HLH-30/TFEB mediates sexual dimorphism in immunity in caenorhabditis elegans.

Sexual dimorphism affects various biological functions, including immune responses. However, the mechanisms by which sex alters immunity remain largely unknown. Using Caenorhabditis elegans as a model species, we showed that males exhibit enhanced immunity against various pathogenic bacteria through the upregulation of HLH-30 (Helix Loop Helix 30/TFEB (transcription factor EB), a transcription factor crucial for macroautophagy/autophagy. Compared with hermaphroditic C. elegans, males displayed increased activity of HLH-30/TFEB, which contributed to enhanced antibacterial immunity. atg-2 (AuTophaGy (yeast Atg homolog) 2) upregulated by HLH-30/TFEB mediated increased immunity in male C. elegans. Thus, the males appear to be equipped with enhanced HLH-30/TFEB-mediated autophagy, which increases pathogen resistance, and this may functionally prolong mate-searching ability with reduced risk of infection.

Impact of Childhood Maltreatment on Cognitive Function and Its Relationship With Emotion Regulation in Young Adults.

Objectives: Childhood maltreatment can negatively impact cognitive development, including executive function, working memory, and processing speed. This study investigated the impact of childhood maltreatment on cognitive function in young adults using various measurements, including computerized tests, and their relationship with emotional dysregulation. Methods: We recruited 149 healthy individuals with and without maltreatment experiences and used the Wechsler Adult Intelligence Scale IV (WAIS-IV) and a computerized battery to analyze cognitive function. Results: Both the WAIS-IV and computerized tests revealed that individuals with a history of childhood maltreatment had decreased cognitive function, especially in terms of working memory and processing speed. These individuals tended to employ maladaptive emotion regulation strategies. Among cognitive functions, working memory is negatively related to maladaptive emotion regulation strategies such as catastrophizing. Conclusion: This study highlights the effects of childhood maltreatment on cognitive function in young adulthood. Moreover, the study suggests clinical implications of cognitive interventions for improving emotion regulation and cognitive function in individuals with a history of childhood maltreatment.

Intravascular Imaging and Angiography Guidance in Complex Percutaneous Coronary Intervention Among Patients With Diabetes: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Data are limited regarding the effects of intravascular imaging guidance during complex percutaneous coronary intervention (PCI) in patients with diabetes. Objective: To compare the clinical outcomes of intravascular imaging-guided vs angiography-guided complex PCI in patients with or without diabetes. Design, Setting, and Participants: This prespecified secondary analysis of a subgroup of patients in RENOVATE-COMPLEX-PCI (Randomized Controlled Trial of Intravascular Imaging Guidance Versus Angiography-Guidance on Clinical Outcomes After Complex Percutaneous Coronary Intervention), an investigator-initiated, open-label multicenter trial, analyzed enrolled patients who underwent complex PCI at 20 sites in Korea from May 2018 through May 2021. Eligible patients were randomly assigned in a 2:1 ratio to undergo either the intravascular imaging-guided PCI or angiography-guided PCI. Data analyses were performed from June 2023 to April 2024. Interventions: Percutaneous coronary intervention was performed either under the guidance of intravascular imaging or angiography alone. Main Outcomes and Measures: The primary end point was target vessel failure (TVF), defined as a composite of cardiac death, target vessel-related myocardial infarction, or target vessel revascularization. Results: Among the 1639 patients included in the analysis (mean [SD] age, 65.6 [10.2] years; 1300 males [79.3%]), 617 (37.6%) had diabetes. The incidence of TVF was significantly higher in patients with diabetes than patients without diabetes (hazard ratio [HR], 1.86; 95% CI, 1.33-2.60; P < .001). Among patients without diabetes, the intravascular imaging-guided PCI group had a significantly lower incidence of TVF compared with the angiography-guided PCI group (4.7% vs 12.2%; HR, 0.41 [95% CI, 0.25-0.67]; P < .001). Conversely, in patients with diabetes, the risk of TVF was not significantly different between the 2 groups (12.9% vs 12.3%; HR, 0.97 [95% CI, 0.60-1.57]; P = .90). There was a significant interaction between the use of intravascular imaging and diabetes for the risk of TVF (P for interaction = .02). Among patients with diabetes, only those with good glycemic control (hemoglobin A1c level ≤7.5%) and who achieved stent optimization by intravascular imaging showed a lower risk of future ischemic events (HR, 0.31; 95% CI, 0.12-0.82; P = .02). Conclusions and Relevance: In this secondary analysis of a subgroup of patients in the RENOVATE-COMPLEX-PCI trial, intravascular imaging guidance reduced the risk of TVF compared with angiography guidance in patients without diabetes (but not in patients with diabetes) during complex PCI. In patients with diabetes undergoing complex PCI, attention should be paid to stent optimization using intravascular imaging and glycemic control to improve outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT03381872.

Improved resilience and proteostasis mediate longevity upon DAF-2 degradation in old age.

Little is known about the possibility of reversing age-related biological changes when they have already occurred. To explore this, we have characterized the effects of reducing insulin/IGF-1 signaling (IIS) during old age. Reduction of IIS throughout life slows age-related decline in diverse species, most strikingly in the nematode Caenorhabditis elegans. Here we show that even at advanced ages, auxin-induced degradation of DAF-2 in single tissues, including neurons and the intestine, is still able to markedly increase C. elegans lifespan. We describe how reversibility varies among senescent changes. While senescent pathologies that develop in mid-life were not reversed, there was a rejuvenation of the proteostasis network, manifesting as a restoration of the capacity to eliminate otherwise intractable protein aggregates that accumulate with age. Moreover, resistance to several stressors was restored. These results support several new conclusions. (1) Loss of resilience is not solely a consequence of pathologies that develop in earlier life. (2) Restoration of proteostasis and resilience by inhibiting IIS is a plausible cause of the increase in lifespan. And (3), most interestingly, some aspects of the age-related transition from resilience to frailty can be reversed to a certain extent. This raises the possibility that the effect of IIS and related pathways on resilience and frailty during aging in higher animals might possess some degree of reversibility.

Increased risk of epilepsy after transient global amnesia: A population-based study in South Korea.

PURPOSE: This study aimed to investigate the risk of epilepsy after transient global amnesia (TGA). METHODS: Study population was recruited using the International Classification of Diseases codes from the Korean National Health Insurance Service database between 2002 and 2020. The incidence of epilepsy was compared between the TGA (n=12,390) and non-TGA (n=33,868) groups, determined using 1:3 propensity score matching. Using Cox proportional hazard regression model, we obtained adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for incident epilepsy in the TGA compared with non-TGA group. Logistic regression was performed to examine the independent variables determining incident epilepsy in the TGA group, and adjusted odds ratios (aORs) and 95% CIs were calculated. RESULTS: The TGA group had a significantly higher cumulative incidence of epilepsy than controls (p <0.001, log-rank test). TGA was significantly associated with incident epilepsy in the Cox model (adjusted HR 1.46, 95% CI 1.36-1.56). The adjusted logistic regression showed that age (per 1 year, aOR 1.02, 95% CI 1.01-1.02), female sex (aOR 0.68, 95% CI 0.60-0.77), hypertension (aOR 1.14, 95% CI 1.00-1.30), diabetes (aOR 1.26, 95% CI 1.10-1.44), stroke (aOR 1.22, 95% CI 1.06-1.40), depression (aOR 1.44, 95% CI 1.22-1.69), anxiety (aOR 1.31, 95% CI 1.14-1.51), alcohol-related disease (aOR 1.96, 95% CI 1.38-2.78), low income (aOR 1.18, 95% CI 1.02-1.36) and rural residence (aOR 1.20, 95% CI 1.02-1.42) were associated with incident epilepsy. CONCLUSIONS: Our results suggest a longitudinal association of TGA with incident epilepsy.

7-MEGA™ inhibits adipogenesis in 3T3-L1 adipocytes and suppresses obesity in high-fat-diet-induced obese C57BL/6 mice.

BACKGROUND: Overweight, often known as obesity, is the abnormal and excessive accumulation of fat that exposes the health of a person at risk by increasing the likelihood that they may experience many chronic conditions. Consequently, obesity has become a global health threat, presenting serious health issues, and attracting a lot of attention in the healthcare profession and the scientific community. METHOD: This study aims to explore the anti-adipogenic properties of 7-MEGA™ in an attempt to address obesity, using both in vitro and in vivo research. The effects of 7MEGA™ at three distinct concentrations were investigated in obese mice who were given a high-fat diet (HFD) and 3T3-L1 adipocytes. RESULTS: 7MEGA™ decreased the total fat mass, overall body weight, and the perirenal and subcutaneous white adipose tissue (PWAT and SWAT) contents in HFD mice. Additionally, 7MEGA™ showed promise in improving the metabolic health of individuals with obesity and regulate the levels of insulin hormone, pro-inflammatory cytokines and adipokines. Furthermore, Peroxisome proliferator-activated receptors (PPAR) α and γ, Uncoupling Protein 1 (UCP-1), Sterol Regulatory Element-Binding Protein 1 (SREBP-1), Fatty Acid-Binding Protein 4 (FABP4), Fatty Acid Synthase (FAS), Acetyl-CoA Carboxylase (ACC), Stearoyl-CoA Desaturase-1 (SCD-1) and CCAAT/Enhancer-Binding Protein (C/EBPα) were among the adipogenic regulators that 7MEGA™ could regulate. CONCLUSION: In summary, this study uncovered that 7MEGA™ demonstrates anti-adipogenic and anti-obesity effects, suggesting its potential in combating obesity.

Potassium Iodide Doping for Vacancy Substitution and Dangling Bond Repair in InP Core-Shell Quantum Dots.

This work highlights the novel approach of incorporating potassium iodide (KI) doping during the synthesis of In0.53P0.47 core quantum dots (QDs) to significantly reduce the concentration of vacancies (i.e., In vacancies; VIn-) within the bulk of the core QD and inhibit the formation of InPOx at the core QD-Zn0.6Se0.4 shell interfaces. The photoluminescence quantum yield (PLQY) of ~97% and full width at half maximum (FWHM) of ~40 nm were achieved for In0.53P0.47/Zn0.6Se0.4/Zn0.6Se0.1S0.3/Zn0.5S0.5 core/multi-shell QDs emitting red light, which is essential for a quantum-dot organic light-emitting diode (QD-OLED) without red, green, and blue crosstalk. KI doping eliminated VIn- in the core QD bulk by forming K+-VIn- substitutes and effectively inhibited the formation of InPO4(H2O)2 at the core QD-Zn0.6Se0.4 shell interface through the passivation of phosphorus (P)-dangling bonds by P-I bonds. The elimination of vacancies in the core QD bulk was evidenced by the decreased relative intensity of non-radiative unpaired electrons, measured by electron spin resonance (ESR). Additionally, the inhibition of InPO4(H2O)2 formation at the core QD and shell interface was confirmed by the absence of the {210} X-ray diffraction (XRD) peak intensity for the core/multi-shell QDs. By finely tuning the doping concentration, the optimal level was achieved, ensuring maximum K-VIn- substitution, minimal K+ and I- interstitials, and maximum P-dangling bond passivation. This resulted in the smallest core QD diameter distribution and maximized optical properties. Consequently, the maximum PLQY (~97%) and minimum FWHM (~40 nm) were observed at 3% KI doping. Furthermore, the color gamut of a QD-OLED display using R-, G-, and B-QD functional color filters (i.e., ~131.1%@NTSC and ~98.2@Rec.2020) provided a nearly perfect color representation, where red-light-emitting KI-doped QDs were applied.

Three new nonenes from culture broth of marine-derived fungus Albifimbria verrucaria and their cytotoxic and anti-viral activities.

Three new nonenes, verrucanonenes A‒C (1‒3), were isolated from culture broth of marine-derived fungus Albifimbria verrucaria. These compounds were isolated using silica gel column chromatography, reversed-phase medium pressure liquid chromatography, Sephadex LH-20 column chromatography, and preparative HPLC. Their structures were determined using a spectroscopic method. Cytotoxicities of these isolated compounds to A549, DU145, HCT116, and HT1080 cancer cell lines were assessed. Compounds 1‒3 exhibited cytotoxicities to DU145 cancer cell line, with IC50 values of 23.4, 28.6, and 20.1 µM, respectively. Compound 2 decreased H1N1-induced cytopathic effects on MDCK cells in a dose-dependent manner.

Predictors of Choledocholithiasis in Cholecystectomy Patients and Their Cutoff Values and Prediction Model in Korea in Comparison with the 2019 ASGE Guidelines.

Background/Aims: : In 2019, the American Society for Gastrointestinal Endoscopy (ASGE) established clinical predictors for choledocholithiasis. Our study was designed to evaluate these predictors within the Korean clinical context, establish cutoff values, and develop a predictive model. Methods: : This retrospective study analyzed patients who underwent laparoscopic cholecystectomy. The relationships between choledocholithiasis and predictors including age, blood tests, and imaging findings were assessed through univariate and multivariate logistic regression analyses. We established Korean cutoff values for these predictors and developed a scoring system for choledocholithiasis using a multivariate logistic regression. The performance of this scoring system was then compared with that of the 2019 ASGE guidelines through a receiver operating characteristic curve. Results: : We established Korean cutoff values for age (>70 years), alanine aminotransferase (>26.5 U/L), aspartate aminotransferase (>28.5 U/L), gamma-glutamyl transferase (GGT; >82.5 U/L), alkaline phosphatase (ALP; >77.5 U/L), and total bilirubin (>0.95 mg/dL). In the multivariate analysis, only age >70 years, GGT >77.5 U/L, ALP >77.5 U/L, and common bile duct dilatation remained significant. We then developed a new Korean risk stratification model from the multivariate analysis, with an area under the curve of 0.777 (95% confidence interval, 0.75 to 0.81). Our model was stratified into the low-risk, intermediate-risk, and high-risk groups with the scores being <1.0, 1.0-5.5, and >5.5, respectively. Conclusions: : Predictors of choledocholithiasis in cholecystectomy patients and their cutoff values in Korean should be adjusted and further studies are needed to develop appropriate guidelines.

Impact of Intravascular Imaging-Guided Stent Optimization According to Clinical Presentation in Patients Undergoing Complex PCI.

BACKGROUND: It is unclear whether the beneficial effects of intravascular imaging-guided stent optimization vary by clinical presentation during complex percutaneous coronary intervention (PCI). OBJECTIVES: In this prespecified, stratified subgroup analysis from RENOVATE-COMPLEX-PCI (Randomized Controlled Trial of Intravascular Imaging Guidance versus Angiography-Guidance on Clinical Outcomes After Complex PCI), we sought to compare the outcomes between intravascular imaging vs angiography guidance according to clinical presentation. METHODS: Patients with complex coronary artery lesions were randomly assigned to undergo either intravascular imaging-guided PCI or angiography-guided PCI in a 2:1 ratio. The primary endpoint was target vessel failure (TVF), which is a composite of cardiac death, target vessel-related myocardial infarction, or clinically driven target vessel revascularization. RESULTS: Of 1,639 patients, 832 (50.8%) presented with acute coronary syndrome (ACS) and 807 (49.2%) with chronic coronary syndrome. During a median follow-up of 2.1 years (Q1-Q3: 1.4-3.0 years), there was no significant interaction between the treatment effect of intravascular imaging and clinical presentation (P for interaction = 0.19). Among patients with ACS, the incidences of TVF were 10.4% in the intravascular imaging group and 14.6% in the angiography group (HR: 0.74; 95% CI: 0.48-1.15; P = 0.18). Among patients with CCS, the incidences of TVF were 5.0% in the intravascular imaging group and 10.4% in the angiography group (HR: 0.46; 95% CI: 0.27-0.80; P = 0.006). Achieving stent optimization by intravascular imaging resulted in a reduced risk of TVF among patients with ACS who were randomly assigned to intravascular imaging-guided PCI for complex coronary lesions (optimized vs unoptimized, 6.5% vs 14.1%; HR: 0.49; 95% CI: 0.27-0.87; P = 0.02) but not those with CCS (5.4% vs 4.7%, HR: 1.18; 95% CI: 0.53-2.59; P = 0.69). CONCLUSIONS: No significant interaction was observed between the benefits of intravascular imaging and clinical presentation in the risk of TVF. Stent optimization by intravascular imaging was particularly important for ACS patients. (Intravascular Imaging- Versus Angiography-Guided Percutaneous Coronary Intervention For Complex Coronary Artery Disease [RENOVATE]; NCT03381872).

Standardization of the Korean Version of the Acceptance and Action Questionnaire for Obsessions and Compulsions in University Students and Patients With Obsessive-Compulsive Disorder.

OBJECTIVE: The Acceptance and Action Questionnaire for Obsessions and Compulsions (AAQ-OC) is a version of the Acceptance and Action Questionnaire (AAQ) that specifically measures unwanted intrusive thoughts and responses (e.g., experiential avoidance) to them. This study aimed to investigate the reliability and validity of the Korean version of the AAQ-OC in clinical and nonclinical Korean samples. METHODS: In this study, 561 university students and 121 patients with obsessive-compulsive disorder (OCD) completed the AAQ-OC and several other psychological scales. Descriptive, correlation, and exploratory and confirmatory factor analyses as well as group comparisons were conducted. RESULTS: The results of the exploratory and confirmatory factor analyses indicated a two-factor structure that best fits the data in the university sample: Factors 1 and 2 matched the original Valued Action and Willingness subscales, respectively. The reliability analyses revealed that the AAQ-OC and its factors had excellent internal consistencies. As regards the concurrent validity, the AAQ-OC and its factors had a positive correlation with the AAQ-II and Cognitive Fusion Questionnaire. Compared with the university students, the OCD patients had higher AAQ-OC scores, and their obsessive-compulsive symptoms, particularly the two symptom dimensions of responsibility for harm and mistakes and unacceptable thoughts, were significantly associated with the AAQ-OC and two subscales. CONCLUSION: The findings of this study confirm the reliability and validity of the Korean version of the AAQ-OC.

Brief guide to RNA sequencing analysis for nonexperts in bioinformatics.

Transcriptome analysis is widely used for current biological research but remains challenging for many experimental scientists. Here, we present a brief but broad guideline for transcriptome analysis, focusing on RNA sequencing, by providing the list of publicly available datasets, tools, and R packages for practical transcriptome analysis. This work will be useful for biologists to perform key transcriptomic analysis with minimum expertise in bioinformatics.

Intravascular Imaging-Guided Optimization of Complex Percutaneous Coronary Intervention by Sex: A Subgroup Analysis of the RENOVATE-COMPLEX-PCI Trial.

Importance: There have been heterogeneous results related to sex differences in prognosis after percutaneous coronary artery intervention (PCI) for complex coronary artery lesions. Objective: To evaluate potential differences in outcomes with intravascular imaging-guided PCI of complex coronary artery lesions between women and men. Design, Setting, and Participants: This prespecified substudy evaluates the interaction of sex in the investigator-initiated, open-label, multicenter RENOVATE-COMPLEX-PCI randomized clinical trial, which demonstrated the superiority of intravascular imaging-guided PCI compared with angiography-guided PCI in patients with complex coronary artery lesions. The trial was conducted at 20 sites in Korea. Patients with complex coronary artery lesions undergoing PCI were enrolled between May 2018 and May 2021, and the median (IQR) follow-up period was 2.1 (1.4-3.0) years. Data were analyzed from December 2022 to December 2023. Interventions: After diagnostic coronary angiography, eligible patients were randomly assigned in a 2:1 ratio to receive intravascular imaging-guided PCI or angiography-guided PCI. The choice and timing of the intravascular imaging device were left to the operators' discretion. Main Outcomes and Measures: The primary end point was target vessel failure, defined as a composite of cardiac death, target vessel-related myocardial infarction, or clinically driven target vessel revascularization. Secondary end points included individual components of the primary end point. Results: Of 1639 included patients, 339 (20.7%) were women, and the mean (SD) age was 65.6 (10.2) years. There was no difference in the risk of the primary end point between women and men (9.4% vs 8.3%; adjusted hazard ratio [HR], 1.39; 95% CI, 0.89-2.18; P = .15). Intravascular imaging-guided PCI tended to have lower incidence of the primary end point than angiography-guided PCI in both women (5.2% vs 14.5%; adjusted HR, 0.34; 95% CI, 0.15-0.78; P = .01) and men (8.3% vs 11.7%; adjusted HR, 0.72; 95% CI, 0.49-1.05; P = .09) without significant interaction (P for interaction = .86). Conclusions and Relevance: In patients undergoing complex PCI, compared with angiographic guidance, intravascular imaging guidance was associated with similar reduction in the risk of target vessel failure among women and men. The treatment benefit of intravascular imaging-guided PCI showed no significant interaction between treatment strategy and sex. Trial Registration: ClinicalTrials.gov Identifier: NCT03381872.

Ferulic Acid Derivatives Ameliorate Intestine Barrier Destruction by Alleviating Inflammatory Responses in Dextran Sulfate Sodium-Induced Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD), a chronic disorder affecting the colon and rectum, involves the overproduction of pro-inflammatory cytokines causing damage to tight junctions (TJ) in the intestinal epithelial cells and chronic inflammation. The current mainstay of treatment, sulfasalazine, often causes adverse effects, thereby necessitating the exploration of alternative herbal medicines with fewer side effects. Portulaca oleracea L. (P. oleracea), a traditional medicinal herb, contains feruloyl amide compounds. We synthesized new compounds by conjugating ferulic acid (FA) with (±)-octopamine. Our study focused on novel FA derivatives that demonstrate protective effects against the intestinal epithelial barrier and inflammatory responses. In lipopolysaccharide-induced cells, C1 and C1a inhibited the production of inflammatory mediators. In Caco-2 cells, these compounds maintained the TJ protein expression, thereby demonstrating their protective effects on the epithelial barrier. In a mouse model of dextran sulfate sodium-induced IBD, a treatment with these compounds ameliorated features including a body weight reduction, colon shortening, an increased disease activity index, and histopathological changes. Furthermore, C1a demonstrated greater efficacy than C1 at the same concentration. These findings suggest that the novel FA derivative (C1a) effectively alleviates clinical signs and inflammatory mediators in IBD, making these compounds potential candidates as natural medicines for the treatment of IBD.

Oleanolic Acid Acetate Alleviates Cisplatin-Induced Nephrotoxicity via Inhibition of Apoptosis and Necroptosis In Vitro and In Vivo.

Cisplatin is a widely used anti-cancer drug for treating solid tumors, but it is associated with severe side effects, including nephrotoxicity. Various studies have suggested that the nephrotoxicity of cisplatin could be overcome; nonetheless, an effective adjuvant drug has not yet been established. Oleanolic acid acetate (OAA), a triterpenoid isolated from Vigna angularis, is commonly used to treat inflammatory and allergic diseases. This study aimed to investigate the protective effects of OAA against cisplatin-induced apoptosis and necroptosis using TCMK-1 cells and a mouse model. In cisplatin-treated TCMK-1 cells, OAA treatment significantly reduced Bax and cleaved-caspase3 expression, whereas it increased Bcl-2 expression. Moreover, in a cisplatin-induced kidney injury mouse model, OAA treatment alleviated weight loss in the body and major organs and also relieved cisplatin-induced nephrotoxicity symptoms. RNA sequencing analysis of kidney tissues identified lipocalin-2 as the most upregulated gene by cisplatin. Additionally, necroptosis-related genes such as receptor-interacting protein kinase (RIPK) and mixed lineage kinase domain-like (MLKL) were identified. In an in vitro study, the phosphorylation of RIPKs and MLKL was reduced by OAA pretreatment in both cisplatin-treated cells and cells boosted via co-treatment with z-VAD-FMK. In conclusion, OAA could protect the kidney from cisplatin-induced nephrotoxicity and may serve as an anti-cancer adjuvant.

Development of a deep learning model to distinguish the cause of optic disc atrophy using retinal fundus photography.

The differential diagnosis for optic atrophy can be challenging and requires expensive, time-consuming ancillary testing to determine the cause. While Leber's hereditary optic neuropathy (LHON) and optic neuritis (ON) are both clinically significant causes for optic atrophy, both relatively rare in the general population, contributing to limitations in obtaining large imaging datasets. This study therefore aims to develop a deep learning (DL) model based on small datasets that could distinguish the cause of optic disc atrophy using only fundus photography. We retrospectively reviewed fundus photographs of 120 normal eyes, 30 eyes (15 patients) with genetically-confirmed LHON, and 30 eyes (26 patients) with ON. Images were split into a training dataset and a test dataset and used for model training with ResNet-18. To visualize the critical regions in retinal photographs that are highly associated with disease prediction, Gradient-Weighted Class Activation Map (Grad-CAM) was used to generate image-level attention heat maps and to enhance the interpretability of the DL system. In the 3-class classification of normal, LHON, and ON, the area under the receiver operating characteristic curve (AUROC) was 1.0 for normal, 0.988 for LHON, and 0.990 for ON, clearly differentiating each class from the others with an overall total accuracy of 0.93. Specifically, when distinguishing between normal and disease cases, the precision, recall, and F1 scores were perfect at 1.0. Furthermore, in the differentiation of LHON from other conditions, ON from others, and between LHON and ON, we consistently observed precision, recall, and F1 scores of 0.8. The model performance was maintained until only 10% of the pixel values of the image, identified as important by Grad-CAM, were preserved and the rest were masked, followed by retraining and evaluation.

Three new phthalide derivatives from culture broth of Dentipellis fragilis and their cytotoxic activities.

Three new phthalide derivatives (1‒3) together with two known compounds, erinaceolactone B (4) and hericerin III (5), were isolated from the culture broth of Dentipellis fragilis. The chemical structures of 1‒5 were determined by analyses of their 1D-, 2D-NMR, and MS. The absolute configuration of 1 was determined by CD analysis. The isolated compounds were assessed for their cytotoxic activities against A549, DU145, HCT116, and HT1080 cancer cell lines. Compounds 1‒5 showed strong cytotoxic activities against DU145, with IC50 values ranging from 14.3 to 16.1 µM. Additionally, all compounds showed moderate or weak cytotoxic activities against all cell lines except for compounds 4 and 1 which showed no cytotoxic activities against A549 and HCT116 cancer cell lines, respectively. Against HT1080 cancer cell line, only compound 2 displayed moderate cytotoxic activity.