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    Carvacrol selectively induces mitochondria-related apoptotic signaling in primary breast cancer-associated fibroblasts

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    Background/Objectives: Cancer-associated fibroblasts (CAFs) are key stromal mediators of breast tumor progression and therapy resistance. Carvacrol, a dietary monoterpenic phenol, exhibits antiproliferative activity in cancer cells, but its effects on primary human breast CAFs remain unclear. This study aimed to determine whether carvacrol selectively induces mitochondria-related apoptotic signaling in breast CAFs while sparing normal fibroblasts (NFs). Methods: Primary fibroblast cultures were established from invasive ductal carcinoma tissues (CAFs, n = 9) and nonmalignant breast tissues (NFs, n = 5) and validated by alpha-SMA and FAP immunofluorescence. Cells were exposed to 400 mu M carvacrol. Apoptosis was assessed by TUNEL assay and BAX/BCL-XL Western blotting. Changes in signaling pathways were evaluated by analyzing PPAR alpha/NF-kappa B, sirtuin (SIRT1, SIRT3), autophagy-related markers (LAMP2A, p62), and matrix metalloproteinases (MMP-2, MMP-3). In silico molecular docking and 100-ns molecular dynamics simulations were performed to examine interactions between carvacrol and caspase-3 and caspase-9. Results: Carvacrol induced a pronounced, time-dependent apoptotic response in CAFs, with TUNEL-based viability declining to approximately 10% of control levels by 12 h and a marked increase in the BAX/BCL-XL ratio. In contrast, NFs exhibited minimal TUNEL positivity and no significant change in BAX/BCL-XL. In CAFs, but not NFs, carvacrol reduced PPAR alpha expression and NF-kappa B nuclear localization, increased SIRT1 and SIRT3 levels, selectively suppressed MMP-3 while partially normalizing MMP-2, and altered autophagy-related markers (decreased LAMP2A and accumulation of p62), consistent with autophagic stress and possible impairment of autophagic flux. Computational analyses revealed stable carvacrol binding to caspase-3 and caspase-9 with modest stabilization of active-site loops, supporting caspase-dependent, mitochondria-related apoptosis. Conclusions: Carvacrol selectively targets breast cancer-associated fibroblasts by inducing mitochondria-related apoptotic signaling while largely sparing normal fibroblasts. This effect is accompanied by coordinated modulation of PPAR alpha/NF-kappa B, sirtuin, autophagy, and MMP pathways. These findings support further evaluation of carvacrol as a microenvironment-directed adjunct in breast cancer therapy

    Modeling the effect of cold stratification on seed germination performance of rudbeckia fulgida aiton using response surface methodology (RSM)

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    This study investigates the influence of varying cold stratification durations (0–165 days) on the germination performance and early seedling development of Rudbeckia fulgida. Seeds were divided into 11 groups at 15-day intervals, using a total of 1320 seeds. For each stratification duration, an equivalent number of seeds stored at room temperature served as non-stratified controls. Results demonstrated a clear and significant increase in germination percentage with longer stratification periods (Kruskal–Wallis, H = 57.03, p < 0.001), with the highest germination observed at 135 and 165 days (96.7%). In contrast, seeds kept at room temperature exhibited low and inconsistent germination. Strong positive correlations were detected between stratification duration and both germination percentage (r = 0.914) and post-stratification seed weight (r = 0.419). Furthermore, a Response Surface Methodology (RSM) model was developed to predict germination behavior, achieving an exceptionally high 99% predictive accuracy. The RSM analysis confirmed that cold stratification duration is the dominant factor shaping germination responses in Rudbeckia fulgida Aiton. Overall, the study demonstrates that cold stratification is essential for breaking seed dormancy in R. fulgida, substantially improving propagation efficiency and offering valuable insights for nursery production, landscape practices, and restoration ecology

    Recent advances in shikonin nanoformulations for managing inflammation-related disease

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    Shikonin, a naphthoquinone compound derived from the root of Lithospermum erythrorhizon, has been extensively studied for its antibacterial, antioxidant, and anti-inflammatory properties. Increasing evidence highlights its potential in treating inflammation-related diseases. However, its clinical application is hindered by challenges such as poor water solubility, rapid metabolism in vivo, and other limitations. Recent advancements have demonstrated that encapsulating shikonin within nanocarriers can significantly enhance its water solubility and pharmacokinetic profile. Building on this, this perspective paper outlines the current landscape of inflammation treatment, explores the anti-inflammatory mechanisms of shikonin, reviews the latest progress in shikonin-based nanomaterials for anti-inflammatory applications, and discusses the challenges and future directions for the clinical translation of shikonin nanoformulations

    Investigating marine venoms: anticancer effects of Aurelia aurita on colorectal cancer cells by inhibiting migration, invasion, and proliferation

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    Aurelia aurita is a marine invertebrate rich in bioactive proteins and peptides with therapeutic potential, yet its anticancer properties remain insufficiently explored. This study investigated the cytotoxic, anti-migratory, and anti-invasive effects of A. aurita venom-derived protein cocktails on colorectal cancer cells. Experimental approach: Protein cocktails were isolated from the umbrella and oral arms of A. aurita. Cytotoxicity was evaluated using MTT assays on normal colon epithelial (CCD841CON) and colorectal cancer (WiDr, HT29) cell lines. Cell migration and invasion were assessed using wound healing and 3D Matrigel-based invasion assays. Key findings: The oral arms-derived protein cocktail selectively reduced proliferation in WiDr and HT29 cells (IC₅。: 271.26 and 142.54 µg/mL), without affecting CCD841CON cells. Migration and invasion were significantly suppressed in cancer cells, while normal epithelial cells were unaffected. Conclusion: Oral arms-derived venom proteins from A. aurita demonstrate selective cytotoxic and anti-invasive effects on colorectal cancer cells, indicating potential as a natural anticancer agent

    Stacked deep learning-based quality classification of dried fish products for post-harvest loss reduction and value chain enhancement

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    This study addresses critical inefficiencies in traditional fish drying practices by developing an artificial intelligence (AI)-powered classification system to standardize quality control and enhance market competitiveness for coastal communities. Unlike existing works that rely solely on isolated classifiers, this study introduces a hybrid stacked architecture incorporating both deep and traditional machine learning models, enabling improved interpretability and robustness. Using a three-stage computational methodology, we integrated deep learning with feature optimization to overcome the longstanding challenges of manual quality assessment. The framework consists of: (1) the utilization of a publicly available dataset containing 8,290 high-resolution images of five commercially important species under controlled drying conditions, (2) hierarchical feature extraction using ResNet50 with Lasso regression (LR) for dimensionality reduction, and (3) a novel ensemble learning strategy based on stacked generalization, combining four diverse classifiers trained on optimized deep feature representations. Unlike prior studies that use off-the-shelf convolutional neural network (CNN), our model integrates LR atop CNN embeddings before stacking, thereby redefining classifier synergy in the dried fish domain. The proposed model achieved 99.94% classification accuracy, outperforming conventional single-algorithm approaches by 0.06%, while reducing computational overhead by 34% through optimized feature selection. This study introduces a novel integration of deep features and ensemble stacking methods for dried seafood authentication. This novel design effectively addresses critical texture and color variability issues arising from inconsistent drying processes. The non-destructive nature of this approach enables real-time species identification with a 0.06% misclassification risk, aligning with FAO priorities to minimize post-harvest losses in small-scale fisheries. Furthermore, this study offers a replicable AI blueprint for other agricultural commodities, demonstrating methodological scalability and domain adaptability. By integrating ancestral preservation techniques with Industry 4.0 innovations, this framework enhances processing efficiency, ensures product traceability, and promotes equitable income distribution for artisanal producers

    Classification: Instance-Based and Linear Learning Models

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    Data Mining 10. Hafta Ders Notu Konusu : Classification: Instance-Based and Linear Learning Model

    Determination of drought tolerance of pepper varieties by changes in physiological and biochemical parameters

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    The aim of this study is to compare the tolerance mechanisms of four pepper (Capsicum annuum) varieties (Yükselince, Tural, Burdem and Varol) under drought stress. 58-day-old pepper seedlings were subjected to 10 days-long drought stress by withholding irrigation. Plants were analyzed with regards to growth parameters, relative water content (RWC), total chlorophyll and carotenoid content, proline levels, lipid peroxidation, antioxidative enzyme activities, and photosynthetic efficiencies. Growth parameters, RWC and total chlorophyll and carotenoid contents of pepper varieties under drought stress decreased while proline contents and lipid peroxidation levels increased. The activities of antioxidant enzymes changed depending on varieties. Drought stress decreased the maximal quantum efficiency of PSII, the quantum yield of PSII photochemistry, photochemical quenching and electron transport rate values of the leaves of four varieties, and the most reduction was more pronounced in Varol. Contrary to these photochemical results, nonphotochemical quenching increased in all varieties and the lowest increase was recorded in Yükselince. From these results, Yükselince, which recorded the lowest reduction in growth parameters and total chlorophyll, the lowest increment in lipid peroxidation, the highest proline content and generally high antioxidative enzyme activities and photosynthetic efficiency, was considered more drought tolerant

    Glycaemic control and complications in haemodialysis patients: The TURK-HEMODIAB Study

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    Background The most common cause of end-stage kidney disease is diabetes mellitus (DM). The most commonly used renal replacement therapy in Turkey and in many countries around the world is haemodialysis (HD). Glycaemia control is important in these populations. In this study we aimed to screen for glycaemic control and complications in a large population of diabetic HD patients in Turkey. Methods A total of 16 043 patients were screened in 253 dialysis centres in Turkey and 5038 diabetic HD patients were included in the study. At participating centres, patients' diabetes history, complications, medications, haemoglobin A1c (HbA1c) and other laboratory data were reviewed and recorded by nephrologists. Results The average age of the patients was 64.0 ± 11.2 years and 56% were male. The mean HbA1c was 7.4 ± 1.5%. Patients were divided into three groups according to the HbA1c level (8%). As the HbA1c levels increased, the mean systolic blood pressure and diastolic blood pressure increased significantly. In addition, as the HbA1c levels increased, the number of patients with coronary artery disease, patients undergoing coronary artery bypass graft surgery and the rate of patients with diabetic retinopathy and vision loss increased. Diabetic foot disease and amputation rates were also higher in the group with poor glycaemic control. The number of patients using intensive or mixed insulin was also higher in the group with high HbA1c levels. In ordinal logistic regression analysis, age significantly decreased and higher body mass index slightly increased the risk of a higher HbA1c. Also, the need for a diabetic diet was greater in those with high HbA1c levels. Conclusion Our study highlights that the target values for diabetic HD patients in Turkey are partially compatible with the 2022 Kidney Disease: Improving Global Outcomes guidelines for diabetes management. Nevertheless, more effort and teamwork are needed to improve patient outcomes

    Generational synergy: exploring the impact of intergenerational leadership on employee outcomes in technology firms

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    Purpose – The purpose of this paper is to investigate the impact of intergenerational leadership on employee well-being and sustainable employability in family-owned technology companies in the Marmara region of Turkey and, in particular, the mediating roles of employee-company identification and corporate reputation in improving these outcomes. Design/methodology/approach – A quantitative research design was adopted focusing on technology companies established in Istanbul, Kocaeli, Bursa and Sakarya between 1980 and 2011. These companies are family companies and are managed by second and third generation leaders. Data were collected through a survey conducted on 385 expert employees in these companies. Structural equation modeling was used to analyze the data and evaluate the relationships between variables using the Jamovi program. Findings – The research confirms that intergenerational leadership positively affects both employee-company identification and corporate reputation, which serve as mediating variables that positively affect employee well-being and sustainable employability. Research limitations/implications – The research is limited to family-owned technology companies in the Marmara region of Turkey, which may affect the generalizability of the findings. Future research can expand the scope to include companies from other regions and industries to validate and expand the findings. Further researches can also examine additional mediating or moderating variables to gain a deeper understanding of the mechanisms linking intergenerational leadership to employee outcomes. Practical implications – The results suggest that family-run technology companies can benefit from developing and promoting intergenerational leadership practices. Such practices can strengthen employee-company identification and corporate reputation, and ultimately improve employee well-being and sustainable employability. This is crucial for companies that aim to retain talent and increase productivity. Social implications – The findings provide insights into how intergenerational leadership fosters employee-company identification and enhances corporate reputation, which positively affects employee well-being and sustainable employability. The research enriches the leadership and organizational behavior literature by emphasizing the importance of intergenerational leadership in family companies. Originality/value – The research is one of the first to examine the dynamics of intergenerational leadership in the context of family-owned technology companies in Turkey. By focusing on employee-company identification and corporate reputation as mediating factors, the research offers a unique perspective on how leadership practices can improve key organizational outcomes

    Relationships between peer bullying, short video addiction, sleep deprivation, and life satisfaction in school-aged children

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    Purpose: This study aimed to examine the complex relationships among peer bullying, short video addiction, sleep deprivation, and life satisfaction in school-age children aged 10–12 years. It further explored the mediating roles of short video addiction and sleep in these associations. Methods: A cross-sectional design was adopted with a sample of 854 students selected via simple random sampling from public middle schools. Data were collected using validated scales and analyzed using Structural Equation Modeling (SEM) and bootstrapping techniques. Model fit indices and indirect effects were tested. Results: Victimization significantly predicted short video addiction (β = 0.148), which in turn predicted higher sleep deprivation (β = 0.475). Sleep deprivation negatively affected life satisfaction (β = − 0.297). Notably, short video addiction had an indirect effect on life satisfaction mediated by sleep deprivation (β = − 0.141). The model demonstrated acceptable fit (RMSEA = 0.047; CFI = 0.879). Conclusion: The findings reveal a multi-layered pathway where peer victimization indirectly reduces life satisfaction through digital behavioral patterns and sleep disruptions. This study provides one of the first empirical models integrating these psychosocial variables in children. Implications: Interventions targeting short video addiction and sleep regulation may enhance children's life satisfaction. Findings also validate the Life Satisfaction Scale for use in the 10–12 age group

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