IL-6 Inhibitory Compounds from the Aerial Parts of Piper attenuatum and Their Anticancer Activities on Ovarian Cancer Cell Lines.

Piper attenuatum Buch-Ham, a perennial woody vine belonging to the Piperaceae family, is traditionally used in Southeast Asia for treating various ailments such as malaria, headache, and hepatitis. This study described the isolation and identification of three new compounds, piperamides I-III (1-3), which belong to the maleimide-type alkaloid skeletons, along with fifteen known compounds (4-18) from the methanol extract of the aerial parts of P. attnuatum. Their chemical structures were elucidated using spectroscopic methods (UV, IR, ESI-Q-TOF-MS, and 1D/2D NMR). All the isolates were evaluated for their ability to inhibit IL-6 activity in the human embryonic kidney-Blue™ IL-6 cell line and their cytotoxic activity against ovarian cancer cell lines (SKOV3/SKOV3-TR) and chemotherapy-resistant variants (cisplatin-resistant A2780/paclitaxel-resistant SKOV3). The compounds 3, 4, 11, 12, 17, and 18 exhibited IL-6 inhibition comparable to that of the positive control bazedoxifene. Notably, compound 12 displayed the most potent anticancer effect against all the tested cancer cell lines. These findings highlight the importance of researching the diverse activities of both known and newly discovered natural products to fully unlock their potential therapeutic benefits.

Electronic Skin: Opportunities and Challenges in Convergence with Machine Learning.

Recent advancements in soft electronic skin (e-skin) have led to the development of human-like devices that reproduce the skin's functions and physical attributes. These devices are being explored for applications in robotic prostheses as well as for collecting biopotentials for disease diagnosis and treatment, as exemplified by biomedical e-skins. More recently, machine learning (ML) has been utilized to enhance device control accuracy and data processing efficiency. The convergence of e-skin technologies with ML is promoting their translation into clinical practice, especially in healthcare. This review highlights the latest developments in ML-reinforced e-skin devices for robotic prostheses and biomedical instrumentations. We first describe technological breakthroughs in state-of-the-art e-skin devices, emphasizing technologies that achieve skin-like properties. We then introduce ML methods adopted for control optimization and pattern recognition, followed by practical applications that converge the two technologies. Lastly, we briefly discuss the challenges this interdisciplinary research encounters in its clinical and industrial transition.

Optimizing tenderness of M. Semitendinosus steak for elderly people with the combination of ficin and sous-vide cooking.

This study aimed to evaluate the sous-vide cooking and ficin treatment effects on the tenderness of beef steak and optimize it for the elderly using response surface methodology (RSM). The M. semitendinosus (ST) from Chikso cattle was shaped into 5 × 5 × 2.54 cm pieces. Ficin solution was injected into the ST steak at 10% of the meat weight, and sous-vide cooked in a water bath at 65 °C for 6 or 12 h. As ficin concentration increased, L*- and a*-value, shear force, and hardness decreased, while soluble peptides increased (P < 0.05). As cooking time increased, cooking loss and collagen solubility of the steak increased (P < 0.05). An interaction effect between ficin and sous-vide cooking was found in L*- and a*-value, shear force, hardness, and soluble peptides (P < 0.05). A model to optimize the hardness for elderly people was established (R2 = 0.7991). Optimization conditions by RSM were 0.86 U/L with 8.87 h (23 N/cm3) for tooth intake (grade 1), 16.31 U/L with 13.24 h (3 N/cm3) for gums intake (grade 2), according to KS H 4897 and Universal Design Foods concept for the elderly. These optimized conditions enable the production of customized products tailored to the oral conditions of elderly people.

Investigation of different cold adaptation abilities in Salmonella enterica serotype Typhimurium strains using extracellular metabolomic approach.

This study explored the extracellular metabolomic responses of three different Salmonella enterica serotype Typhimurium (S. Typhimurium) strains-ATCC 13311 (STy1), NCCP 16964 (STy4), and NCCP 16958 (STy8)-cultured at refrigeration temperatures. The objective was to identify the survival mechanisms of S. Typhimurium under cold stress by analyzing variations in their metabolomic profiles. Qualitative and quantitative assessments identified significant metabolite alterations on day 6, marking a critical inflection point. Key metabolites such as trehalose, proline, glycerol, and tryptophan were notably upregulated in response to cold stress. Through multivariate analyses, the strains were distinguished using three metabolites-4-aminobutyrate, ethanol, and uridine-as potential biomarkers, underscoring distinct metabolic responses to refrigeration. Specifically, STy1 exhibited unique adaptive capabilities through enhanced metabolism of betaine and 4-aminobutyrate. These findings highlight the variability in adaptive strategies among S. Typhimurium strains, suggesting that certain strains may possess more robust metabolic pathways for enhancing survival in refrigerated conditions.

Synthesis of graphitic carbon nitride-based nanocomposites and their mechanical properties in epoxy compositions.

Thermoset epoxy resins are widely used in research and commercial applications. Zeolite imidazole framework-8 (ZIF-8), graphitic carbon nitride (GCN, g-C3N4), and S-doped graphitic carbon nitride (SCN, S-g-C3N4) composites were synthesized as accelerators and their effects on the physical properties of epoxies were examined. An ultrasound-assisted method was used to prepare ZIF-8/GCN and ZIF-8/SCN nanocomposites while g-C3N4 and S-g-C3N4 were prepared from the calcination of melamine and thiourea, respectively. The surface morphology, and particle size were characterized by scanning electron microscopy, and X-ray diffraction. The properties of synthesized nanocomposites were measured using Fourier-transform infrared spectroscopy. After the accelerator was added to the epoxy composites, their activation energies were calculated using differential scanning calorimetry. The tensile strength and flexural strength were measured using a universal testing machine and impact strength was measured by using an Izod impact strength tester. The impact strength of ZIF-8/SCN nanocomposites was enhanced by 45.2%. The storage stability of the epoxy compositions with different catalysts was evaluated by measuring the variation of viscosity with time at a constant temperature.

Systemic Inflammatory Response Following Preoperative Chemoradiotherapy Can Affect Oncologic Outcomes in MSI-H/dMMR Rectal Cancer.

Systemic inflammatory response (SIR) is a crucial determinant of disease progression and survival in patients with colorectal cancer. This study investigated the prognostic relevance of changes in the platelet count on survival and the predictive value of changes in the platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) on the pathological tumor response to preoperative chemoradiotherapy (CRT) in patients with microsatellite instability-high (MSI-H) rectal cancer. From 2011 to 2022, data of 46 consecutive patients with MSI-H rectal cancer who were treated with preoperative CRT followed by curative surgery at Kyungpook National University Chilgok Hospital (Daegu, South Korea) were retrospectively analyzed. A 235 cut-off value was used to define whether PLR was high or low. Any change in the PLR or NLR was calculated on the basis of subtracting the pre-CRT PLR or NLR from the post-CRT values. Both pre-CRT and post-CRT values of the NLR and PLR were not significantly associated with clinical outcomes. Simple logistic regression analysis showed that a change in the PLR following CRT was not significantly associated with survival outcomes; however, patients who maintained a high change in the PLR following CRT showed significantly better pathologic T-stage. No statistically significant association was noted between changes in the platelet count and clinical outcomes of patients. The results suggested that changes in the PLR following CRT are associated with pathologic T-stage of the group. However, the SIR markers showed no prognostic values on the survival outcomes of the patients with MSI-H/mismatch repair-deficient (dMMR) locally advanced rectal cancer (LARC).

Evolutionary Approach to Optimal Oil Skimmer Assignment for Oil Spill Response: A Case Study.

We propose a genetic algorithm for optimizing oil skimmer assignments, introducing a tailored repair operation for constrained assignments. Methods essentially involve simulation-based evaluation to ensure adherence to South Korea's regulations. Results show that the optimized assignments, compared to current ones, reduced work time on average and led to a significant reduction in total skimmer capacity. Additionally, we present a deep neural network-based surrogate model, greatly enhancing efficiency compared to simulation-based optimization. Addressing inefficiencies in mobilizing locations that store oil skimmers, further optimization aimed to minimize mobilized locations and was validated through scenario-based simulations resembling actual situations. Based on major oil spills in South Korea, this strategy significantly reduced work time and required locations. These findings demonstrate the effectiveness of the proposed genetic algorithm and mobilized location minimization strategy in enhancing oil spill response operations.

Investigation of the Efficacy of Benzylidene-3-methyl-2-thioxothiazolidin-4-one Analogs with Antioxidant Activities on the Inhibition of Mushroom and Mammal Tyrosinases.

Based on the fact that substances with a ß-phenyl-α,ß-unsaturated carbonyl (PUSC) motif confer strong tyrosinase inhibitory activity, benzylidene-3-methyl-2-thioxothiazolidin-4-one (BMTTZD) analogs 1-8 were prepared as potential tyrosinase inhibitors. Four analogs (1-3 and 5) inhibited mushroom tyrosinase strongly. Especially, analog 3 showed an inhibitory effect that was 220 and 22 times more powerful than kojic acid in the presence of l-tyrosine and l-dopa, respectively. A kinetic study utilizing mushroom tyrosinase showed that analogs 1 and 3 competitively inhibited tyrosinase, whereas analogs 2 and 5 inhibited tyrosinase in a mixed manner. A docking simulation study indicated that analogs 2 and 5 could bind to both the tyrosinase active and allosteric sites with high binding affinities. In cell-based experiments using B16F10 cells, analogs 1, 3, and 5 effectively inhibited melanin production; their anti-melanogenic effects were attributed to their ability to inhibit intracellular tyrosinase activity. Moreover, analogs 1, 3, and 5 inhibited in situ B16F10 cellular tyrosinase activity. In three antioxidant experiments, analogs 2 and 3 exhibited strong antioxidant efficacy, similar to that of the positive controls. These results suggest that the BMTTZD analogs are promising tyrosinase inhibitors for the treatment of hyperpigmentation-related disorders.

Impact of product packaging messages on consumer perceptions and choice: The role of health claims and bonus pack promotions.

This study used mixed methods to explore the impact of front-of-package health claims and bonus pack messages on consumer evaluations. First, a comprehensive audit of cereal box packages at the world's largest retailer examined how these messages are presented in practice. It was found that negative claims are more frequent and positive claims are less frequent on products with a bonus pack message compared to those without. A subsequent experiment investigated how combinations of health claims and bonus pack messages influence consumer evaluations. It also found that health claims significantly influenced consumer preferences, while bonus pack messages diminished perceptions of food healthiness but increased perceived value. Pairing positive health claims with bonus pack messages, such as "Family Size," improved perceptions of healthiness. Moreover, positive health claims made products seem of lower value, whereas negative health claims did not affect perceived value. Health claims negatively affected value perceptions, even when paired with bonus pack messages like "Large Size." However, the negative effect of health claims on tastiness perceptions was mitigated with "Large Size". The study underscores the complexity of consumer decision-making, and offer insights for food marketers, emphasizing the need of a strategic approach in crafting health-related messaging and promotional strategies for product packaging.

Self-Powered Electrical Bandage Based on Body-Coupled Energy Harvesting.

Self-powered electrical bandages (SEBs), integrated with wearable energy harvesters, can provide an effective and autonomous electrical stimulation (ES) solution for rapid and scarless wound healing. A continuously operating, wireless, and applicable-to-comprehensive-wound ES device is essential for the quick restoration of wounds and convenience. This work illustrates a SEB powered by body-coupled energy harvesting. The SEB continuously treats the wound with 60-Hz sinusoidal electrical potential gained from the coupling of the human body and ambient electrical waves. It is demonstrated that enough level of electrical potential can be applied to the wound, further enhanced by strong capacitive coupling arising from the use of high-permittivity poly(vinylidene fluoride-trifluoroethylene):CaCu3Ti4O12 (P(VDF-TrFE):CCTO) nanocomposite. The potential clinical efficacy of the SEB is illustrated by preclinical analysis of human fibroblasts and mouse wound model, thus confirming the successful expedition of wound recovery. This work suggests a new class of wearable devices to provide ES events and its potential for extension to other conventional wound care materials and device technology.

Stretchable Functional Nanocomposites for Soft Implantable Bioelectronics.

Material advances in soft bioelectronics, particularly those based on stretchable nanocomposites─functional nanomaterials embedded in viscoelastic polymers with irreversible or reversible bonds─have driven significant progress in translational medical device research. The unique mechanical properties inherent in the stretchable nanocomposites enable stiffness matching between tissue and device, as well as its spontaneous mechanical adaptation to in vivo environments, minimizing undesired mechanical stress and inflammation responses. Furthermore, these properties allow percolative networks of conducting fillers in the nanocomposites to be sustained even under repetitive tensile/compressive stresses, leading to stable tissue-device interfacing. Here, we present an in-depth review of materials strategies, fabrication/integration techniques, device designs, applications, and translational opportunities of nanocomposite-based soft bioelectronics, which feature intrinsic stretchability, self-healability, tissue adhesion, and/or syringe injectability. Among many, applications to brain, heart, and peripheral nerves are predominantly discussed, and translational studies in certain domains such as neuromuscular and cardiovascular engineering are particularly highlighted.

Reynoutria japonica consisted of emodin-8-ß-D-glucoside ameliorates Dermatophagoides farinae extract-induced atopic dermatitis-like skin inflammation in mice by inhibiting JAK/STAT signaling.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by skin barrier dysfunction and chronic inflammatory responses. Reynoutria japonica, known as Huzhang in traditional Chinese Medicine, can enhance blood circulation to eliminate wind pathogens and terminate coughing. Despite pharmacological evidence supporting the efficacy of R. japonica in suppressing edema-induced skin inflammation or connective tissue diseases, its pharmaceutical potential for treating AD-like skin inflammation remains unexplored. This study investigated the possible effects of R. japonica ethanol extract (RJE) on Dermatophagoides farinae extract (DfE)-induced AD-like skin inflammation in NC/Nga mice. To elucidate the underlying mechanisms by which RJE inhibits skin inflammation, we examined the effect of RJE on IFN-γ/TNF-α-induced signal transducer and activator of transcription (STAT) signaling in human epidermal keratinocytes (HEKs) and human dermal fibroblasts (HDFs). Our findings revealed that RJE mitigates DfE-induced AD-like symptoms and skin barrier disruptions in mouse skin lesions. Moreover, RJE attenuated DfE-induced mast cell infiltration and serum levels of inflammatory cytokines (IL-1α, IL-1ß, IL-6, IL-23, IFN-γ, TNF-α, and GM-CSF). RJE also inhibited IFN-γ/TNF-α-induced chemokine levels and STAT3 phosphorylation in HEKs and HDFs. Virtual binding analysis of the RJE components suggested that emodin-8-ß-D-glucoside binds to Janus kinase (JAK) 1/2, thereby suppressing STAT signaling, which was confirmed by Western blot analysis. In conclusion, our results suggest that RJE may alleviate DfE-induced skin barrier dysfunction by inhibiting JAK/STAT signaling and the proinflammatory immune response through the suppression of inflammatory mediators in AD-like skin disease. These findings suggest that RJE has potential as an effective therapy for AD management.

A non-destructive predictive model for estimating the freshness/spoilage of packaged chicken meat using changes in drip metabolites.

This study investigates the possibility of utilizing drip as a non-destructive method for assessing the freshness and spoilage of chicken meat. The quality parameters [pH, volatile base nitrogen (VBN), and total aerobic bacterial counts (TAB)] of chicken meat were evaluated over a 13-day storage period in vacuum packaging at 4 °C. Simultaneously, the metabolites in the chicken meat and its drip were measured by nuclear magnetic resonance. Correlation (Pearson's and Spearman's rank) and pathway analyses were conducted to select the metabolites for model training. Binary logistic regression (model 1 and model 2) and multiple linear regression models (model 3-1 and model 3-2) were trained using selected metabolites, and their performance was evaluated using receiver operating characteristic (ROC) curves. As a result, the chicken meat was spoiled after 7 days of storage, exceeding 20 mg/100 g VBN and 5.7 log CFU/g TAB. The correlation analysis identified one organic acid, eight free amino acids, and five nucleic acids as highly correlated with chicken meat and its drip during storage. Pathway analysis revealed tyrosine and purine metabolism as metabolic pathways highly correlated with spoilage. Based on these findings, specific metabolites were selected for model training: ATP, glutamine, hypoxanthine, IMP, tyrosine, and tyramine. To predict the freshness and spoilage of chicken meat, model 1, trained using tyramine, ATP, tyrosine, and IMP from chicken meat, achieved a 99.9 % accuracy and had an ROC value of 0.884 when validated using drip metabolites. This model 1 was improved by training with tyramine and IMP from both chicken meat and its drip (model 2), which increased the ROC value for drip metabolites from 0.884 to 0.997. Finally, selected two metabolites (tyramine and IMP) can predict TAB and VBN quantitatively through models 3-1 and 3-2, respectively. Therefore, the model developed using metabolic changes in drip demonstrated the capability to non-destructively predict the freshness and spoilage of chicken meat at 4 °C. To make generic predictions, it is necessary to expand the model's applicability to various conditions, such as different temperatures, and validate its performance across multiple chicken batches.

Nutrition and exercise: Cornerstones of health with emphasis on obesity and type 2 diabetes management-A narrative review.

While a broad consensus exists that integrated nutrition and regular exercise are foundational for health maintenance and serve as a robust non-pharmacological strategy against cardiometabolic diseases, the nuanced interplay between these elements remains incompletely understood. Through multifaceted interactions, these factors profoundly influence primary metabolic organs, notably the skeletal muscle and adipose tissue. Despite the critical nature of this interactivity, a holistic understanding of the combined effects of physical activity and dietary practices is still emerging. This narrative review aims to elucidate the intertwined roles of nutrition and exercise. It provides a comprehensive overview of their synergistic dynamics and emphasizes the importance of a dual-focus approach in mitigating and managing cardiometabolic disorders, predominantly obesity and type 2 diabetes.

Characteristics of Purified Horse Oil by Supercritical Fluid Extraction with Different Deodorants Agents.

This study investigated the impact of activated carbon, palm activated carbon, and zeolite on horse oil (HO) extracted from horse neck fat using supercritical fluid extraction with deodorant-untreated HO (CON) as a comparison. The yield and lipid oxidation of deodorant untreated HO (CON) were not significantly affected by the three deodorants. However, deodorant-treated HOs exhibited significantly elevated levels of α-linolenic acid (C18:3n3) and eicosenoic acid (C20:1n9) compared to CON (p<0.05), while other fatty acids remained consistent. Zeolite-purified HO demonstrated significantly lower levels of volatile organic compounds (VOCs) than other treatments (p<0.05). Remarkably, zeolite decreased the concentration of pentane, 2,3-dimethyl (gasoline odor), by over 90%, from 177.17 A.U. ×106 in CON to 15.91 A.U. ×106. Zeolite also effectively eliminates sec-butylamine (ammonia and fishy odor) as compared to other deodorant-treated HOs (p<0.05). Additionally, zeolite reduced VOCs associated with the fruity citrus flavor, such as nonanal, octanal, and D-limonene in HO (p<0.05). This study suggests that integrating zeolite in supercritical fluid extraction enhances HO purification by effectively eliminating undesirable VOCs, presenting a valuable approach for producing high-quality HO production in the cosmetic and functional food industries.

Antioxidants and Mechanistic Insights for Managing Dry Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) severely affects central vision due to progressive macular degeneration and its staggering prevalence is rising globally, especially in the elderly population above 55 years. Increased oxidative stress with aging is considered an important contributor to AMD pathogenesis despite multifaceted risk factors including genetic predisposition and environmental agents. Wet AMD can be managed with routine intra-vitreal injection of angiogenesis inhibitors, but no satisfactory medicine has been approved for the successful management of the dry form. The toxic carbonyls due to photo-oxidative degradation of accumulated bisretinoids within lysosomes initiate a series of events including protein adduct formation, impaired autophagy flux, complement activation, and chronic inflammation, which is implicated in dry AMD. Therapy based on antioxidants has been extensively studied for its promising effect in reducing the impact of oxidative stress. This paper reviews the dry AMD pathogenesis, delineates the effectiveness of dietary and nutrition supplements in clinical studies, and explores pre-clinical studies of antioxidant molecules, extracts, and formulations with their mechanistic insights.

Near Infrared Autofluorescence Lifetime Imaging of Human Retinal Pigment Epithelium Using Adaptive Optics Scanning Light Ophthalmoscopy.

Purpose: To demonstrate the first near-infrared adaptive optics fluorescence lifetime imaging ophthalmoscopy (NIR-AOFLIO) measurements in vivo of the human retinal pigment epithelial (RPE) cellular mosaic and to visualize lifetime changes at different retinal eccentricities. Methods: NIR reflectance and autofluorescence were captured using a custom adaptive optics scanning light ophthalmoscope in 10 healthy subjects (23-64 years old) at seven eccentricities and in two eyes with retinal abnormalities. Repeatability was assessed across two visits up to 8 weeks apart. Endogenous retinal fluorophores and hydrophobic whole retinal extracts of Abca4-/- pigmented and albino mice were imaged to probe the fluorescence origin of NIR-AOFLIO. Results: The RPE mosaic was resolved at all locations in five of seven younger subjects (<35 years old). The mean lifetime across near-peripheral regions (8° and 12°) was longer compared to near-foveal regions (0° and 2°). Repeatability across two visits showed moderate to excellent correlation (intraclass correlation: 0.88 [τm], 0.75 [τ1], 0.65 [τ2], 0.98 [a1]). The mean lifetime across drusen-containing eyes was longer than in age-matched healthy eyes. Fluorescence was observed in only the extracts from pigmented Abca4-/- mouse. Conclusions: NIR-AOFLIO was repeatable and allowed visualization of the RPE cellular mosaic. An observed signal in only the pigmented mouse extract infers the fluorescence signal originates predominantly from melanin. Variations observed across the retina with intermediate age-related macular degeneration suggest NIR-AOFLIO may act as a functional measure of a biomarker for in vivo monitoring of early alterations in retinal health.

Production of H2 and Glucaric Acid Using Electrocatalyst Glucose Oxidation by the Ta NiFe LDH Electrode.

The slow anodic oxygen evolution reaction (OER) significantly limits electrocatalytic water splitting for hydrogen production. We proposed the electrocatalyst for glucose oxidation by Ta-doping NiFe LDH nanosheets to simultaneously obtain glucaric acid (GRA) and hydrogen gas as a useful byproduct. Superior glucose oxidation reaction (GOR) activity is demonstrated by the optimized Ta-NiFe LDH, which has a low overpotential of 192 mV, allowing for a small Tafel slope of 70 mV dec-1 and a current density of 50 mA cm-2. The Ta NiFe LDH-oxidized glucose to GRA with a 72.94% yield and 64.3% Faradaic efficiency at 1.45 VRHE. Herein, we report the Ta NiFe LDH/NF electrode for the GOR&hydrogen evolution reaction (HER), which exhibits a cell voltage of 1.62 V to reach a current density of 10 mA cm-2, which is 250 mV lower compared to OER&HER (1.87 V). This study reveals that GOR is an energy-efficient and cost-effective method for producing H2 and valorizing biomass.

Alleviating depressive-like behavior in DSS-induced colitis mice: Exploring naringin and poncirin from Poncirus trifoliata extracts.

Patients with inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn's disease (CD), often have concomitant mental disorders such as depression and anxiety. Therefore, a bidirectional approach involving the gut and brain axes is necessary for the prevention and treatment thereof. In this study, we explored the potential of Poncirus trifoliata extract (PT), traditionally known for its neuroprotective effects against gastrointestinal diseases, as a natural treatment agent for IBD in a dextran sulfate sodium (DSS)-induced colitis model. Oral administration of PT ameliorated weight loss and inflammatory responses in mice with DSS-induced colitis. Furthermore, PT treatment effectively restored the colon length and ameliorated enterocyte death by inhibiting DSS-induced reactive oxygen species (ROS)-mediated necroptosis. The main bioactive components of PT, poncirin and naringin, confirmed using ultra-performance liquid chromatography-quadrupole time-of-flight (UPLC-qTOF), can be utilized to regulate necroptosis. The antidepressant-like effects of PT were confirmed using open field test (OFT) and tail suspension test (TST). PT treatment also restored vascular endothelial cell integrity in the hippocampus. In the Cornu Ammonis 1 (CA1) and dentate gyrus (DG) regions of the hippocampus, PT controlled the neuroinflammatory responses of proliferated microglia. In conclusion, PT, which contains high levels of poncirin and naringin, has potential as a bidirectional therapeutic agent that can simultaneously improve IBD-associated intestinal and mental disorders.

SYNGAP1-related developmental and epileptic encephalopathy: Genotypic and phenotypic characteristics and longitudinal insights.

The clinical and genetic characteristics of SYNGAP1 mutations in Korean pediatric patients are not well understood. We retrospectively analyzed 13 individuals with SYNGAP1 mutations from a longitudinal aspect. Clinical data, genetic profiles, and electroencephalography (EEG) patterns were examined. Genotypic analyses included gene panels and whole-exome sequencing. All patients exhibited global developmental delay from early infancy, with motor development eventually reaching independent ambulation by 3 years of age. Language developmental delay varied significantly from nonverbal to simple sentences, which plateaued in all patients. Patients with the best language outcomes typically managed 2-3-word sentences, corresponding to a developmental age of 2-3 years. Epilepsy developed in 77% of patients, with onset consistently following developmental delays at a median age of 31 months. Longitudinal EEG data revealed a shift from occipital to frontal epileptiform discharges with age, suggesting a correlation with synaptic maturation. These findings suggest that the critical developmental plateau occurs between the ages of 2 and 5 years and is potentially influenced by epilepsy. By analyzing longitudinal data, our study contributes to a deeper understanding of SYNGAP1-related DEE, provides potential EEG biomarkers, and underlines the importance of early diagnosis and intervention to address this complex disorder.