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Plant polyphenols are widely used to treat various inflammatory diseases, owing to their ability to suppress reactive oxygen species production and the expression of inflammatory cytokines. Herein, we investigated phenolic compounds from Calystegia soldanella using UPLC Q-TOF MS/MS and their antioxidative and anti-inflammatory activities were analyzed. The C. soldanella ethyl acetate fraction (CsEF) had the strongest antioxidative activity, given its high polyphenol compound content. It also exhibited anti-inflammatory effects, inhibiting the production of inflammatory cytokines such as NO, PGE2, IL-1β, IL-6, and TNF-α in LPS-stimulated mouse macrophages. CsEF activated the nuclear transcription factor Nrf-2, thereby upregulating antioxidant enzymes such as HO-1 and NQO-1 and inhibiting NF-κB expression, which in turn, suppressed the expression of COX-2, iNOS, and inflammatory cytokines, ultimately exerting anti-inflammatory effects. Further, UPLC-Q-TOF-MS/MS was used to analyze the polyphenol compound contents in CsEF. The quercetin glycosides isoquercitrin and quercitrin were the primary flavonoid compounds, while the caffeic acid derivatives, chlorogenic acid and dicaffeoylquinic acid, were the primary phenolic acids. Thus, C. soldanella, which had only a limited use thus far as a medicinal plant, may serve as a natural medicinal resource for treating inflammatory diseases.

Background and Objectives: Early intensive exercise after total knee replacement arthroplasty (TKRA) has become increasingly popular due to its ability to enhance knee physical function and reduce pain. When implemented exclusively, aquatic exercise (AE) appears to be more advantageous than land exercise (LE), particularly in the early phase after TKRA. Our study aimed to compare the clinical efficacy of AE and LE with respect to their effects on pain and physical function after TKRA. Materials and Methods: Between February 2008 and January 2020, 100 female patients who underwent TKRA were enrolled in this retrospective study. We measured the range of motion (ROM) of the knee, the isokinetic strength of the knee joint (function), and pain both initially and one month after TKRA. Two weeks after TKRA, the participants were enrolled in either the AE or the LE program for a total of two weeks. Two 30 min sessions of intensive ROM and knee strengthening exercises and balance training were provided to the AE and LE groups for 10 days. The home exercise group (HE) only received information on ROM and strengthening exercises. There were 33, 21, and 46 patients allocated to the AE, LE, and HE groups, respectively. Results: The ROM of the side on which surgery was performed improved significantly in all groups, as did the pain scores. In the AE group, the knee flexor strength showed a tendency toward improvement. Contrastingly, there was no significant improvement in the knee extensor strength in the AE group. Conclusions: Overall, the AE and LE groups showed superior outcomes compared with HE. In addition, the AE group demonstrated some improvement in knee muscle strength even with a short hospital stay. Further study with long-term follow-up should be performed to better define the outcomes.

This study investigates the effect of Licochalcone A (Lico-A), a flavonoid from licorice roots known for its anti-inflammatory, anti-cancer, and antioxidant properties, on NMDA-induced neurotoxicity in primary cultured rat hippocampal neurons. The study measured cell survival following NMDA and Lico-A exposure, revealing that Lico-A at a 2.5 μg/ml significantly improved cell viability, countering the detrimental effects of NMDA. The study also analyzed synaptic changes by examining both postsynaptic density 95 (PSD95) and synaptophysin-targeted imaging, showing that Lico-A treatment resulted in a significant increase in synaptic puncta, contrasting with the reduction observed under NMDA exposure. Furthermore, levels of phosphorylated mixed lineage kinase domain-like pseudokinase (P-MLKL) and phosphorylated receptor-interacting serine/threonine-protein kinase 3 (P-RIP3), key necroptosis regulators, were measured using Western blotting. The results showed an increase in P-MLKL and P-RIP3 in neurons exposed to NMDA, which was reduced following Lico-A treatment. The response of astrocyte and microglia was also evaluated by immunostaining for glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor molecule 1 (IBA-1) and tumor necrosis factor alpha (TNF-α). These markers exhibited heightened expression in the NMDA group, which was substantially reduced by Lico-A treatment. These findings suggest that Lico-A has neuroprotective effects against NMDA-induced neurotoxicity, potentially contributing to synaptic preservation, inhibition of neuronal necroptosis, and modulation of glial activation. Therefore, Lico-A shows promise as a neuroprotective agent for conditions associated with NMDA-related neurotoxicity.

Abstract Background Accurate attenuation correction (AC) is vital in nuclear medicine, particularly for quantitative single-photon emission computed tomography/computed tomography (SPECT/CT) imaging. This study aimed to establish a CT-free quantification technology in kidney SPECT imaging using deep learning to generate synthetic attenuation maps (μ-maps) from SPECT data, thereby reducing radiation exposure and eliminating the need for CT scans. Results A dataset of 1000 Tc-99m DTPA SPECT/CT scans was analyzed for training (n = 800), validation (n = 100), and testing (n = 100) using a modified 3D U-Net for deep learning. The study investigated the use of primary emission and scattering SPECT data, normalization methods, loss function optimization, and up-sampling techniques for optimal μ-map generation. The problem of checkerboard artifacts, unique to μ-map generation from SPECT signals, and the effects of iodine contrast media were evaluated. The addition of scattering SPECT to primary emission SPECT imaging, logarithmic maximum normalization, the combination of absolute difference loss (L1) and three times the absolute gradient difference loss (3 × LGDL), and the nearest-neighbor interpolation significantly enhanced AI performance in μ-map generation (p < 0.00001). Checkerboard artifacts were effectively eliminated using the nearest-neighbor interpolation technique. The developed AI algorithm produced μ-maps neutral to the presence of iodine contrast and showed negligible contrast effects on quantitative SPECT measurement, such as glomerular filtration rate (GFR). The potential reduction in radiation exposure by transitioning to AI-based CT-free SPECT imaging ranges from 45.3 to 78.8%. Conclusion The study successfully developed and optimized a deep learning algorithm for generating synthetic μ-maps in kidney SPECT images, demonstrating the potential to transition from conventional SPECT/CT to CT-free SPECT imaging for GFR measurement. This advancement represents a significant step towards enhancing patient safety and efficiency in nuclear medicine.

Background:. Oenanthe javanica (O. javanica) has been known to have high antioxidant properties via scavenging reactive oxygen species. We examined the effect of O. javanica extract (OJE) on antioxidant enzymes in the rat liver. Methods:. We examined the effect of the OJE on copper, zinc-superoxide dismutase (SOD1), manganese superoxide dismutase (SOD2), catalase (CAT), and glutathione peroxidase (GPx) in the rat liver using immunohistochemistry and western blot analysis. Sprague-Dawley rats were randomly assigned to three groups; (1) normal diet fed group (normal-group), (2) diet containing ascorbic acid (AA)-fed group (AA-group) as a positive control, (3) diet containing OJE-fed group (OJE-group). Results:. In this study, no histopathological finding in the rat liver was found in all the experimental groups. Numbers of SOD1, SOD2, CAT, and GPx immunoreactive cells and their protein levels were significantly increased in the AA-fed group compared with those in the normal-group. On the other hand, in the OJE-group, numbers of SOD1, SOD2, CAT, and GPx immunoreactive cells in the liver were significantly increased by about 190%, 478%, 685%, and 346%, respectively, compared with those in the AA-group. In addition, protein levels of SOD1, SOD2, CAT, and GPx in the OJE-group were also significantly much higher than those in the AA-group. Conclusion:. OJE significantly increased expressions of SOD1 and SOD2, CAT, and GPx in the liver cells of the rat, and these suggests that significant enhancements of endogenous enzymatic antioxidants by OJE might be a legitimate strategy for decreasing oxidative stresses in the liver.

Background: The Fourth Industrial Revolution highlights the importance of artificial intelligence (AI) and digital literacy in dental hygiene education. However, research on students’ attitudes toward AI and their digital literacy levels is limited. Therefore, this study investigated the attitudes of dental hygiene students toward AI and digital literacy levels. Methods: In total, 167 dental hygiene students in Baekseok University participated in the study and provided informed consent. The survey tool included general characteristics, smartphone usage patterns, attitudes toward AI, and digital literacy levels. Attitudes toward AI and digital literacy based on general characteristics and smart device usage were analyzed using t-tests and one-way ANOVA. Correlations among attitudes toward AI, digital literacy awareness, and digital literacy behaviors were analyzed using Pearson’s correlation analysis. The impact of AI attitudes and digital literacy awareness on digital literacy behavior was examined using linear regression analysis. Results: Students with higher interest in their major had more positive attitudes toward AI, and those with higher smart device usage showed increased AI attitudes and digital literacy (p＜0.05). Simple frequency or duration of smartphone use did not affect digital literacy, but students who perceived their smart device usage positively and believed that they used smart devices effectively in their studies exhibited higher levels of digital literacy (p＜0.05). A positive attitude toward AI is associated with higher levels of digital literacy (p＜0.05). Digital literacy awareness and attitudes toward AI influenced digital literacy behavior (p＜0.05). Conclusion: These results suggest that the qualified utilization and application of digital devices in dental hygiene education are important. Improving the educational curriculum is necessary; as a result, digital technology can be effectively utilized, and various educational programs should be introduced to enhance digital literacy.

Background and objectives: The effects of noninvasive focused magnetothermal brain stimulation using magnetic nanoparticles (MNPs) on post-stroke motor deficits and metabolic dormancy in subacute ischemic injury are not well-established. This study examined if magnetothermal brain stimulation using magnetic nanoparticles (Nano-MS) enhances motor recovery after stroke. Methods: We randomly distributed rats into Sham, Control, MNP injection only, and Nano-MS groups. We administered focused magnetic stimulation for 30 min daily following an MNP injection (15 mg/mL) into the targeted motor cortex via the carotid artery three weeks after the transient (90 min) middle cerebral artery occlusion. We assessed motor functionality via behavioral tests and conducted positron emission tomography (PET) imaging to verify cerebral metabolic activity. We assessed neuronal excitability, neuroinflammation, blood-brain barrier (BBB) integrity, and neurogenesis four weeks post-stroke. Results: The Nano-MS group exhibited significantly improved motor deficits and cerebral metabolic activity compared to the Control and MNP groups (p

Purpose: We aimed to identify the genetic causes of hypospadias in children using targeted gene panel sequencing for disorders of sex development (DSD). Materials and Methods: This study included 18 twin boys with hypospadias: seven and two pairs were monozygotic and dizygotic twins, respectively, and six were discordant and three were concordant twins. Targeted gene panel sequencing for 67 known DSD genes was performed. Sequence variants were classified into five different categories, pathogenic, likely pathogenic, variants of uncertain significance, likely benign, and benign, following the American College of Medical Genetics and Genomics Standards and Guidelines. Results: The mean gestational age and birth weight were 35.3±2.0 weeks and 1.96±0.61 kg, respectively, with seven patients being small for gestational age. Hypospadias was present in 12 patients, with posterior type in 33.3% and anterior type in 66.7%. In three families with twins, both siblings had hypospadias. In addition, cryptorchidism was observed in one subject. Surgical correction of hypospadias was performed at a mean age of 22.1 months. Molecular analysis identified 12 different genetic variants, including two pathogenic mutations in the AMH (p.E389*) and SRD5A2 (p.R246Q) genes, found in subjects with hypospadias, respectively. However, only heterozygous mutations were detected. Conclusions: This study did not identify a definitive genetic component contributing to the development of hypospadias; however, the findings suggest that intrauterine growth retardation may play a significant role.

Abstract As childhood obesity rates increase worldwide, the prevalence of obesity-related hypertension is also on the rise. Obesity has been identified as a significant risk factor for hypertension in this age group. National Health Surveys and meta-analyses show increasing trends in obesity and pediatric hypertension in obese children. The diagnosis of hypertension in children involves percentiles relative to age, sex, and height, unlike in adults, where absolute values are considered. Elevated blood pressure (BP) in childhood is consistently associated with cardiovascular disease in adulthood, emphasizing the need for early detection and intervention. The pathogenesis of hypertension in obesity involves multiple factors, including increased sympathetic nervous system activity, activation of the renin-angiotensin-aldosterone system (RAAS), and renal compression due to fat accumulation. Obesity disrupts normal RAAS suppression and contributes to impaired pressure natriuresis and sodium retention, which are critical factors in the development of hypertension. Risk factors for hypertension in obesity include degree, duration, and distribution of obesity, patient age, hormonal changes during puberty, high-sodium diet, sedentary lifestyle, and socioeconomic status. Treatment involves lifestyle changes, with weight loss being crucial to lowering BP. Medications such as angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers may be considered first, and surgical approaches may be an option for severe obesity, requiring tailored antihypertensive medications that consider individual pathophysiology to avoid exacerbating insulin resistance and dyslipidemia.

We report a case of Taenia solium taeniasis in a 10-year-old child in Timor-Leste, confirmed by molecular analysis, suggesting T. solium transmission to humans is occurring in Timor-Leste. Proactive measures are needed to improve public understanding of prevalence, geographic spread, and health implications of human taeniasis and cysticercosis in Timor-Leste.

Abstract Low-level somatic mutations in the human brain are implicated in various neurological disorders. The contribution of low-level brain somatic mutations to autism spectrum disorder (ASD), however, remains poorly understood. Here, we performed high-depth exome sequencing with an average read depth of 559.3x in 181 cortical, cerebellar, and peripheral tissue samples to identify brain somatic single nucleotide variants (SNVs) in 24 ASD subjects and 31 controls. We detected ~2.4 brain somatic SNVs per exome per single brain region, with a variant allele frequency (VAF) as low as 0.3%. The mutational profiles, including the number, signature, and type, were not significantly different between the ASD patients and controls. Intriguingly, when considering genes with low-level brain somatic SNVs and ASD risk genes with damaging germline SNVs together, the merged set of genes carrying either somatic or germline SNVs in ASD patients was significantly involved in ASD-associated pathophysiology, including dendrite spine morphogenesis (p = 0.025), mental retardation (p = 0.012), and intrauterine growth retardation (p = 0.012). Additionally, the merged gene set showed ASD-associated spatiotemporal expression in the early and mid-fetal cortex, striatum, and thalamus (all p

Background Ibuprofen and acetaminophen are widely used as adjuvant analgesics for postoperative pain. This meta-analysis compared the effects of intravenous (IV) ibuprofen and acetaminophen on postoperative opioid consumption and pain intensity after general anesthesia. Methods PubMed/MEDLINE, EMBASE, and Cochrane Library databases were searched to identify relevant studies published up to May 2023. Randomized controlled trials comparing the effects of perioperative IV ibuprofen and acetaminophen on postoperative opioid consumption and pain after general anesthesia were included in the meta-analysis and trial sequential analysis (TSA). Results Eight studies with 494 participants were included. Compared to IV acetaminophen, IV ibuprofen significantly reduced 24 h opioid consumption, presented as morphine equivalents (mean difference [MD]: –6.01 mg, 95% CI [–8.60, –3.42], P < 0.00001, I2 = 55%), and pain scores (on a scale of 0–10) at 4–6 h (MD: –0.83, 95% CI [–1.29, –0.37], P = 0.0004, I2 = 65%) and 12 h (MD: –0.38, 95% CI [–0.68, –0.08], P = 0.01, I2 = 11%) postoperatively. These results were statistically significant in TSA. Pain scores at 24 h postoperatively and side effects were not significantly different between the two groups in the meta-analysis, and TSA revealed that the sample size was too small to adequately evaluate the effects, requiring further studies for conclusive results. Conclusions Perioperative IV ibuprofen reduced 24 h opioid consumption and pain severity up to 12 h postoperatively compared to acetaminophen. Additional research is required to assess pain intensity beyond 12 h and side effects.

Background Whether advanced age is associated with poor outcomes of elderly patients with acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT) is controversial. This study aimed to evaluate age effect and predictors for mortality in elderly AKI patients undergoing CRRT. Methods Data of 480 elderly AKI patients who underwent CRRT were retrospectively analyzed. Subjects were stratified into two groups according to age: younger-old (age, 65–74 years; n = 205) and older-old (age, ≥75 years; n = 275). Predictors for 28-day and 90-day mortality and age effects were analyzed using multivariable Cox regression analysis and propensity score matching. Results Urine output at the start of CRRT (adjusted hazard ratio [aHR], 0.99; 95% confidence interval [CI], 0.99–1.00; p = 0.04), operation (aHR, 0.53; 95% CI, 0.30–0.93; p = 0.03), and use of an intra-aortic balloon pump (aHR, 3.60; 95% CI, 1.18–10.96; p = 0.02) were predictors for 28-day mortality. Ischemic heart disease (aHR, 1.74; 95% CI, 1.02–2.98; p = 0.04) and use of a ventilator (aHR, 0.56; 95% CI, 0.36–0.89; p = 0.01) were predictors for 90-day mortality. The older-old group did not exhibit a higher risk for 28-day or 90-day mortality than the younger-old group in multivariable or propensity score-matched models. Conclusion Advanced age was not a risk factor for mortality among elderly AKI patients undergoing CRRT, suggesting that advanced age should not be considered for therapeutic decisions in critically ill elderly patients with AKI requiring CRRT.

Background/Aims: The gut microbiome has emerged as a key player that mechanistically links various risk factors to colorectal cancer (CRC) etiology. However, the role of the gut microbiome in CRC pathogenesis remains unclear. This study aimed to characterize the gut microbiota in healthy controls (HCs) and patients with colorectal adenoma (AD) and CRC in subgroups based on sex and age. Methods: Study participants who visited the hospital for surveillance of CRC or gastrointestinal symptoms were prospectively enrolled, and the gut microbiome was analyzed based on fecal samples. Results: In terms of HC-AD-CRC sequence, commensal bacteria, including lactate-producing (Streptococcus salivarius) and butyrate-producing (Faecalibacterium prausnitzii, Anaerostipes hadrus, and Eubacterium hallii) bacteria, were more abundant in the HC group than in the AD and CRC groups. In the sex comparison, the female HC group had more lactate-producing bacteria (Bifidobacterium adolescentis, Bifidobacterium catenulatum, and Lactobacillus ruminis) than the male HC group. In age comparison, younger subjects had more butyrate-producing bacteria (Agathobaculum butyriciproducens and Blautia faecis) than the older subjects in the HC group. Interestingly, lactate-producing bacteria (B. catenulatum) were more abundant in females than males among younger HC group subjects. However, these sex- and age-dependent differences were not observed in the AD and CRC groups. Conclusion : s: The gut microbiome, specifically lactate- and butyrate-producing bacteria, which were found to be abundant in the HC group, may play a role in preventing the progression of CRC. In particular, lactate-producing bacteria, which were found to be less abundant in healthy male controls may contribute to the higher incidence of CRC in males.

Mucopolysaccharidosis type I (MPS I) is a rare metabolic disorder caused by deficiency of α-L-iduronidase (IDUA), resulting in glycosaminoglycan (GAG) accumulation and multisystemic disease. Current treatments include hematopoietic stem cell transplantation and enzyme replacement therapy, but these do not address all manifestations of the disease. We infused MPS I mice with an adeno-associated virus 9 (AAV9)-IDUA vector (RGX-111) at doses from 107 to 1010 vector genomes (vg) via intrathecal (IT), intravenous (IV), and intrathecal+intravenous (IT+IV) routes of administration. In mice administered doses ≤109 vg IT or ≤108 vg IV, there was no therapeutic benefit, while in mice administered 109 vg IV, there was a variable increase in IDUA activity with inconclusive neurocognitive and cardiac assessments. However, at the 1010 vg dose, we observed substantial metabolic correction, with restored IDUA levels and normalized tissue GAGs for all treatment groups. Aortic insufficiency was mostly normalized, neurologic deficit was prevented, and microcomputed tomography (micro-CT) analysis showed normalization of skeletal parameters. Histologic analysis showed minimal GAG storage and lysosomal pathology. We thus report a minimal effective dose of 1010 vg (5 × 1011 per kg) RGX-111 for IV and IT routes of administration in MPS I mice, which prevented neurocognitive deficit, cardiac insufficiency, and skeletal manifestations, as a model for genetic therapy of human MPS I.

The objective of this study was to evaluate the effects of dietary mangosteen peel preparations, either powdered (MspP) or ethanolic extract (MspE), on the growth performance, meat quality, immune response, gut health, serum biochemical profiles, and antioxidant activity of broiler chicks. A total of 480 day-old straight-run broiler chicks (Ross 308) were randomly placed into four treatments, with eight replicates of 12 chicks each, and subjected to one of the four experimental diets for 21 days. The corn and soybean meal-based diet was supplemented with 2% MspP (20 g per kg of diet) or 0.05% and 0.1% MspE (0.5 g and 1.0 g per kg of diet). Data were analyzed using analysis of variance, and post hoc comparisons of treatments were performed using Tukey's Honestly Significant Difference test. From days 0 to 21, dietary mangosteen peel preparations did not affect growth performance (body weight gain, feed intake, and feed conversion ratio), thigh meat and tibia characteristics, serum markers of innate immunity (interferon-r, interleukin-10, alpha-1-acid glycoprotein, and nitric oxide), and ileal morphology in broiler chicks (P > 0.05). Dietary mangosteen peel preparations increased the percentage of high-density lipoprotein cholesterol and decreased the relative concentrations of isobutyrate and branched-chain fatty acids in the cecal digesta compared with the control chickens. Notably, dietary mangosteen peel preparations altered the antioxidant characteristics of the serum, liver, and thigh meat. Dietary MspE increased glutathione peroxidase (P = 0.039) in the serum and catalase in the serum (P = 0.008), liver (P = 0.05), and thigh meat (P = 0.01) compared to the control group. In addition, dietary MspP increased catalase levels in thigh meat compared to those in the control diet-fed chickens (P = 0.01). The concentration of malondialdehyde, an indicator of lipid peroxidation, was lower in all chicks-fed diets containing mangosteen peel preparations; however, statistical significance was only noted in the serum samples (P < 0.0001). Collectively, our study shows that dietary mangosteen peel preparations are potent natural antioxidants that can be used as functional dietary additives to effectively mitigate oxidative stress in broiler chicks.

IntroductionChewing has been reported to enhance cognitive function through the increase in cerebral blood flow. However, the mechanisms linking cerebral blood flow increase to metabolic changes in the brain affecting cognition remain unclear. We hypothesized that glutathione (GSH) plays a pivotal role in these mechanisms. Therefore, this study aimed to investigate changes in brain GSH levels following chewing and their association with cognitive function in healthy young adults.MethodsA total of 52 university students were recruited, and the Korean version of the Repeatable Battery for the Assessment of Neuropsychological Status was used for the neurocognitive evaluations. Brain GSH levels following chewing gum or wood blocks were measured using MEscher-GArwood Point RESolved Spectroscopy (MEGA-PRESS) sequence, and their relevance to neurocognitive evaluation results was investigated.ResultsChewing significantly increased brain GSH concentration, particularly in the wood-chewing group compared to the gum-chewing group, as observed in the anterior cingulate cortex. Furthermore, the rise in GSH concentration in the wood-chewing group was positively correlated with memory function.ConclusionChewing moderately hard material elevates brain antioxidant levels such as GSH, potentially influencing cognitive function.

Pancreatic cancer is among the most lethal cancers with limited treatment options. Traditional herbal medicines have been explored as potential adjunct therapies for enhancing the effectiveness of standard chemotherapies. In this study, we investigated the safety and efficacy of Rhus verniciflua Stokes (RVS) in combination with first-line chemotherapy for unresectable locally advanced and metastatic pancreatic cancer in a prospective setting. This prospective observational pilot study enrolled patients with confirmed inoperable stage III or IV pancreatic cancer undergoing or scheduled to receive 5-fluorouracil-based or gemcitabine-based first-line chemotherapy with RVS treatment and were followed up for up to 20 months. The primary endpoint was the safety profile of RVS, which was assessed through adverse events. The secondary endpoints included overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Cox regression analysis identified possible prognostic factors for PFS and OS. Of the enrolled 25 patients, 18 completed the follow-up. The median RVS treatment duration was 6.14 months (range 2.23–8.01 months) and the median RVS daily dose was 3.8 capsules/day (range 2.1–5.7 capsules/day). RVS showed a favorable safety profile, with only one case of non-severe pruritus possibly related to RVS treatment. No hepatotoxicity and nephrotoxicity related to RVS was reported. The ORR and DCR were 5.6% and 72.2%, respectively. The median PFS and OS were 7.24 months (95% CI: 3.15–12.9) and 13.9 months (95% CI: 1.14–27.72), respectively. Cox regression analysis showed that baseline CA19-9 level was an independent prognostic factor for OS, and the daily dose of RVS was an independent prognostic factor for PFS and OS. In conclusion, RVS can be administered safely to patients with unresectable locally advanced metastatic pancreatic cancer who are undergoing first-line chemotherapy, and the daily dose was an independent prognostic factor for cancer survival. Further randomized controlled studies are warranted to confirm the exact benefits of RVS treatment.Clinical trial registrationhttps://cris.nih.go.kr, identifier KCT0007496.

Introduction Technetium thyroid uptake (TcTU) measured by single-photon emission CT/CT (SPECT/CT) is an important diagnostic tool for the differential diagnosis of Graves’ disease and destructive thyroiditis. Artificial intelligence (AI) may reduce CT-induced radiation exposure by substituting the role of CT in attenuation correction (AC) and thyroid segmentation, thus realising CT-free SPECT. This study aims to compare the diagnostic accuracy for the differential diagnosis of thyrotoxicosis between CT-free SPECT and SPECT/CT.Methods and analysis The AI-based CT-free SPECT is a single-blind, multicentre, prospective, non-inferiority, clinical trial with a paired design conducted in the Republic of Korea. Eligible participants are adult (≥19 years old) thyrotoxicosis patients without a previous history of hyperthyroidism or hypothyroidism. Approximately 160 subjects will be screened for quantitative thyroid SPECT/CT using Tc-99m pertechnetate. CT-free thyroid SPECT will be realised using only SPECT data by the trained convolutional neural networks. TcTU will be calculated by SPECT/CT and CT-free SPECT in each subject. The primary endpoint is the accuracy of diagnosing Graves’ disease using TcTU. The trial will continue until 152 completed datasets have been enrolled to assess whether the 95% (two-sided) lower confidence limit of the accuracy difference (CT-free SPECT accuracy—SPECT/CT accuracy) for Graves’ disease is greater than −0.1. The secondary endpoints include the accuracy of diagnosing destructive thyroiditis and predicting the need for antithyroid drug prescription within 1 month of the SPECT/CT.Ethics and dissemination The study protocol has been approved by the institutional review board of Seoul National University Bundang Hospital (IRB No. B-2304-824-301), Konkuk University Medical Center (IRB No. 2023-05-022-006) and Chonnam National University Hospital (IRB No. CNUH-2023-108). Findings will be disseminated as reports, presentations and peer-reviewed journal articles.Trial registration number KCT0008387, Clinical Research Information Service of the Republic of Korea (CRIS).

The incidence of hypertension has increased dramatically in both elderly and young populations. The incidence of hypertension also increased with the outbreak of the COVID-19 pandemic. To enhance hypertension detection accuracy, we proposed a multivariate outlier removal method based on the deep autoencoder (DAE) technique. The method was applied to the Korean National Health and Nutrition Examination Survey (KNHANES) database. Several studies have identified various risk factors for chronic hypertension. Chronic diseases are often multifactorial rather than isolated and have been associated with COVID-19. Therefore, it is necessary to study disease detection by considering complex factors. This study was divided into two main parts. The first module, data preprocessing, integrated external features for COVID-19 patients merged by region, age, and gender for the KHNANE-2020 and Kaggle datasets. We then performed multicollinearity (MC)-based feature selection for the KNHANES and integrated datasets. Notably, our MC analysis revealed that the "COVID-19 statement" feature, with a variance inflation factor (VIF) of 1.023 and a p-value < 0.01, is significant in predicting hypertension, underscoring the interrelation between COVID-19 and hypertension risk. The next module used a predictive analysis step to detect and predict hypertension based on an ordinal encoder (OE) transformation and multivariate outlier removal using a DAE from the KNHANES data. We compared each classification model's accuracy, F1 score, and area under the curve (AUC). The experimental results showed that the proposed XGBoost model achieved the best results, with an accuracy rate of 87.78% (86.49%–88.1%, 95% CI), an F1 score of 89.95%, and an AUC of 92.28% for the COVID-19 cases, and an accuracy rate of 87.72% (85.86%–89.69%, 95% CI), an F1 score of 89.94%, and an AUC of 92.23% for the non-COVID-19 cases with the DAE_OE model. We improved the prediction performance of the classifiers used in all experiments by developing a high-quality training dataset implementing the DAE and OE in our method. Moreover, we experimentally demonstrated how the steps of the proposed method improved performance. Our approach has potential applications beyond hypertension detection, including other diseases such as stroke and cardiovascular disease.

Abstract The human microbiome contains genetic information that regulates metabolic processes in response to host health and disease. While acidic vaginal pH is maintained in normal conditions, the pH level increases in infectious vaginitis. We propose that this change in the vaginal environment triggers the biosynthesis of anti-vaginitis metabolites. Gene expression levels of Chryseobacterium gleum, a vaginal symbiotic bacterium, were found to be affected by pH changes. The distinctive difference in the metabolic profiles between two C. gleum cultures incubated under acidic and neutral pH conditions was suggested to be an anti-vaginitis molecule, which was identified as phenylacetic acid (PAA) by spectroscopic data analysis. The antimicrobial activity of PAA was evaluated in vitro, showing greater toxicity toward Gardnerella vaginalis and Candida albicans, two major vaginal pathogens, relative to commensal Lactobacillus spp. The activation of myeloperoxidase, prostaglandin E2, and nuclear factor-κB, and the expression of cyclooxygenase-2 were reduced by an intravaginal administration of PAA in the vaginitis mouse model. In addition, PAA displayed the downregulation of mast cell activation. Therefore, PAA was suggested to be a messenger molecule that mediates interactions between the human microbiome and vaginal health.

MRI plays a crucial role in bone marrow (BM) assessment, and has very high sensitivity in diagnosing marrow disorders. However, for radiologists who may not frequently encounter pediatric imaging, distinguishing pathologic BM lesion from normal BM can be challenging. Conditions involving the BM in pediatric patients, such as leukemia and metastatic neuroblastoma, often manifest with diverse musculoskeletal symptoms and may be diagnosed using musculoskeletal MRI examinations. Accurate interpretation of pediatric MRI requires not only an understanding of the normal composition of BM but also an awareness of agerelated developmental changes in the marrow and familiarity with conditions that commonly involve pediatric BM. We aim to describe the composition of normal BM and outline the normal and abnormal MRI findings in pediatric BM. Additionally, we aim to present clinical cases of malignant BM disorders including leukemia, neuroblastoma metastasis, and other malignant BM disorders.

Abstract Objectives Since the enactment of the School Nutrition Act in 1981, school lunch programs in South Korea have grown quantitatively and qualitatively with a current student participation rate of 99.8%. Nonetheless, educational materials are needed to reduce misunderstanding and ignorance about school lunch programs. This study aimed to develop 3 educational videos that help students of various ages (kindergarteners/lower-grade elementary, upper-grade elementary, and secondary school, respectively), understand the school lunch program. Methods A scenario was created, was made, and the opinions on the scenario from experts in foodservice sectors were collected. A survey was conducted to students and parents to determine topics they wanted to know about school foodservice. The final videos were produced using this information and the expert opinions. The data were analyzed using SPSS 27.0 for Mac (IBM Corp., Armonk, NY, USA); a P-value of < 0.05 was considered significant. Results Three videos on school foodservice were developed for various age levels of students: kindergarten/lower-grade elementary, upper-grade elementary, and secondary school. Additionally, English subtitles were included for the multicultural student population. These videos, each lasting about 7 minutes, cover topics such as nutrition, hygiene, and the cultural significance of the school lunch program. The survey results showed that parents and students wanted to know the following topics about the school lunch program: “nutritionally balanced diet” (11.9%), “purchasing safe food ingredients” (10.9%), and “healthy eating habits” (9.9%). Conclusions The developed videos will serve as valuable educational resources on school foodservice, foster a deeper understanding of the school lunch program in parents and students, and potentially address their inquiries regarding production processes, nutrition, hygiene, cultural heritage, and health.

Abstract Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent because it kills cancer cells while sparing normal cells. However, many cancers, including pancreatic ductal adenocarcinoma (PDAC), exhibit intrinsic or acquired resistance to TRAIL, and the molecular mechanisms underlying TRAIL resistance in cancers, particularly in PDAC, remain unclear. In this study, we demonstrated that glutamine (Gln) endows PDAC cells with resistance to TRAIL through KDM4C-mediated epigenetic regulation of cFLIP. Inhibition of glutaminolysis significantly reduced the cFLIP level, leading to TRAIL-mediated formation of death-inducing signaling complexes. Overexpression of cFLIP dramatically rescued PDAC cells from TRAIL/Gln deprivation-induced apoptosis. Alpha-Ketoglutarate (aKG) supplementation significantly reversed the decrease in the cFLIP level induced by glutaminolysis inhibition and rescued PDAC cells from TRAIL/Gln deprivation-induced apoptosis. Knockdown of glutamic-oxaloacetic transaminase 2, which facilitates the conversion of oxaloacetate and glutamate into aspartate and aKG, decreased aKG production and the cFLIP level and activated TRAIL-induced apoptosis. AKG-mediated epigenetic regulation was necessary for maintaining a high level of cFLIP. Glutaminolysis inhibition increased the abundance of H3K9me3 in the cFLIP promoter, indicating that Gln-derived aKG production is important for Jumonji-domain histone demethylase (JHDM)-mediated cFLIP regulation. The JHDM KDM4C regulated cFLIP expression by binding to its promoter, and KDM4C knockdown sensitized PDAC cells to TRAIL-induced apoptosis. The present findings suggest that Gln-derived aKG production is required for KDM4C-mediated epigenetic regulation of cFLIP, which leads to resistance to TRAIL.

Abstract Background The exosome-mediated extracellular secretion of miRNAs occurs in many cancers, and RAB27A is a potent regulator of exosome secretion. For metastatic renal cell carcinoma (RCC), this study examines the mechanisms of cancer metastasis via the RAB27A-regulated secretion of specific miRNAs. Methods RAB27A knockdown (KD) and overexpressing (OE) RCC cells were used to examine cell migration and adhesion. The particle counts and sizes of exosomes in RAB27A OE cells were analyzed using Exoview, and those of intraluminal vesicles (ILV) and multivesicular bodies (MVB) were measured using an electron microscope. Analysis of RNA sequences, protein–protein interaction networks, and the competing endogenous RNA (ceRNA) network were used to identify representative downregulated miRNAs that are likely to undergo cargo-sorting into exosomes and subsequent secretion. A molecular beacon of miR-137-3p, one of the most representatively downregulated genes with a fold change of 339, was produced, and its secretion was analyzed using Exoview. RAB27A OE and control cells were incubated in an exosome-containing media to determine the uptake of tumor suppressor miRNAs that affect cancer cell metastasis. Results Migration and cell adhesion were higher in RAB27A OE cells than in RAB27A KD cells. Electron microscopy revealed that the numbers of multivesicular bodies and intraluminal vesicles per cell were higher in RAB27A OE cells than in control cells, suggesting their secretion. The finding revealed that miR-127-3p was sorted into exosomes and disposed of extracellularly. Protein–protein interaction analysis revealed MYCN to be the most significant hub for RAB27A-OE RCC cells. ceRNA network analysis revealed that MAPK4 interacted strongly with miR-127-3p. Conclusion The disposal of miR-127-3p through exosome secretion in RAB27A overexpressing cells may not inhibit the MAPK pathway to gain metastatic potential by activating MYCN. The exosomes containing miRNAs are valuable therapeutic targets for cancer treatment.

Purpose As the survival rate from pediatric cancers has increased significantly with advances in treatment modalities, long-term endocrine complications have also risen. This study investigated the frequencies and risks of endocrine sequelae in childhood cancer survivors who received hematopoietic stem cell transplantation (HSCT). Methods This study included 200 pediatric patients who underwent HSCT. Clinical and endocrinological findings were collected retrospectively. The median follow-up duration after HSCT was 14 years. Results Endocrine complications occurred in 135 patients (67.5%). Children who underwent HSCT at pubertal age (n=100) were at higher risk of endocrine complications than those who received it at prepubertal age (79% vs. 56%, P=0.001). The most common complication was hypogonadism (40%), followed by dyslipidemia (22%). Short stature and diabetes mellitus were more prevalent in the prepubertal group, whereas hypogonadism and osteoporosis were more common in the pubertal group. Being female, pubertal age at HSCT, and glucocorticoid use were predictors of an increased risk for any complication. Radiation exposure increased the risk of short stature and hypothyroidism. Hypogonadism was significantly associated with being female, pubertal age at HSCT, and high-dose radiation. Pubertal age at HSCT also increased the risks of osteoporosis and dyslipidemia. Conclusions This study demonstrates that long-term endocrine complications are common after HSCT in children and adolescents. Age at HSCT is a critical factor for endocrine complications after HSCT. These findings suggest that surveillance strategies for endocrine complications in childhood cancer survivors should be specified according to age at HSCT.

There is increasing concern regarding the risks posed by plastics to human health. Nano-sized plastics enter the body through various exposure routes. Although nano-sized particles circulate through the bloodstream and access the blood-brain barrier (BBB), the harmful impacts of nano-sized plastics on BBB function including endothelial cells are not well known. In this study, polystyrene nanoplastics (PS-NP) resulted in hyperpermeability and damaged tight junction proteins in brain endothelial cells. We identified that PS-NP increased intracellular iron levels by inhibiting the autophagy pathway in brain endothelial cells. Our study showed that dysregulated autophagy pathways led to increased BBB permeability induced by PS-NP treatment. In addition, PS-NP caused excessive erythrophagocytosis in brain endothelial cells via damaged red blood cells. PS-NP-treated RBCs (NP-RBC) induced the BBB dysfunction and increased intracellular iron levels and ferroptosis in brain endothelial cells. We provide novel insights into the potential risks of nano-sized plastics in BBB function by interaction between cells as well as direct exposure. Our study will help to understand the cardiovascular toxicity of nano-sized plastics.

Background Disease control in chronic diseases is an overarching concept that reflects the degree to which the goals of therapy are met. However, to date, there is no consensus on the definition of disease control in chronic cough. This study aimed to provide a conceptual exploration of patient-reported cough control in chronic cough. Methods This research is comprised of two subanalyses. First, patients with chronic cough receiving care at referral clinics were evaluated. Correlation analyses were performed between patient-reported cough control (a 5-point Likert scale), cough-specific patient-reported outcomes (PROs) and generic health PRO scores. Second, a survey was conducted among patients with refractory chronic cough and physicians to identify factors pertinent to cough control. Results The analysis of 341 patients (mean age: 55.5±15.1 years; female: 66.6%) revealed that cough control rating was moderately correlated with cough severity visual analogue scale and Leicester Cough Questionnaire scores, while demonstrating weaker correlations with cough-associated throat symptoms, cough-related complications or general health-related quality of life (QoL). In the survey of patients and physicians, both groups considered certain factors, such as cough frequency, severity and impact on QoL, to be relevant to the concept of cough control. However, patients rated “need for cough rescue drug” notably higher than physicians. Conclusion Patient-reported cough control was associated with cough severity or impact on QoL; however, cough control may not be fully captured by conventional cough PRO measurement tools. Further studies are warranted to define the consensus and tools to measure disease control in chronic cough.

Due to the large amounts of pharmaceuticals and personal care products (PPCPs) currently being consumed and released into the environment, this study provides a comprehensive analysis of pharmaceutical pollution in both raw and treated water from full-scale drinking water treatment plants nationwide. Our investigation revealed that 30 out of 37 PPCPs were present in raw water with mean concentrations ranging from 0.01–131 ng/L. The raw water sources, surface water (ND – 147 ng/L), subsurface water (ND – 123 ng/L) and reservoir sources (ND – 135 ng/L) exhibited higher mean concentration levels of pharmaceutical residues compared to groundwater sources (ND – 1.89 ng/L). Meanwhile, in treated water, 17 of the 37 analyzed PPCPs were present with carbamazepine, clarithromycin, fluconazole, telmisartan, valsartan, and cotinine being the most common (detection frequency > 40 %), and having mean concentrations of 1.22, 0.12, 3.48, 40.1, 6.36, and 3.73 ng/L, respectively. These findings highlight that, while water treatment processes are effective, there are some persistent compounds that prove challenging to fully eliminate. Using Monte Carlo simulations, risk assessment indicated that most of these compounds are likely to have negligible impact on human health, except for the antihypertensives. Telmisartan was identified as posing the highest ecological risk (RQ > 1), warranting further investigation, and monitoring. The study concludes by prioritizing specific 14 pharmaceuticals, including telmisartan, clarithromycin, lamotrigine, cotinine, lidocaine, tramadol, and others, for future monitoring to safeguard both ecological and human health.

Background: Anti-type 2 (T2) biologic therapies (biologics) improve exacerbation rates, lung function, and asthma-related quality of life (QoL) in patients with severe T2 asthma. However, studies comparing different biologics are lacking. We evaluated the QoL in patients with severe asthma comprehensively and compare the efficacy of different T2-directed biologics using QoL questionnaires. Methods: We compared the QoL between severe and mild-to-moderate asthma and between severe asthma with and without biologics treatment. Data of mild-to-moderate were extracted from the Cohort for Reality and Evolution of Adult Asthma in Korea, and data of severe asthma were collected from the Precision Medicine Intervention in Severe Asthma. We included 183 patients with severe asthma treated with T2 biologics or conventional therapy between April 2020 and May 2021 and assessed QoL of them using the Questionnaire for Adult Korean Asthmatics (QLQAKA), Severe Asthma Questionnaire (SAQ), and EuroQoL-5Dimensions (EQ-5D) at baseline and 6 months. Results: The EQ-5D index (0.803) of severe asthma was lower than that of other chronic diseases representing a worse QoL. The scores for all questions of QLQAKA, except “cough,” were lower (less control) in the severe asthma group than in the mild-to-moderate asthma group at baseline and 6 months (P 0.05). Conclusion: QoL was worse in severe asthma than in mild-to-moderate asthma and other chronic diseases. T2 biologics equally improved QoL in patients with severe asthma.

ABSTRACT: The objective of this study was to determine the effects of dietary available phosphorus (P) levels and dietary phytase added into the very low-P diet on the performance, mineral balance, odor emission, and stress responses in growing pullets and laying hens during 13 to 32 wk of age. One hundred sixty-eight pullets (Hy-Line Brown) were randomly assigned into 1 of 4 dietary treatments with 7 replicates of 6 birds each. Experimental diets were formulated to contain 3 graded P levels at 0.25, 0.35, and 0.45% during 13 to 15 wk (phase 1), 0.25, 0.35, and 0.45% during 16 to 18 wk (phase 2), and 0.20, 0.30, and 0.40% during 19 to 32 wk (phase 3). In addition, dietary phytase (500 FTU/kg matrix values) was added into the very low-P diets (0.20% during 13–15 wk, 0.25% during 16–18 wk, and 0.20% during 19–32 wk) to meet the nutritional adequacy with standard P diets. In all phases, decreasing dietary P levels did not affect (P > 0.05) growth, laying performance, and egg qualities. Decreasing dietary P levels linearly increased the relative duodenal and oviduct weights (P < 0.05), and quadratically increased the relative ovary weight in pullets (P = 0.016). Dietary phytase lowered (P = 0.021) the relative duodenal weight compared with the very low-P diet. Tibia breaking strength and tibia Mg contents in pullets were linearly lowered (P < 0.05) as dietary P levels decreased. Dietary phytase tended to increase (P = 0.091) tibia breaking strength and significantly increased (P = 0.025) tibia Mg content compared with the very low-P diet. Dietary P levels and dietary phytase affected (P < 0.05) ileal crypt depth and ileal villus height: crypt depth ratio in pullets. Decreasing dietary P levels linearly decreased (P < 0.01) crude fat digestibility and P excretion in both pullets and laying hens. Dietary phytase reversed (P < 0.05) the very low-P diet-mediated decrease of crude fat digestibility in pullets and laying hens. Dietary P levels and dietary phytase affected (P < 0.05) odor emission including ammonia in pullets and total volatile fatty acids in laying hens. Finally, lowering dietary P levels increased (P < 0.01) yolk corticosterone concentrations and the increased corticosterone concentration by the very low-P diet was reversed by dietary phytase. Collectively, our study shows that decreasing dietary P levels induced nutritional and physiological responses in pullets and laying hens and these P-mediated negative effects were mitigated by dietary phytase.

Gastric metastasis (GM) from cervical cancer is extremely rare, and only a few cases have been reported in the English literature. Gastric-type mucinous adenocarcinomas (GAS) of the uterine cervix are rare. GAS is an aggressive cancer commonly found in advanced stages; however, GM has not been reported. This study presents a rare case of GM from GAS of the uterine cervix in a 61-year-old female and describes the radiological findings of both the GM and cervical mucinous adenocarcinoma. GM appeared as a poor enhancing submucosal mass. The cervical mucinous adenocarcinoma appeared as an infiltrating mass with poor contrast enhancement. It exhibited mildly high and low signal intensities on the diffusion-weighted image and apparent diffusion coefficient map, respectively. This case is extremely rare and challenging to diagnose; however, if cervical cancer is an human papillomavirus-independent GAS type and a submucosal lesion is found in the stomach, the possibility of metastasis with a pattern similar to our case could be considered.

Concomitant renal cell carcinomas (RCC) of both native and allograft kidneys are extremely rare, and only a few cases have been reported in the available English literature. A particularly rare variant within the adult population is the Xp11.2 translocation/transcription factor E3 (TFE3)-rearranged RCC. Although few case reports of TFE3-rearranged RCC have been reported in children who underwent kidney transplantation (KT), no case of adults with TFE3-rearranged RCC following KT has been reported. Herein, we presented the radiological and pathological findings of a rare metachronous papillary RCC in the allograft kidney and TFE3-rearranged RCC in the native kidney. The TFE3-rearranged RCC in the native kidney exhibited slow expansion in size over five years. Radiologically, it appeared as a slightly enhanced, lobulated mass on contrast-enhanced CT. MRI revealed high signal intensity on T1-weighted images and low signal intensity on T2-weighted images.

Abstract Background Retinal vascular occlusions, including retinal vein occlusion and retinal artery occlusion, are common causes of visual impairment. In order to evaluate the national medical burden and help improve ophthalmic health care policy planning, we investigated the incidence of retinal vascular occlusive diseases from 2011 to 2020 in Korea. Methods This study is a nationwide population-based retrospective study using data from the Korea national health claim database of the Health Insurance Review and Assessment (HIRA) service. We identified retinal vascular occlusive diseases registered from January 1, 2009, to December 31, 2020, according to the retinal vascular occlusion code (H34) and its sub-codes from international classification of disease, tenth revision diagnosis code. We used data from the entire Korean population based on the 2015 census of the population in Korea to calculate standardized incidence rates. Results We identified 348,775 individuals (male, 161,673 [46.4%]; female, 187,102 [53.6%]) with incident retinal vascular occlusion (H34), 10,451 individuals (males, 6,329 [60.6%]; females, 4,122 [39.4%]) with incident central retinal artery occlusion (H34.1), and 252,810 individuals (males, 114,717 [45.4%]; females, 138,093 [54.6%]) with incident retinal vein occlusion (H34.8) during the 10-year study period. The weighted mean incidence rate of retinal vascular occlusion was 70.41 (95% CI, 70.18–70.65) cases/100,000 person-years. The weighted mean incidence rate of central retinal artery occlusion was 2.10 (95% CI, 2.06–2.14) cases/100,000 person-years. The weighted mean incidence rate of retinal vein occlusion was 50.99 (95% CI, 50.79–51.19) cases/100,000 person-years. Conclusion The total retinal vascular occlusion and retinal vein occlusion showed a decreasing trend until 2020. However, the central retinal artery occlusion decreased until 2014 and remained stable without a significant further decline until 2020. The incidence of total retinal vascular occlusion and retinal vein occlusion was higher in females than in males, while the incidence of central retinal artery occlusion was higher in males. All retinal vascular occlusive diseases showed an increasing incidence with older age; the peak age incidence was 75–79 years for total retinal vascular occlusion and retinal vein occlusion, and 80–85 years for central retinal artery occlusion.

Background: Recently, plant-derived exosome-like nanoparticles (PDENs) have been isolated, and active research was focusing on understanding their properties and functions. In this study, the characteristics and molecular properties of ginseng root-derived exosome-like nanoparticles (GrDENs) were examined in terms of skin protection. Methods: HPLC-MS protocols were used to analyze the ginsenoside contents in GrDENs. To investigate the beneficial effect of GrDENs on skin, HaCaT cells were pre-treated with GrDENs (0–2 × 109 particles/mL), and followed by UVB irradiation or H2O2 exposure. In addition, the antioxidant activity of GrDENs was measured using a fluorescence microscope or flow cytometry. Finally, molecular mechanisms were examined with immunoblotting analysis. Results: GrDENs contained detectable levels of ginsenosides (Re, Rg1, Rb1, Rf, Rg2 (S), Gyp17, Rd, C-Mc1, C–O, and F2). In UVB-irradiated HaCaT cells, GrDENs protected cells from death and reduced ROS production. GrDENs downregulated the mRNA expression of proapoptotic genes, including BAX, caspase-1, -3, -6, -7, and -8 and the ratio of cleaved caspase-8, -9, and -3 in a dose-dependent manner. In addition, GrDENs reduced the mRNA levels of aging-related genes (MMP2 and 3), proinflammatory genes (COX-2 and IL-6), and cellular senescence biomarker p21, possibly by suppressing activator protein-1 signaling. Conclusions: This study demonstrates the protective effects of GrDENs against skin damage caused by UV and oxidative stress, providing new insights into beneficial uses of ginseng. In particular, our results suggest GrDENs as a potential active ingredient in cosmeceuticals to promote skin health.

Purpose Deficiency of 21-hydroxylase (21-OHD) is an autosomal recessively inherited disorder that is characterized by adrenal insufficiency and androgen excess. This study was performed to investigate the clinical utility of prenatal diagnosis of 21-OHD using molecular genetic testing in families at risk. Methods This study included 27 pregnant women who had previously borne a child with 21-OHD. Fetal tissues were obtained using chorionic villus sampling (CVS) or amniocentesis. After the genomic DNA was isolated, Sanger sequencing of CYP21A2 and multiplex ligation-dependent probe amplification were performed. The clinical and endocrinological findings were reviewed retrospectively. Results A total of 39 prenatal genetic tests was performed on 27 pregnant women and their fetal tissues. The mean gestational age at the time of testing was 11.7 weeks for CVS and 17.5 weeks for amniocentesis. Eleven fetuses (28.2%) were diagnosed with 21-OHD. Among them, 10 fetuses (90.9%) harbored the same mutation as siblings who were previously diagnosed with 21-OHD. Among these, 4 fetuses (3 males and 1 female) identified as affected were born alive. All 4 patients have been treated with hydrocortisone, 9α-fludrocortisone, and sodium chloride since a mean of 3.7 days of life. The male patients did not show hyponatremia and dehydration, although they harbored pathogenic variants associated with the salt-wasting type of 21-OHD. Conclusions This study demonstrated the diagnostic efficacy and clinical consequences of diagnosis by prenatal genetic testing in families at risk for 21-OHD. All patients identified as affected were treated with hydrocortisone and 9α-fludrocortisone early after birth, which can prevent a life-threatening adrenal crisis.

Abstract Salts play a crucial role in maintaining human health by regulating fluid levels and supporting various physiological processes. However, conventional seawater-derived salts are associated with microplastic pollution and pose potential health risks. Jeju lava seawater (JLS), sourced exclusively from Jeju Island, has emerged as a unique alternative, free of microplastics and enriched with essential minerals such as magnesium, calcium, zinc, and iron. In this study, we investigated the effects of JLS on osteoarthritis (OA) pathogenesis, focusing on chondrocyte metabolism and OA development. We performed surgical destabilization of the medial meniscus to establish a murine model of OA. We examined the expression of catabolic and anabolic factors in JLS-treated chondrocytes. Our cell viability assay revealed that JLS treatment was not cytotoxic to chondrocytes at concentrations ≤ 0.5%. Additionally, JLS treatment resulted in a concentration-dependent increase in the expression of anabolic factors like aggrecan, SOX9, and COL2A1 while decreasing the expression of catabolic factors such as MMP3, MMP13, ADAMTS4, and ADAMTS5 in the chondrocytes stimulated with pro-inflammatory cytokines. Although not statistically significant compared to the control group, JLS intake slightly attenuated the OARSI score, osteophyte score, synovitis score, subchondral bone thickness, and osteophyte size in the mouse model of OA. Conclusively, these results suggest that JLS ameliorates OA by positively influencing chondrocyte metabolism, making it a promising therapeutic candidate for OA management.

Objective: To evaluate the effects of Capsosiphon fulvescens (C. fulvescens) ethanolic extract on inflammation in lipopolysaccharide (LPS)-induced RAW296.7 macrophages. Methods: The protective effects of C. fulvescens ethanolic extract on LPS-induced inflammation in RAW264.7 macrophages were assessed using biochemical analysis, including enzyme-linked immunosorbent assay, quantitative reverse transcription-polymerase chain reaction, and Western blot analysis. To examine reactive oxygen species (ROS) production, flow cytometry analysis, and immunofluorescence staining were used. Furthermore, the modulatory effect of C. fulvescens ethanolic extract on NF-κB activation was investigated. Results: C. fulvescens ethanolic extract significantly attenuated LPS-induced levels of pro-inflammatory cytokines and notably reduced the secretion and mRNA levels of LPS-mediated matrix metalloproteinases. In addition, C. fulvescens ethanolic extract decreased ROS production and suppressed the TLR4/NF-κB signaling pathway. Conclusions: C. fulvescens ethanolic extract alleviates inflammation as well as oxidative stress by modulating the TLR4/NF-κB signaling in LPS-induced RAW264.7 macrophages. C. fulvescens can be used as a potential therapeutic agent to suppress inflammation and oxidative stress-associated diseases.

Malrotation and midgut volvulus are surgical emergencies that commonly occur within the first month of life. The classic symptom is acute bilious vomiting, while nonspecific symptoms such as recurrent abdominal pain may be present in older children. Malrotation can be associated with duodenal obstruction caused by an abnormal peritoneal fibrous band or congenital anomalies, such as an annular pancreas or a preduodenal portal vein. Volvulus can lead to bowel ischemia and a life-threatening condition, thus prompt and accurate diagnosis is crucial. Diagnosis can be made through upper gastrointestinal series, ultrasonography, and CT, with ultrasonography being preferred as a screening tool due to its rapid and accurate diagnosis, without radiation exposure, in children. This pictorial essay discusses the key imaging findings and diagnostic approaches for malrotation and midgut volvulus, as well as diagnostic pitfalls based on actual cases.

Black rice (BR) is considered one of the healthiest foods worldwide. This study assessed the bioactive compound contents and antioxidant activities of the distilled water (DW) and 80% ethanol (EtOH) extracts of BR, black rice bran (BRB), and milled black rice (MBR). In addition, their anti-obesity, anti-obesogenic, and anti-muscle atrophy effects were comparatively evaluated. The results revealed that the 80% EtOH extract of BR contained higher contents of β-glucan, total flavonoids, and total phenolics (26.97 ± 0.70 mg gallic acid equivalents (GAE)/g and 16.58 ± 0.37 mg quercetin equivalents (QE)/g, respectively) and showed higher antioxidant activity than those of the BRB and MBR extracts. On the other hand, BRB contained the highest content of γ-oryzanol, which was 15.12 ± 0.03 mg/g. Moreover, the 80% EtOH extract of BR exhibited a stronger anti-obesogenic effect by downregulating adipogenesis-related proteins (PPAR-γ, C/EBP-α, and FAS) and upregulating lipolysis-related proteins (PGC-1α and CPT-1), while the BRB extract effectively increased myotube diameter and fusion index. Overall, these findings indicate that the 80% EtOH extracts of BR, BRB, and MBR, particularly the BR extract, have high potential as natural antioxidants and anti-obesity agents, with BRB showing promise in preventing muscle atrophy.

Gaussia luciferase (GLuc) is the preeminent secreted luciferase widely used in cell-based reporter assays. By employing sequence-guided mutagenesis informed by alignments of diverse copepod luciferase sequences, we identified key amino acids that significantly enhance bioluminescence (BL) intensity. Among the mutated proteins expressed in bacteria, five individual mutations (M60L, K88Q, F89Y, I90L, or S103T) independently increased BL intensity by 1.8 to 7.5-fold compared to wild-type GLuc in the presence of coelenterazine substrates. Remarkably, the combination of all five mutations in GLuc (designated as GLuc5) resulted in an unexpected 29-fold enhancement in BL intensity. Subsequent evaluation of the GLuc5-secreted reporter in transfected mammalian cells confirmed its superior BL performance across multiple cell lines. These findings suggest that the mutated residues are likely crucial for enhancing BL intensity in GLuc, supporting its potential to serve as a highly sensitive biosensor or reporter for a wide range of biological applications.

Abstract Lipid nanoparticles (LNPs) exhibit remarkable mRNA delivery efficiency, yet their majority accumulate in the liver or spleen after injection. Tissue‐specific mRNA delivery can be achieved through modulating LNP properties, such as tuning PEGylation or varying lipid components systematically. In this paper, a streamlined method is used for incorporating tumor‐targeting peptides into the LNPs; the programmed death ligand 1 (PD‐L1) binding peptides are conjugated to PEGylated lipids via a copper‐free click reaction, and directly incorporated into the LNP composition (Pep LNPs). Notably, Pep LNPs display robust interaction with PD‐L1 proteins, which leads to the uptake of LNPs into PD‐L1 overexpressing cancer cells both in vitro and in vivo. To evaluate anticancer immunotherapy mediated by restoring tumor suppressor, mRNA encoding phosphatase and tensin homolog (PTEN) is delivered via Pep LNPs to PTEN‐deficient triple‐negative breast cancers (TNBCs). Pep LNPs loaded with PTEN mRNA specifically promotes autophagy‐mediated immunogenic cell death in 4T1 tumors, resulting in effective anticancer immune responses. This study highlights the potential of tumor‐targeted LNPs for mRNA‐based cancer therapy.

Background: Exposure to allergens or irritants in the workplace may affect asthma control and the quality of life (QoL) of patients with asthma. Objective: To examine the prevalence and characteristics of work-related asthma (WRA) in adult patients with severe asthma. Methods: We analyzed data from the Korean Severe Asthma Registry (KoSAR), which is a nationwide multicenter observational study on severe asthma in Korea. Severe asthma was defined according to the American Thoracic Society (ATS) and the European Respiratory Society (ERS) guidelines. WRA was identified on the basis of asthma symptom aggravation at the workplace, as indicated by responses to a structured questionnaire. We compared the demographic and clinical characteristics and QoL between adult patients with severe asthma and WRA and those without WRA. Results: Among 364 patients with severe asthma who were employed at the time of enrollment, 65 (17.9%) had WRA. There were no significant differences in age, sex, obesity, or smoking history between the WRA and non-WRA groups. However, individuals with WRA exhibited a higher prevalence of anxiety (7.7% vs 2.4%, P = 0.046) and depression (12.3% vs 3.7%, P = 0.010) than those without. The levels of asthma control, lung function, and frequency of asthma exacerbations were similar between the two groups, but patients with WRA reported lower QoL, as determined by the Quality of Life Questionnaire for Adult Korean Asthmatics (56.6 ± 14.6 vs. 63.5 ± 13.9, P

Abstract Copper iodide (CuI) has garnered considerable attention as a promising alternative to p‐type transparent conducting oxides owing to its low cation vacancy formation energy, shallow acceptor level, and readily modifiable conductivity via doping. Although sulfur (S) doping through liquid iodination has exhibited high efficacy in enhancing the conductivity with record high figure of merit (FOM) of 630 00 MΩ−1, solution‐processed S‐doped CuI (CuI:S) for low‐cost large area fabrication has yet to be explored. Here, a highly conducting CuI:S thin‐film for p‐type transparent conducting electrode (TCE) is reported using low temperature solution‐processing with thiourea derivatives. The optimization of thiourea dopant is determined through a comprehensive acid‐base study, considering the effects of steric hindrance. The modification of active groups of thioureas facilitated a varying carrier concentration range of 9 × 1018–2.52 × 1020 cm−3 and conductivities of 4.4–390.7 S cm−1. Consequently, N‐ethylthiourea‐doped CuI:S exhibited a FOM value of 7 600 MΩ−1, which is the highest value among solution‐processed p‐type TCEs to date. Moreover, the formulation of CuI:S solution for highly conductive p‐type TCEs can be extended to CuI:S inks, facilitating high‐throughput solution‐processes such as inkjet printing and spray coating.

ABSTRACT: This study was performed to investigate supplementary effects of probiotic Lacticaseibacillus paracasei NSMJ56 strain on laying performance, egg quality, intestinal histology, antioxidant status, gut immunity and microbiota in laying hens. A total of ninety-six 21-wk-old Hy-Line Brown laying hens were randomly subjected to one of 2 dietary treatments: a control group fed a non-supplemented diet, or a probiotic group fed with a diet supplemented with 1 g of Lacticaseibacillus paracasei NSMJ56 (5 × 108 CFU/kg of diet). The trial lasted for 4 wk. Egg weight was increased (P < 0.05) in laying hens fed probiotic-fed diet compared with the control group. Dietary probiotics did not affect egg quality except for Haugh unit, which was improved (P < 0.05) in the probiotic-fed group. Neither jejunal histology nor cecal short-chain fatty acids were affected by dietary treatments. Dietary probiotics increased the activity of catalase compared with the control group. Flow cytometry analysis revealed that dietary probiotics elevated the CD4+ T cells, but not CD8+ T cells, in jejunal lamina propria. Based on the LEfSe analysis at the phylum and genus levels, Erysipelotrichales, Erysipelotrichia, Flintibater, Dielma, Hespellia, Coprobacter, Roseburia, Anaerotignum, and Coprococcus were enriched in the probiotic group compared with the control group. Taken together, our study showed that dietary probiotics could be used to improve some parameters associated with egg freshness and antioxidant capacity, and to partially alter T cell population and microbial community in laying hens.

Recent advances in molecular genetics have advanced our understanding of the molecular mechanisms involved in pediatric endocrine disorders and now play a major role in mainstream medical practice. The spectrum of endocrine genetic disorders has 2 extremes: Mendelian and polygenic. Mendelian or monogenic diseases are caused by rare variants of a single gene, each of which exerts a strong effect on disease risk. Polygenic diseases or common traits are caused by the combined effects of multiple genetic variants in conjunction with environmental and lifestyle factors. Testing for a single gene is preferable if the disease is phenotypically and/or geneically homogeneous. Next-generation sequencing (NGS) can be applied to phenotypically and genetically heterogeneous conditions. Genome-wide association studies (GWASs) have examined genetic variants across the entire genome in a large number of individuals who have been matched for population ancestry and assessed for a disease or trait of interest. Common endocrine diseases or traits, such as type 2 diabetes mellitus, obesity, height, and pubertal timing, result from the combined effects of multiple variants in various genes that are frequently found in the general population, each of which contributes a small individual effect. Isolated founder mutations can result from a true founder effect or an extreme reduction in population size. Studies of founder mutations offer powerful advantages for efficiently localizing the genes that underlie Mendelian disorders. The Korean population has settled in the Korean peninsula for thousands of years, and several recurrent mutations have been identified as founder mutations. The application of molecular technology has increased our understanding of endocrine diseases, which have impacted on the practice of pediatric endocrinology related to diagnosis and genetic counseling. This review focuses on the application of genomic research to pediatric endocrine diseases using GWASs and NGS technology for diagnosis and treatment.

Abstract Protein lysine methyltransferases (PKMTs) play crucial roles in histone and nonhistone modifications, and their dysregulation has been linked to the development and progression of cancer. While the majority of studies have focused on the oncogenic functions of PKMTs, extensive evidence has indicated that these enzymes also play roles in tumor suppression by regulating the stability of p53 and β-catenin, promoting α-tubulin-mediated genomic stability, and regulating the transcription of oncogenes and tumor suppressors. Despite their contradictory roles in tumorigenesis, many PKMTs have been identified as potential therapeutic targets for cancer treatment. However, PKMT inhibitors may have unintended negative effects depending on the specific cancer type and target enzyme. Therefore, this review aims to comprehensively summarize the tumor-suppressive effects of PKMTs and to provide new insights into the development of anticancer drugs targeting PKMTs.

Objective To analyze the changes in muscle mass and quality with time on the paretic and non-paretic sides in subacute stroke patients and identify correlations between the variation of muscle mass and quality and lower limb functions. Methods Thirty hemiplegia patients diagnosed with stroke participated in this study. To evaluate poststroke muscle changes, longitudinal measurement of muscle mass and quality was conducted with bilateral lower limbs. The elastic shear modulus was measured using shear wave elastography and muscle thickness (MT) of rectus femoris, vastus intermedius, vastus lateralis (VL), vastus medialis, tibialis anterior, and gastrocnemius (GCM) muscles. Functional evaluation was performed using Berg Balance Scale (BBS), Five Times Sit to Stand Test (FTSST). Follow-up was performed at discharge. The muscle mass and quality were compared according to time. We analyzed whether muscle quantity and quality were related to function. Results MT demonstrated no significant change with time. The elastic shear modulus increased significantly in the paretic VL and GCM muscles and did not change significantly in the muscles on the non-paretic side. Correlation analysis detected that elastic shear modulus in the VL has a cross-sectional negative relationship between BBS and positive relationship between FTSST. There were significant correlation between variation of FTSST and the variation of the elastic shear modulus in VL. Conclusion Only paretic VL and GCM muscle quality changed in subacute stroke patients and muscle’s property related to lower limb functions. Therefore, the lower extremity requires an approach to muscle quality rather than quantity for subacute stroke patients.