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24 pages, 2584 KiB  
Article
Precise and Continuous Biomass Measurement for Plant Growth Using a Low-Cost Sensor Setup
by Lukas Munser, Kiran Kumar Sathyanarayanan, Jonathan Raecke, Mohamed Mokhtar Mansour, Morgan Emily Uland and Stefan Streif
Sensors 2025, 25(15), 4770; https://doi.org/10.3390/s25154770 (registering DOI) - 2 Aug 2025
Abstract
Continuous and accurate biomass measurement is a critical enabler for control, decision making, and optimization in modern plant production systems. It supports the development of plant growth models for advanced control strategies like model predictive control, and enables responsive, data-driven, and plant state-dependent [...] Read more.
Continuous and accurate biomass measurement is a critical enabler for control, decision making, and optimization in modern plant production systems. It supports the development of plant growth models for advanced control strategies like model predictive control, and enables responsive, data-driven, and plant state-dependent cultivation. Traditional biomass measurement methods, such as destructive sampling, are time-consuming and unsuitable for high-frequency monitoring. In contrast, image-based estimation using computer vision and deep learning requires frequent retraining and is sensitive to changes in lighting or plant morphology. This work introduces a low-cost, load-cell-based biomass monitoring system tailored for vertical farming applications. The system operates at the level of individual growing trays, offering a valuable middle ground between impractical plant-level sensing and overly coarse rack-level measurements. Tray-level data allow localized control actions, such as adjusting light spectrum and intensity per tray, thereby enhancing the utility of controllable LED systems. This granularity supports layer-specific optimization and anomaly detection, which are not feasible with rack-level feedback. The biomass sensor is easily scalable and can be retrofitted, addressing common challenges such as mechanical noise and thermal drift. It offers a practical and robust solution for biomass monitoring in dynamic, growing environments, enabling finer control and smarter decision making in both commercial and research-oriented vertical farming systems. The developed sensor was tested and validated against manual harvest data, demonstrating high agreement with actual plant biomass and confirming its suitability for integration into vertical farming systems. Full article
(This article belongs to the Special Issue Feature Papers in Smart Agriculture 2025)
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22 pages, 486 KiB  
Review
Unraveling NETs in Sepsis: From Cellular Mechanisms to Clinical Relevance
by Giulia Pignataro, Stefania Gemma, Martina Petrucci, Fabiana Barone, Andrea Piccioni, Francesco Franceschi and Marcello Candelli
Int. J. Mol. Sci. 2025, 26(15), 7464; https://doi.org/10.3390/ijms26157464 (registering DOI) - 1 Aug 2025
Abstract
Sepsis is a clinical syndrome characterized by a dysregulated host response to infection, frequently resulting in septic shock and multi-organ failure. Emerging evidence highlights the critical role of neutrophil extracellular traps (NETs) in the pathophysiology of sepsis. NETs are extracellular structures composed of [...] Read more.
Sepsis is a clinical syndrome characterized by a dysregulated host response to infection, frequently resulting in septic shock and multi-organ failure. Emerging evidence highlights the critical role of neutrophil extracellular traps (NETs) in the pathophysiology of sepsis. NETs are extracellular structures composed of chromatin DNA, histones, and granular proteins released by neutrophils through a specialized form of cell death known as NETosis. While NETs contribute to the containment of pathogens, their excessive or dysregulated production in sepsis is associated with endothelial damage, immunothrombosis, and organ dysfunction. Several NET-associated biomarkers have been identified, including circulating cell-free DNA (cfDNA), histones, MPO-DNA complexes, and neutrophil elastase–DNA complexes, which correlate with the disease severity and prognosis. Therapeutic strategies targeting NETs are currently under investigation. Inhibition of NET formation using PAD4 inhibitors or ROS scavengers has shown protective effects in preclinical models. Conversely, DNase I therapy facilitates the degradation of extracellular DNA, reducing the NET-related cytotoxicity and thrombotic potential. Additionally, heparin and its derivatives have demonstrated the ability to neutralize NET-associated histones and mitigate coagulopathy. Novel approaches include targeting upstream signaling pathways, such as TLR9 and IL-8/CXCR2, offering further therapeutic promise. Full article
(This article belongs to the Collection Advances in Cell and Molecular Biology)
26 pages, 685 KiB  
Article
Novel Research Regarding Topical Use of Diclofenac in Dermatology—Non-Clinical and Clinical Data
by Diana Ana-Maria Nițescu, Horia Păunescu, Mihnea Costescu, Bogdan Nițescu, Laurențiu Coman, Ion Fulga and Oana Andreia Coman
Sci. Pharm. 2025, 93(3), 34; https://doi.org/10.3390/scipharm93030034 - 30 Jul 2025
Viewed by 125
Abstract
Diclofenac, an aryl-acetic acid derivative from the non-steroidal anti-inflammatory drug class, is the subject of multiple non-clinical and clinical studies regarding its usefulness in treating some dermatologic pathologies with an inflammatory, auto-immune, or proliferative component. Diclofenac is now approved for the topical treatment [...] Read more.
Diclofenac, an aryl-acetic acid derivative from the non-steroidal anti-inflammatory drug class, is the subject of multiple non-clinical and clinical studies regarding its usefulness in treating some dermatologic pathologies with an inflammatory, auto-immune, or proliferative component. Diclofenac is now approved for the topical treatment of actinic keratoses (AK), pre-malignant entities that have the risk of transformation into skin carcinomas. The hypothesis that diclofenac increases granular layer development in the mice tail model, having an anti-psoriatic effect, was demonstrated in a previous study in which 1% and 2% diclofenac ointment was evaluated. The aim of the present study was to perform experimental research on the topical effect of diclofenac in the mice tail model, by testing 4% and 8% diclofenac ointment, which is presented in the first part of the manuscript. In the second part of the manuscript, we also aimed to conduct a literature review regarding topical diclofenac uses in specific dermatological entities by evaluating the articles published in PubMed and Scopus databases during 2014–2025. The studies regarding the efficacy of topical diclofenac in dermatological diseases such as AK and field cancerization, actinic cheilitis, basal cell carcinoma, Bowen disease, Darier disease, seborrheic keratoses, and porokeratosis, were analyzed. The results of the experimental work showed a significant effect of 4% and 8% diclofenac ointment on orthokeratosis degree when compared to the negative control groups. Diclofenac in the concentration of 4% and 8% significantly increased the orthokeratosis degree compared to the negative control with untreated mice (p = 0.006 and p = 0.011, respectively, using the Kruskal–Wallis test) and to the negative control with vehicle (p = 0.006 and p = 0.011, respectively, using the Kruskal–Wallis test). The mean epidermal thickness was increased for the diclofenac groups, but not significantly when compared to the control groups. The results are concordant with our previous experiment, emphasizing the need for future clinical trials on the use of topical diclofenac in psoriasis. Full article
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18 pages, 6054 KiB  
Article
Mitotic Activity, Cell Survival, and Neuronal Differentiation in the Hilus of the Dentate Gyrus Under Physiological and Hypothyroid Conditions in Adult Wistar Rats
by Karla Sánchez-Huerta, Ana Karen García-Juárez, Lía Diana Colmenero-Rodríguez, Yuliana García-Martínez and Jorge Pacheco-Rosado
Cells 2025, 14(14), 1112; https://doi.org/10.3390/cells14141112 - 19 Jul 2025
Viewed by 262
Abstract
The adult rodent hippocampus is capable of maintaining its capacity to generate new neurons in the subgranular zone (SGZ) of the dentate gyrus (DG). Interestingly, proliferative cells have also been described in the hilus. The involvement of the hilar neurogenesis process in hippocampal [...] Read more.
The adult rodent hippocampus is capable of maintaining its capacity to generate new neurons in the subgranular zone (SGZ) of the dentate gyrus (DG). Interestingly, proliferative cells have also been described in the hilus. The involvement of the hilar neurogenesis process in hippocampal physiology is unknown. Thyroid hormones (THs) are necessary for the survival of postmitotic progenitor cells, neuroblasts, and immature granule neurons in the SGZ. In contrast, evidence concerning the role of THs in the hilar neurogenesis process is limited. The present study characterized the mitotic activity, cell survival, and neuronal differentiation of hilar neurogenesis under physiological and hypothyroid conditions and compared them with those of the granular layer (GL) and the SGZ of the DG in adult Wistar rats. We found that, under physiological conditions, the hilus harbors fewer proliferative cells than the neurogenic zone (GL/SGZ) does, with a rate of cell survival of 18.9% and a rate of differentiation into granular neurons of 19%. Interestingly, hypothyroidism provokes decreased cell proliferation and an increased rate of cell survival without affecting neuronal differentiation. These effects induced by hypothyroidism in the hilus were different or inclusive, contrary to those observed in the neurogenic zone. Full article
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16 pages, 2609 KiB  
Article
Comparative Life Cycle and Techno-Economic Assessment of Constructed Wetland, Microbial Fuel Cell, and Their Integration for Wastewater Treatment
by Nicholas Miwornunyuie, Samuel O. Alamu, Guozhu Mao, Nihed Benani, James Hunter and Gbekeloluwa Oguntimein
Clean Technol. 2025, 7(3), 57; https://doi.org/10.3390/cleantechnol7030057 - 10 Jul 2025
Viewed by 404
Abstract
This study systematically compares the environmental and economic performance of three wastewater treatment systems: constructed wetlands (CWs), microbial fuel cells (MFCs), and their integration (CW–MFC). Lab-scale units of each system were constructed using a multi-media matrix (gravel, zeolite, and granular activated carbon), composite [...] Read more.
This study systematically compares the environmental and economic performance of three wastewater treatment systems: constructed wetlands (CWs), microbial fuel cells (MFCs), and their integration (CW–MFC). Lab-scale units of each system were constructed using a multi-media matrix (gravel, zeolite, and granular activated carbon), composite native wetland species (Juncus effusus, Iris sp., and Typha angustifolia), carbon-based electrodes (graphite), and standard inoculum for CW and CW–MFC. The MFC system employed carbon-based electrodes and proton-exchange membrane. The experimental design included a parallel operation of all systems treating domestic wastewater under identical hydraulic and organic loading rates. Environmental impacts were quantified across construction and operational phases using life cycle assessment (LCA) with GaBi software 9.2, employing TRACI 2021 and ReCiPe 2016 methods, while techno-economic analysis (TEA) evaluated capital and operational costs. The key results indicate that CW demonstrates the lowest global warming potential (142.26 kg CO2-eq) due to its reliance on natural biological processes. The integrated CW–MFC system achieved enhanced pollutant removal (82.8%, 87.13%, 78.13%, and 90.3% for COD, NO3, TN, and TP) and bioenergy generation of 2.68 kWh, balancing environmental benefits with superior treatment efficiency. In contrast, the stand-alone MFC shows higher environmental burdens, primarily due to energy-intensive material requirements and fabrication processes. TEA results highlight CW as the most cost-effective solution (USD 627/m3), with CW–MFC emerging as a competitive alternative when considering environmental benefits and operational efficiencies (USD 718/m3). This study highlights the potential of hybrid systems, such as CW–MFC, to advance sustainable wastewater treatment technologies by minimizing environmental impacts and enhancing resource recovery, supporting their broader adoption in future water management strategies. Future research should focus on optimizing materials and energy use to improve scalability and feasibility. Full article
(This article belongs to the Collection Water and Wastewater Treatment Technologies)
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10 pages, 2014 KiB  
Article
A Study on the Morphology of Poly(Triaryl Amine)-Based Hole Transport Layer via Solvent Optimization for High-Performance Inverted Perovskite Solar Cells
by Xiaoyin Xie, Xi Liu, Chufei Ding, Han Yang, Xueyi Liu, Guanchen Liu, Zhihai Liu and Eun-Cheol Lee
Inorganics 2025, 13(7), 232; https://doi.org/10.3390/inorganics13070232 - 9 Jul 2025
Viewed by 308
Abstract
Poly[bis(4-phenyl) (2,5,6-trimethylphenyl) amine (PTAA), as a hole transfer material, has been widely used in perovskite solar cells (PSCs). However, the optimal solvent for preparing the PTAA solution and coating the PTAA layer is still uncertain. In this work, we investigated three types of [...] Read more.
Poly[bis(4-phenyl) (2,5,6-trimethylphenyl) amine (PTAA), as a hole transfer material, has been widely used in perovskite solar cells (PSCs). However, the optimal solvent for preparing the PTAA solution and coating the PTAA layer is still uncertain. In this work, we investigated three types of organic solvents (toluene, chlorobenzene and dichlorobenzene) for processing PTAA layers as the hole transport layer in PSCs. Based on the experimental verification and molecular dynamics simulation results, all the evidence indicated that toluene performs best among the three candidates. This is attributed to the significant polarity difference between toluene and PTAA, which leads to the formation of a uniform surface morphology characterized by granular protuberances after spin coating. The contact area of the hole transfer layer with the surface aggregation is increased in reference to the rough surface, and the hydrophilicity of the PTAA layer is also increased. The improvement of these two aspects are conducive to the effective interfacial charge transfer. This leads to the generation of more photocurrent. The PSCs employing toluene-processed PTAA exhibit an average power conversion efficiency (PCE) of 19.1%, which is higher than that of PSCs using chlorobenzene- and dichlorobenzene-processed PTAA (17.3–17.9%). This work provides a direct optimization strategy for researchers aiming to fabricate PSCs based on PTAA as a hole transport layer and lays a solid foundation for the development of high-efficiency inverted PSCs. Full article
(This article belongs to the Special Issue Optical and Quantum Electronics: Physics and Materials)
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17 pages, 2685 KiB  
Article
Co-Effect of pH Control Agent and pH Value on the Physical Properties of ZnO Thin Films Obtained by Chemical Bath Deposition for Potential Application in Dye-Sensitized Solar Cells
by Alphonse Déssoudji Gboglo, Mazabalo Baneto, Komlan Segbéya Gadedjisso-Tossou, Ognanmi Ako, Ayayi Claude Ahyi, Muthiah Haris, Muthusamy Senthilkumar, Kekeli N’konou, Bruno Grandidier, Katawoura Beltako, Komi Apélété Amou and Milohum Mikesokpo Dzagli
Surfaces 2025, 8(3), 46; https://doi.org/10.3390/surfaces8030046 - 1 Jul 2025
Viewed by 356
Abstract
This study presents the influence of pH control agents and pH value on the physical properties of ZnO thin films obtained by chemical bath deposition. ZnO thin films were synthesized on glass substrates using precursor solutions of different pHs prepared from two bases: [...] Read more.
This study presents the influence of pH control agents and pH value on the physical properties of ZnO thin films obtained by chemical bath deposition. ZnO thin films were synthesized on glass substrates using precursor solutions of different pHs prepared from two bases: sodium hydroxide (NaOH) and ammonia (NH3). The effect of pH values on the morphological, structural, and optical properties of ZnO thin films was investigated using X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and UV–Visible spectroscopy. XRD results showed that all the synthesized ZnO thin films are polycrystalline and crystallize in a hexagonal wurtzite structure. The crystallite size, calculated using the Debye–Scherrer formula, varied from 10.50 nm to 11.69 nm for ZnO thin films obtained with NH3 and from 20.79 nm to 27.76 nm for those obtained with NaOH. FTIR analysis confirmed the presence of functional groups. SEM images indicated that not only the base but also the pH affects the morphology of the films, giving rise to different granular shapes. Overall, the ZnO thin films obtained with NaOH looked more mesoporous compared to those obtained with NH3. Optical characterization results showed that whatever the base used, the pH of the precursor solution affected the ZnO thin film transmittance. Films synthesized with NH3 exhibited the best transmittance (80%) at pH 8.5, while the best transmittance (81%) of films synthesized with NaOH was obtained at pH 8 in the visible region. Based on optical and morphological properties, ZnO films obtained from NH3 at pH 8.5 are found to be more suitable as photoanodes in dye-sensitized solar cells. Full article
(This article belongs to the Special Issue Surface Engineering of Thin Films)
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16 pages, 1419 KiB  
Review
Histopathological Types, Clinical Presentation, Imaging Studies, Treatment Strategies, and Prognosis of Posterior Pituitary Tumors: An Updated Review
by Pedro Iglesias
J. Clin. Med. 2025, 14(13), 4553; https://doi.org/10.3390/jcm14134553 - 26 Jun 2025
Viewed by 496
Abstract
Posterior pituitary tumors (PPTs) are rare, non-neuroendocrine neoplasms derived from pituicytes of the neurohypophysis or infundibulum. According to the 2025 WHO classification, PPTs comprise four distinct but related low-grade entities: pituicytoma, granular cell tumor of the sellar region, spindle cell oncocytoma, and ependymal [...] Read more.
Posterior pituitary tumors (PPTs) are rare, non-neuroendocrine neoplasms derived from pituicytes of the neurohypophysis or infundibulum. According to the 2025 WHO classification, PPTs comprise four distinct but related low-grade entities: pituicytoma, granular cell tumor of the sellar region, spindle cell oncocytoma, and ependymal pituicytoma. All share nuclear TTF-1 expression, confirming their common origin, but differ in morphology, immunophenotype, and ultrastructure. Histologically, pituicytomas consist of bipolar spindle cells in fascicles; granular cell tumors show polygonal cells with PAS-positive, diastase-resistant cytoplasmic granules; spindle cell oncocytomas display oncocytic change and abundant mitochondria; and ependymal pituicytomas exhibit perivascular pseudorosettes and EMA positivity in apical or dot-like patterns. Immunohistochemically, all are S100 and vimentin positive, and negative for pituitary hormones and lineage-specific transcription factors. Clinically, PPTs are typically non-functioning but may be associated with corticotroph or somatotroph hyperfunction. Imaging features are nonspecific. Surgical resection is the treatment of choice, although hypervascularity and adherence—especially in spindle cell oncocytomas—can hinder complete excision. Radiotherapy is reserved for recurrences. Molecular analyses reveal recurrent alterations in MAPK/PI3K pathways (e.g., HRAS, BRAF, FGFR1, NF1, TSC1) and suggest a shared histogenesis. Copy number imbalances correlate with reduced progression-free survival in some subtypes. Despite a generally favorable prognosis, recurrence—particularly in spindle cell oncocytomas—necessitates long-term follow-up. The WHO 2025 update provides a unified framework for classification, diagnosis, and prognostic stratification of these rare tumors. Full article
(This article belongs to the Section Oncology)
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31 pages, 1849 KiB  
Review
The Application of Single-Cell Technologies for Vaccine Development Against Viral Infections
by Hong Nhi Nguyen, Isabel O. Vanderzee and Fei Wen
Vaccines 2025, 13(7), 687; https://doi.org/10.3390/vaccines13070687 - 26 Jun 2025
Viewed by 895
Abstract
The development of vaccines against viral infections has advanced rapidly over the past century, propelled by innovations in laboratory and molecular technologies. These advances have expanded the range of vaccine platforms beyond live-attenuated and inactivated vaccines to include recombinant platforms, such as subunit [...] Read more.
The development of vaccines against viral infections has advanced rapidly over the past century, propelled by innovations in laboratory and molecular technologies. These advances have expanded the range of vaccine platforms beyond live-attenuated and inactivated vaccines to include recombinant platforms, such as subunit proteins and virus-like particles (VLPs), and more recently, mRNA-based vaccines, while also enhancing methods for evaluating vaccine performance. Despite these innovations, a persistent challenge remains: the inherent complexity and heterogeneity of immune responses continue to impede efforts to achieve consistently effective and durable protection across diverse populations. Single-cell technologies have emerged as transformative tools for dissecting this immune heterogeneity, providing comprehensive and granular insights into cellular phenotypes, functional states, and dynamic host–pathogen interactions. In this review, we examine how single-cell epigenomic, transcriptomic, proteomic, and multi-omics approaches are being integrated across all stages of vaccine development—from infection-informed discovery to guide vaccine design, to high-resolution evaluation of efficacy, and refinement of cell lines for manufacturing. Through representative studies, we highlight how insights from these technologies contribute to the rational design of more effective vaccines and support the development of personalized vaccination strategies. Full article
(This article belongs to the Special Issue Virus-Like Particle Vaccine Development)
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19 pages, 9714 KiB  
Article
Study on Shear Wave Attenuation Laws in Granular Sediments Based on Bender Element Test Simulations
by Jingyu Tan, Yong Wang, Xuewen Lei and Jingqiang Miao
J. Mar. Sci. Eng. 2025, 13(6), 1132; https://doi.org/10.3390/jmse13061132 - 5 Jun 2025
Viewed by 397
Abstract
The propagation characteristics of shear waves in granular sediments are usually used to assess the dynamic response and liquefaction potential of marine engineering foundations. However, the mesoscopic processes by which the excitation frequency influences the shear wave propagation and attenuation remain unclear. In [...] Read more.
The propagation characteristics of shear waves in granular sediments are usually used to assess the dynamic response and liquefaction potential of marine engineering foundations. However, the mesoscopic processes by which the excitation frequency influences the shear wave propagation and attenuation remain unclear. In this study, based on a triaxial bender element (BE) test model, the shear wave behavior in uniform spherical particles was simulated by the discrete element method (DEM). It revealed that the BE excites shear waves in a point source manner and that the propagation processes within a triaxial unit cell assembly follow exponential attenuation patterns. Near the vibration source (10–100 kHz), the attenuation law of spherical wave propagation is dominated by friction slip and geometric diffusion in particles. At 0.7–3.5 wavelengths, the shear waves progressively transition to plane waves, and the attenuation law is governed by boundary absorption and viscous damping. At 2.9–10 wavelengths, near-field effects diminish, and planar wave propagation stabilizes. Higher excitation frequencies enhance friction slip, boundary absorption, and viscous damping, leading to frequency-dependent attenuation. The granular system exhibits segmented filtering, with cutoff frequencies dependent on the receiver location but independent of the excitation frequency. Full article
(This article belongs to the Section Ocean Engineering)
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12 pages, 2980 KiB  
Article
Morphological Insights into Echinometra lucunter Spines Reveal Cellular Sources of Bioactive Molecules
by Juliana Mozer Sciani, Marta Maria Antoniazzi, Carlos Jared, José Roberto Machado Cunha da Silva and Daniel Carvalho Pimenta
Oceans 2025, 6(2), 33; https://doi.org/10.3390/oceans6020033 - 5 Jun 2025
Viewed by 511
Abstract
Echinometra lucunter, the most abundant sea urchin in Brazil, causes numerous accidents by puncture wounds, primarily on hands and feet. Beyond mechanical trauma, recent research has identified bioactive molecules in spine extracts and coelomic fluid contributing to these inflammatory reactions. This study [...] Read more.
Echinometra lucunter, the most abundant sea urchin in Brazil, causes numerous accidents by puncture wounds, primarily on hands and feet. Beyond mechanical trauma, recent research has identified bioactive molecules in spine extracts and coelomic fluid contributing to these inflammatory reactions. This study investigated spine morphology to better understand the envenomation and defense processes for the animal. Using various microscopy techniques, the spines were revealed to be mineral structures with longitudinal canals and a sponge-like central mesh rich in granular cells. These cells extend from the spine’s center to its edges, terminating in fimbriae-like structures, likely involved in molecular exchange with the environment. The spine tip is more cellular than the base, suggesting a defensive role, while the base provides structural support. Several cell types were identified, including granulocytes, red spherulocytes, and phagocytic amoebocytes, also found in the coelomic fluid. Other cells displayed prominent Golgi apparatuses and secretory granules, indicating specialized secretory functions, likely the source of bioactive molecules involved in chemical defense and spine regeneration. Understanding this cellular structure is crucial for comprehending the urchin’s envenomation and defense mechanisms. Full article
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18 pages, 3022 KiB  
Article
Interaction Between Rumen Microbiota and Epithelial Mitochondrial Dynamics in Tibetan Sheep: Elucidating the Mechanism of Rumen Epithelial Energy Metabolism
by Ying Xu, Yuzhu Sha, Xiaowei Chen, Qianling Chen, Xiu Liu, Yanyu He, Wei Huang, Yapeng He and Xu Gao
BioTech 2025, 14(2), 43; https://doi.org/10.3390/biotech14020043 - 5 Jun 2025
Viewed by 887
Abstract
Investigating the functional interactions between rumen microbial fermentation and epithelial mitochondrial dynamics/energy metabolism in Tibetan sheep at different altitudes, this study examined ultrastructural changes in rumen epithelial tissues, expression levels of mitochondrial dynamics-related genes (fusion: Mfn1, Mfn2, OPA1, Mic60; [...] Read more.
Investigating the functional interactions between rumen microbial fermentation and epithelial mitochondrial dynamics/energy metabolism in Tibetan sheep at different altitudes, this study examined ultrastructural changes in rumen epithelial tissues, expression levels of mitochondrial dynamics-related genes (fusion: Mfn1, Mfn2, OPA1, Mic60; fission: Drp1, Fis1, MFF), and ketogenesis pathway genes (HMGS2, HMGCL) in Tibetan sheep raised at three altitudes (TS 2500m, TS 3500m, TS 4500m). Correlation analysis was performed between rumen microbiota/metabolites and mitochondrial energy metabolism. Results: Ultrastructural variations were observed across altitudes. With increasing altitude, keratinized layer became more compact; desmosome connections between granular layer cells increased; mitochondrial quantity and distribution in spinous and basal layers increased. Mitochondrial dynamics regulation: Fission genes (FIS1, DRP1, MFF) showed significantly higher expression at TS 4500m (p < 0.01); fusion genes (Mfn1, OPA1) exhibited altitude-dependent upregulation. Energy metabolism markers: Pyruvate (PA) decreased significantly at TS 3500m/TS 4500m (p < 0.01); citrate (CA) increased with altitude; NAD+ peaked at TS 3500m but decreased significantly at TS 4500m (p < 0.01); Complex II (SDH) and Complex IV (CO) activities decreased at TS 4500m (p < 0.01). Ketogenesis pathway: β-hydroxybutyrate increased significantly with altitude (p < 0.01); acetoacetate peaked at TS 2500 m/TS 4500 m; HMGCS2 expression exceeded HMGCL, showing altitude-dependent upregulation at TS 4500m (p < 0.01). Microbiome–metabolism correlations: Butyrivibrio_2 and Fibrobacter negatively correlated with Mic60 (p < 0.01); Ruminococcaceae_NK4A214_Group positively correlated with Mfn1/OPA1 (p < 0.05); WGCNA identified 17 metabolite modules, with MEturquoise module positively correlated with DRP1/Mfn2/MFF (p < 0.05). Conclusion: Altitude-induced ultrastructural adaptations in rumen epithelium correlate with mitochondrial dynamics stability and ketogenesis upregulation. Mitochondrial fission predominates at extreme altitudes, while microbiota–metabolite interactions suggest compensatory energy regulation mechanisms. Full article
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19 pages, 2183 KiB  
Article
Perfluorooctanoic Acid and Its Short-Chain Substitutes Induce Cytotoxic and Prooxidative Changes in Human Peripheral Blood Mononuclear Cells: A Comparative Study
by Izabela Kaczmarska, Katarzyna Mokra and Jaromir Michałowicz
Int. J. Mol. Sci. 2025, 26(11), 5408; https://doi.org/10.3390/ijms26115408 - 5 Jun 2025
Viewed by 538
Abstract
Perfluorooctanoic acid (PFOA) and its short-chain substitutes, perfluorohexanoic acid (PFHxA) and perfluorobutanoic acid (PFBA), are persistent environmental pollutants associated with widespread human exposure through occupational and environmental routes. The aim of this was to investigate the effects of PFOA, PFHxA, and PFBA on [...] Read more.
Perfluorooctanoic acid (PFOA) and its short-chain substitutes, perfluorohexanoic acid (PFHxA) and perfluorobutanoic acid (PFBA), are persistent environmental pollutants associated with widespread human exposure through occupational and environmental routes. The aim of this was to investigate the effects of PFOA, PFHxA, and PFBA on the intracellular level of adenosine-5’-triphosphate (ATP) in human peripheral blood mononuclear cells (PBMCs) and their viability, size, and granularity. Moreover, oxidative and nitrosative stress was assessed based on the levels of reactive oxygen species (ROS), reactive nitrogen species (RNS), and highly reactive oxygen species (hROS, mainly hydroxyl radical). Finally, oxidative damage to protein and lipids in PBMCs was measured. The cells were incubated for 1 h and 24 h at concentrations correlated to human occupational and environmental exposure (0.001–200 µg/mL) to the substances. Our findings indicate that PFOA and its short-chain analogs cause different effects in human PBMCs. PFOA induced statistically significant alterations almost in all studied parameters, substantially decreasing cell viability and ATP level and altering the size and granularity of tested cells; in contrast, PFHxA and PFBA induced significant changes only at some studied parameters. PFOA also induced a notable increase in intracellular ROS and RNS levels, which suggest that both oxidative stress and nitrosative stress influence its cytotoxic potential. Interestingly, the shortest-chain compound, PFBA, induced changes that were not observed for PFHxA. This suggests that the length of the chain determines the triggering of certain alterations in PBMCs. Importantly, the changes were noted at concentrations corresponding to those associated with occupational exposure. These findings contribute to our understanding of the immunotoxicity of PFOA and its substitutes, indicating the potential health risks associated with chronic exposure, particularly in populations with occupational exposure or high environmental PFOA burdens. Full article
(This article belongs to the Section Molecular Biology)
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12 pages, 3124 KiB  
Article
Imaging Features and Clinical Characteristics of Granular Cell Tumors: A Single-Center Investigation
by Hui Gu, Lan Yu and Yu Wu
Diagnostics 2025, 15(11), 1336; https://doi.org/10.3390/diagnostics15111336 - 26 May 2025
Viewed by 530
Abstract
Background/Objectives: Granular cell tumors (GCTs) are rare neurogenic tumors with Schwann cell differentiation. Although most are benign, 1–2% exhibit malignant behavior. The imaging features of GCTs remain poorly characterized due to their rarity and anatomic variability. This study aims to elucidate the manifestations [...] Read more.
Background/Objectives: Granular cell tumors (GCTs) are rare neurogenic tumors with Schwann cell differentiation. Although most are benign, 1–2% exhibit malignant behavior. The imaging features of GCTs remain poorly characterized due to their rarity and anatomic variability. This study aims to elucidate the manifestations of GCTs in multimodal imaging across different anatomic locations. Methods: We retrospectively analyzed 66 histopathologically confirmed GCT cases (2011–2024), assessing their clinical presentations, pathological characteristics, and imaging findings from ultrasound (n = 31), CT (n = 14), MRI (n = 8), and endoscopy (n = 15). Two radiologists independently reviewed the imaging features (location, size, morphology, signal/density, and enhancement). Results: The cohort (mean age: 42 ± 12 years; 72.7% female) showed tendency in location towards soft tissue (48.4%), the digestive tract (30.3%), the respiratory system (7.6%), the breasts (7.6%), and the sellar region (6.1%). Six cases (9.1%) were malignant. The key imaging findings by modality were as follows: Ultrasound: Well-circumscribed hypoechoic masses in soft tissue (96.1%) and irregular margins in the breasts (80%, BI-RADS 4B) were found. MRI: The sellar GCTs exhibited T1-isointensity, variable T2-signals (with 50% showing “star-like crack signs”), and heterogeneous enhancements. The soft tissue GCTs were T1-hypointense (75%) with variable T2-signals. CT: Pulmonary/laryngeal GCTs appeared as well-defined hypodense masses with mild/moderate enhancements. Endoscopy: Submucosal/muscularis hypoechoic nodules with smooth surfaces were found. Malignant GCTs were larger (mean: 93 mm vs. 30 mm) but lacked pathognomonic imaging features. Three malignant cases demonstrated metastases. Conclusions: GCTs exhibit distinct imaging patterns based on their anatomical location. While certain features (e.g., star-like crack signs) are suggestive, imaging cannot reliably differentiate benign from malignant variants. Histopathological confirmation remains essential to diagnosis, particularly given the potential for malignant transformations (at 9.1% in our series). Multimodal imaging guides the localization and biopsy planning, but clinical–radiological–pathological correlation is crucial for the optimal management. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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19 pages, 33190 KiB  
Article
Jun N-Terminal Kinase Inhibitor Suppresses CASK Deficiency-Induced Cerebellar Granular Cell Death in MICPCH Syndrome Model Mice
by Qi Guo, Emi Kouyama-Suzuki, Yoshinori Shirai and Katsuhiko Tabuchi
Cells 2025, 14(10), 750; https://doi.org/10.3390/cells14100750 - 20 May 2025
Viewed by 830
Abstract
Microcephaly with pontine and cerebellar hypoplasia (MICPCH) syndrome is a severe neurodevelopmental disorder caused by a deficiency in the X-linked gene calcium/calmodulin-dependent serine protein kinase (CASK). A better understanding of the role of CASK in the pathophysiology of neurodevelopmental disorders may provide insights [...] Read more.
Microcephaly with pontine and cerebellar hypoplasia (MICPCH) syndrome is a severe neurodevelopmental disorder caused by a deficiency in the X-linked gene calcium/calmodulin-dependent serine protein kinase (CASK). A better understanding of the role of CASK in the pathophysiology of neurodevelopmental disorders may provide insights into novel therapeutic and diagnostic strategies for MICPCH syndrome and other neurodegenerative diseases. To investigate this, we generated CASK knockout (KO) cerebellar granule (CG) cell culture from CASK floxed (CASKflox/flox) mice by infecting lentiviruses expressing codon-improved Cre recombinase (iCre). We performed RNA-sequencing (RNA-seq) on these cells and found that CASK-KO CG cells underwent apoptosis by activating intracellular Jun N-terminal kinase (JNK) signaling and upregulating reactive oxygen species (ROS)-related gene expression. We also performed mouse gait analysis and limb clasping behavior experiments on trans-heterozygous CASK-KO and Hprt-eGFP (CASK+/- HprteGFP/+) mice. The CASK+/- HprteGFP/+ mice exhibited cerebellar ataxic phenotypes as judged by the scores of these experiments compared to the CASK wild-type control (CASK+/+ HprteGFP/+) mice. Interestingly, the administration of the JNK inhibitor, JNK-IN-8, in CASK-KO CG cell cultures increased CG cell survival by reducing ROS generation. Moreover, injection of JNK-IN-8 into the cerebellum of CASK+/- HprteGFP/+ mice suppressed CG cell death and alleviated cerebellar ataxic phenotypes in vivo. In conclusion, JNK-IN-8 suppresses the cell death and activation of the ROS pathway in CASK-KO CG cells in both in vitro and in vivo models, suggesting its potential as a therapeutic strategy for cerebellar neurodegeneration in MICPCH syndrome. Full article
(This article belongs to the Section Cells of the Nervous System)
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