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Search Results (19,102)

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Keywords = sensitivity assessment

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17 pages, 2085 KiB  
Article
Identification Method of Weak Nodes in Distributed Photovoltaic Distribution Networks for Electric Vehicle Charging Station Planning
by Xiaoxing Lu, Xiaolong Xiao, Jian Liu, Ning Guo, Lu Liang and Jiacheng Li
World Electr. Veh. J. 2025, 16(8), 433; https://doi.org/10.3390/wevj16080433 (registering DOI) - 2 Aug 2025
Abstract
With the large-scale integration of high-penetration distributed photovoltaic (DPV) into distribution networks, its output volatility and reverse power flow characteristics are prone to causing voltage violations, necessitating the accurate identification of weak nodes to enhance operational reliability. This paper investigates the definition, quantification [...] Read more.
With the large-scale integration of high-penetration distributed photovoltaic (DPV) into distribution networks, its output volatility and reverse power flow characteristics are prone to causing voltage violations, necessitating the accurate identification of weak nodes to enhance operational reliability. This paper investigates the definition, quantification criteria, and multi-indicator comprehensive determination methods for weak nodes in distribution networks. A multi-criteria assessment method integrating voltage deviation rate, sensitivity analysis, and power margin has been proposed. This method quantifies the node disturbance resistance and comprehensively evaluates the vulnerability of voltage stability. Simulation validation based on the IEEE 33-node system demonstrates that the proposed method can effectively identify the distribution patterns of weak nodes under different penetration levels (20~80%) and varying numbers of DPV access points (single-point to multi-point distributed access scenarios). The study reveals the impact of increased penetration and dispersed access locations on the migration characteristics of weak nodes. The research findings provide a theoretical basis for the planning of distribution networks with high-penetration DPV, offering valuable insights for optimizing the siting of volatile loads such as electric vehicle (EV) charging stations while considering both grid safety and the demand for distributed energy accommodation. Full article
(This article belongs to the Special Issue Fast-Charging Station for Electric Vehicles: Challenges and Issues)
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17 pages, 516 KiB  
Article
Incidence and Predictive Factors of Acute Kidney Injury After Major Hepatectomy: Implications for Patient Management in Era of Enhanced Recovery After Surgery (ERAS) Protocols
by Henri Mingaud, Jean Manuel de Guibert, Jonathan Garnier, Laurent Chow-Chine, Frederic Gonzalez, Magali Bisbal, Jurgita Alisauskaite, Antoine Sannini, Marc Léone, Marie Tezier, Maxime Tourret, Sylvie Cambon, Jacques Ewald, Camille Pouliquen, Lam Nguyen Duong, Florence Ettori, Olivier Turrini, Marion Faucher and Djamel Mokart
J. Clin. Med. 2025, 14(15), 5452; https://doi.org/10.3390/jcm14155452 (registering DOI) - 2 Aug 2025
Abstract
Background: Acute kidney injury (AKI) frequently occurs following major liver resection, adversely affecting both short- and long-term outcomes. This study aimed to determine the incidence of AKI post-hepatectomy and identify relevant pre- and intraoperative risk factors. Our secondary objectives were to develop [...] Read more.
Background: Acute kidney injury (AKI) frequently occurs following major liver resection, adversely affecting both short- and long-term outcomes. This study aimed to determine the incidence of AKI post-hepatectomy and identify relevant pre- and intraoperative risk factors. Our secondary objectives were to develop a predictive score for postoperative AKI and assess the associations between AKI, chronic kidney disease (CKD), and 1-year mortality. Methods: This was a retrospective study in a cancer referral center in Marseille, France, from 2018 to 2022. Results: Among 169 patients, 55 (32.5%) experienced AKI. Multivariate analysis revealed several independent risk factors for postoperative AKI, including age, body mass index, the use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, time to liver resection, intraoperative shock, and bile duct reconstruction. Neoadjuvant chemotherapy was protective. The AKIMEBO score was developed, with a threshold of ≥15.6, demonstrating a sensitivity of 89.5%, specificity of 76.4%, positive predictive value of 61.8%, and negative predictive value of 94.4%. AKI was associated with increased postoperative morbidity and one-year mortality following major hepatectomy. Conclusion: AKI is a common complication post-hepatectomy. Factors such as time to liver resection and intraoperative shock management present potential clinical intervention points. The AKIMEBO score can provide a valuable tool for postoperative risk stratification. Full article
(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)
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16 pages, 2227 KiB  
Article
Physiological and Transcriptomic Mechanisms Underlying Vitamin C-Mediated Cold Stress Tolerance in Grafted Cucumber
by Panpan Yu, Junkai Wang, Xuyang Zhang, Zhenglong Weng, Kaisen Huo, Qiuxia Yi, Chenxi Wu, Sunjeet Kumar, Hao Gao, Lin Fu, Yanli Chen and Guopeng Zhu
Plants 2025, 14(15), 2398; https://doi.org/10.3390/plants14152398 (registering DOI) - 2 Aug 2025
Abstract
Cucumbers (Cucumis sativus L.) are highly sensitive to cold, but grafting onto cold-tolerant rootstocks can enhance their low-temperature resilience. This study investigates the physiological and molecular mechanisms by which exogenous vitamin C (Vc) mitigates cold stress in grafted cucumber seedlings. Using cucumber [...] Read more.
Cucumbers (Cucumis sativus L.) are highly sensitive to cold, but grafting onto cold-tolerant rootstocks can enhance their low-temperature resilience. This study investigates the physiological and molecular mechanisms by which exogenous vitamin C (Vc) mitigates cold stress in grafted cucumber seedlings. Using cucumber ‘Chiyu 505’ as the scion and pumpkin ‘Chuangfan No.1’ as the rootstock, seedlings were grafted using the whip grafting method. In the third true leaf expansion stage, seedlings were foliar sprayed with Vc at concentrations of 50, 100, 150, and 200 mg L−1. Three days after initial spraying, seedlings were subjected to cold stress (8 °C) for 3 days, with continued spraying. After that, morphological and physiological parameters were assessed. Results showed that 150 mg L−1 Vc treatment was most impactive, significantly reducing the cold damage index while increasing the root-to-shoot ratio, root vitality, chlorophyll content, and activities of antioxidant enzymes (SOD, POD, CAT). Moreover, this treatment enhanced levels of soluble sugars, soluble proteins, and proline compared to control. However, 200 mg L−1 treatment elevated malondialdehyde (MDA) content, indicating potential oxidative stress. For transcriptomic analysis, leaves from the 150 mg L−1 Vc and CK treatments were sampled at 0, 1, 2, and 3 days of cold stress. Differential gene expression revealed that genes associated with photosynthesis (LHCA1), stress signal transduction (MYC2-1, MYC2-2, WRKY22, WRKY2), and antioxidant defense (SOD-1, SOD-2) were initially up-regulated and subsequently down-regulated, as validated by qRT-PCR. Overall, we found that the application of 150 mg L−1 Vc enhanced cold tolerance in grafted cucumber seedlings by modulating gene expression networks related to photosynthesis, stress response, and the antioxidant defense system. This study provides a way for developing Vc biostimulants to enhance cold tolerance in grafted cucumbers, improving sustainable cultivation in low-temperature regions. Full article
(This article belongs to the Section Plant Response to Abiotic Stress and Climate Change)
10 pages, 236 KiB  
Review
The Concept of “Platinum Sensitivity” in Endometrial Cancer
by Shoji Nagao, Atsushi Fujikawa, Ryoko Imatani, Yoshinori Tani, Hirofumi Matsuoka, Naoyuki Ida, Junko Haraga, Chikako Ogawa, Keiichiro Nakamura and Hisashi Masuyama
Cancers 2025, 17(15), 2557; https://doi.org/10.3390/cancers17152557 (registering DOI) - 2 Aug 2025
Abstract
The concept of “platinum sensitivity” has long guided prognostic assessment and treatment selection in recurrent ovarian cancer. However, the emergence of targeted agents, such as bevacizumab and poly (ADP-ribose) polymerase inhibitors, has complicated its clinical utility. In contrast, emerging evidence suggests that platinum [...] Read more.
The concept of “platinum sensitivity” has long guided prognostic assessment and treatment selection in recurrent ovarian cancer. However, the emergence of targeted agents, such as bevacizumab and poly (ADP-ribose) polymerase inhibitors, has complicated its clinical utility. In contrast, emerging evidence suggests that platinum sensitivity may also be applicable to recurrent endometrial cancer. As in ovarian cancer, a prolonged platinum-free interval (PFI) in recurrent endometrial cancer is associated with an improved efficacy of subsequent platinum-based chemotherapy. The PFI is linearly correlated with the response rate to platinum re-administration, progression-free survival, and overall survival. Patients are typically classified as having platinum-resistant or platinum-sensitive disease based on a PFI cutoff of 6 or 12 months. However, unlike in ovarian cancer—where the duration of response to second-line platinum-based chemotherapy rarely exceeds the prior PFI (~3%)—approximately 30% of patients with recurrent endometrial cancer exhibit a sustained response to platinum rechallenge that extends beyond their preceding PFI. Despite the incorporation of immune checkpoint inhibitors into the treatment landscape of endometrial cancer, the role of platinum sensitivity in clinical decision-making—particularly regarding treatment sequencing and drug selection—remains a critical and unresolved issue. Further research is warranted to elucidate the mechanisms underlying platinum resistance and to guide optimal therapeutic strategies. Full article
(This article belongs to the Special Issue Endometrial Cancer—from Diagnosis to Management)
48 pages, 4602 KiB  
Article
Multiplex Targeted Proteomic Analysis of Cytokine Ratios for ICU Mortality in Severe COVID-19
by Rúben Araújo, Cristiana P. Von Rekowski, Tiago A. H. Fonseca, Cecília R. C. Calado, Luís Ramalhete and Luís Bento
Proteomes 2025, 13(3), 35; https://doi.org/10.3390/proteomes13030035 (registering DOI) - 2 Aug 2025
Abstract
Background: Accurate and timely prediction of mortality in intensive care unit (ICU) patients, particularly those with COVID-19, remains clinically challenging due to complex immune responses. Proteomic cytokine profiling holds promise for refining mortality risk assessment. Methods: Serum samples from 89 ICU patients (55 [...] Read more.
Background: Accurate and timely prediction of mortality in intensive care unit (ICU) patients, particularly those with COVID-19, remains clinically challenging due to complex immune responses. Proteomic cytokine profiling holds promise for refining mortality risk assessment. Methods: Serum samples from 89 ICU patients (55 discharged, 34 deceased) were analyzed using a multiplex 21-cytokine panel. Samples were stratified into three groups based on time from collection to outcome: ≤48 h (Group 1: Early), >48 h to ≤7 days (Group 2: Intermediate), and >7 days to ≤14 days (Group 3: Late). Cytokine levels, simple cytokine ratios, and previously unexplored complex ratios between pro- and anti-inflammatory cytokines were evaluated. Machine learning-based feature selection identified the most predictive ratios, with performance evaluated by area under the curve (AUC), sensitivity, and specificity. Results: Complex cytokine ratios demonstrated superior predictive accuracy compared to traditional severity markers (APACHE II, SAPS II, SOFA), individual cytokines, and simple ratios, effectively distinguishing discharged from deceased patients across all groups (AUC: 0.918–1.000; sensitivity: 0.826–1.000; specificity: 0.775–0.900). Conclusions: Multiplex cytokine profiling enhanced by computationally derived complex ratios may offer robust predictive capabilities for ICU mortality risk stratification, serving as a valuable tool for personalized prognosis in critical care. Full article
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19 pages, 1767 KiB  
Article
Dynamics of a Fractional-Order Within-Host Virus Model with Adaptive Immune Responses and Two Routes of Infection
by Taofeek O. Alade, Furaha M. Chuma, Muhammad Javed, Samson Olaniyi, Adekunle O. Sangotola and Gideon K. Gogovi
Math. Comput. Appl. 2025, 30(4), 80; https://doi.org/10.3390/mca30040080 (registering DOI) - 2 Aug 2025
Abstract
This paper introduces a novel fractional-order model using the Caputo derivative operator to investigate the virus dynamics of adaptive immune responses. Two infection routes, namely cell-to-cell and virus-to-cell transmissions, are incorporated into the dynamics. Our research establishes the existence and uniqueness of positive [...] Read more.
This paper introduces a novel fractional-order model using the Caputo derivative operator to investigate the virus dynamics of adaptive immune responses. Two infection routes, namely cell-to-cell and virus-to-cell transmissions, are incorporated into the dynamics. Our research establishes the existence and uniqueness of positive and bounded solutions through the application of the generalized mean-value theorem and Banach fixed-point theory methods. The fractional-order model is shown to be Ulam–Hyers stable, ensuring the model’s resilience to small errors. By employing the normalized forward sensitivity method, we identify critical parameters that profoundly influence the transmission dynamics of the fractional-order virus model. Additionally, the framework of optimal control theory is used to explore the characterization of optimal adaptive immune responses, encompassing antibodies and cytotoxic T lymphocytes (CTL). To assess the influence of memory effects, we utilize the generalized forward–backward sweep technique to simulate the fractional-order virus dynamics. This study contributes to the existing body of knowledge by providing insights into how the interaction between virus-to-cell and cell-to-cell dynamics within the host is affected by memory effects in the presence of optimal control, reinforcing the invaluable synergy between fractional calculus and optimal control theory in modeling within-host virus dynamics, and paving the way for potential control strategies rooted in adaptive immunity and fractional-order modeling. Full article
10 pages, 586 KiB  
Article
The Role of Systemic Immune-Inflammation Index (SII) in Diagnosing Pediatric Acute Appendicitis
by Binali Firinci, Cetin Aydin, Dilek Yunluel, Ahmad Ibrahim, Murat Yigiter and Ali Ahiskalioglu
Diagnostics 2025, 15(15), 1942; https://doi.org/10.3390/diagnostics15151942 (registering DOI) - 2 Aug 2025
Abstract
Background and Objectives: Accurately diagnosing acute appendicitis (AA) in children remains clinically challenging due to overlapping symptoms with other pediatric conditions and limitations in conventional diagnostic tools. The systemic immune-inflammation index (SII) has emerged as a promising biomarker in adult populations; however, [...] Read more.
Background and Objectives: Accurately diagnosing acute appendicitis (AA) in children remains clinically challenging due to overlapping symptoms with other pediatric conditions and limitations in conventional diagnostic tools. The systemic immune-inflammation index (SII) has emerged as a promising biomarker in adult populations; however, its utility in pediatrics is still unclear. This study aimed to evaluate the diagnostic accuracy of SII in distinguishing pediatric acute appendicitis from elective non-inflammatory surgical procedures and to assess its predictive value in identifying complicated cases. Materials and Methods: This retrospective, single-center study included 397 pediatric patients (5–15 years), comprising 297 histopathologically confirmed appendicitis cases and 100 controls. Demographic and laboratory data were recorded at admission. Inflammatory indices including SII, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were calculated. ROC curve analysis was performed to evaluate diagnostic performance. Results: SII values were significantly higher in the appendicitis group (median: 2218.4 vs. 356.3; p < 0.001). SII demonstrated excellent diagnostic accuracy for AA (AUROC = 0.95, 95% CI: 0.92–0.97), with 91% sensitivity and 88% specificity at a cut-off > 624. In predicting complicated appendicitis, SII showed moderate discriminative ability (AUROC = 0.66, 95% CI: 0.60–0.73), with 83% sensitivity but limited specificity (43%). Conclusions: SII is a reliable and easily obtainable biomarker for diagnosing pediatric acute appendicitis and may aid in early detection of complicated cases. Its integration into clinical workflows may enhance diagnostic precision, particularly in resource-limited settings. Age-specific validation studies are warranted to confirm its broader applicability. Full article
(This article belongs to the Special Issue Diagnosis and Treatment of Pediatric Emergencies—2nd Edition)
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27 pages, 2143 KiB  
Review
The Allium cepa Model: A Review of Its Application as a Cytogenetic Tool for Evaluating the Biosafety Potential of Plant Extracts
by Daniela Nicuță, Luminița Grosu, Oana-Irina Patriciu, Roxana-Elena Voicu and Irina-Claudia Alexa
Methods Protoc. 2025, 8(4), 88; https://doi.org/10.3390/mps8040088 (registering DOI) - 2 Aug 2025
Abstract
In establishing the safety or tolerability profile of bioactive plant extracts, it is important to perform toxicity studies using appropriate, accessible, and sustainable methods. The Allium cepa model is well known and frequently used for accurate environmental risk assessments, as well as for [...] Read more.
In establishing the safety or tolerability profile of bioactive plant extracts, it is important to perform toxicity studies using appropriate, accessible, and sustainable methods. The Allium cepa model is well known and frequently used for accurate environmental risk assessments, as well as for evaluating the toxic potential of the bioactive compounds of plant extracts. The present review focuses on this in vivo cytogenetic model, highlighting its widespread utilization and advantages as a first assessment in monitoring the genotoxicity and cytotoxicity of herbal extracts, avoiding the use of animals for testing. This plant-based assay allows for the detection of the possible cytotoxic and genotoxic effects induced on onion meristematic cells. The outcomes of the Allium cepa assay are comparable to other tests on various organisms, making it a reliable screening test due to its simplicity in terms of implementation, as well as its high sensitivity and reproducibility. Full article
(This article belongs to the Special Issue Feature Papers in Methods and Protocols 2025)
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33 pages, 4098 KiB  
Systematic Review
Pharmacological Inhibition of the PI3K/AKT/mTOR Pathway in Rheumatoid Arthritis Synoviocytes: A Systematic Review and Meta-Analysis (Preclinical)
by Tatiana Bobkova, Artem Bobkov and Yang Li
Pharmaceuticals 2025, 18(8), 1152; https://doi.org/10.3390/ph18081152 (registering DOI) - 2 Aug 2025
Abstract
Background/Objectives: Constitutive activation of the PI3K/AKT/mTOR signaling cascade underlies the aggressive phenotype of fibroblast-like synoviocytes (FLSs) in rheumatoid arthritis (RA); however, a quantitative synthesis of in vitro data on pathway inhibition remains lacking. This systematic review and meta-analysis aimed to (i) aggregate [...] Read more.
Background/Objectives: Constitutive activation of the PI3K/AKT/mTOR signaling cascade underlies the aggressive phenotype of fibroblast-like synoviocytes (FLSs) in rheumatoid arthritis (RA); however, a quantitative synthesis of in vitro data on pathway inhibition remains lacking. This systematic review and meta-analysis aimed to (i) aggregate standardized effects of pathway inhibitors on proliferation, apoptosis, migration/invasion, IL-6/IL-8 secretion, p-AKT, and LC3; (ii) assess heterogeneity and identify key moderators of variability, including stimulus type, cell source, and inhibitor class. Methods: PubMed, Europe PMC, and the Cochrane Library were searched up to 18 May 2025 (PROSPERO CRD420251058185). Twenty of 2684 screened records met eligibility. Two reviewers independently extracted data and assessed study quality with SciRAP. Standardized mean differences (Hedges g) were pooled using a Sidik–Jonkman random-effects model with Hartung–Knapp confidence intervals. Heterogeneity (τ2, I2), 95% prediction intervals, and meta-regression by cell type were calculated; robustness was tested with REML-HK, leave-one-out, and Baujat diagnostics. Results: PI3K/AKT/mTOR inhibition markedly reduced proliferation (to –5.1 SD), IL-6 (–11.1 SD), and IL-8 (–6.5 SD) while increasing apoptosis (+2.7 SD). Fourteen of seventeen outcome clusters showed large effects (|g| ≥ 0.8), with low–moderate heterogeneity (I2 ≤ 35% in 11 clusters). Prediction intervals crossed zero only in small k-groups; sensitivity analyses shifted pooled estimates by ≤0.05 SD. p-AKT and p-mTOR consistently reflected functional changes and emerged as reliable pharmacodynamic markers. Conclusions: Targeted blockade of PI3K/AKT/mTOR robustly suppresses the proliferative and inflammatory phenotype of RA-FLSs, reaffirming this axis as a therapeutic target. The stability of estimates across multiple analytic scenarios enhances confidence in these findings and highlights p-AKT and p-mTOR as translational response markers. The present synthesis provides a quantitative basis for personalized dual-PI3K/mTOR strategies and supports the adoption of standardized long-term preclinical protocols. Full article
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20 pages, 10013 KiB  
Article
Addressing Challenges in Rds,on Measurement for Cloud-Connected Condition Monitoring in WBG Power Converter Applications
by Farzad Hosseinabadi, Sachin Kumar Bhoi, Hakan Polat, Sajib Chakraborty and Omar Hegazy
Electronics 2025, 14(15), 3093; https://doi.org/10.3390/electronics14153093 (registering DOI) - 2 Aug 2025
Abstract
This paper presents the design, implementation, and experimental validation of a Condition Monitoring (CM) circuit for SiC-based Power Electronics Converters (PECs). The paper leverages in situ drain–source resistance (Rds,on) measurements, interfaced with cloud connectivity for data processing and lifetime assessment, [...] Read more.
This paper presents the design, implementation, and experimental validation of a Condition Monitoring (CM) circuit for SiC-based Power Electronics Converters (PECs). The paper leverages in situ drain–source resistance (Rds,on) measurements, interfaced with cloud connectivity for data processing and lifetime assessment, addressing key limitations in current state-of-the-art (SOTA) methods. Traditional approaches rely on expensive data acquisition systems under controlled laboratory conditions, making them unsuitable for real-world applications due to component variability, time delay, and noise sensitivity. Furthermore, these methods lack cloud interfacing for real-time data analysis and fail to provide comprehensive reliability metrics such as Remaining Useful Life (RUL). Additionally, the proposed CM method benefits from noise mitigation during switching transitions by utilizing delay circuits to ensure stable and accurate data capture. Moreover, collected data are transmitted to the cloud for long-term health assessment and damage evaluation. In this paper, experimental validation follows a structured design involving signal acquisition, filtering, cloud transmission, and temperature and thermal degradation tracking. Experimental testing has been conducted at different temperatures and operating conditions, considering coolant temperature variations (40 °C to 80 °C), and an output power of 7 kW. Results have demonstrated a clear correlation between temperature rise and Rds,on variations, validating the ability of the proposed method to predict device degradation. Finally, by leveraging cloud computing, this work provides a practical solution for real-world Wide Band Gap (WBG)-based PEC reliability and lifetime assessment. Full article
(This article belongs to the Section Industrial Electronics)
15 pages, 3579 KiB  
Article
Dual-Control-Gate Reconfigurable Ion-Sensitive Field-Effect Transistor with Nickel-Silicide Contacts for Adaptive and High-Sensitivity Chemical Sensing Beyond the Nernst Limit
by Seung-Jin Lee, Seung-Hyun Lee, Seung-Hwa Choi and Won-Ju Cho
Chemosensors 2025, 13(8), 281; https://doi.org/10.3390/chemosensors13080281 (registering DOI) - 2 Aug 2025
Abstract
In this study, we propose a bidirectional chemical sensor platform based on a reconfigurable ion-sensitive field-effect transistor (R-ISFET) architecture. The device incorporates Ni-silicide Schottky barrier source/drain (S/D) contacts, enabling ambipolar conduction and bidirectional turn-on behavior for both p-type and n-type configurations. Channel polarity [...] Read more.
In this study, we propose a bidirectional chemical sensor platform based on a reconfigurable ion-sensitive field-effect transistor (R-ISFET) architecture. The device incorporates Ni-silicide Schottky barrier source/drain (S/D) contacts, enabling ambipolar conduction and bidirectional turn-on behavior for both p-type and n-type configurations. Channel polarity is dynamically controlled via the program gate (PG), while the control gate (CG) suppresses leakage current, enhancing operational stability and energy efficiency. A dual-control-gate (DCG) structure enhances capacitive coupling, enabling sensitivity beyond the Nernst limit without external amplification. The extended-gate (EG) architecture physically separates the transistor and sensing regions, improving durability and long-term reliability. Electrical characteristics were evaluated through transfer and output curves, and carrier transport mechanisms were analyzed using band diagrams. Sensor performance—including sensitivity, hysteresis, and drift—was assessed under various pH conditions and external noise up to 5 Vpp (i.e., peak-to-peak voltage). The n-type configuration exhibited high mobility and fast response, while the p-type configuration demonstrated excellent noise immunity and low drift. Both modes showed consistent sensitivity trends, confirming the feasibility of complementary sensing. These results indicate that the proposed R-ISFET sensor enables selective mode switching for high sensitivity and robust operation, offering strong potential for next-generation biosensing and chemical detection. Full article
(This article belongs to the Section Electrochemical Devices and Sensors)
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18 pages, 2432 KiB  
Article
Alkali Lignin-Based Biopolymer Formulations for Electro-Assisted Drug Delivery of Natural Antioxidants in Breast Cancer Cells—A Preliminary Study
by Severina Semkova, Radina Deneva, Georgi Antov, Donika Ivanova and Biliana Nikolova
Int. J. Mol. Sci. 2025, 26(15), 7481; https://doi.org/10.3390/ijms26157481 (registering DOI) - 2 Aug 2025
Abstract
Recently, a number of natural biologically active substances have been proven to be attractive alternatives to conventional anticancer medicine or as adjuvants in contemporary combination therapies. Although lignin-based materials were previously accepted as waste materials with limited usefulness, recent studies increasingly report the [...] Read more.
Recently, a number of natural biologically active substances have been proven to be attractive alternatives to conventional anticancer medicine or as adjuvants in contemporary combination therapies. Although lignin-based materials were previously accepted as waste materials with limited usefulness, recent studies increasingly report the possibility of their use for novel applications in various industrial branches, including biomedicine. In this regard, the safety, efficiency, advantages and limitations of lignin compounds for in vitro/in vivo applications remain poorly studied and described. This study was carried out to investigate the possibility of using newly synthesized, alkali lignin-based micro-/nano-biopolymer formulations (Lignin@Formulations/L@F) as carriers for substances with antioxidant and/or anticancer effectiveness. Moreover, we tried to assess the opportunity for using an electro-assisted approach for achieving improved intracellular internalization. An investigation was conducted on an in vitro panel of breast cell lines, namely two breast cancer lines with different metastatic potentials and one non-tumorigenic line as a control. The characterization of all tested formulations was performed via DLS (dynamic light scattering) analysis. We developed an improved separation procedure via size/charge unification for all types of Lignin@Formulations. Moreover, in vitro applications were investigated. The results demonstrate that compared to healthy breast cells, both tested cancer lines exhibited slight sensitivity after treatment with different formulations (empty or loaded with antioxidant substances). This effect was also enhanced after applying electric pulses. L@F loaded with Quercetin was also explored only on the highly metastatic cancer cell line as a model for the breast cancer type most aggressive and non-responsive to traditional treatments. All obtained data suggest that the tested formulations have potential as carriers for the electro-assisted delivery of natural antioxidants such as Quercetin. Full article
(This article belongs to the Special Issue Natural Products in Cancer Prevention and Treatment)
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24 pages, 6999 KiB  
Article
Plasmid DNA Delivery to Cancer Cells with Poly(L-lysine)-Based Copolymers Bearing Thermally Sensitive Segments: Balancing Polyplex Tightness, Transfection Efficiency, and Biocompatibility
by Mustafa Kotmakci, Natalia Toncheva-Moncheva, Sahar Tarkavannezhad, Bilge Debelec Butuner, Ivaylo Dimitrov and Stanislav Rangelov
Pharmaceutics 2025, 17(8), 1012; https://doi.org/10.3390/pharmaceutics17081012 (registering DOI) - 2 Aug 2025
Abstract
Background/Objectives. Efficient nucleic acid delivery into target cells remains a critical challenge in gene therapy. Due to its advantages in biocompatibility and safety, recent research has increasingly focused on non-viral gene delivery. Methods. A series of copolymers—synthesized by integrating thermally sensitive poly(N-isopropylacrylamide) [...] Read more.
Background/Objectives. Efficient nucleic acid delivery into target cells remains a critical challenge in gene therapy. Due to its advantages in biocompatibility and safety, recent research has increasingly focused on non-viral gene delivery. Methods. A series of copolymers—synthesized by integrating thermally sensitive poly(N-isopropylacrylamide) (PNIPAm), hydrophilic poly(ethylene glycol) (PEG) grafts, and a polycationic poly(L-lysine) (PLL) block of varying lengths ((PNIPAm)77-graft-(PEG)9-block-(PLL)z, z = 10–65)—were investigated. Plasmid DNA complexation with the copolymers was achieved through temperature-modulated methods. The resulting polyplexes were characterized by evaluating complex strength, particle size, zeta potential, plasmid DNA loading capacity, resistance to anionic stress, stability in serum, and lysosomal membrane destabilization assay. The copolymers’ potential for plasmid DNA delivery was assessed through cytotoxicity and transfection studies in cancer cell lines. Results. Across all complexation methods, the copolymers effectively condensed plasmid DNA into stable polyplexes. Particle sizes (60–90 nm) ranged with no apparent correlation to copolymer type, complexation method, or N/P ratio, whereas zeta potentials (+10–+20 mV) and resistance to polyanionic stress were dependent on the PLL length and N/P ratio. Cytotoxicity analysis revealed a direct correlation between PLL chain length and cell viability, with all copolymers demonstrating minimal cytotoxicity at concentrations required for efficient transfection. PNL-20 ((PNIPAm)77-graft-(PEG)9-block-(PLL)20) exhibited the highest transfection efficiency among the tested formulations while maintaining low cytotoxicity. Conclusions. The study highlights the promising potential of (PNIPAm)77-graft-(PEG)9-block-(PLL)z copolymers for effective plasmid DNA delivery to cancer cells. It reveals the importance of attaining the right balance between polyplex tightness and plasmid release to achieve improved biocompatibility and transfection efficiency. Full article
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20 pages, 489 KiB  
Article
Development of Preliminary Candidate Surface Guidelines for Air Force-Relevant Dermal Sensitizers Using New Approach Methodologies
by Andrew J. Keebaugh, Megan L. Steele, Argel Islas-Robles, Jakeb Phillips, Allison Hilberer, Kayla Cantrell, Yaroslav G. Chushak, David R. Mattie, Rebecca A. Clewell and Elaine A. Merrill
Toxics 2025, 13(8), 660; https://doi.org/10.3390/toxics13080660 (registering DOI) - 2 Aug 2025
Abstract
Allergic contact dermatitis (ACD) is an immunologic reaction to a dermal chemical exposure that, once triggered in an individual, will result in an allergic response following subsequent encounters with the allergen. Air Force epidemiological consultations have indicated that aircraft structural maintenance workers may [...] Read more.
Allergic contact dermatitis (ACD) is an immunologic reaction to a dermal chemical exposure that, once triggered in an individual, will result in an allergic response following subsequent encounters with the allergen. Air Force epidemiological consultations have indicated that aircraft structural maintenance workers may experience ACD at elevated rates compared to other occupations. We aimed to better understand the utility of non-animal testing methods in characterizing the sensitization potential of chemicals used during Air Force operations by evaluating the skin sensitization hazard of Air Force-relevant chemicals using new approach methodologies (NAMs) in a case study. We also evaluated the use of NAM data to develop preliminary candidate surface guidelines (PCSGs, maximum concentrations of chemicals on workplace surfaces to prevent induction of dermal sensitization) for chemicals identified as sensitizers. NAMs for assessing skin sensitization, including in silico models and experimental assays, were leveraged into an integrated approach to predict sensitization hazard for 19 chemicals. Local lymph node assay effective concentration values were predicted from NAM assay data via previously published quantitative models. The derived values were used to calculate PCSGs, which can be used to compare the presence of these chemicals on work surfaces to better understand the risk of Airmen developing ACD from occupational exposures. Full article
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21 pages, 2240 KiB  
Review
A Review of Fluorescent pH Probes: Ratiometric Strategies, Extreme pH Sensing, and Multifunctional Utility
by Weiqiao Xu, Zhenting Ma, Qixin Tian, Yuanqing Chen, Qiumei Jiang and Liang Fan
Chemosensors 2025, 13(8), 280; https://doi.org/10.3390/chemosensors13080280 (registering DOI) - 2 Aug 2025
Abstract
pH is a critical parameter requiring precise monitoring across scientific, industrial, and biological domains. Fluorescent pH probes offer a powerful alternative to traditional methods (e.g., electrodes, indicators), overcoming limitations in miniaturization, long-term stability, and electromagnetic interference. By utilizing photophysical mechanisms—including intramolecular charge transfer [...] Read more.
pH is a critical parameter requiring precise monitoring across scientific, industrial, and biological domains. Fluorescent pH probes offer a powerful alternative to traditional methods (e.g., electrodes, indicators), overcoming limitations in miniaturization, long-term stability, and electromagnetic interference. By utilizing photophysical mechanisms—including intramolecular charge transfer (ICT), photoinduced electron transfer (PET), and fluorescence resonance energy transfer (FRET)—these probes enable high-sensitivity, reusable, and biocompatible sensing. This review systematically details recent advances, categorizing probes by operational pH range: strongly acidic (0–3), weakly acidic (3–7), strongly alkaline (>12), weakly alkaline (7–11), near-neutral (6–8), and wide-dynamic range. Innovations such as ratiometric detection, organelle-specific targeting (lysosomes, mitochondria), smartphone colorimetry, and dual-analyte response (e.g., pH + Al3+/CN) are highlighted. Applications span real-time cellular imaging (HeLa cells, zebrafish, mice), food quality assessment, environmental monitoring, and industrial diagnostics (e.g., concrete pH). Persistent challenges include extreme-pH sensing (notably alkalinity), photobleaching, dye leakage, and environmental resilience. Future research should prioritize broadening functional pH ranges, enhancing probe stability, and developing wide-range sensing strategies to advance deployment in commercial and industrial online monitoring platforms. Full article
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