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44 pages, 4024 KiB  
Review
Exploring Purpose-Driven Methods and a Multifaceted Approach in Dam Health Monitoring Data Utilization
by Zhanchao Li, Ebrahim Yahya Khailah, Xingyang Liu and Jiaming Liang
Buildings 2025, 15(15), 2803; https://doi.org/10.3390/buildings15152803 (registering DOI) - 7 Aug 2025
Abstract
Dam monitoring tracks environmental variables (water level, temperature) and structural responses (deformation, seepage, and stress) to assess safety and performance. Structural health monitoring (SHM) refers to the systematic observation and analysis of the structural condition over time, and it is essential in maintaining [...] Read more.
Dam monitoring tracks environmental variables (water level, temperature) and structural responses (deformation, seepage, and stress) to assess safety and performance. Structural health monitoring (SHM) refers to the systematic observation and analysis of the structural condition over time, and it is essential in maintaining the safety, functionality, and long-term performance of dams. This review examines monitoring data applications, covering structural health assessment methods, historical motivations, and key challenges. It discusses monitoring components, data acquisition processes, and sensor roles, stressing the need to integrate environmental, operational, and structural data for decision making. Key objectives include risk management, operational efficiency, safety evaluation, environmental impact assessment, and maintenance planning. Methodologies such as numerical modeling, statistical analysis, and machine learning are critically analyzed, highlighting their strengths and limitations and the demand for advanced predictive techniques. This paper also explores future trends in dam monitoring, offering insights for engineers and researchers to enhance infrastructure resilience. By synthesizing current practices and emerging innovations, this review aims to guide improvements in dam safety protocols, ensuring reliable and sustainable dam operations. The findings provide a foundation for the advancement of monitoring technologies and optimization of dam management strategies worldwide. Full article
(This article belongs to the Section Construction Management, and Computers & Digitization)
22 pages, 5700 KiB  
Article
Genome-Wide Identification and Expression Analysis of the GH19 Chitinase Gene Family in Sea Island Cotton
by Jingjing Ma, Yilei Long, Jincheng Fu, Nengshuang Shen, Le Wang, Shuaijun Wu, Jing Li, Quanjia Chen, Qianli Zu and Xiaojuan Deng
Curr. Issues Mol. Biol. 2025, 47(8), 633; https://doi.org/10.3390/cimb47080633 (registering DOI) - 7 Aug 2025
Abstract
In this study, GH19 chitinase (Chi) gene family was systematically identified and characterized using genomic assemblies from four cotton species: Gossypium barbadense, G. hirsutum, G. arboreum, and G. raimondii. A suite of analyses was performed, including genome-wide gene identification, [...] Read more.
In this study, GH19 chitinase (Chi) gene family was systematically identified and characterized using genomic assemblies from four cotton species: Gossypium barbadense, G. hirsutum, G. arboreum, and G. raimondii. A suite of analyses was performed, including genome-wide gene identification, physicochemical property characterization of the encoded proteins, subcellular localization prediction, phylogenetic reconstruction, chromosomal mapping, promoter cis-element analysis, and comprehensive expression profiling using transcriptomic data and qRT-PCR (including tissue-specific expression, hormone treatments, and Fusarium oxysporum infection assays). A total of 107 GH19 genes were identified across the four species (35 in G. barbadense, 37 in G. hirsutum, 19 in G. arboreum, and 16 in G. raimondii). The molecular weights of GH19 proteins ranged from 9.9 to 97.3 kDa, and they were predominantly predicted to localize to the extracellular space. Phylogenetic analysis revealed three well-conserved clades within this family. In tetraploid cotton, GH19 genes were unevenly distributed across 12 chromosomes, often clustering in certain regions, whereas in diploid species, they were confined to five chromosomes. Promoter analysis indicated that GH19 gene promoters contain numerous stress- and hormone-responsive motifs, including those for abscisic acid (ABA), ethylene (ET), and gibberellin (GA), as well as abundant light-responsive elements. The expression patterns of GH19 genes were largely tissue-specific; for instance, GbChi23 was predominantly expressed in the calyx, whereas GbChi19/21/22 were primarily expressed in the roots and stems. Overall, this study provides the first comprehensive genomic and functional characterization of the GH19 family in G. barbadense, laying a foundation for understanding its role in disease resistance mechanisms and aiding in the identification of candidate genes to enhance plant defense against biotic stress. Full article
23 pages, 2252 KiB  
Article
The Influence of the Geometric Configuration of the Drive System on the Motion Dynamics of Jaw Crushers
by Emilian Mosnegutu, Claudia Tomozei, Oana Irimia, Vlad Ciubotariu, Diana Mirila, Mirela Panainte-Lehadus, Marcin Jasiński, Nicoleta Sporea and Ivona Camelia Petre
Processes 2025, 13(8), 2498; https://doi.org/10.3390/pr13082498 (registering DOI) - 7 Aug 2025
Abstract
This study presents a comparative analysis of two double-toggle drive systems for jaw crushers that are tension based and compression based (this refers to the way in which the connecting rod is mechanically stressed within the drive mechanism), with the objective of identifying [...] Read more.
This study presents a comparative analysis of two double-toggle drive systems for jaw crushers that are tension based and compression based (this refers to the way in which the connecting rod is mechanically stressed within the drive mechanism), with the objective of identifying the optimal configuration from both kinematic and functional perspectives. Jaw crushers play a critical role in the extractive industry, and their performance is strongly influenced by the geometry and positioning of the drive mechanism. A theoretical approach based on mathematical modeling and numerical simulation was applied to a real constructive model (SMD-117), assessing variations in the linear velocity of the moving links as a function of mechanism placement. The study employed Mathcad 15, Roberts Animator, and GIM (Graphical Interactive Mechanisms) 2025.4 software to perform calculations and simulate motion. Results revealed a sinusoidal velocity pattern with significant differences between the two systems: the tension-based drive achieves peak velocities at the beginning of the angular variation interval, while the compression-based system reaches its maximum toward the end. Link C consistently exhibits higher velocities than link E, indicating increased mechanical stress. Polar graphic analysis identified critical velocity angles, and simulations confirmed the model’s validity with a maximum error of just 1.79%. The findings emphasize the importance of selecting an appropriate drive system to enhance performance, durability, and energy efficiency, offering concrete recommendations for equipment design and operation. Full article
(This article belongs to the Section Manufacturing Processes and Systems)
13 pages, 7865 KiB  
Article
FlbD: A Regulator of Hyphal Growth, Stress Resistance, Pathogenicity, and Chlamydospore Production in the Nematode-Trapping Fungus Arthrobotrys flagrans
by Yu Zhang, Shun-Qiao Peng, Wang-Ting He, Fei-Fei Gao, Qian-Fei Shi and Guo-Hong Li
Microorganisms 2025, 13(8), 1847; https://doi.org/10.3390/microorganisms13081847 (registering DOI) - 7 Aug 2025
Abstract
Arthrobotrys flagrans is a typical nematode-trapping fungus that captures nematodes by producing three-dimensional networks. FlbD is a DNA-binding protein containing a Myb domain, which plays a significant role in fungal development. However, the biological function of FlbD in nematode-trapping fungi remains unknown. In [...] Read more.
Arthrobotrys flagrans is a typical nematode-trapping fungus that captures nematodes by producing three-dimensional networks. FlbD is a DNA-binding protein containing a Myb domain, which plays a significant role in fungal development. However, the biological function of FlbD in nematode-trapping fungi remains unknown. In this study, we analyzed the physicochemical properties and conserved domains of AfFlbD and constructed the AfFlbD knockout strains (ΔAfFlbD) using homologous recombination. Our functional analysis revealed that the mutants produced more cottony aerial mycelia at the colony center. Additionally, the cell length of the mutants was reduced, indicating that AfFlbD regulates cell morphology in A. flagrans. Chemical stress tolerance assays of the mutants demonstrated reduced sensitivity to NaCl and sorbitol stresses but increased sensitivity to SDS and H2O2 stresses compared to the WT strain. Interestingly, the mutants spontaneously produced traps, and its pathogenicity to nematodes was significantly enhanced, suggesting that AfFlbD negatively regulates the pathogenicity of A. flagrans. Furthermore, the number of chlamydospores produced by the mutants was markedly reduced, though their morphology remained unchanged. Fluorescence localization analysis showed that AfFlbD localizes to the nuclei of chlamydospores, thereby regulating chlamydospore formation. This study provides important theoretical insights into the biological function of the FlbD transcription factor and offers new perspectives for the application of nematode-trapping fungi as a method of controlling plant-parasitic nematodes. Full article
(This article belongs to the Special Issue Microorganisms as Biocontrol Agents in Plant Pathology, 2nd Edition)
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43 pages, 2840 KiB  
Review
Oxytocin, Vasopressin and Stress: A Hormetic Perspective
by Hans P. Nazarloo, Marcy A. Kingsbury, Hannah Lamont, Caitlin V. Dale, Parmida Nazarloo, John M. Davis, Eric C. Porges, Steven P. Cuffe and C. Sue Carter
Curr. Issues Mol. Biol. 2025, 47(8), 632; https://doi.org/10.3390/cimb47080632 (registering DOI) - 7 Aug 2025
Abstract
The purpose of this article is to examine a previously unrecognized role for the vasopressin–oxytocin (VP-OT) system in mammalian “stress-response hormesis.” The current review adds hormesis to the long list of beneficial effects of OT. Hormesis, a biphasic adaptive response to low-level stressors, [...] Read more.
The purpose of this article is to examine a previously unrecognized role for the vasopressin–oxytocin (VP-OT) system in mammalian “stress-response hormesis.” The current review adds hormesis to the long list of beneficial effects of OT. Hormesis, a biphasic adaptive response to low-level stressors, is introduced here to contextualize the dynamic roles of oxytocin and vasopressin. As with hormesis, the properties of the VP-OT system are context-, time-, and dose-sensitive. Here we suggest that one key to understanding hormesis is the fact that VP and OT and their receptors function as an integrated system. The VP-OT system is capable of changing and adapting to challenges over time, including challenges necessary for survival, reproduction and sociality. Prior research suggests that many beneficial effects of OT are most apparent only following stressful experiences, possibly reflecting interactions with VP, its receptors and other components of the hypothalamic–pituitary–adrenal axis. The release of OT is documented following various kinds of hormetic experiences such as birth, vigorous exercise, ischemic events and the ingestion of emetics, including psychedelics. The phasic or cyclic modulation of VP and related “stress” hormones, accompanied or followed by the release of OT, creates conditions that conform to the core principles of hormesis. This concept is reviewed here in the context of other hormones including corticotropin releasing hormone (CRH) and urocortin, as well as cytokines. In general, VP and classic “stress hormones” support an active response, helping to quickly mobilize body systems. OT interacts with all of these, and may subsequently re-establish homeostasis and precondition the organism to deal with future stressors. However, the individual history of an organism, including epigenetic modifications of classical stress hormones such as VP, can moderate the effects of OT. Oxytocin’s effects also help to explain the important role of sociality in mammalian resilience and longevity. A hormetic perspective, focusing on a dynamic VP-OT system, offers new insights into emotional and physical disorders, especially those associated with the management of chronic stress, and helps us to understand the healing power of social behavior and perceived safety. Full article
(This article belongs to the Special Issue Current Advances in Oxytocin Research)
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17 pages, 5080 KiB  
Article
Effect of External Constraints on Deformation Behavior of Aluminum Single Crystals Cold-Rolled to High Reduction: Crystal Plasticity FEM Study and Experimental Verification
by Hui Wang, Junyao Dong, Shunjie Yao, Shuqi Liu, Letian Cao and Xi Huang
Metals 2025, 15(8), 885; https://doi.org/10.3390/met15080885 (registering DOI) - 7 Aug 2025
Abstract
In this study, aluminum single crystals with a {1 0 0} <0 0 1> (Cube) orientation were rolled under two conditions: with external constraints imposed by an external aluminum frame (3DRC) and without external constraints (3DR). The crystal plasticity finite element method (CPFEM) [...] Read more.
In this study, aluminum single crystals with a {1 0 0} <0 0 1> (Cube) orientation were rolled under two conditions: with external constraints imposed by an external aluminum frame (3DRC) and without external constraints (3DR). The crystal plasticity finite element method (CPFEM) was used to simulate texture evolution, and the results corresponded well with experimental observations. The minor discrepancies observed were primarily attributed to the idealized conditions in the simulation. The results demonstrate that in the 3DR model, crystal orientations predominantly rotate around the transverse direction (TD), with non-TD rotations playing a secondary role. In contrast, the 3DRC model exhibits similar rotation patterns to 3DR at lower reductions, but at higher reductions, non-TD rotations become comparable to TD rotations. This difference results in more concentrated orientations in 3DR and more dispersed orientations in 3DRC. Additionally, analysis reveals that external constraints cause deformation behavior to deviate from the plane strain condition rather than move closer to it. The presence of external constraints alters stress and strain states, modifying the activation of slip systems and crystal rotations, leading to significant variations in slip activity, shear strain, and crystal rotation along TD. Full article
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18 pages, 677 KiB  
Review
Advances of Peptides for Plant Immunity
by Minghao Liu, Guangzhong Zhang, Suikang Wang and Quan Wang
Plants 2025, 14(15), 2452; https://doi.org/10.3390/plants14152452 (registering DOI) - 7 Aug 2025
Abstract
Plant peptides, as key signaling molecules, play pivotal roles in plant growth, development, and stress responses. This review focuses on research progress in plant peptides involved in plant immunity, providing a detailed classification of immunity-related plant polypeptides, including small post-translationally modified peptides, cysteine-rich [...] Read more.
Plant peptides, as key signaling molecules, play pivotal roles in plant growth, development, and stress responses. This review focuses on research progress in plant peptides involved in plant immunity, providing a detailed classification of immunity-related plant polypeptides, including small post-translationally modified peptides, cysteine-rich peptides, and non-cysteine-rich peptides. It discusses the mechanisms by which plant polypeptides confer disease resistance, such as their involvement in pattern-triggered immunity (PTI), effector-triggered immunity (ETI), and regulation of hormone-mediated defense pathways. Furthermore, it explores potential agricultural applications of plant polypeptides, including the development of novel biopesticides and enhancement of crop disease resistance via genetic engineering. By summarizing current research, this review aims to provide a theoretical basis for in-depth studies on peptide-mediated disease resistance and offer innovative insights for plant disease control. Full article
(This article belongs to the Section Plant Physiology and Metabolism)
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12 pages, 924 KiB  
Article
Houttuynia cordata Exhibits Anti-Inflammatory Activity Against Interleukin-1β-Induced Inflammation in Human Gingival Epithelial Cells: An In Vitro Study
by Ryo Kunimatsu, Sawako Ikeoka, Yuma Koizumi, Ayaka Odo, Izumi Tanabe, Yoshihito Kawashima, Akinori Kiso, Yoko Hashii, Yuji Tsuka and Kotaro Tanimoto
Dent. J. 2025, 13(8), 360; https://doi.org/10.3390/dj13080360 - 7 Aug 2025
Abstract
Background/Objectives: Periodontitis is a chronic infectious inflammatory disorder that affects the supporting structures of the teeth. The gingival epithelium plays a crucial role as a physical and immunological barrier, producing pro-inflammatory cytokines in response to microbial pathogens. Modulation of gingival epithelial function [...] Read more.
Background/Objectives: Periodontitis is a chronic infectious inflammatory disorder that affects the supporting structures of the teeth. The gingival epithelium plays a crucial role as a physical and immunological barrier, producing pro-inflammatory cytokines in response to microbial pathogens. Modulation of gingival epithelial function has been proposed as a therapeutic strategy to prevent the progression of periodontal disease. Houttuynia cordata, a perennial herb traditionally used in Asian medicine, is recognized for its anti-inflammatory properties, with documented benefits in the cardiovascular, respiratory, and gastrointestinal systems. However, its potential therapeutic role in oral pathologies, such as periodontitis, remains underexplored. This study aimed to investigate the anti-inflammatory effects of H. cordata extract on interleukin (IL)-1β-stimulated primary gingival keratinocytes (PGKs) subjected to IL-1β-induced inflammatory stress, simulating the conditions encountered during orthodontic treatment. Methods: Inflammation was induced in PGKs using IL-1β, and the impact of H. cordata extract pretreatment was assessed using quantitative real-time reverse transcription polymerase chain reaction, enzyme-linked immunosorbent assay, and immunoblotting. Results: H. cordata extract significantly downregulated the mRNA and protein expression levels of tumor necrosis factor-alpha, IL-8, and intercellular adhesion molecule-1 in IL-1β-stimulated PGKs without inducing cytotoxicity. Conclusions: These findings suggest that H. cordata holds promise as a preventive agent against periodontitis by attenuating inflammatory responses in gingival epithelial tissues. We believe that our findings will inform the development of prophylactic interventions to reduce periodontitis risk in patients undergoing orthodontic therapy. Full article
(This article belongs to the Special Issue Dentistry in the 21st Century: Challenges and Opportunities)
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17 pages, 1428 KiB  
Article
The Influence of Bitumen Nature and Production Conditions on the Mechanical and Chemical Properties of Asphalt Mixtures Containing Reclaimed Asphalt Pavement
by Emiliano Prosperi, Edoardo Bocci and Giovanni Marchegiani
Materials 2025, 18(15), 3713; https://doi.org/10.3390/ma18153713 - 7 Aug 2025
Abstract
Several variables influence the performance of hot asphalt mixtures including reclaimed asphalt pavement (RAP). Among these, the virgin bitumen’s origin, the mix production temperature and the time the mix is kept at a high temperature between mixing and compaction play a fundamental role [...] Read more.
Several variables influence the performance of hot asphalt mixtures including reclaimed asphalt pavement (RAP). Among these, the virgin bitumen’s origin, the mix production temperature and the time the mix is kept at a high temperature between mixing and compaction play a fundamental role but are often neglected. This study aimed to quantify the negative effects associated with the improper choice of these variables. Therefore, their influence on the mechanical (indirect tensile stiffness modulus and strength, Cracking Tolerance Index) and chemical (Fourier Transform Infra-Red spectroscopy) characteristics of asphalt mixtures containing 50% RA were investigated. In particular, two rejuvenators, two types of virgin bitumen (visbreaker and straight-run), two production temperatures (140 °C and 170 °C) and three conditioning times in the oven (30 min, 90 min and 180 min) were analyzed. The results showed interesting findings that allow us to recommend selecting the virgin bitumen type carefully and to avoid excessively stressing the binder during the production of the mix. Full article
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24 pages, 1967 KiB  
Article
Water Stress Promotes Secondary Sexual Dimorphism in Ecophysiological Traits of Papaya Seedlings
by Ingrid Trancoso, Guilherme A. R. de Souza, João Vitor Paravidini de Souza, Rosana Maria dos Santos Nani de Miranda, Diesily de Andrade Neves, Miroslava Rakocevic and Eliemar Campostrini
Plants 2025, 14(15), 2445; https://doi.org/10.3390/plants14152445 - 7 Aug 2025
Abstract
Plant genders could express different functional strategies to compensate for different reproductive costs, as females have an additional role in fruit and seed production. Secondary sexual dimorphism (SSD) expression is frequently greater under stress than under optimal growth conditions. The early gender identification [...] Read more.
Plant genders could express different functional strategies to compensate for different reproductive costs, as females have an additional role in fruit and seed production. Secondary sexual dimorphism (SSD) expression is frequently greater under stress than under optimal growth conditions. The early gender identification in papaya may help to reduce orchard costs because the most desirable fruit shape is formed by hermaphrodite plants. We hypothesized that (a) gender ecophysiological phenotyping can be an alternative to make gender segregations in papaya seedlings, and (b) such gender segregation will be more efficient after a short drought exposure than under adequate water conditions. To test such hypotheses, seedlings of two papaya varieties (‘Candy’ and ‘THB’) were exposed to two kind of treatments: (1) water shortage (WS) for 45 h, after which they were well watered, and (2) continuously well-watered (WW). Study assessed the ecophysiological responses, such as stomatal conductance (gs), SPAD index, optical reflectance indices, morphological traits, and biomass accumulation in females (F) and hermaphrodites (H). In WS treatment, the SSD was expressed in 14 of 18 traits investigated, while in WW treatment, the SSD was expressed only in 7 of 18 traits. As tools for SSD expression, gs and simple ratio pigment index (SRPI) must be measured on the first or second day after the imposed WS was interrupted, respectively, while the other parameters must be measured after a period of four days. In some traits, the SSD was expressed in only one variety, or the response of H and F plants were of opposite values for two varieties. The choice of the clearest responses of gender segregation in WS treatment will be greenness index, combination of normalized difference vegetation index (CNDVI), photochemical reflectance index (PRI), water band index (WBI), SRPI, leaf number, leaf dry mass, and leaf mass ratio. If the WW conditions are maintained for papaya seedling production, the recommendation in gender segregation will be the analysis of CNDVI, carotenoid reflectance index 2 (CRI2), WBI, and SRPI. The non-destructive optical leaf indices segregated papaya hermaphrodites from females under both water conditions and eventually could be adjusted for wide-scale platform evaluations, with planned space arrangements of seedlings, and sensor’s set. Full article
(This article belongs to the Section Horticultural Science and Ornamental Plants)
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18 pages, 3976 KiB  
Article
Impact of Salinity Stress on Antioxidant Enzyme Activity, Histopathology, and Gene Expression in the Hepatopancreas of the Oriental River Prawn, Macrobrachium nipponense
by Shubo Jin, Zhenghao Ye, Hongtuo Fu, Yiwei Xiong, Hui Qiao, Wenyi Zhang and Sufei Jiang
Animals 2025, 15(15), 2319; https://doi.org/10.3390/ani15152319 - 7 Aug 2025
Abstract
Macrobrachium nipponense represents a commercial decapod species that predominantly inhabits freshwater ecosystems or environments with low salinity. However, the species exhibits normal survival and reproductive capacity in natural aquatic habitats with salinity levels up to 10 parts per thousand (ppt). The present study [...] Read more.
Macrobrachium nipponense represents a commercial decapod species that predominantly inhabits freshwater ecosystems or environments with low salinity. However, the species exhibits normal survival and reproductive capacity in natural aquatic habitats with salinity levels up to 10 parts per thousand (ppt). The present study aimed to elucidate the molecular mechanisms underlying salinity acclimation in M. nipponense by investigating alterations in oxidative stress, morphological adaptations, and hepatopancreatic gene expression profiles following exposure to a salinity level of 10 ppt. The present study demonstrates that glutathione peroxidase and Na+/K+-ATPase play critical roles in mitigating oxidative stress induced by elevated salinity in M. nipponense. Furthermore, histological analysis revealed distinct pathological alterations in the hepatopancreas of M. nipponense following 7-day salinity exposure, including basement-membrane disruption, luminal expansion, vacuolization, and a marked reduction in storage cells. Transcriptomic profiling of M. nipponense hepatopancreas suggested coordinated activation of both immune (lysosome and protein processing in endoplasmic reticulum pathways) and energy (pyruvate metabolism, glycolysis/gluconeogenesis, and citrate cycle) metabolic processes during salinity acclimation in M. nipponense. Quantitative real-time PCR validation confirmed the reliability of RNA-seq data. This study provides molecular insights into the salinity adaptation mechanisms in M. nipponense, offering potential applications for improving cultivation practices in brackish water environments. Full article
(This article belongs to the Special Issue Developmental Genetics of Adaptation in Aquatic Animals)
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18 pages, 508 KiB  
Review
RNF213-Related Vasculopathy: An Entity with Diverse Phenotypic Expressions
by Takeshi Yoshimoto, Sho Okune, Shun Tanaka, Hiroshi Yamagami and Yuji Matsumaru
Genes 2025, 16(8), 939; https://doi.org/10.3390/genes16080939 - 7 Aug 2025
Abstract
Moyamoya disease (MMD) is primarily associated with genetic variants in RNF213. RNF213 p.R4810K (c.14429G>A, p.Arg4810Lys) is a founder variant predominantly found in East Asian populations and is strongly associated with MMD, a rare cerebrovascular condition characterized by progressive stenosis of intracranial arteries [...] Read more.
Moyamoya disease (MMD) is primarily associated with genetic variants in RNF213. RNF213 p.R4810K (c.14429G>A, p.Arg4810Lys) is a founder variant predominantly found in East Asian populations and is strongly associated with MMD, a rare cerebrovascular condition characterized by progressive stenosis of intracranial arteries and the development of abnormal collateral networks. Recent evidence suggests that RNF213 variants are also enriched in non-moyamoya intracranial arteriopathies, such as large-artery atherosclerotic stroke and intracranial arterial stenosis/occlusion (ICASO), particularly in east Asian individuals with early-onset or cryptogenic stroke. This expanded phenotypic spectrum, termed RNF213-related vasculopathy (RRV), represents a distinct pathogenic entity that may involve unique pathogenic processes separate from traditional atherosclerosis. In this review, we synthesize current genetic, clinical, radiological, and experimental findings that delineate the unique features of RRV. Patients with RRV typically exhibit a lower burden of traditional vascular risk factors, negative vascular remodeling in the absence of atheromatous plaques, and an increased propensity for disease progression. RNF213 variants may compromise vascular resilience by impairing adaptive responses to hemodynamic stress. Furthermore, emerging cellular and animal model data indicate that RNF213 influences angiogenesis, lipid metabolism, and stress responses, offering mechanistic insights into its role in maintaining vascular integrity. Recognizing RRV as a distinct clinical entity has important implications for diagnosis, risk stratification, and the development of genome-informed therapeutic strategies. Full article
(This article belongs to the Special Issue Genetic Research on Cerebrovascular Disease and Stroke)
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21 pages, 7477 KiB  
Article
Bidirectional Hypoxic Extracellular Vesicle Signaling Between Müller Glia and Retinal Pigment Epithelium Regulates Retinal Metabolism and Barrier Function
by Alaa M. Mansour, Mohamed S. Gad, Samar Habib and Khaled Elmasry
Biology 2025, 14(8), 1014; https://doi.org/10.3390/biology14081014 - 7 Aug 2025
Abstract
The retina is highly sensitive to oxygen and blood supply, and hypoxia plays a key role in retinal diseases such as diabetic retinopathy (DR) and age-related macular degeneration (AMD). Müller glial cells, which are essential for retinal homeostasis, respond to injury and hypoxia [...] Read more.
The retina is highly sensitive to oxygen and blood supply, and hypoxia plays a key role in retinal diseases such as diabetic retinopathy (DR) and age-related macular degeneration (AMD). Müller glial cells, which are essential for retinal homeostasis, respond to injury and hypoxia with reactive gliosis, characterized by the upregulation of the glial fibrillary acidic protein (GFAP) and vimentin, cellular hypertrophy, and extracellular matrix changes, which can impair retinal function and repair. The retinal pigment epithelium (RPE) supports photoreceptors, forms part of the blood–retinal barrier, and protects against oxidative stress; its dysfunction contributes to retinal degenerative diseases such as AMD, retinitis pigmentosa (RP), and Stargardt disease (SD). Extracellular vesicles (EVs) play a crucial role in intercellular communication, protein homeostasis, and immune modulation, and have emerged as promising diagnostic and therapeutic tools. Understanding the role of extracellular vesicles’ (EVs’) signaling machinery of glial cells and the retinal pigment epithelium (RPE) is critical for developing effective treatments for retinal degeneration. In this study, we investigated the bidirectional EV-mediated crosstalk between RPE and Müller cells under hypoxic conditions and its impact on cellular metabolism and retinal cell integrity. Our findings demonstrate that RPE-derived extracellular vesicles (RPE EVs) induce time-dependent metabolic reprogramming in Müller cells. Short-term exposure (24 h) promotes pathways supporting neurotransmitter cycling, calcium and mineral absorption, and glutamate metabolism, while prolonged exposure (72 h) shifts Müller cell metabolism toward enhanced mitochondrial function and ATP production. Conversely, Müller cell-derived EVs under hypoxia influenced RPE metabolic pathways, enhancing fatty acid metabolism, intracellular vesicular trafficking, and the biosynthesis of mitochondrial co-factors such as ubiquinone. Proteomic analysis revealed significant modulation of key regulatory proteins. In Müller cells, hypoxic RPE-EV exposure led to reduced expression of Dyskerin Pseudouridine Synthase 1 (DKc1), Eukaryotic Translation Termination Factor 1 (ETF1), and Protein Ser/Thr phosphatases (PPP2R1B), suggesting alterations in RNA processing, translational fidelity, and signaling. RPE cells exposed to hypoxic Müller cell EVs exhibited elevated Ribosome-binding protein 1 (RRBP1), RAC1/2, and Guanine Nucleotide-Binding Protein G(i) Subunit Alpha-1 (GNAI1), supporting enhanced endoplasmic reticulum (ER) function and cytoskeletal remodeling. Functional assays also revealed the compromised barrier integrity of the outer blood–retinal barrier (oBRB) under hypoxic co-culture conditions. These results underscore the adaptive but time-sensitive nature of retinal cell communication via EVs in response to hypoxia. Targeting this crosstalk may offer novel therapeutic strategies to preserve retinal structure and function in ischemic retinopathies. Full article
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26 pages, 2011 KiB  
Review
Substance Abuse and Cognitive Decline: The Critical Role of Tau Protein as a Potential Biomarker
by Liliana Rebolledo-Pérez, Jorge Hernández-Bello, Alicia Martínez-Ramos, Rolando Castañeda-Arellano, David Fernández-Quezada, Flavio Sandoval-García and Irene Guadalupe Aguilar-García
Int. J. Mol. Sci. 2025, 26(15), 7638; https://doi.org/10.3390/ijms26157638 - 7 Aug 2025
Abstract
Tau protein is essential for the structural stability of neurons, particularly through its role in microtubule assembly and axonal transport. However, when abnormally hyperphosphorylated or cleaved, Tau can aggregate into insoluble forms that disrupt neuronal function, contributing to the pathogenesis of neurodegenerative diseases [...] Read more.
Tau protein is essential for the structural stability of neurons, particularly through its role in microtubule assembly and axonal transport. However, when abnormally hyperphosphorylated or cleaved, Tau can aggregate into insoluble forms that disrupt neuronal function, contributing to the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease (AD). Emerging evidence suggests that similar Tau-related alterations may occur in individuals with chronic exposure to psychoactive substances. This review compiles experimental, clinical, and postmortem findings that collectively indicate a substance-specific influence on Tau dynamics. Alcohol and opioids, for instance, promote Tau hyperphosphorylation and fragmentation through the activation of kinases such as GSK-3β and CDK5, as well as proteases like caspase-3, leading to neuroinflammation and microglial activation. Stimulants and dissociatives disrupt insulin signaling, increase oxidative stress, and impair endosomal trafficking, all of which can exacerbate Tau pathology. In contrast, cannabinoids and psychedelics may exert protective effects by modulating kinase activity, reducing inflammation, or enhancing neuroplasticity. Psychedelic compounds such as psilocybin and harmine have been demonstrated to decrease Tau phosphorylation and facilitate cognitive restoration in animal models. Although the molecular mechanisms differ across substances, Tau consistently emerges as a convergent target altered in substance-related cognitive disorders. Understanding these pathways may provide not only mechanistic insights into drug-induced neurotoxicity but also identify Tau as a valuable biomarker and potential therapeutic target for the prevention or treatment of cognitive decline associated with substance use. Full article
(This article belongs to the Special Issue Neurobiological Mechanisms of Addictive Disorders)
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31 pages, 984 KiB  
Review
Anti-Obesity Mechanisms of Plant and Fungal Polysaccharides: The Impact of Structural Diversity
by Guihong Fang, Baolian Li, Li Zhu, Liqian Chen, Juan Xiao and Juncheng Chen
Biomolecules 2025, 15(8), 1140; https://doi.org/10.3390/biom15081140 - 7 Aug 2025
Abstract
Obesity, a multifactorial metabolic syndrome driven by genetic–epigenetic crosstalk and environmental determinants, manifests through pathological adipocyte hyperplasia and ectopic lipid deposition. With the limitations of conventional anti-obesity therapies, which are characterized by transient efficacy and adverse pharmacological profiles, the scientific community has intensified [...] Read more.
Obesity, a multifactorial metabolic syndrome driven by genetic–epigenetic crosstalk and environmental determinants, manifests through pathological adipocyte hyperplasia and ectopic lipid deposition. With the limitations of conventional anti-obesity therapies, which are characterized by transient efficacy and adverse pharmacological profiles, the scientific community has intensified efforts to develop plant and fungal polysaccharide therapeutic alternatives. These polysaccharide macromolecules have emerged as promising candidates because of their diverse biological activities and often act as natural prebiotics, exerting beneficial effects through multiple pathways. Plant and fungal polysaccharides can reduce blood glucose levels, alleviate inflammation and oxidative stress, modulate metabolic signaling pathways, inhibit nutrient absorption, and reshape gut microbial composition. These effects have been shown in cellular and animal models and are associated with mechanisms underlying obesity and related metabolic disorders. This review discusses the complexity of obesity and multifaceted role of plant and fungal polysaccharides in alleviating its symptoms and complications. Current knowledge on the anti-obesity properties of plant and fungal polysaccharides is also summarized. We highlight their regulatory effects, potential intervention pathways, and structure–function relationships, thereby providing novel insights into polysaccharide-based strategies for obesity management. Full article
(This article belongs to the Section Natural and Bio-derived Molecules)
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