis. Conversely, overexpression of survivin using AAV-Survivin restored neurogenesis in NSCs that had been suppressed by YM155 treatment. Furthermore, the expression level of survivin decreased in the 9-month-old 5XFAD compared with that in wild-type mice. AAV-Survivin-mediated overexpression of survivin in the DG in 5XFAD mice enhanced neurogenesis and cognitive function. CONCLUSION: Hippocampal neurogenesis can be enhanced by survivin overexpression, suggesting that survivin could serve as a promising therapeutic target for the treatment of AD.

Generating ICS Anomaly Data Reflecting Cyber-Attack Based on Systematic Sampling and Linear Regression.

Cyber threats to industrial control systems (ICSs) have increased as information and communications technology (ICT) has been incorporated. In response to these cyber threats, we are implementing a range of security equipment and specialized training programs. Anomaly data stemming from cyber-attacks are crucial for effectively testing security equipment and conducting cyber training exercises. However, securing anomaly data in an ICS environment requires a lot of effort. For this reason, we propose a method for generating anomaly data that reflects cyber-attack characteristics. This method uses systematic sampling and linear regression models in an ICS environment to generate anomaly data reflecting cyber-attack characteristics based on benign data. The method uses statistical analysis to identify features indicative of cyber-attack characteristics and alters their values from benign data through systematic sampling. The transformed data are then used to train a linear regression model. The linear regression model can predict features because it has learned the linear relationships between data features. This experiment used ICS_PCAPS data generated based on Modbus, frequently used in ICS. In this experiment, more than 50,000 new anomaly data pieces were generated. As a result of using some of the new anomaly data generated as training data for the existing model, no significant performance degradation occurred. Additionally, comparing some of the new anomaly data with the original benign and attack data using kernel density estimation confirmed that the new anomaly data pattern was changing from benign data to attack data. In this way, anomaly data that partially reflect the pattern of the attack data were created. The proposed method generates anomaly data like cyber-attack data quickly and logically, free from the constraints of cost, time, and original cyber-attack data required in existing research.

Inhibition of microfold cells ameliorates early pathological phenotypes by modulating microglial functions in Alzheimer's disease mouse model.

BACKGROUND: The gut microbiota has recently attracted attention as a pathogenic factor in Alzheimer's disease (AD). Microfold (M) cells, which play a crucial role in the gut immune response against external antigens, are also exploited for the entry of pathogenic bacteria and proteins into the body. However, whether changes in M cells can affect the gut environments and consequently change brain pathologies in AD remains unknown. METHODS: Five familial AD (5xFAD) and 5xFAD-derived fecal microbiota transplanted (5xFAD-FMT) naïve mice were used to investigate the changes of M cells in the AD environment. Next, to establish the effect of M cell depletion on AD environments, 5xFAD mice and Spib knockout mice were bred, and behavioral and histological analyses were performed when M cell-depleted 5xFAD mice were six or nine months of age. RESULTS: In this study, we found that M cell numbers were increased in the colons of 5xFAD and 5xFAD-FMT mice compared to those of wild-type (WT) and WT-FMT mice. Moreover, the level of total bacteria infiltrating the colons increased in the AD-mimicked mice. The levels of M cell-related genes and that of infiltrating bacteria showed a significant correlation. The genetic inhibition of M cells (Spib knockout) in 5xFAD mice changed the composition of the gut microbiota, along with decreasing proinflammatory cytokine levels in the colons. M cell depletion ameliorated AD symptoms including amyloid-ß accumulation, microglial dysfunction, neuroinflammation, and memory impairment. Similarly, 5xFAD-FMT did not induce AD-like pathologies, such as memory impairment and excessive neuroinflammation in Spib-/- mice. CONCLUSION: Therefore, our findings provide evidence that the inhibiting M cells can prevent AD progression, with therapeutic implications.

Eugenol relieves the pathological manifestations of Alzheimer's disease in 5×FAD mice.

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by the accumulation of amyloid-ß (Aß) and excessive neuroinflammation, resulting in neuronal cell death and cognitive impairments. Eugenol, a phenylpropene, is the main component of Syzygium aromaticum L. (Myrtaceae) and has multiple therapeutic effects, including neuroprotective and anti-inflammatory effects, through multimodal mechanisms. PURPOSE: We aimed to investigate the effect of eugenol on AD pathologies using a 5× familiar AD (5×FAD) mouse model. METHODS: Eight-month-old 5×FAD and wild-type mice were administered with eugenol (10 or 30 mg/kg/day, p.o) for 2 months. Y-maze and Morris water maze tests were performed to assess the cognitive function of mice. After the behavioral test, molecular analysis was conducted to investigate the therapeutic mechanism of eugenol. RESULTS: Our findings indicate that eugenol treatment effectively mitigated cognitive impairments in 5×FAD mice. This beneficial effect was associated with a decrease in AD pathologies, including neuronal cell loss and Aß deposition. Specifically, eugenol inhibited necroptosis activation and increased microglial phagocytosis, which were the underlying mechanisms for the observed reductions in neuronal cell loss and Aß deposition, respectively. CONCLUSION: Overall, our data suggest that eugenol would be a potential therapeutic candidate for AD.

Bidirectional association between Parkinson's disease and obstructive sleep apnea: a cohort study.

STUDY OBJECTIVES: Chronic intermittent hypoxia due to obstructive sleep apnea (OSA) causes oxidative stress, which may contribute to the pathophysiology of Parkinson's disease (PD). However, the bidirectional relationship between PD and OSA has not been satisfactorily established. The objective of this study was to try to estimate whether there is a bidirectional relationship between PD and OSA through a retrospective cohort study in the South Korean population. METHODS: This study used data from the Korean National Health Information Database of the National Health Insurance Service, which contains data from 3.5 million individuals evenly distributed. In study 1, patients with OSA were matched in a 1:2 ratio with non-OSA controls. In study 2, patients with PD were matched in a 1:2 ratio with non-PD controls. A stratified Cox proportional hazards model was used to calculate hazard ratios. RESULTS: In study 1, which included 6,396 patients with OSA and 12,792 non-OSA controls, the incidence of PD per 10,000 person-years was 11.59 in the OSA group and 8.46 in the non-OSA group. The OSA group demonstrated a 1.54-fold higher incidence of PD than the non-OSA group (95% confidence interval, 1.14-2.07; P < .05). In study 2, which included 3,427 patients with PD and 6,854 non-PD controls, the incidence of OSA per 10,000 person-years was 14.97 in the PD group and 7.72 in the non-PD group. The PD group demonstrated a 1.92-fold higher incidence of OSA than the non-PD group (95% confidence interval, 1.32-2.78; P < .05). CONCLUSIONS: This study supports a possible bidirectional relationship between PD and OSA. CITATION: Jeon S-H, Hwang YS, Oh S-Y, et al. Bidirectional association between Parkinson's disease and obstructive sleep apnea: a cohort study. J Clin Sleep Med. 2023;19(9):1615-1623.

Measurement Issue in Antecollis.

Background: Antecollis is defined as an involuntary forward flexion of the neck. Previous reports have measured the neck flexion angles based on the line perpendicular to the ground. This led to an inflation of the neck flexion angles in patients who had combined forward truncal flexions, especially upper camptocormia. Methods: We examined the neck flexion angles and the upper camptocormia angle in the published photographs of antecollis. MEDLINE search was conducted using the following search terms: antecollis OR anterocollis. Lateral-view photographs of patients diagnosed with antecollis were collected. Neck flexion angles were measured with the classic 'perpendicular method' and the 'antecollis method' we developed. Results: Nine patient photographs were identified. While antecollis was the only described postural abnormality in eight cases, these patients exhibited upper camptocormia angles of 45° or larger. The mean neck flexion angle measured with the antecollis method was 49.7°, while the perpendicular method yielded 103.4°. Discussion: Upper camptocormia should be considered in the evaluation of antecollis. We propose a new method to measure neck flexion in relation to the torso, instead of the vertical line.

Hesperidin Improves Memory Function by Enhancing Neurogenesis in a Mouse Model of Alzheimer's Disease.

Alzheimer's disease (AD) is an irreversible neurodegenerative disease characterized by memory and cognitive impairments. Neurogenesis, which is related to memory and cognitive function, is reduced in the brains of patients with AD. Therefore, enhancing neurogenesis is a potential therapeutic strategy for neurodegenerative diseases, including AD. Hesperidin (HSP), a bioflavonoid found primarily in citrus plants, has anti-inflammatory, antioxidant, and neuroprotective effects. The objective of this study was to determine the effects of HSP on neurogenesis in neural stem cells (NSCs) isolated from the brain of mouse embryos and five familial AD (5xFAD) mice. In NSCs, HSP significantly increased the proliferation of NSCs by activating adenosine monophosphate (AMP)-activated protein kinase (AMPK)/cAMP-response element-binding protein (CREB) signaling, but did not affect NSC differentiation into neurons and astrocytes. HSP administration restored neurogenesis in the hippocampus of 5xFAD mice via AMPK/brain-derived neurotrophic factor/tropomyosin receptor kinase B/CREB signaling, thereby decreasing amyloid-beta accumulation and ameliorating memory dysfunction. Collectively, these preclinical findings suggest that HSP is a promising candidate for the prevention and treatment of AD.

Long-Term Outcomes of Deep Brain Stimulation in Pantothenate Kinase-Associated Neurodegeneration-Related Dystonia.

OBJECTIVE: To investigate the long-term clinical outcomes of pallidal deep brain stimulation (GPi-DBS) in patients with pantothenate kinase-associated neurodegeneration (PKAN). METHODS: We reviewed the records of patients with genetically confirmed PKAN who received bilateral GPi-DBS for refractory dystonia and were clinically followed up for at least 2 years postoperatively at two centers in Korea. Pre- and postoperative Burke- Fahn-Marsden Dystonia Rating Scale motor subscale (BFMDRS-M) scores, disability subscale (BFMDRS-D) scores, and qualitative clinical information were prospectively collected. Descriptive analysis was performed for BFMDRS-M scores, BFMDRSD scores, and the orofacial, axial, and limb subscores of the BFMDRS-M at 6-12, 24-36, and 60-72 months postoperatively. RESULTS: Five classic-type, four atypical-type, and one unknown-type PKAN cases were identified. The mean preoperative BFMDRS-M score was 92.1 for the classic type and 38.5 for the atypical or unknown type, with a mean BFMDRS follow-up of 50.7 months and a clinical follow-up of 69.0 months. The mean improvements in BFMDRS-M score were 11.3%, 41.3%, and 30.5% at 6-12, 24-36, and 60-72 months, respectively. In four patients with full regular evaluations until 60-72 months, improvements in the orofacial, axial, and limb subscores persisted, but the disability scores worsened from 24-36 months post-operation compared to the baseline, mainly owing to the aggravation of eating and feeding disabilities. CONCLUSION: The benefits of GPi-DBS on dystonia may persist for more than 5 years in PKAN. The effects on patients' subjective disability may have a shorter duration despite improvements in dystonia owing to the complex manifestations of PKAN.

Serum Inflammatory Markers and Progression of Nonmotor Symptoms in Early Parkinson's Disease.

BACKGROUND: The influence of peripheral inflammation on nonmotor symptoms (NMSs) in Parkinson's disease (PD) remains unclear. OBJECTIVE: The aim of this study was to explore whether serum inflammatory marker profiles are associated with the progression of NMSs in early PD. METHODS: We included 45 patients with early PD and 20 healthy control subjects. Six inflammatory markers, including interleukin (IL)-1ß, IL-2, IL-6, IL-10, tumor necrosis factor-α, and high-sensitivity C-reactive protein, were measured. NMSs were assessed using the Non-Motor Symptoms Scale, Montreal Cognitive Assessment, and Composite Autonomic Symptom Score-31 at baseline and after 3 years. RESULTS: Principal component (PC) analysis showed that only PC3 scores, mainly loaded by IL-2 and IL-6, were significantly elevated in the PD group compared with the control group. Higher PC3 scores in the PD group were associated with faster progression of Non-Motor Symptoms Scale total and mood/apathy domain scores. There were no significant associations of PC scores with Montreal Cognitive Assessment and Composite Autonomic Symptom Score-31 score changes. CONCLUSIONS: Peripheral inflammation may be related to the evolution of NMSs, particularly mood symptoms, in the early stages of PD. © 2022 International Parkinson and Movement Disorder Society.

Beneficial Activities of Alisma orientale Extract in a Western Diet-Induced Murine Non-Alcoholic Steatohepatitis and Related Fibrosis Model via Regulation of the Hepatic Adiponectin and Farnesoid X Receptor Pathways.

The hepatic adiponectin and farnesoid X receptor (FXR) signaling pathways play multiple roles in modulating lipid and glucose metabolism, reducing hepatic inflammation and fibrosis, and altering various metabolic targets for the management of non-alcoholic fatty liver disease (NAFLD). Alisma orientale (AO, Ze xie in Chinese and Taeksa in Korean) is an herbal plant whose tubers are enriched with triterpenoids, which have been reported to exhibit various bioactive properties associated with NAFLD. Here, the present study provides a preclinical evaluation of the biological functions and related signaling pathways of AO extract for the treatment of NAFLD in a Western diet (WD)-induced mouse model. The findings showed that AO extract significantly reversed serum markers (liver function, lipid profile, and glucose) and improved histological features in the liver sections of mice fed WD for 52 weeks. In addition, it also reduced hepatic expression of fibrogenic markers in liver tissue and decreased the extent of collagen-positive areas, as well as inhibited F4/80 macrophage aggregation and inflammatory cytokine secretion. The activation of adiponectin and FXR expression in hepatic tissue may be a major mechanistic signaling cascade supporting the promising role of AO in NAFLD pharmacotherapy. Collectively, our results demonstrated that AO extract improves non-alcoholic steatohepatitis (NASH) resolution, particularly with respect to NASH-related fibrosis, along with the regulation of liver enzymes, postprandial hyperglycemia, hyperlipidemia, and weight loss, probably through the modulation of the hepatic adiponectin and FXR pathways.

Automatic Measurement of Postural Abnormalities With a Pose Estimation Algorithm in Parkinson's Disease.

OBJECTIVE: This study aims to develop an automated and objective tool to evaluate postural abnormalities in Parkinson's disease (PD) patients. METHODS: We applied a deep learning-based pose-estimation algorithm to lateral photos of prospectively enrolled PD patients (n = 28). We automatically measured the anterior flexion angle (AFA) and dropped head angle (DHA), which were validated with conventional manual labeling methods. RESULTS: The automatically measured DHA and AFA were in excellent agreement with manual labeling methods (intraclass correlation coefficient > 0.95) with mean bias equal to or less than 3 degrees. CONCLUSION: The deep learning-based pose-estimation algorithm objectively measured postural abnormalities in PD patients.

Resveratrol-enriched rice identical to original Dongjin rice variety with respect to major agronomic traits in different cultivation years and regions.

Resveratrol is synthesized by the catalysis of resveratrol synthases (RS) in a limited number of higher plants. Resveratrol shows potential health-promoting properties, including as an antioxidant and in preventing cardiovascular diseases. Recently, resveratrol-enriched rice has been produced as a novel source of resveratrol. This study aimed to investigate the major agronomic characteristics of resveratrol-enriched rice, Iksan526 (I526) and compared them with those of a nontransgenic and commercial rice variety, Dongjin (DJ). Transgene (RS) integration was confirmed using Southern blot analysis, and homologous recombination was achieved after digestion with the SacI restriction enzyme. The phenotypic traits of I526 grown in Iksan were similar to those grown in Milyang but not similar to those grown in Suwon. In Suwon, I526 had slightly earlier heading dates [i.e., number of days from sowing to heading) and shorter culm lengths. When I526 was treated with 0.4% Basta in the seedling stage, no significant difference was observed among all the agronomic traits compared with nontreated I526; particularly, the culm length, panicle length, number of panicles per hill, 1,000 grain weight of brown rice, and brown rice yield of the Basta-treated rice were similar to those of the nontreated I526, regardless of their cultivation region. The resveratrol content of I526 grown in Suwon and Milyang was increased by 18% and 37%, respectively, than that of I526 grown in the Iksan area. Therefore, DJ and I526 are not significantly different in terms of major agronomic traits depending on variety/year and variety/cultivation region. The results indicated that I526 has the potential to become a commercialized variety in the near future.

Transplantation of gut microbiota derived from Alzheimer's disease mouse model impairs memory function and neurogenesis in C57BL/6 mice.

Alzheimer's disease (AD) is a neurodegenerative disease that causes memory and cognitive decline. Although many studies have attempted to clarify the causes of AD occurrence, it is not clearly understood. Recently, the emerging role of the gut microbiota in neurodegenerative diseases, including AD, has received much attention. The gut microbiota composition of AD patients and AD mouse models is different from that of healthy controls, and these changes may affect the brain environment. However, the specific mechanisms by which gut microbiota that influence memory decline are currently unclear. In this study, we performed fecal microbiota transplantation (FMT) to clarify the role of 5xFAD mouse-derived microbiota in memory decline. We observed that FMT from 5xFAD mice into normal C57BL/6 mice (5xFAD-FMT) decreased adult hippocampal neurogenesis and brain-derived neurotrophic factor expression and increased p21 expression, resulting in memory impairment. Microglia in the hippocampus of the 5xFAD-FMT mice were activated, which caused the elevation of pro-inflammatory cytokines (tumor necrosis factor-α and interleukin-1ß). Moreover, we observed that pro-inflammatory cytokines increased in the colon and plasma of 5xFAD-FMT mice. The gut microbiota composition of the 5xFAD-FMT mice was different from that of the control mice or wild type-FMT mice. Collectively, 5xFAD mouse-derived microbiota decreased neurogenesis by increasing colonic inflammation, thereby contributing to memory loss. Our findings provide further evidence concerning the role of gut microbial dysbiosis in AD pathogenesis and suggest that targeting the gut microbiota may be a useful therapeutic strategy for the development of novel candidates for the treatment of AD.

Quantitative Gait Analysis Using a Pose-Estimation Algorithm with a Single 2D-Video of Parkinson's Disease Patients.

BACKGROUND: Clinician-based rating scales or questionnaires for gait in Parkinson's disease (PD) are subjective and sensor-based analysis is limited in accessibility. OBJECTIVE: To develop an easily accessible and objective tool to evaluate gait in PD patients, we analyzed gait from a single 2-dimensional (2D) video. METHODS: We prospectively recorded 2D videos of PD patients (n = 16) and healthy controls (n = 15) performing the timed up and go test (TUG). The gait was simultaneously evaluated with a pressure-sensor (GAITRite). We estimated the 3D position of toes and heels with a deep-learning based pose-estimation algorithm and calculated gait parameters including step length, step length variability, gait velocity and step cadence which was validated with the result from the GAITRite. We further calculated the time and steps required for turning. Then, we applied the algorithm to previously recorded and archived videos of PD patients (n = 32) performing the TUG. RESULTS: From the validation experiment, gait parameters derived from video tracking were in excellent agreement with the parameters obtained with the GAITRite. (Intraclass correlation coefficient > 0.9). From the analysis with the archived videos, step length, gait velocity, number of steps, and the time required for turning were significantly correlated (Absolute R > 0.4, p < 0.005) with the Freezing of gait questionnaire, Unified PD Rating scale part III total score, HY stage and postural instability. Furthermore, the video-based tracking objectively measured significant improvement of step length, gait velocity, steps and the time required for turning with antiparkinsonian medication. CONCLUSION: 2D video-based tracking could objectively evaluate gait in PD patients.