PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
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Article Nanoencapsulation of Hydroxytyrosol Extract of Fermented Olive Leaf Brine Using Proniosomes(Wiley, 2025) Kadiroglu, Pinar; Kilincli, Betul; Ilgaz, Ceren; Bayindir, Zerrin Sezgin; Kelebek, Hasim; Helvacioglu, Selin; Ozhan, GunesBACKGROUND: Olive leaves are rich in bioactive compounds with potential health benefits; however, their limited bioavailability and stability hinder their effective utilization. Emerging technologies, nanocarrier-based delivery systems, have shown promise in enhancing these properties. RESULTS: The optimal conditions for proniosome formulation were 50 rpm rotational speed and 35 degrees C, achieving 81.20 +/- 0.80% encapsulation efficiency. Particle sizes ranged from 188.6 to 248.9 nm, with a zeta potential of similar to-30 mV, indicating high stability and resistance to aggregation. Advanced instrumental analysis confirmed interactions between the extract and proniosome components. After 30 days at 4 degrees C, extract-loaded proniosomes maintained better homogeneity and lower polydispersity index. Cytotoxicity studies showed that both the extract and its proniosomal form were nontoxic to HEK293T cells up to 200 mu g mL(-1). In zebrafish assays, minimal larval mortality was observed up to 3200 mu g mL(-1) for the extract, while no mortality occurred up to 1600 mu g mL(-1) for the proniosomal extract, highlighting its improved safety profile. CONCLUSION: The findings from this research could contribute to the advancement of sustainable and health-promoting food innovations by integrating cutting-edge nanotechnology-driven encapsulation strategies into plant-based food formulations. (c) 2025 Society of Chemical Industry.Article Silver-Loaded Titania-Based Metal-Organic Frameworks as a Platform for Silver Ion Release for Antibacterial Applications(Amer Chemical Soc, 2025) Mazare, Anca; Goldmann, Wolfgang H.; Kocak, Esra; Osuagwu, Benedict; Qin, Shanshan; Cao, Ran; Schmuki, PatrikConventional Ag-decorated TiO2 coatings suffer from low adsorption capacity and burst release kinetics, limiting long-term antibacterial efficacy and risking cytotoxicity. An entirely different payload release approach can be based on metal-organic frameworks (MOFs), which offer tunable porosity, high surface area, and internal diffusion channels. Here, we report a thermally stabilized Ti-based MOF [NH2-MIL-125(Ti)] functionalized with Ag+ via reactive deposition, enabling high Ag loading (similar to 14.7 wt %) and sustained release. Annealing at 250 degrees C enhances aqueous stability, allowing diffusion-governed Ag+ delivery over >48 h, with 77% of the Ag still present in the MOF after a 24 h release. The system exhibits dose-dependent antibacterial activity in powders and comparable efficacy in coatings, with a more gradual release profile. This scalable platform is promising for long-acting coatings, wound interfaces, and implantable materials.Article A Comprehensive MicroRNA-Seq Transcriptomic Analysis of Tay-Sachs Disease Mice Revealed Distinct MiRNA Profiles in Neuroglial Cells(Springernature, 2025) Kaya, Beyza; Orhan, Mehmet Emin; Yanbul, Selman; Demirci, Muserref Duygu Sacar; Demir, Secil Akyildiz; Seyrantepe, VolkanTay-Sachs disease (TSD) is a rare lysosomal storage disorder marked by the progressive buildup of GM2 in the central nervous system (CNS). This condition arises from mutations in the HEXA gene, which encodes the alpha subunit of the enzyme beta-hexosaminidase A. A newly developed mouse model for early-onset TSD (Hexa-/-Neu3-/-) exhibited signs of neurodegeneration and neuroinflammation, evidenced by elevated levels of pro-inflammatory cytokines and chemokines, as well as significant astrogliosis and microgliosis. Identifying disease-specific microRNAs (miRNAs) may aid the development of targeted therapies. Although previous small-scale studies have investigated miRNA expression in some regions of GM2 gangliosidosis mouse models, thorough profiling of miRNAs in this innovative TSD model remains to be done. In this study, we employed next-generation sequencing to analyze the complete miRNA profile of neuroglial cells from Hexa-/-Neu3-/- mice. By comparing KEGG and Reactome pathways associated with neurodegeneration, neuroinflammation, and sphingolipid metabolism in Hexa-/-Neu3-/- neuroglial cells, we discovered new microRNAs and their targets related to the pathophysiology of GM2 gangliosidosis. For the first time, our findings showed that miR-708-5p, miR-672-5p, miR-204-5p, miR-335-5p, and miR-296-3p were upregulated, while miR-10 b-5p, miR-615-3p, miR-196a-5p, miR-214-5p, and miR-199a-5p were downregulated in Hexa-/-Neu3-/- neuroglial cells in comparison to age-matched wild-type (WT). These specific changes in miRNA expression deepen our understanding of the disease's neuropathological characteristics in Hexa-/-Neu3-/- mice. Our study suggests that miRNA-based therapeutic strategies may improve clinical outcomes for TSD patients.Article Electrically Controlled Heat Transport in Graphite Films Via Reversible Ionic Liquid Intercalation(Amer Assoc Advancement Science, 2025) Steiner, Pietro; Adnan, Saqeeb; Ergoktas, M. Said; Barrier, Julien; Yu, Xiaoxiao; Orts, Vicente; Kocabas, CoskunThe ability to control heat transport with electrical signals has been an outstanding challenge due to the lack of efficient electrothermal materials. Previous attempts have mainly concentrated on low-thermal conductivity materials and encountered various problems such as narrow dynamic range and modest on/off ratios. Here, using high-thermal conductivity graphite films, we demonstrate an electrothermal switch enabling electrically tunable heat flow at the device level. The device uses reversible electro-intercalation of ions to modulate the in-plane thermal conductivity of graphite film by more than 13-fold via tunable phonon scattering, enabling observable modulation of the thermal conductivity at the device level. We anticipate that our results could provide a realistic pathway for adaptive thermal transport, enabling electrically driven thermal devices that would find a broad spectrum of applications in aerospace and microelectronics.Article Task-Specific Dynamical Entropy Variations in EEG as a Biomarker for Parkinson's Disease Progression(Springer, 2025) Onay, Fatih; Karacali, BilgeUncovering the neuronal mechanisms un-derlying optimal behavioral performance is essential to understand how the brain dynamically adapts to changing conditions. In Parkinson's disease (PD), these neuronal mechanisms are disrupted and lead to impairments in motor coordination and higher-order cognitive functions. This study investigates neuronal dynamics during a lower-limb pedaling task by analyzing the dynamical entropy of EEG signals in healthy controls (HC), PD patients, and PD patients with freezing of gait (PDFOG). We examined both average entropy changes and entropy variability across trials to characterize task-specific neural adaptations across disease progression. Results showed that PD and PDFOG patients exhibited decreased levels of permutation entropy in frontal and parietal regions, which may be associated with loss of cognitive adapta-tion due to altered information processing. Additionally, Vasicek's entropy variability in both PD groups was significantly diminished in occipital and left frontal regions, suggesting reduced cognitive capacity to dy-namically allocate neuronal resources during task engagement. We extended this analysis to the classification of groups using LDA and SVM classifiers, where entropy-derived features achieved a classification accuracy of up to 96.15% when distinguishing HC from PDFOG patients. This dynamical entropic framework provides a novel approach for capturing neural complexity changes during task performance, revealing subtle cognitive-motor impairments in PD. Understanding the maintenance of cognitive information processing and flexibility in response to motor and cognitive task demands could be a useful tool to track PD diagnosis and progression in addition to resting-state analyses.Article Disruption of Glutamine Transport Uncouples the NUPR1 Stress-Adaptation Program and Induces Prostate Cancer Radiosensitivity(BMC, 2025) Kahya, Ugur; Lukiyanchuk, Vasyl; Gorodetska, Ielizaveta; Weigel, Matthias M.; Koeseer, Ayse Sedef; Alkan, Berke; Dubrovska, AnnaBackgroundMetabolic and stress response adaptations in prostate cancer (PCa) mediate tumor resistance to radiation therapy (RT). Our study investigated the roles of glutamine (Gln) transporters SLC1A5, SLC7A5, and SLC38A1 in regulating NUPR1-mediated stress response, PCa cell survival, metabolic reprogramming, and response to RT.MethodsThe radiosensitizing potential of GLS inhibition with CB-839 was analyzed in prostate cancer xenograft models. The level of gene expression was analyzed by RNA sequencing and RT-qPCR in the established cell lines or patient-derived tumor and adjacent non-cancerous tissues. Phosphoproteomic analysis was employed to identify the underlying signaling pathways. The publicly available PCa patient datasets, and a dataset for the patients treated with RT were analyzed by SUMO software. The key parameters of mitochondrial functions were measured by Seahorse analysis. Analysis of the general oxidative stress level and mitochondrial superoxide detection were conducted using flow cytometry. gamma H2A.X foci analysis was used to assess the DNA double strand break. Relative cell sensitivity to RT was evaluated by radiobiological clonogenic assays. Aldefluor assay and sphere-forming analysis were used to determine cancer stem cell (CSC) phenotype.ResultsA siRNA-mediated knockdown of Gln transporters SLC1A5, SLC7A5, and SLC38A1 resulted in significant radiosensitization of PCa cells. Consistently, the first-in-clinic glutaminase (GLS) inhibitor CB-839, combined with RT, demonstrated a synergistic effect with radiotherapy in vivo, significantly delaying tumor growth. Inhibition of Gln metabolism or knockdown of Gln transporters SLC1A5, SLC7A5, or SLC38A1 induces expression of NUPR1, a stress response transcriptional regulator, but simultaneously uncouples the NUPR1-driven metabolic stress-adaptation program. Similarly to the effect from NUPR1 knockdown, depletion of these Gln transporters led to reduced cell viability, accumulation of mitochondrial ROS, and increased PCa radiosensitivity. This effect is more pronounced in PCa cells with high dependency on OXPHOS for energy production.ConclusionsOur work underscores the role of Gln transporters and the NUPR1-mediated stress response in PCa cell survival, oxidative stress, mitochondrial functions, and radioresistance. Our findings provide a potential therapeutic in vivo strategy to enhance the efficacy of RT and suggest a potential synergism between the depletion of Gln transporters or NUPR1 and OXPHOS inhibition.Article Comparative Proteomic Analysis of Dental-Origin Stem Cells: Insights Into Regenerative Potential(Springer, 2025) Tez, Banu Cicek; Durukan, Sebahat Melike; Yildir, Selin Kubra; Cokkececi, Murat; Boyvat, Dudu; Altinsoy, Nilay; Ozcan, ServetTeeth are a significant source of stem cells and have clinical importance for regenerative medicine. A human tooth harbors different kinds of stem cells in the dental pulp (DPSC) or the periodontal ligament (PDLSC). Also exfoliated teeth in childhood contain a special type of stem cells in their pulp called Stem cells from Human Exfoliated Deciduous teeth (SHED). All these stem cells have features and capacities that vary depending on their niche. Here we investigated the proteomic properties of three types of stem cells that originated from human teeth. We isolated and cultured the DPSCs, PDLSCs, and SHED cells. After validating MSC populations via immunophenotyping, we performed a mass spectrometry-based proteomic approach to identify and relatively quantify whole cell and secreted proteins. Identified proteins were evaluated by using Gene Ontology and Reactome pathway analysis tools. Our data reveal that SHED cells represented inflammation, hypoxia, and nutrient deficiency-associated ontologies in both their secretome and whole-cell proteomes. The whole-cell proteome of PDLSCs consisted of differentiation and proliferation-associated molecules while their secretory molecules were mainly associated with inflammation, ECM organization, and immune response. Among dental-originated stem cells, DPSCs appeared to be the healthiest and clinically relevant in terms of proteomic properties with their proliferation, growth factor signaling, and stemness-associated molecules in their secretome and whole-cell proteome. Obtained results demonstrated that every type of stem cell from dental origin has unique proteomic features that are altered by their location and physiological conditions. The findings may help researchers improve the dental stem-cell-based regenerative medicine approaches.Article Recent Advances in Hydrogel-Based 3D Disease Modeling and Drug Screening Platforms(2025) Bilginer-Kartal, R.; Çoban, B.; Yildirim-Semerci, Ö.; Arslan-Yildiz, A.Three-dimensional (3D) disease modeling and drug screening systems have become important in tissue engineering, drug screening, and development. The newly developed systems support cell and extracellular matrix (ECM) interactions, which are necessary for the formation of the tissue or an accurate model of a disease. Hydrogels are favorable biomaterials due to their properties: biocompatibility, high swelling capacity, tunable viscosity, mechanical properties, and their ability to biomimic the structure and function of ECM. They have been used to model various diseases such as tumors, cancer diseases, neurodegenerative diseases, cardiac diseases, and cardiovascular diseases. Additive manufacturing approaches, such as 3D printing/bioprinting, stereolithography (SLA), selective laser sintering (SLS), and fused deposition modeling (FDM), enable the design of scaffolds with high precision; thus, increasing the accuracy of the disease models. In addition, the aforementioned methodologies improve the design of the hydrogel-based scaffolds, which resemble the complicated structure and intricate microenvironment of tissues or tumors, further advancing the development of therapeutic agents and strategies. Thus, 3D hydrogel-based disease models fabricated through additive manufacturing approaches provide an enhanced 3D microenvironment that empowers personalized medicine toward targeted therapeutics, in accordance with 3D drug screening platforms. © 2025. The Author(s), under exclusive license to Springer Nature Switzerland AG.Article Tc-99m Erythromycin Lactobionate Inhalation Scintigraphy in Parenchymal Lung Diseases(Elsevier Science inc, 1999) Durak, H; Aktogu, S; Degirmenci, B; Sayit, E; Ertay, T; Dereli, SWe have investigated Technetium 99m erythromycin lactobionate (Tc 99m EL) clearance from the lungs after inhalation, in the presence of an alveolitis. Eighteen patients (6 sarcoidosis, 7 idiopathic fibrosis, and 5 miliary tuberculosis) were imaged after the patients inhaled 1,110 MBq of Tc 99m EL. Clearance half time for the first 45 min, for 24 h, and retention at 24 h correlated with percentage of lymphocytes in bronchoalveolar lavage fluid (BAL) (r =.729, r =.883, and r =.826, respectively). There was a positive correlation between peripheral penetration (PP) and forced expiratory volume in 1 s (FEV1) (r =.806) and forced vital capacity (FVC) (r =.781). Retention was more marked in sarcoidosis compared with tuberculosis (0.025 < p less than or equal to 0.05). Radioaerosol lung imaging may reflect the pulmonary function impairment in parenchymal lung diseases. Retention of Tc 99m EL may be related to number of BAL cells or presence of a lymphocytic alveolitis. Long residency time of Tc 99m EL in the lungs implies that erythromycin can also be administered by inhalation for therapeutic purposes. NUCL MED BIOL 26;6:695-698, 1999. (C) 1999 Elsevier Science Inc. All rights reserved.Article Elastic and Anelastic Behavior Associated With Structural Transitions in CsPbBr3(Amer Chemical Soc, 2025) Luo, Pingjing; He, Zhengwang; Yang, Dexin; Aktas, Oktay; Ding, Xiangdong; Zhang, XuefengStrain coupling and relaxation dynamics critically influence the photovoltaic and photoluminescent performances of metal halide perovskites. Here, resonant ultrasound spectroscopy is employed to study the elastic and anelastic properties associated with the octahedral tilting transitions in the optoelectronic semiconductor CsPbBr3 over the temperature range 303-468 K. The cubic-to-tetragonal transition near 405 K is marked by pronounced elastic softening accompanied by a sharp increase in acoustic loss. High anelastic loss below this transition reveals the presence of mobile ferroelastic twin walls that become pinned by lead vacancies at a temperature interval near 380 K in the tetragonal phase. The elastic softening in the cubic phase is strongly correlated to dynamic effects such as the local polar fluctuations. This local disordered effect is further verified by the anomalously high attenuation in the orthorhombic structure, in which the ferroelastic twin walls might become mobile.Article Nanostructured Ox-MWCNT-Ppy-Au Electrochemical Sensor for Ultralow Detection of Retrorsine and Evaluation of Its Cytotoxic Effects on Liver Cells(Taylor & Francis Ltd, 2025) Akturk, Ezgi Zekiye; Njjar, Muath; Ata, Melek Tunc; Kaya, Ahmet; Akdogan, Abdullah; Onac, CananThis study presents the development of a novel retrorsine (RTS)-imprinted sensor utilizing oxidized multi-walled carbon nanotubes (Ox-MWCNTs), polypyrrole (PPy), and gold nanoparticles (AuNPs), employing square wave voltammetry for the sensitive and selective detection of RTS which causes oxidative-stress and DNA damage. The fabricated Ox-MWCNT-PPy-AuNP sensor demonstrated a surface-area of (0.218 cm2) is 4.25 times larger than a bare glassy carbon electrode, with a low charge transfer resistance (10.9 Omega), enhancing electron transfer kinetics. The sensor showed excellent sensitivity in detecting retrorsine, with a limit of detection of 0.035 nM in synthetic matrices and -0.030 nM in HepaRG cell culture medium. Toxicity assays in HepaRG cells revealed dose-dependent oxidative-stress, with glutathione levels decreasing from 23.08 +/- 0.21 mu mol/109 to 21.21 +/- 0.02 mu mol/109 at 35 mu M retrorsine. Concurrently, GSSG levels increased from 1.32 +/- 0.26 mu mol/109 to 2.22 +/- 0.02 mu mol/109. DNA-damage assessed via comet assay, showed significant increases in tail-moment (2.53 mu m) and tail-migration (16.13 mu m). Oxidative DNA-damage, indicated by 8-OHdG levels, increased significantly from 0.29 +/- 0.02 ng.mL- (control) to 0.47 +/- 0.07 ng.mL- at 35 mu M retrorsine. These findings demonstrate the sensor's effectiveness for retrorsine detection and its applicability in toxicological studies. The integration of nanomaterial engineering and molecular imprinting provides a highly sensitive, selective, and eco-friendly solution for monitoring toxic agents and assessing their biological impacts.Article Citation - WoS: 1Citation - Scopus: 2A Holistic Overview of the Applications of Grace-Observed Terrestrial Water Storage in Hydrology and Climate Science(Springer, 2025) Khorrami, Behnam; Gunduz, Orhan; 03.07. Department of Environmental Engineering; 03. Faculty of Engineering; 01. Izmir Institute of TechnologyTerrestrial Water Storage (TWS) represents a vital element of the hydrological cycle, with its fluctuations significantly impacting the climate of the Earth and its ecological balance. Since its launch in 2002, the Gravity Recovery and Climate Experiment (GRACE) satellite mission has revolutionized the ability to observe and analyze large-scale mass changes within Earth's system components. This paper offers a comprehensive and current overview of GRACE satellite gravimetry, highlighting its relevance to hydrological and climate-related studies. It outlines the fundamental measurement principles of the GRACE mission, provides an in-depth explanation of GRACE data products (including spherical harmonic and mascon solutions), examines emerging trends in GRACE-based research, and reviews key applications in hydrology and climate science. Additionally, it addresses the major challenges in utilizing GRACE data and explores promising avenues for future research and applications.Article Understanding the Role of a Specific Microenvironment in Personal Exposure To Semi-Volatile Organic Compounds Using Silicone Wristbands(Royal Soc Chemistry, 2025) Akmermer, Zulfikar; Demirtepe, Hale; 03.07. Department of Environmental Engineering; 03. Faculty of Engineering; 01. Izmir Institute of TechnologyAssessment of personal exposure to semi-volatile organic compounds was facilitated using silicone wristbands (SWBs), an easy-to-use sampler that reflects total inhalation and dermal exposure from all the microenvironments and the activities in which the user was involved. Hence, SWBs help understand exposure from various routes, activities, and microenvironments. Offices are critical microenvironments where workers spend one-third of their daily time on weekdays; hence exposure from offices should be more extensively studied. This study aimed to investigate the personal exposure of university personnel and elaborate on the contribution of the exposure due to the office air to their overall exposure using SWBs. One SWB was worn by the participant, and another was hung in their office. After seven days of sampling on the wrist, exposure to polycyclic aromatic hydrocarbons (PAHs) was found to be related to combustion activities at home or from open fire, whereas exposure to organophosphate esters and phthalates was suggested to originate from building materials, such as flooring materials and paints, and consumer products, e.g. mattresses and furniture. PAHs in the participants' offices were influenced by the transport of outdoor air and phthalates from the ceiling material. Then, we estimated the equivalent air concentrations using the SWBs sampled from the offices and previously developed sampling rates and partition coefficients. The estimated office air exposure contributions to total inhalation and dermal exposure were 83%, 51%, and 39% for fluorene, tri(n-butyl) phosphate, and tris(2-chloro isopropyl) phosphate, respectively. These findings were consistent with the statistical analysis of personal data. To conclude, this study highlighted the importance of specific microenvironments in our exposure to particular SVOCs, offering strategies for indoor air quality management and human health risk assessment.Article Vision Transformers-Based Deep Feature Generation Framework for Hydatid Cyst Classification in Computed Tomography Images(Springer, 2025) Sagik, Metin; Gumus, Abdurrahman; 03.05. Department of Electrical and Electronics Engineering; 03. Faculty of Engineering; 01. Izmir Institute of TechnologyHydatid cysts, caused by Echinococcus granulosus, form progressively enlarging fluid-filled cysts in organs like the liver and lungs, posing significant public health risks through severe complications or death. This study presents a novel deep feature generation framework utilizing vision transformer models (ViT-DFG) to enhance the classification accuracy of hydatid cyst types. The proposed framework consists of four phases: image preprocessing, feature extraction using vision transformer models, feature selection through iterative neighborhood component analysis, and classification, where the performance of the ViT-DFG model was evaluated and compared across different classifiers such as k-nearest neighbor and multi-layer perceptron (MLP). Both methods were evaluated independently to assess classification performance from different approaches. The dataset, comprising five cyst types, was analyzed for both five-class and three-class classification by grouping the cyst types into active, transition, and inactive categories. Experimental results showed that the proposed VIT-DFG method achieves higher accuracy than existing methods. Specifically, the ViT-DFG framework attained an overall classification accuracy of 98.10% for the three-class and 95.12% for the five-class classifications using 5-fold cross-validation. Statistical analysis through one-way analysis of variance (ANOVA), conducted to evaluate significant differences between models, confirmed significant differences between the proposed framework and individual vision transformer models (p<0.05\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$p < 0.05$$\end{document}). These results highlight the effectiveness of combining multiple vision transformer architectures with advanced feature selection techniques in improving classification performance. The findings underscore the ViT-DFG framework's potential to advance medical image analysis, particularly in hydatid cyst classification, while offering clinical promise through automated diagnostics and improved decision-making.Article A Pragmatic Grouping Model for Bone-Only De Novo Metastatic Breast Cancer (MetS Protocol MF22-03)(MDPI, 2025) Goktepe, Berk; Demirors, Berkay; Senol, Kazim; Ozbas, Serdar; Sezgin, Efe; Lucci, Anthony; Soran, Atilla; 03.08. Department of Food Engineering; 03. Faculty of Engineering; 01. Izmir Institute of TechnologyDe novo metastatic breast cancer (dnMBC) accounts for 3-10% of newly diagnosed cases, with 20-40% presenting as a bone-only metastatic disease, which can achieve survival outcomes exceeding 10 years with multimodal therapy. However, the role of multimodal therapy remains controversial in the guidelines. Objective: This study aims to identify dnBOMBC subgroups to develop a pragmatic staging system for guiding locoregional therapy decisions. Materials and Methods: Data from the MF07-01 phase III randomized trial (2021, median follow-up time (mFT): 40 months (range 1-131)) and the BOMET prospective multi-institutional registry trial (2021, mFT: 34 months (range 25-45)) were combined for analysis, including only patients who presented with bone-only metastases. Exclusion criteria were patients under 18 and those with a history of prior cancer or cancer metastases. Patients with missing data and positive surgical margins were excluded. Out of 770 patients, 589 were included. Survival analyses were first conducted according to molecular subgroups, after which patients were further stratified by hormone receptor status, human epidermal human epidermal growth factor receptor 2 (HER2) status, tumor grade, and clinical T (cT) stage. Group A (GrA) included hormone receptor (HR)-positive, low- or intermediate-grade tumors at any cT; HR-positive, high-grade tumors with cT0-3; or any HER2-positive tumors. Group B (GrB) included HR-positive, high-grade tumors with cT4 disease or any triple-negative (TN) tumors. Results: The hazard of death (HoD) was 43% lower in GrA than in GrB. Median OS was 65 months (39-104) for GrA patients and 44 months (28-72) for GrB patients (HR 0.57, 95% CI 0.41-0.78, p = 0.0003). Primary tumor surgery (PTS) significantly improved OS in GrA patients, regardless of the number of metastases (solitary: HR, 0.375, 95% CI 0.259-0.543, p < 0.001; multiple: HR 0.435, 95% CI 0.334-0.615, p < 0.001). Conversely, GrB patients did not experience a significant benefit from PTS. Conclusions: This study demonstrates that GrA patients have better OS than GrB patients, and PTS reduces the HoD in GrA patients compared to systemic therapy alone. These findings support using a modified staging system in dnBOBMC to identify patients who may benefit from multimodal therapy including PTS.Article Citation - Scopus: 1Analysis of Microplastic Flux From the Gediz River To the Aegean Sea: a Modeling Study for Environmental Management(Academic Press Ltd- Elsevier Science Ltd, 2025) Kazanci, Yigithan; Alyuruk, Nefise; Alpergun, Cumana; Kara, Nursena; Baycan, Neval; Gunduz, Orhan; 03.07. Department of Environmental Engineering; 03. Faculty of Engineering; 01. Izmir Institute of TechnologyIt is critical to determine the abundance of microplastics in terrestrial inland waters, understand their fate and transport mechanisms, and reveal their status in aquatic environments. This study aimed to develop and calibrate a mathematical model to simulate microplastic (MP) pollution in the Gediz River Basin, T & uuml;rkiye, which focused on MP fate and transport under existing conditions and various management scenarios. The baseline scenario revealed that, despite a ninefold difference in flow rates, the midstream and upstream parts of the basin also exhibited significant contamination, with an average concentration of 25 n/L compared to the downstream average of 29 n/L. The model was later simulated to test the effects of various mitigation scenarios including but not limited to reducing MP discharges from wastewater treatment plants (WWTPs) and implementing vegetative barriers in tributaries. Scenario 4, which involves reducing MP concentrations in upstream tributaries with vegetative barriers, achieved the highest average reduction across all segments (32 %) and specifically in the downstream area (47 %). In contrast, Scenario 1, aimed at reducing wastewater discharges from urban and industrial WWTPs through water reclamation, and Scenario 2, which focused on eliminating MP in Organized Industrial Zone (OIZ) discharges by changing industrial inputs, achieved the most effective MP reductions in the upper basin, with reductions of 20 % and 17 %, respectively. Scenario 3, targeting flow reduction and accumulation through constructed wetlands, had minimal impact, with reductions close to 0 % in most areas. These results highlight the need for comprehensive approaches to effectively reduce MP pollution, particularly in managing upstream and tributary sources.Article Citation - WoS: 1Citation - Scopus: 2A Novel MIP Electrochemical Sensor Based on a CuFe2O4NPs@rGO Nanocomposite and Its Application in Breast Milk Samples for the Determination of Fipronil(Royal Soc Chemistry, 2025) Njjar, Muath; Akturk, Ezgi Zekiye; Kaya, Ahmet; Onac, Canan; Akdogan, AbdullahBackground: fipronil, a widely utilized insecticide in agriculture, has been shown to have potential health implications as it can accumulate in the environment and affect human health. Electrochemical sensors, specifically those incorporating molecularly imprinted polymers (MIPs), provide an efficient way for the detection of fipronil because of their selectivity and specificity. The combination of CuFe2O4NPs and reduced graphene oxide (rGO) exhibits a synergistic effect that enhances sensitivity and selectivity. The composite's effective properties provide a robust platform for fipronil determination in various matrices. This study detected fipronil using an electrochemical sensor based on a glassy carbon electrode (GCE) modified with MIP@CuFe2O4NPs@rGO. Results: the synthesized MIP@CuFe2O4NPs@rGO material was characterized using various techniques such as Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (FESEM), X-ray diffraction (XRD) analysis, energy dispersive X-ray (EDX) analysis, Brunauer-Emmett-Teller (BET) analysis, X-ray photoelectron spectroscopy (XPS) analysis, and electrochemical impedance spectroscopy (EIS). The modified GCE showed enhanced electrochemical behavior for fipronil, as demonstrated by cyclic voltammetry (CV) and square wave voltammetry (SWV) techniques. Optimization of parameters such as pH, pyrrole concentration, and template concentration further improved sensor performance. The sensor exhibited a linear dynamic range of 1 to 6 nM, with a limit of detection (LOD) of 0.30 nM (S/N = 3) and a limit of quantification (LOQ) of 1.08 nM (S/N = 10), highlighting its sensitivity and reliability. The precision of the method was excellent, with a relative standard deviation of less than 4.0%. When applied to quantify fipronil in breast milk samples, the sensor showed high accuracy and precision, with recoveries ranging from 96.24% to 97.75%. Significance: the sensor offers several advantages, including high sensitivity, specificity, and accuracy. Its ability to detect fipronil in complex matrices such as breast milk highlights its potential for real-world applications in environmental and health monitoring. Overall, this research paves the way for the development of efficient, rapid and eco-friendly sensors for detecting pesticide residues in various environmental and biological samples.Article Role of Long Non-Coding RNA X-Inactive Transcript (XIST) in Neuroinflammation and Myelination: Insights From Cerebral Organoids and Implications for Multiple Sclerosis(MDPI, 2025) Pepe, Nihan Aktas; Acar, Busra; Zararsiz, Gozde Erturk; Guner, Serife Ayaz; Sen, AlaattinBackground/Objectives: X-inactive-specific transcript (XIST) is a factor that plays a role in neuroinflammation. This study investigated the role of XIST in neuronal development, neuroinflammation, myelination, and therapeutic responses within cerebral organoids in the context of Multiple Sclerosis (MS) pathogenesis. Methods: Human cerebral organoids with oligodendrocytes were produced from XIST-silenced H9 cells, and the mature organoids were subsequently treated with either FTY720 or DMF. Gene expression related to inflammation and myelination was subsequently analyzed via qRT-PCR. Immunofluorescence staining was used to assess the expression of proteins related to inflammation, myelination, and neuronal differentiation. Alpha-synuclein protein levels were also checked via ELISA. Finally, transcriptome analysis was conducted on the organoid samples. Results: XIST-silenced organoids presented a 2-fold increase in the expression of neuronal stem cells, excitatory neurons, microglia, and mature oligodendrocyte markers. In addition, XIST silencing increased IL-10 mRNA expression by 2-fold and MBP and PLP1 expression by 2.3- and 0.6-fold, respectively. Although XIST silencing tripled IBA1 protein expression, it did not affect organoid MBP expression. FTY720, but not DMF, distinguished MBP and IBA1 expression in XIST-silenced organoids. Furthermore, XIST silencing reduced the concentration of alpha-synuclein from 300 to 100 pg/mL, confirming its anti-inflammatory role. Transcriptomic and gene enrichment analyses revealed that the differentially expressed genes are involved in neural development and immune processes, suggesting the role of XIST in neuroinflammation. The silencing of XIST modified the expression of genes associated with inflammation, myelination, and neuronal growth in cerebral organoids, indicating a potential involvement in the pathogenesis of MS. Conclusions: XIST may contribute to the MS pathogenesis as well as neuroinflammatory diseases such as and Alzheimer's and Parkinson's diseases and may be a promising therapeutic target.Article Time-Dependent Effects of Low-Intensity Pulsed Ultrasound on Apoptosis and Autophagy in Malignant Melanoma Stem Cells(Wiley, 2025) Dikici, Omer; Ozdil, Berrin; Yesin, Taha Kadir; Dikici, Aylin; Adali, Yasemin; Aktug, HuseyinCancer stem cells (CSCs) in malignant melanoma contribute to therapeutic resistance and tumour recurrence. While low-intensity pulsed ultrasound (LIPUS) has been proposed as a non-invasive strategy to induce cell death, its effects on CSC-specific apoptotic and autophagic responses remain unclear. This study aimed to explore the time-dependent effects of LIPUS on apoptosis and autophagy in CD133+ melanoma CSCs and CD133- non-stem melanoma cells. Human melanoma cells (CHL-1) were sorted via FACS into CD133+ and CD133- populations. Cells were exposed to LIPUS (1 MHz, 20% duty cycle, 1 W/cm2) for 1, 5, and 10 min. Protein expression levels of Caspase-3, Caspase-8, mTOR, and LC3 were evaluated via immunofluorescence and quantified by image-based analysis. Both cell populations showed significant increases in Casp3, Casp8, mTOR, and LC3 intensities following LIPUS application. Notably, CD133+ cells exhibited delayed but sustained increases in Casp3 and LC3 expression, while CD133- cells responded more rapidly. mTOR activity demonstrated distinct temporal dynamics between the two groups, suggesting differential modulation of autophagy-related pathways. LIPUS triggers temporally distinct apoptotic and autophagic responses in melanoma CSCs and non-stem cancer cells. These findings suggest a potential therapeutic avenue to selectively disrupt CSC survival mechanisms using mechanical stimulation.Article An Analytical Methodology for the Determination of Cadmium Bound To Whey-Proteins by Laser-Induced Breakdown Spectroscopy at Low Pressures(Elsevier, 2026) Erdogrul, Ilayda Yaman; Yalcin, Serife H.In this study, a dried-droplet LIBS methodology for determining cadmium in cow milk has been developed. The performance of the methodology was shown by standard and real protein samples. A standard protein, bovine serum albumin (BSA), and whey protein extracted from skim cow milk were incubated in standard Cd solutions, and the complex solution was filtered through cut-off filters by centrifugation. The unreacted cadmium in the filtrate and Cd-bound protein in the filtered fraction were loaded separately onto a Si-wafer substrate and analyzed via dried-droplet LIBS methodology. Measurements were performed at reduced pressures by taking advantage of the signal enhancement effect. The optimum pressure for most Cd emission lines was found to be 100 mbar. It has been shown that the dried-droplet LIBS methodology at reduced pressures can be used for the identification and determination of free and protein-bound Cd in the whey matrix. The concentration-based detection limit of Cd bound to whey proteins was determined to be 20.2 ng mL- 1, which corresponds to as low as 10 pg in absolute amount with a sample volume of 500 nL. The LOQ value is estimated as 67.3 ng mL- 1 and 33.3 pg, in terms of concentration unit and absolute amount, respectively. The use of small sample volumes is important in the analysis of limited amounts of samples, such as body fluids. Preconcentration studies with multiple loadings of the sample on the same spot resulted in improvements in concentration-based detection. 8 ng mL- 1 Cd in the whey matrix that could not be determined by a single droplet loading due to being below the detection limit; could be determined after 10 consecutive loadings. The methodology may also be applied to the determination of other toxic metals bound to proteins for food quality control.
