Search Results (316)

Background: Cervical cancer remains a major global health concern, with existing chemotherapy facing limited effectiveness owing to resistance. Polo-like kinase 1 (PLK1) overexpression in cervical cancer cells is a promising target for developing novel therapies to overcome chemoresistance and improve treatment efficacy. Methods: In this study, we developed a novel PROTAC, NC1, targeting PLK1 PBD via the N-end rule pathway. Results: This PROTAC effectively depleted the PLK1 protein in HeLa cells by inducing protein degradation. The crystal structure of the PBD-NC1 complex identified key PLK1 PBD binding interactions and isothermal titration calorimetry (ITC) confirmed a binding affinity of 6.06 µM between NC1 and PLK1 PBD. NC1 significantly decreased cell viability with an IC₅₀ of 5.23 µM, induced G2/M phase arrest, and triggered apoptosis in HeLa cells. In vivo, NC1 suppressed tumor growth in a HeLa xenograft mouse model. Conclusions: This research highlights the potential of N-degron-based PROTACs targeting the PLK1 protein in cancer therapies, highlighting their potential in future cervical anticancer treatment strategies. Full article

As ad-supported subscription models proliferate across over-the-top (OTT) media platforms, understanding the psychological mechanisms and perceptual factors that underlie consumers’ transition decisions becomes increasingly consequential. This study integrates the Uses and Gratifications framework with a contemporary motivation-based perspective to examine how users’ media consumption motivations and advertising attitudes predict intentions to adopt ad-supported OTT plans. Data were collected via a nationally representative online survey in South Korea (N = 813). The sample included both premium subscribers (n = 708) and non-subscribers (n = 105). The findings reveal distinct segmentation in decision-making patterns. Among premium subscribers, switching intentions were predominantly driven by intrinsic motivations—particularly identity alignment with content—and by the perceived informational value of advertisements. These individuals are more likely to consider ad-supported plans when ad content is personally relevant and cognitively enriching. Conversely, non-subscribers exhibited greater sensitivity to extrinsic cues such as the entertainment value of ads and the presence of tangible incentives (e.g., discounts), suggesting a hedonic-reward orientation. By advancing a dual-pathway explanatory model, this study contributes to the theoretical discourse on digital subscription behavior and offers actionable insights for OTT service providers. The results underscore the necessity of segment-specific advertising strategies: premium subscribers may be engaged through informative and identity-consistent advertising, while non-subscribers respond more favorably to enjoyable and benefit-laden ad experiences. These insights inform platform monetization efforts amid the evolving dynamics of consumer attention and subscription fatigue. Full article

Accurate forecasting of household waste generation is essential for sustainable urban planning and the development of data-driven environmental policies. Conventional statistical models, while simple and interpretable, often fail to capture the nonlinear and multidimensional relationships inherent in waste production patterns. This study proposes a machine learning-based regression framework utilizing Random Forest and XGBoost algorithms to predict annual household waste generation across four metropolitan regions in South Korea Seoul, Gyeonggi, Incheon, and Jeju over the period from 2000 to 2023. Independent variables include demographic indicators (total population, working-age population, elderly population), economic indicators (Gross Regional Domestic Product), and regional identifiers encoded using One-Hot Encoding. A derived feature, elderly ratio, was introduced to reflect population aging. Model performance was evaluated using R², RMSE, and MAE, with artificial noise added to simulate uncertainty. Random Forest demonstrated superior generalization and robustness to data irregularities, especially in data-scarce regions like Jeju. SHAP-based interpretability analysis revealed total population and GRDP as the most influential features. The findings underscore the importance of incorporating economic indicators in waste forecasting models, as demographic variables alone were insufficient for explaining waste dynamics. This approach provides valuable insights for policymakers and supports the development of adaptive, region-specific strategies for waste reduction and infrastructure investment. Full article

This study presents a national-scale mapping of Ecosystem Functional Groups (EFGs) in the Republic of Korea using the International Union for Conservation of Nature (IUCN) Global Ecosystem Typology (GET), a hierarchical classification system, integrated with spatial datasets, satellite imagery, and a random forest (RF) classifier. By incorporating locally relevant ecological data, the original typology was refined to resolve issues of overgeneralization and spatial overlap. The resulting map delineates 20 distinct ecosystem types, offering improved spatial accuracy and better alignment with the actual land extent. To evaluate the potential of EFG classification, the RF model was trained on seasonal satellite composites and environmental variables, achieving an overall accuracy of 80%. Elevation and temperature were found to be the most influential predictors, effectively distinguishing ecological patterns across diverse landscapes. This integrated approach supports consistent tracking of ecosystem changes and helps address the limitations of static or infrequently updated spatial datasets. The developed EFG map supports biodiversity conservation by providing a practical foundation for national spatial planning and contributing to the Red List of Ecosystems assessments, which is in line with the goals of the Global Biodiversity Framework. Full article

Articular cartilage has limited regenerative potential due to its anatomical characteristics, making complete recovery from damage challenging. Microfracture (MFx) is a widely used technique to promote cartilage healing, often enhanced with scaffolds to improve outcomes. In this study, we compared the efficacy of bilayer atelocollagen and standard collagen scaffolds combined with MFx in treating osteochondral defects in a rabbit model. Three articular cartilage defects were created in the femoral condyle of each rabbit and treated with either MFx plus a bilayer atelocollagen scaffold (test group), MFx plus a standard collagen scaffold (positive group), or MFx alone (negative group). Macroscopic and histological assessments were performed at 3, 6, and 12 weeks. By week 12, macroscopic examination showed hyaline-like cartilage restoration in the test group, while the positive group exhibited restoration with some overgrowth, and the negative group showed no restoration. Histological analysis revealed significantly better restoration in the test group than in the negative group, with comparable outcomes between the test and positive groups. These findings suggest that bilayer atelocollagen scaffold implantation following MFx is a promising treatment for articular cartilage defects and may provide a viable therapeutic option for patients with cartilage damage. Full article

Background/Aim: Bacterial and viral gastroenteritis present with overlapping symptoms, including vomiting, diarrhea, and abdominal pain. Stool tests have been used to differentiate between them; however, stool cultures are time-consuming and stool polymerase chain reaction (PCR) tests are expensive. The role of the clinical value of procalcitonin (PCT) and C-reactive protein (CRP) as diagnostic markers of bacterial gastroenteritis remains to be investigated. This study evaluated the diagnostic value of PCT for the early diagnosis of bacterial gastroenteritis. Methods: The medical records of patients diagnosed with gastroenteritis by the emergency department with positive stool PCR results confirming the diagnosis between 1 January 2020 and 31 July 2024 were retrospectively reviewed. Demographic characteristics and laboratory findings, including PCT and CRP levels, were analyzed. The area under the curve (AUC) for the diagnosis of bacterial gastroenteritis was assessed to determine the diagnostic potential of PCT and CRP. Results: Among the 1882 cases identified, 1435 met the inclusion criteria. CRP exhibited a sensitivity of 79.0% and specificity of 78.6% (AUC: 0.848, 95% CI: 0.815–0.881) in diagnosing bacterial gastroenteritis. In comparison, PCT showed lower sensitivity (60.3%) and specificity (62.6%) (AUC: 0.660, 95% CI: 0.614–0.706). However, in patients aged >17 years with fever (≥38 °C), PCT demonstrated an improved AUC of 0.767 (95% CI: 0.603–0.932; p = 0.019). Conclusions: CRP demonstrated moderate sensitivity in predicting bacterial gastroenteritis; however, its false-negative rate suggests limitations in clinical decision-making. While PCT may assist clinicians in identifying bacterial gastroenteritis in febrile adult patients, its diagnostic accuracy remains suboptimal, necessitating further validation through larger studies. Full article

Background/Objectives: This study examined the effects of alcohol consumption on chronic kidney disease (CKD) risk in community-dwelling older adults. Methods: A nationwide retrospective observational study was conducted using NHIS-Senior cohort data (2009–2018). Adults aged ≥ 65 years with an estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m² were included. Alcohol consumption was classified as non-drinking, mild, moderate, or heavy drinking. CKD onset was defined as eGFR < 60 mL/min/1.73 m². Results: Of the 122,319 subjects, the non-, mild, moderate, and heavy drinking groups comprised 99,091 (81.0%), 14,842 (12.1%), 4257 (3.5%), and 4139 (3.4%), respectively. During follow-up, 19,796 (20.0%), 4636 (31.2%), 1696 (39.8%), and 1695 (41.0%) patients developed CKD in the non-, mild, moderate, and heavy drinking groups, respectively. Univariate Cox regression analyses showed a significantly increased risk of incident CKD in all drinking groups compared with non-drinkers (all p < 0.001). However, hazard ratios (HR) for developing CKD were 0.90 (95% confidence interval [CI] 0.87–0.94, p < 0.001) for mild, 0.89 (95% CI 0.84–0.95, p < 0.001) for moderate, and 0.93 (95% CI 0.88–0.99, p = 0.027) for heavy drinkers. In subgroup analysis, the beneficial effect of alcohol consumption on incident CKD was prominent among moderate drinkers aged 65–74 years and mild drinkers aged ≥ 75 years, in males and mild drinkers aged < 85 years in females. Conclusions: This study shows that alcohol consumption is negatively associated with the risk of incident CKD in older adults, particularly among males. Full article

Background: Cardiogenic shock (CS) frequently leads to multiorgan failure, often necessitating continuous renal replacement therapy (CRRT) or extracorporeal membrane oxygenation (ECMO). We evaluated the association between CRRT, ECMO, and its prognostic implication in patients with CS. Methods: A total of 1247 patients with CS were enrolled from the RESCUE (Retrospective and Prospective Observational Study to Investigate Clinical Outcomes and Efficacy of Left Ventricular Assist Device for Korean Patients with Cardiogenic Shock) registry between January 2014 and December 2018. The primary outcomes, including the 72 h and 30-day all-cause mortality rates, were analyzed in relation to the use of ECMO and CRRT among CS patients. Results: Among 751 non-ECMO patients, 90 (12%) underwent CRRT, while among 496 ECMO patients, 195 (39.3%) underwent CRRT. Overall, CRRT was associated with higher 30-day mortality. However, among ECMO patients, CRRT was linked to lower 72 h mortality (19.6% versus 12.3%; p = 0.045). Multivariate analysis showed that CRRT reduced 72 h mortality in ECMO patients (hazard ratio: 0.44; 95% confidence interval: 0.21–0.91; p = 0.027). Independent predictors for CRRT included an estimated GFR < 44 mL/min/1.73 m², mechanical ventilation, ECMO use, IABP use, and increased lactate. Conclusions: CS patients receiving CRRT had higher 30-day mortality. Nonetheless, CRRT administration was more common in ECMO patients, potentially improving early in-hospital clinical outcomes. Full article

Patient-derived xenograft (PDX) models are powerful tools in cancer research, offering an accurate platform for evaluating cancer treatment efficacy and predicting responsiveness. However, these models necessitate surgical techniques for tumor tissue transplantation and face challenges with non-uniform tumor growth among animals. To address these issues, we attempted to develop a new PDX modeling method using high-grade serous ovarian cancer (HGSC), a fatal disease with a 5-year survival rate of 29%, which requires personalized research due to its morphological, genetic, and molecular heterogeneities. In this study, we developed a new patient-derived cancer cell xenograft (PDCX) model with high engraftment efficiency (64%) that utilizes primary cancer cells instead of patient tissues. Primary cancer cells can be stably cryopreserved for extended periods (up to 485 days), and when transplanted into female NSGA mice, they maintain morphological and molecular characteristics without significant genetic differences compared to their original primary tumors. Furthermore, PDCX models can be easily produced using a syringe, allowing for uniform tumor sizes across multiple animals. Additionally, M2 PDCXs exhibited a significantly faster growth rate compared to M2 PDTXs. Consequently, our PDCX model offers a streamlined approach for evaluating personalized cancer treatments with minimal experimental variability. Full article

Epilepsy, a chronic neurological disorder, is triggered by various insults, including traumatic brain injury and stroke. Acid sphingomyelinase (ASMase), an enzyme that hydrolyzes sphingomyelin into ceramides, is implicated in oxidative stress, neuroinflammation, and neuronal apoptosis. Ceramides, which have pro-apoptotic properties, contribute to oxidative damage and lysosomal dysfunction, exacerbating neuronal injury. This study investigates the role of ASMase in epilepsy, hypothesizing that seizure activity upregulates ASMase, increasing ceramide levels, DNA damage, and neuronal apoptosis. We employed a pilocarpine-induced rat seizure model and examined the effects of imipramine, an ASMase inhibitor, administered intraperitoneally (10 mg/kg) for four weeks post-seizure induction. Histological and cognitive analyses showed that while imipramine did not prevent early neuronal death within the first week, it significantly reduced markers of neuronal apoptosis by four weeks. Imipramine also promoted hippocampal neurogenesis and preserved cognitive function, which is often impaired following seizures. These findings suggest that ASMase inhibition could mitigate neuronal apoptosis and improve cognitive recovery after seizures. Imipramine may serve as a promising therapeutic strategy for epilepsy-associated neuronal damage and cognitive deficits. Further studies should delineate the molecular mechanisms of ASMase inhibition and evaluate its long-term efficacy in addressing epilepsy-related neurodegeneration and functional impairments. Full article

Our group has previously demonstrated that tissue-engineered dermis containing cultured fibroblasts or adipose-derived stromal vascular fraction cells is superior to artificial dermis in terms of scar quality for covering facial defects. However, using these cells for clinical applications requires Food and Drug Administration approval and involves complex procedures for cell culture or isolation. This retrospective study aimed to compare effects of tissue-engineered dermis containing micronized adipose tissue (MAT) and artificial dermis for facial reconstruction. Tissue-engineered dermis consisting of MAT seeded on artificial dermis was applied in 30 cases, while artificial dermis without MAT was grafted in 35 cases. Healing time and severities of scar contraction, color mismatch, and landmark distortion at one year after healing were evaluated. Wounds in the tissue-engineered dermis group re-epithelialized in 30.0 ± 4.3 days compared to 34.3 ± 5.4 days in the artificial dermis group (p < 0.05). The average dE2000 score in color mismatch analysis was 4.9 ± 1.7 in the tissue-engineered dermis group and 5.1 ± 1.7 in the artificial dermis group (p = 0.57). The extent of scar contraction was 16.2 ± 12.3% in the tissue-engineered dermis group and 23.2 ± 12.8% in the artificial dermis group (p < 0.05). The average severity grade of landmark distortion was 0.20 ± 0.50 in the tissue-engineered dermis group and 0.50 ± 0.71 in the artificial dermis group (p < 0.05). These findings indicate that tissue-engineered dermis grafts containing MAT are superior to artificial dermis grafts for facial reconstruction in terms of healing time, scar contraction, and landmark distortion severity. However, there was no significant difference in color mismatch between the two groups. Full article

Tomato fruit color is primarily influenced by the accumulation of pigments such as carotenoids and anthocyanins, which are regulated by a complex network of genes and environmental factors. The presence of anthocyanins, in particular, contributes to the purple phenotype in tomatoes, which has been associated with improved nutritional quality and disease resistance. Previous studies have identified key regulatory genes, including SlMYBATV and SlANT1, that control anthocyanin biosynthesis in tomatoes. A total of 48 tomato accessions were selected, including both anthocyanin-producing and non-producing cultivars, to assess genetic variation in relation to fruit color. GWAS analysis identified significant associations between single-nucleotide polymorphisms (SNPs) on chromosomes 7 and 10 and the purple fruit phenotype. These genomic regions contained key anthocyanin regulatory genes, SlMYBATV on chromosome 7 and SlANT1 on chromosome 10, confirming their roles in anthocyanin biosynthesis. Linkage disequilibrium (LD) analysis further revealed strong correlations between SNPs within these regions, facilitating the selection of representative SNPs for genotyping. The genotyping of SNPs Ch07_60981501 and Ch10_64354129 using HPM demonstrated clear differentiation between purple and non-purple cultivars based on melting temperature differences, validating the functional significance of the identified loci. The results confirmed that the nonfunctional SlMYBATV allele at the atv locus allows for enhanced anthocyanin accumulation by relieving repression of anthocyanin activators like SlANT1. This interaction between the Aft and atv loci drives light-dependent anthocyanin biosynthesis in purple tomatoes. HPM genotyping offers a cost-effective tool for allele identification, supporting breeding programs for anthocyanin-rich tomatoes. SNP markers enable marker-assisted selection (MAS) for improved nutritional and aesthetic traits. This study highlights SlMYBATV and SlANT1 in anthocyanin biosynthesis, advancing efforts to develop enriched tomato varieties and supporting agricultural productivity and health. Full article

(1) Background: MicroRNA-129 (miR-129) participates in tumor progression and chemoresistance in various cancer types. In this study, the role of miR-129-3p, the main mature form of miR-129, in tumor progression and chemoradiotherapy resistance in head and neck cancer was evaluated. (2) Methods: RT-PCR, western blotting, cell proliferation assays, cell apoptosis assays, and cell invasion and migration assays were used. (3) Results: In this study, the miR-129-3p overexpression suppressed the proliferation, invasion, and migration of SNU1041, SCC15, and SCC25 human HNSCC cell lines. Additionally, it induced apoptosis and enhanced radiation-/cisplatin-induced apoptosis of SNU1041, SCC15, and SCC25 cells. Therefore, miR-129-3p could suppress tumor progression and enhance chemoradiosensitivity in human HNSCC. Furthermore, miR-129-3p was downregulated in fresh tumor tissues from patients with HNSCC compared with that in the adjacent normal mucosa. In a nude mouse xenograft model with SNU15 cells, the miR-129-3p overexpression significantly decreased tumor growth, as measured by tumor weight and volume. (4) Conclusions: Our study provides evidence that miR-129-3p suppresses tumor progression and chemoradioresistance in HNSCC. This finding may serve as a basis for developing miR-129-3p-based therapeutic strategies. Full article

The incidence of mammary gland tumors in dogs is a significant issue, characterized by notable rates of malignancy, recurrence, and disease burden. However, the lack of comprehensive information and correlated studies has presented challenges in establishing an effective surgical treatment strategy. In this study, a cohort of 95 dogs diagnosed with mammary tumors underwent evaluation using various surgical methods, medications, ovariohysterectomy, and assessments of margin completeness to analyze clinical outcomes. Significant clinical outcomes were observed following radical mastectomy and conservative surgeries, irrespective of TNM stages and histopathological grade of malignancy. Complete excision demonstrated significantly improved survival time and disease-free interval compared to incomplete excision. It is noted that complete surgical excision provides benefits, even in cases where lymphatic invasion is present. However, further investigations are necessary to validate the clinical results and mitigate side effects from radical mastectomy. Despite postoperative complications, several studies continue to advocate for more radical mastectomies due to their favorable risk-benefit ratio. Moreover, advanced inpatient treatments can now effectively manage or mitigate many of these complications. This study emphasizes the critical role of surgical proficiency and postoperative medication in treating malignant mammary tumors in dogs, and it provides insights that may contribute to the development of more effective treatment strategies for this condition. Full article