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19 pages, 4136 KB  
Article
Neuroprotective Effects of N-Acetylcysteine-Amide (AD4) in a Survival Mouse Model of Paraoxon Intoxication: Targeting Oxidative Stress, Neuroinflammation and Memory Impairments
by Edurne Urquizu, Marine Cuiller, Georgia Papadopoulou, David Pubill, Demetrio Raldúa, Jordi Camarasa, Elena Escubedo and Raul López-Arnau
Antioxidants 2025, 14(12), 1463; https://doi.org/10.3390/antiox14121463 (registering DOI) - 6 Dec 2025
Abstract
Neurotoxicity induced by organophosphorus (OP) compounds such as paraoxon (POX) leads to severe brain damage and cognitive impairments. Although current treatments alleviate acute cholinergic symptoms, they fail to address secondary neurotoxicity. This study investigated the therapeutic potential of N-acetylcysteine-amide (AD4), a blood–brain-barrier permeable [...] Read more.
Neurotoxicity induced by organophosphorus (OP) compounds such as paraoxon (POX) leads to severe brain damage and cognitive impairments. Although current treatments alleviate acute cholinergic symptoms, they fail to address secondary neurotoxicity. This study investigated the therapeutic potential of N-acetylcysteine-amide (AD4), a blood–brain-barrier permeable antioxidant, in a survival mouse model of acute POX intoxication. Male Swiss CD-1 mice received POX (4 mg/kg) followed by standard emergency therapy (atropine, pralidoxime and diazepam). AD4 (150 mg/kg) was administered 2 and 6 h post-exposure. AD4 treatment effectively prevented oxidative stress by reducing lipid peroxidation and restoring the expression in hippocampus (HP) and/or prefrontal cortex (PFC) of key antioxidant enzymes such as glutathione peroxidase-1 (GPx-1) and catalase (CAT) suppressed by POX acute exposure. Moreover, AD4 attenuated neuroinflammation in specific hippocampal subregions, as evidenced by reduced Glial Fibrillary Acidic Protein (GFAP) and Ionized Calcium Binding Adaptor Molecule 1 (Iba-1) immunoreactivity. Importantly, AD4 also rescued recognition memory deficits, as assessed by the Novel Object Recognition Test (NORT). In summary, these findings demonstrate that AD4 mitigates oxidative stress, neuroinflammation, and cognitive dysfunction following acute POX intoxication, supporting its potential as an adjuvant therapy for mitigating the secondary neurotoxicity derived from organophosphorus poisoning. Full article
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31 pages, 8254 KB  
Article
A Coandă-Surface-Assisted Ejector as a Turbine Tip Leakage Mitigator
by Gohar T. Khokhar and Cengiz Camci
Int. J. Turbomach. Propuls. Power 2025, 10(4), 51; https://doi.org/10.3390/ijtpp10040051 - 5 Dec 2025
Abstract
This paper presents an experimental and computational investigation of novel, ejector-based, Coandă-surface-assisted tip leakage mitigation schemes. The predicted changes in the key performance metrics are presented after explaining the aerodynamic concept development for the novel tip geometries. The performance metrics are the stage [...] Read more.
This paper presents an experimental and computational investigation of novel, ejector-based, Coandă-surface-assisted tip leakage mitigation schemes. The predicted changes in the key performance metrics are presented after explaining the aerodynamic concept development for the novel tip geometries. The performance metrics are the stage total-to-total isentropic efficiency, tip-gap mass flow rate, and a figure of merit based on rotor exit total pressure. The schemes are based on direct geometric modifications to the turbine blade tip, effectively promoting an effective redirection of tip leakage fluid via specific channels. The proposed ejector channels operate in conjunction with strategically located Coandă surfaces to alter the path of the leakage fluid, promoting an effective leakage fluid delivery into the blade’s wake. Multiple schemes are assessed, including single-ejector, single-ejector with “hybrid” squealer, double-channeled, and triple-channeled designs. The designs are evaluated computationally for the HP stage of the Axial Flow Turbine Research Facility AFTRF at Penn State University. Extensive experimental validation of the baseline flow computations for the HP stage is also presented. Upper-bound efficiency gains of 0.49% and mass flow reductions of 14.80% compared to an untreated flat tip for the large-scale turbine test rig AFTRF are reported. Evaluation of the current tip designs in a high-speed turbine cascade environment with a transonic exit flow has also been completed. The detailed results from the high-speed investigation and heat transfer impact are in the process of being published. Implementation in the high-speed environment of the same design concepts also returned non-negligible performance gains. Full article
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22 pages, 1484 KB  
Article
Recycling of Glass Fibers from Wind Turbine Blade Wastes via Chemical-Assisted Solvolysis
by Maria Modestou, Dionisis Semitekolos, Tao Liu, Christina Podara, Savvas Orfanidis, Ana Teresa Lima and Costas Charitidis
Fibers 2025, 13(12), 163; https://doi.org/10.3390/fib13120163 - 5 Dec 2025
Abstract
Wind turbine blades (WTBs) have always been considered one of the greatest engineering achievements. They primarily use glass fiber-reinforced polymers (GFRPs) because of their lightweight nature, impressive strength-to-weight ratio, and durability. Until now, typical disposal methods of End-of-Life (EoL) WTBs are landfill or [...] Read more.
Wind turbine blades (WTBs) have always been considered one of the greatest engineering achievements. They primarily use glass fiber-reinforced polymers (GFRPs) because of their lightweight nature, impressive strength-to-weight ratio, and durability. Until now, typical disposal methods of End-of-Life (EoL) WTBs are landfill or incineration. However, such practices are neither environmentally sustainable nor compliant with current regulations. This study investigates a low-temperature solvolysis process using a poly(ethylene glycol)/NaOH system under ambient pressure for efficient decomposition of the polyester matrix, promoting the potential of chemical recycling as an alternative to landfilling and incineration by offering a viable method for recovering glass fibers from WTB waste. A parametric study evaluated the influence of reaction time (4–5.5 h) and catalyst-to-resin ratio (0.1–2.0 g NaOH per g resin) on solvolysis efficiency. Optimal conditions (200 g PEG200, 12.5 g NaOH, 10 g GFRP, 5.5 h) achieved an ~80% decomposition efficiency and fibers exhibiting minimal surface degradation. SEM and EDX analyses confirmed limited morphological damage, while excessive NaOH (>15 g) caused notable etching of the glass fibers. ICP-OES of liquid residues detected high Na (780 mg/L) and Si (139 mg/L) concentrations, verifying partial dissolution of the fiber structure under strongly alkaline conditions. After applying a commercial sizing agent (Hydrosize HP2-06), TGA confirmed ~1.2% sizing mass, and nanoindentation analysis showed the interfacial modulus and hardness of re-sized fibers improved by over 70% compared to unsized recycled fibers, approaching the performance of virgin fibers. Full article
10 pages, 1836 KB  
Article
The Role of High-Resolution Lung Computed Tomography to Distinguish Between Fibrosing Hypersensitivity Pneumonitis and Usual Interstitial Pneumonia
by Dmitry A. Kuleshov, Svetlana Yu. Chikina, Galina V. Nekludova, Igor E. Tyurin and Sergey N. Avdeev
Life 2025, 15(12), 1867; https://doi.org/10.3390/life15121867 - 5 Dec 2025
Abstract
Background: Hypersensitivity pneumonitis (HP) is an interstitial lung disease (ILD) caused by repeated exposure to inhaled antigens in susceptible subjects. High-resolution computed tomography (HRCT) of the lungs is the leading diagnostic method for ILDs, but in some cases HRCT findings are not [...] Read more.
Background: Hypersensitivity pneumonitis (HP) is an interstitial lung disease (ILD) caused by repeated exposure to inhaled antigens in susceptible subjects. High-resolution computed tomography (HRCT) of the lungs is the leading diagnostic method for ILDs, but in some cases HRCT findings are not sufficient to distinguish HP and other ILDs, particularly, fibrotic HP (fHP) and usual interstitial pneumonia (UIP). Objective: The aim of this study was to develop HRCT criteria to diagnose fHP in patients with a UIP-like pattern. Methods: In this retrospective study, we analyzed HRCT scans of patients with fHP and a UIP-like pattern who underwent lung biopsy, and patients with idiopathic pulmonary fibrosis (IPF) and a UIP pattern in HRCT. Results: We included 51 patients with confirmed fHP and 24 patients with IPF/UIP in the analysis. IPF/UIP patients were older, were prevalently males, and did not have any systemic autoimmune diseases or risk factors for other ILDs. fHP patients were younger, with an equal number of males and females, and were more likely to be exposed to environmental antigens. HRCT abnormalities in the fHP group predominated in the lower lung areas or were diffuse in axial scans, whereas IPF/UIP patients mostly demonstrated a diffuse craniocaudal distribution and subpleural axial predominance. Centrilobular nodules and mosaic attenuation were present significantly more often in the fHP group; honeycombing, traction bronchiectasis, and emphysema prevailed in IPF/UIP patients. In the logistic regression analysis, patients with fHP and IPF/UIP differed in the presence of centrilobular nodules, honeycombing, and in both craniocaudal and axial distributions of HRCT abnormalities. In the ROC analysis, the combination of centrilobular nodules, honeycombing, and diffuse axial and craniocaudal distributions can predict the diagnosis of fHP (AUC, 0.953 ± 0.022; 95%CI, 0.910–0.995; p < 0.001). Mosaic attenuation and reticulation did not change the probability of fHP. Conclusions: The most significant HRCT features of fHP compared to the UIP pattern were centrilobular nodules, honeycombing, and a diffuse axial and craniocaudal distribution of abnormal findings. Reticulation, mosaic attenuation, and GGO do not increase the probability of fHP. Full article
(This article belongs to the Section Medical Research)
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26 pages, 5909 KB  
Article
Vitamin D3-Deficient Diet Promotes Pulmonary Fibrosis Development in Murine Model of Hypersensitivity Pneumonitis
by Marta Kinga Lemieszek, Michał Chojnacki, Iwona Paśnik, Wiktoria Gawryś, Alicja Wilczyńska, Ilona Leśniowska, Jakub Anisiewicz and Michał Kiełbus
Int. J. Mol. Sci. 2025, 26(24), 11770; https://doi.org/10.3390/ijms262411770 - 5 Dec 2025
Abstract
Although vitamin D3 (VD3) deficiency has been recognized as a harmful agent in several respiratory diseases, the present study is the first one to investigate its influence on the development of hypersensitivity pneumonitis (HP). This research was conducted in a murine model of [...] Read more.
Although vitamin D3 (VD3) deficiency has been recognized as a harmful agent in several respiratory diseases, the present study is the first one to investigate its influence on the development of hypersensitivity pneumonitis (HP). This research was conducted in a murine model of HP, wherein pulmonary fibrosis was induced by antigen of Pantoea agglomerans. VD3 deficiency was provoked by diet with 10-times less cholecalciferol than feed given to VD3-sufficient mice. Before and after 14 and 28 days of nebulization, lung function was evaluated. Moreover, at indicated time points, lungs were collected and subjected to histological assessment, flow cytometry, gene expression assays, and ELISA. The performed research showed a higher sensitivity of VD3-deficient mice to fibrosis response to P. agglomerans antigen, which was strongly associated with enhanced epithelial-to-mesenchymal transition, the signs of which were over-expression of EMT-transcription factors (Snail2, Zeb1, Zeb2) and mesenchymal cell markers (Cdh2/N-cadherin, Acta2/SMA, Fn1/Fibronectin, Vim/Vimentin). Indicated negative changes in VD3-deficient mice with developed HP were supported by deepening calcitriol deficiency and worsening respiratory functions, including the frequency of breathing, minute volume, total cycle times, expiratory and inspiratory time. Moreover, typical for VD3-deficient mice with HP, there was also an increased influx of immune cells into the lungs (especially neutrophils, macrophages, dendritic cells and lymphocytes Tc), a disturbed cytokine profile with over-production of growth factors favoring fibrosis (FGF2 and TGFβ), and lowered synthesis of several cytokines (IL1β, IL6, IL12, IL4 IL10, IL13). The present study reveals that VD3 deficiency promotes the development of pulmonary fibrosis in the murine model of HP. Full article
(This article belongs to the Special Issue Pulmonary Fibrosis: Molecular Mechanisms and Therapeutic Strategies)
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13 pages, 3273 KB  
Article
Recovery of Metals from Lithium-Ion Batteries Using Green Solvents: A Sustainable Approach to Reducing Waste and Environmental Impact
by Katherine Moreno, Josselyn López, Carlos F. Aragón-Tobar, Diana Endara, Fernando Sánchez and José-Luis Palacios
Recycling 2025, 10(6), 218; https://doi.org/10.3390/recycling10060218 - 5 Dec 2025
Abstract
The recovery of critical metals from spent lithium-ion batteries (LIBs) is essential to reduce environmental impacts and promote circular economy strategies. This study developed a sustainable and scalable process for the recovery and complete valorization of lithium, cobalt, and other valuable components from [...] Read more.
The recovery of critical metals from spent lithium-ion batteries (LIBs) is essential to reduce environmental impacts and promote circular economy strategies. This study developed a sustainable and scalable process for the recovery and complete valorization of lithium, cobalt, and other valuable components from end-of-life LIBs. Hydrometallurgical treatment using biodegradable citric and oxalic acids was employed as a green alternative to conventional inorganic acids, achieving high selectivity and reduced environmental impact. Experimental work was conducted on 3 kg of LIBs from discarded laptop batteries (Dell and HP). After safe discharge and dismantling, the cathode materials were thermally treated at 300 °C to detach active components, followed by acid leaching in 1 M citric acid at 30 °C, pH 2.5, and 6 h of reaction. Lithium and cobalt were recovered as oxalates with efficiencies of 90% and 85%, respectively, while copper, aluminum, and graphite were separated through mechanical and thermal processes. Beyond metal recovery, the process demonstrates a circular upcycling approach, transforming recovered materials into functional products such as aluminum keychains, copper jewelry, and graphite-based pencils. This integrated strategy connects hydrometallurgical extraction with material reuse, advancing toward a zero-waste, closed-loop system for sustainable LIB recycling and local resource valorization. Full article
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29 pages, 10502 KB  
Article
Performance Enhancement of Wireless BLDC Motor Using Adaptive Reinforcement Learning for Sustainable Pumping Applications
by Richard Pravin Antony, Pongiannan Rakkiya Goundar Komarasamy, Moustafa Ahmed Ibrahim, Abdulaziz Alanazi and Narayanamoorthi Rajamanickam
Sustainability 2025, 17(23), 10881; https://doi.org/10.3390/su172310881 - 4 Dec 2025
Abstract
This paper presents an adaptive reinforcement learning (RL)-based control strategy for a wireless power transfer (WPT)-fed brushless DC (BLDC) motor drive, aimed at enhancing efficiency in industrial applications. Conventional control methods for BLDC motors often result in higher energy consumption and increased torque [...] Read more.
This paper presents an adaptive reinforcement learning (RL)-based control strategy for a wireless power transfer (WPT)-fed brushless DC (BLDC) motor drive, aimed at enhancing efficiency in industrial applications. Conventional control methods for BLDC motors often result in higher energy consumption and increased torque ripple under dynamic load and voltage variations. To address this, an adaptive RL framework is implemented with pulse density modulation (PDM), enabling the controller to augment motor speed, torque, and input power in real time. The system is modeled and tested for a 48 V, 1 HP BLDC motor, powered through a 1.1 kW WPT system. Training is carried out across 10 learning episodes with varying load torque and speed demands, allowing the RL agent to adaptively minimize losses while maintaining performance. Results indicate a significant reduction in torque ripple to a minimum of 0.20 Nm, stable speed regulation within ±30 rpm, and improved power utilization compared to existing controllers. The integration of RL with WPT provides a robust, contactless, and energy-efficient solution that is suitable for sustainable industrial motor-pump applications. Full article
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19 pages, 9510 KB  
Article
Thermal Management Performance of Phase Change Material Coupled with Heat Pipe for Photovoltaic Modules: Experimental Exploration
by Liang Tang, Rumei Yang, Peixian Zuo, Ziyu Leng, Xuanxun Zhou, Jinwei Li and Xiaoling Cao
Energies 2025, 18(23), 6349; https://doi.org/10.3390/en18236349 - 3 Dec 2025
Viewed by 106
Abstract
Solar photovoltaic (PV) power generation has become an important source of global renewable energy. The photoelectric conversion efficiency of crystalline silicon PV modules decreases as their surface temperature rises, while excessively high operating temperatures can also affect their service life. Therefore, reducing the [...] Read more.
Solar photovoltaic (PV) power generation has become an important source of global renewable energy. The photoelectric conversion efficiency of crystalline silicon PV modules decreases as their surface temperature rises, while excessively high operating temperatures can also affect their service life. Therefore, reducing the temperature of photovoltaic modules is one of the effective methods of enhancing their photoelectric conversion efficiency. Passive thermal management methods, such as the use of phase change materials (PCM) and heat pipes (HP), can be used to control the temperature of PV modules, but they manifest the problems of poor thermal conductivity and low heat transfer efficiency at low heat flux density, respectively. On the other hand, previous experimental studies have mostly focused on small-scale non-standard PV cell modules, without considering encapsulation and installation issues in practical applications. Meanwhile, passive cooling technology exhibits strong regional characteristics, with significant variations in temperature control and energy efficiency improvements under different climatic conditions. To address these issues, this paper proposes a novel PV module temperature control unit that couples PCM and HP. Standard commercial PV cell modules are used as experimental subjects, and tests are conducted in four different regions of China to study the adaptability and effectiveness of the coupled PCM and HP control method. The experimental results show that the power generation pattern of PV modules is consistent with the variation in solar radiation intensity. When the operating temperature of the PV module is below 40 °C, the high thermal conductivity of the heat pipe plays a dominant role in dissipating heat. When the operating temperature of PV rises above 40 °C, the phase change material begins to play a role in heat storage and temperature control. Compared to using PCM alone for temperature control, the coupled method further enhances the cooling effect, preventing a sharp temperature increase after the PCM has completely melted, and increases the power generation of PV by 4–5%. The temperature control effect of the PV module is influenced by local ambient temperature and wind speed. The coupled temperature control method exerts a relatively low improvement effect under high-temperature and low-radiation environmental conditions, but it performs better when used under low-temperature and high-radiation environmental conditions. Full article
(This article belongs to the Section A2: Solar Energy and Photovoltaic Systems)
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16 pages, 2526 KB  
Article
Mitigating Mucoadhesion of β–Cyclodextrins via PEGylation: Insights from 19F Diffusion NMR Analysis
by Kim Trang Huu Nguyen and Yong Ba
Int. J. Mol. Sci. 2025, 26(23), 11690; https://doi.org/10.3390/ijms262311690 - 2 Dec 2025
Viewed by 168
Abstract
β–Cyclodextrin (β–CD)-based materials are widely used in drug delivery, yet their interactions with mucosal barriers remain insufficiently understood. Because the mucus layer coating epithelial surfaces can hinder drug transport, elucidating β–CD–mucin interactions is critical for optimizing cyclodextrin-based carriers. In this study, we examined [...] Read more.
β–Cyclodextrin (β–CD)-based materials are widely used in drug delivery, yet their interactions with mucosal barriers remain insufficiently understood. Because the mucus layer coating epithelial surfaces can hinder drug transport, elucidating β–CD–mucin interactions is critical for optimizing cyclodextrin-based carriers. In this study, we examined whether PEGylation can attenuate the mucoadhesive behavior of β–CD. Monomethoxy poly(ethylene glycol)-modified β–CDs (MPEG–β–CDs) were evaluated using 19F self-diffusion NMR spectroscopy coupled with a kinetic diffusion model describing reversible binding to stationary substrates. Mucin hydrogels were prepared from bovine submaxillary mucin and served as a model mucus environment. Diffusion coefficients were extracted from the 19F NMR signals of 1-fluoroadamantane (1FA) molecules encapsulated within HP-β–CD or MPEG–β–CD cavities. The results demonstrate that PEGylation substantially reduces β–CD–mucin adhesion, with longer PEG chains (2000 Da) providing more effective steric shielding than shorter chains (500 Da). These findings indicate that PEGylation can protect β–CD-included drugs during transport across mucosal barriers by minimizing unwanted β–CD–mucin interactions. Full article
(This article belongs to the Special Issue Research on Cyclodextrin)
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17 pages, 2629 KB  
Article
Mechanical Pruning Induces Distinct Metabolic Responses in Slender Spindle-Shaped Apple Orchards
by Juhyeon Park, Youngsuk Lee, Nay Myo Win, Van Giap Do, Jung-Geun Kwon, Seonae Kim, Soon-Il Kwon, Hun-Joong Kweon and In-Kyu Kang
Plants 2025, 14(23), 3663; https://doi.org/10.3390/plants14233663 - 1 Dec 2025
Viewed by 125
Abstract
Mechanical pruning has emerged as a viable alternative to traditional hand pruning in apple orchards in labor-constrained and aging population workforces. While mechanical pruning reduces labor demand and enhances operational efficiency, their effects on tree physiology and fruit development remain poorly understood. In [...] Read more.
Mechanical pruning has emerged as a viable alternative to traditional hand pruning in apple orchards in labor-constrained and aging population workforces. While mechanical pruning reduces labor demand and enhances operational efficiency, their effects on tree physiology and fruit development remain poorly understood. In this study, we examined the physiological and transcriptional responses of apple trees to mechanical pruning (MP) and hand pruning (HP), with a focus on hormone metabolism, photosynthetic activity, and stress adaptation. Pruning treatments were applied in an orchard using a tractor-mounted mechanical pruner and manual shears, and distinct metabolic responses after pruning were assessed over multiple time points using transcriptomic analysis. At 168 h after MP, trees exhibited downregulation of MdLhcb genes, indicating a reduction in light harvesting capacity. In addition, MdDFR, a key gene in flavonoid biosynthesis, was also downregulated, suggesting a suppression of secondary metabolism and a distinct physiological response to MP. In addition, stress-responsive genes such as MdNHL3 were rather upregulated, indicating the activation of adaptive signaling networks. Conversely, HP trees showed relatively moderate responses in the same pathways, suggesting pruning method-specific regulatory mechanisms. These findings highlight how pruning methods distinctly influence tree recovery and gene expression dynamics, offering insights into optimizing pruning systems for sustainable and high-quality apple production under labor-constrained conditions. Full article
(This article belongs to the Section Plant Physiology and Metabolism)
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19 pages, 2477 KB  
Article
Comparative Analysis of Three Different Cooking Methods on Structures and Volatile Compounds of Fresh Lyophyllum decastes
by Xiaoshu Wu, Yan Wang, Weiyu Li, Chuannan Long and Jingjing Cui
Foods 2025, 14(23), 4106; https://doi.org/10.3390/foods14234106 - 29 Nov 2025
Viewed by 140
Abstract
This study investigated the effects of three cooking methods—fragmenting process (FP), boiling treatment (BT), and high-pressure steam (HPS) treatment—on the structure and volatile compounds (VOCs) of fresh Lyophyllum decastes. The surface morphology and functional groups of L. decastes were analyzed by scanning [...] Read more.
This study investigated the effects of three cooking methods—fragmenting process (FP), boiling treatment (BT), and high-pressure steam (HPS) treatment—on the structure and volatile compounds (VOCs) of fresh Lyophyllum decastes. The surface morphology and functional groups of L. decastes were analyzed by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR), respectively. The VOCs in L. decastes were analyzed by comprehensive two-dimensional gas chromatography–mass spectrometry (GC×GC-MS) and gas chromatography–ion mobility spectrometry (GC-IMS). SEM results showed that HPS resulted in the most pronounced structural disruption, forming a honeycomb-like porous surface, whereas FP yielded smaller fragments with smoother surfaces. FTIR spectra indicated that none of the treatments significantly altered the characteristic functional groups. A total of 73 VOCs were identified by GC×GC-MS, including 23 hydrocarbons, 14 alcohols, 10 ketones, seven aldehydes, six ethers, three esters, two terpenes, and eight other compounds. Additionally, 22 VOCs were identified by GC-IMS, including seven alcohols, six aldehydes, five esters, three ketones, and one other compound. The four compounds benzaldehyde, benzeneacetaldehyde, (E)-2-hexen-1-ol, and 1-hexanal were detected by both methods. Among the three methods, FP induced the least structural damage and better preserved the VOCs. These results offer theoretical insights and technical support for the flavor-oriented deep processing of L. decastes. Full article
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26 pages, 4345 KB  
Article
Integrative Computational Approaches for the Discovery of Triazole-Based Urease Inhibitors: A Machine Learning, Virtual Screening, and Meta-Dynamics Framework
by Sofía E. Ríos-Rozas, Natalia Morales, Elizabeth Valdés-Muñoz, Gabriela Urra, Camila A. Flores-Morales, Javier Farías-Abarca, Erix W. Hernández-Rodríguez, Jonathan M. Palma, Manuel I. Osorio, Osvaldo Yáñez-Osses, Luis Morales-Quintana, Reynier Suardíaz and Daniel Bustos
Int. J. Mol. Sci. 2025, 26(23), 11576; https://doi.org/10.3390/ijms262311576 - 28 Nov 2025
Viewed by 188
Abstract
Helicobacter pylori urease (HpU) plays a central role in bacterial survival and virulence by hydrolyzing urea into ammonia and carbon dioxide, neutralizing gastric acidity, and facilitating host colonization. The increasing prevalence of antibiotic resistance underscores the need for alternative strategies targeting [...] Read more.
Helicobacter pylori urease (HpU) plays a central role in bacterial survival and virulence by hydrolyzing urea into ammonia and carbon dioxide, neutralizing gastric acidity, and facilitating host colonization. The increasing prevalence of antibiotic resistance underscores the need for alternative strategies targeting essential bacterial enzymes such as urease. In this study, a multistage computational pipeline integrating pharmacophore modeling, machine learning (ML), ensemble docking, and enhanced molecular dynamics simulations were applied to identify novel triazole-based HpU inhibitors. Starting from over seven million compounds in the ZINC15 database, pharmacophore- and ML-based filters progressively reduced the chemical space to 7062 candidates. Ensemble docking across 25 conformational frames of HpU, followed by quantum-polarized ligand docking (QPLD), identified seven promising ligands exhibiting strong binding energies and stable metal coordination. Molecular dynamics (MD) simulations under progressively relaxed restraints revealed three highly stable complexes (CA1, CA3, and CA6). Subsequent well-tempered metadynamics (WT-MetaD) simulations reconstructed free-energy landscapes showing deep, localized basins for CA3 and CA6, comparable to the potent reference inhibitor DJM, supporting their potential as strong urease binders. Finally, unsupervised chemical space mapping using the UMAP algorithm positioned these candidates within molecular regions associated with potent urease inhibitors, further validating their structural coherence and pharmacophoric relevance. An ADMET assessment confirmed that the selected candidates exhibit physicochemical and early safety properties compatible with subsequent in vitro evaluation. This multilevel screening strategy demonstrates the power of combining ML-driven classification, ensemble docking, and enhanced sampling simulations to discover non-hydroxamic urease inhibitors. Although the current findings are computational, they provide a rational foundation for future in vitro validation and for expanding the discovery of triazole-based scaffolds targeting ureolytic enzymes. Full article
(This article belongs to the Special Issue Computer Simulation Insight into Ligand–Receptor Interaction)
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12 pages, 7382 KB  
Article
Usefulness of DNA Obtained from FFPE Tissue Sections Stained with Masson’s Trichrome in Forensic Identification: A Pilot Study
by María-de-Lourdes Chávez-Briones, Adriana Ancer-Arellano, Ivett Miranda-Maldonado, Juan M. Solís-Soto, Jaime García-Juárez, Marta Ortega-Martínez and Gilberto Jaramillo-Rangel
Genes 2025, 16(12), 1416; https://doi.org/10.3390/genes16121416 - 28 Nov 2025
Viewed by 204
Abstract
Background/Objectives: Formalin-fixed paraffin-embedded (FFPE) tissues are sometimes the only DNA source for forensic applications. The quantity and integrity of the DNA extracted from these samples depend on multiple factors. In this work, we analyzed, for the first time, whether Masson’s trichrome (MT) staining [...] Read more.
Background/Objectives: Formalin-fixed paraffin-embedded (FFPE) tissues are sometimes the only DNA source for forensic applications. The quantity and integrity of the DNA extracted from these samples depend on multiple factors. In this work, we analyzed, for the first time, whether Masson’s trichrome (MT) staining alters the results of genetic profiles obtained from DNA extracted from FFPE tissue sections. Methods: Three pairs of sections from the year 2024 and three pairs from the year 2001 were analyzed. Each pair consisted of serial sections, one stained with hematoxylin and eosin and the other with MT. DNA was extracted using the PrepFiler Express BTA™ Forensic DNA Extraction Kit and quantified by real-time PCR using the Quantifiler™ HP DNA Quantification Kit. DNA samples were processed for short tandem repeat (STR) profiling using the GlobalFiler™ PCR Amplification Kit. The amplified alleles were separated and analyzed using an ABI PRISM® 3500 genetic analyzer. Results: All MT-stained samples showed deficiency in most or all of the parameters assessed: DNA yield, degradation index, number of alleles detected, random match probability value, and intensity of the electropherogram peaks. In fact, DNA could not even be quantified in the samples processed in 2001. Conclusions: These results could be due to the large number of acids used in MT staining, which cause chemical modification and hydrolysis of DNA, affecting the success of PCR-based methods used subsequently. In conclusion, DNA obtained from MT-stained FFPE tissue sections may be highly degraded and should therefore be used with great caution in forensic settings. Full article
(This article belongs to the Special Issue Forensic DNA Profiling: PCR Techniques and Innovations)
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19 pages, 1652 KB  
Article
Impact of Continuous Renal Replacement Therapy on Outcomes in Septic Shock Patients Receiving Polymyxin B Hemoperfusion: A Retrospective Cohort Study
by Wei-Hung Chang, Sheng Hsiung Yang, Hsiu-Fang Shen, Ting-Yu Hu and Wen-Jui Wu
Biomedicines 2025, 13(12), 2904; https://doi.org/10.3390/biomedicines13122904 - 27 Nov 2025
Viewed by 328
Abstract
Background: Polymyxin B hemoperfusion (PMX-HP) is increasingly used as an adjunctive therapy for severe sepsis and septic shock, yet the prognostic significance of continuous renal replacement therapy (CRRT) and vasoactive-inotropic score (VIS) dynamics under real-world ICU practice remains unclear. This study aimed to [...] Read more.
Background: Polymyxin B hemoperfusion (PMX-HP) is increasingly used as an adjunctive therapy for severe sepsis and septic shock, yet the prognostic significance of continuous renal replacement therapy (CRRT) and vasoactive-inotropic score (VIS) dynamics under real-world ICU practice remains unclear. This study aimed to evaluate whether CRRT requirement and hemodynamic responses to PMX-HP influence short-term mortality among critically ill patients. Methods: We conducted a retrospective cohort study of 64 ICU patients in Taiwan with severe sepsis or septic shock who received PMX-HP. Clinical characteristics, illness severity, VIS measurements before and after PMX-HP, organ-support therapies, and outcomes—including 28-day mortality, ICU and hospital mortality, and lengths of stay—were analyzed. Patients were stratified by CRRT use, and multivariate logistic regression was performed to identify independent predictors of 28-day mortality. Results: Among 64 patients (mean age 66 years; 67% male), 67.2% received CRRT and the overall 28-day mortality was 46.9%. CRRT users exhibited higher crude mortality and higher APACHE II scores. Survivors were younger and had lower baseline severity. Hemodynamic trajectories differed substantially: VIS increased after PMX-HP more frequently in non-survivors than survivors. In multivariate analysis, post-PMX-HP VIS elevation and higher APACHE II were independent predictors of 28-day mortality, whereas CRRT requirement was not an independent determinant. Conclusions: In this real-world cohort, PMX-HP did not significantly reduce mortality. Illness severity and inadequate vasopressor improvement, rather than CRRT use, primarily determined outcomes. VIS elevation following PMX-HP may serve as an early indicator of poor hemodynamic recovery in septic shock. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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Article
An Insight into Strain-Specificity of Streptomyces chrestomyceticus ADP4 and Identification of a Novel Peptide with Potential Antiviral Activities Against Significant Human Viruses, Including SARS-CoV2, HCV, and HIV
by Varsha Verma, Medicherla Krishna Mohan and Ashok K. Dubey
Microbiol. Res. 2025, 16(12), 249; https://doi.org/10.3390/microbiolres16120249 - 26 Nov 2025
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Abstract
This study aimed to unravel the genomic uniqueness of Streptomyces chrestomyceticus ADP4 using whole-genome sequence analysis, with a focus on identifying strain-specific genes/proteins associated with a novel therapeutic source. The genome of the strain ADP4 was sequenced and assembled to a total size [...] Read more.
This study aimed to unravel the genomic uniqueness of Streptomyces chrestomyceticus ADP4 using whole-genome sequence analysis, with a focus on identifying strain-specific genes/proteins associated with a novel therapeutic source. The genome of the strain ADP4 was sequenced and assembled to a total size of 9.64 MB. A total of 8378 coding regions were identified. Strain ADP4 was found to be clustered into a clade of the species S. chrestomyceticus. Fifty-one biosynthetic gene clusters were predicted in the genome of the strain ADP4, and three of them were common to all the strains of S. chrestomyceticus. A comparative metabolic profile of S. chrestomyceticus revealed a unique metabolic protein, supporting strain-level variations. Comparative genome analysis led to the identification of the genomic sequences that were specific to the strain ADP4. These strain-specific unique sequences of ADP4 were identified across the available data, underscoring their distinct genetic identity. Among these eight functionally uncharacterized hypothetical proteins (HPs), only two could be assigned with functional attributes, wherein one of them, HP2, was ascertained to be a peptide with possible antiviral activity, underscoring its potential as a novel drug candidate for aantiviraltherapy. The structural validation and peptide–protein molecular docking have evidently demonstrated anantiviralctivity of HP2 against significant human viral pathogens, for example, HIV, SARS-CoV2, HCV, ZIKV, JEV, and DENV. Full article
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