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Keywords = temporal mediator stability

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36 pages, 3632 KB  
Article
Integrated Modeling of Maritime Accident Hotspots and Vessel Traffic Networks in High-Density Waterways: A Case Study of the Strait of Malacca
by Sien Chen, Xuzhe Cai, Jiao Qiao and Jian-Bo Yang
J. Mar. Sci. Eng. 2025, 13(11), 2052; https://doi.org/10.3390/jmse13112052 - 27 Oct 2025
Viewed by 322
Abstract
The Strait of Malacca faces persistent maritime safety challenges due to high vessel density and complex navigational conditions. Current risk assessment methods often lean towards treating static accident analysis and dynamic traffic modeling separately, although some nascent hybrid approaches exist. However, these hybrids [...] Read more.
The Strait of Malacca faces persistent maritime safety challenges due to high vessel density and complex navigational conditions. Current risk assessment methods often lean towards treating static accident analysis and dynamic traffic modeling separately, although some nascent hybrid approaches exist. However, these hybrids frequently lack the capacity for comprehensive, real-time factor integration. This study proposes an integrated framework coupling accident hotspot identification with vessel traffic network analysis. The framework combines trajectory clustering using improved DBSCAN with directional filters, Kernel Density Estimation (KDE) for accident hotspots, and Fuzzy Analytic Hierarchy Process (FAHP) for multi-factor risk evaluation, acknowledging its subjective and region-specific nature. The model was trained and tuned exclusively on the 2023 dataset (47 incidents), reserving the 2024 incidents (24 incidents) exclusively for independent, zero-information-leakage validation. Results demonstrate superior performance: Area Under the ROC Curve (AUC) improved by 0.14 (0.78 vs. 0.64; +22% relative to KDE-only), and Precision–Recall AUC (PR-AUC) improved by 0.16 (0.65 vs. 0.49); both p < 0.001. Crucially, all model tuning and parameter finalization (including DBSCAN/Fréchet, FAHP weights, and adaptive thresholds) relied solely on 2023 data, with the 2024 incidents reserved exclusively for independent temporal validation. The model captures 75.2% of reported incidents within 20% of the study area. Cross-validation confirms stability across all folds. The framework reveals accidents concentrate at network bottlenecks where traffic centrality exceeds 0.15 and accident density surpasses 0.6. Model-based associations suggest amplification through three pathways: environmental-mediated (34%), traffic convergence (34%), and historical persistence (23%). The integrated approach enables identification of both where and why maritime accidents cluster, providing practical applications for vessel traffic services, risk-aware navigation, and evidence-based safety regulation in congested waterways. Full article
(This article belongs to the Special Issue Recent Advances in Maritime Safety and Ship Collision Avoidance)
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15 pages, 1945 KB  
Article
Effect of Inoculation with Arbuscular Mycorrhizal Fungi (Rhizophagus irregularis BGC AH01) on the Soil Bacterial Community Assembly
by Xueli Wang, Xuemin Jing, Yan Wang, Youran Ma, Xiangyang Shu, Wei Fu, Shuping Xing, Weijia Liu, Qinxin Ye, Yalan Zhu, Ping Ren, Xin Zhang, Baodong Chen and Xia Wang
J. Fungi 2025, 11(10), 739; https://doi.org/10.3390/jof11100739 - 15 Oct 2025
Viewed by 499
Abstract
Soil bacterial communities are crucial drivers of nutrient cycling and ecosystem functioning; however, their temporal dynamics under arbuscular mycorrhizal (AM) fungi colonization remain insufficiently characterized. In this study, we used a non-destructive continuous sampling method and undertook a 90-day pot experiment to examine [...] Read more.
Soil bacterial communities are crucial drivers of nutrient cycling and ecosystem functioning; however, their temporal dynamics under arbuscular mycorrhizal (AM) fungi colonization remain insufficiently characterized. In this study, we used a non-destructive continuous sampling method and undertook a 90-day pot experiment to examine the process of shaping the bacterial community of hyphosphere soil. Following inoculation with AM fungi, we found an increase in the α-diversity index of the hyphosphere bacterial community. The community diversity and richness and the key bacterial taxa in the hyphosphere both gradually increased from 30 to 60 days and stabilized thereafter. Principal coordinated (PCoA) analysis and network analysis further confirmed these findings. Stabilized by 60 days post-inoculation, with deterministic processes dominating assembly in inoculated AM fungi soils, while stochastic processes prevailed in non-inoculated controls. Inoculation strengthened bacterial associations with available phosphorus, while making the key bacterial communities more responsive to multiple soil physicochemical properties (available P, CEC, N, and TOC). These findings provide critical insights into AM fungi mediation of soil microbiome dynamics, with the identified 60-day stabilization period offering a key temporal framework for understanding tripartite soil–AM fungi-bacteria interactions. Full article
(This article belongs to the Section Environmental and Ecological Interactions of Fungi)
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44 pages, 2405 KB  
Review
Plasma Membrane Epichaperome–Lipid Interface: Regulating Dynamics and Trafficking
by Haneef Ahmed Amissah, Ruslana Likhomanova, Gabriel Opoku, Tawfeek Ahmed Amissah, Zsolt Balogi, Zsolt Török, László Vigh, Stephanie E. Combs and Maxim Shevtsov
Cells 2025, 14(20), 1582; https://doi.org/10.3390/cells14201582 - 11 Oct 2025
Viewed by 1224
Abstract
The plasma membrane (PM) of eukaryotic cells plays a key role in the response to stress, acting as the first line of defense against environmental changes and protecting cells against intracellular perturbations. In this work, we explore how membrane-bound chaperones and membrane lipid [...] Read more.
The plasma membrane (PM) of eukaryotic cells plays a key role in the response to stress, acting as the first line of defense against environmental changes and protecting cells against intracellular perturbations. In this work, we explore how membrane-bound chaperones and membrane lipid domains work together to shape plasma membrane properties—a partnership we refer to as the “epichaperome–plasma membrane lipid axis.” This axis influences membrane fluidity, curvature, and domain organization, which in turn shapes the spatial and temporal modulation of signaling platforms and pathways essential for maintaining cellular integrity and homeostasis. Changes in PM fluidity can modulate the activity of ion channels, such as transient receptor potential (TRP) channels. These changes also affect processes such as endocytosis and mechanical signal transduction. The PM proteome undergoes rapid changes in response to membrane perturbations. Among these changes, the expression of heat shock proteins (HSPs) and their accumulation at the PM are essential mediators in regulating the physical state and functional properties of the membrane. Because of the pivotal role in stress adaptation, HSPs influence a wide range of cellular processes, which we grouped into three main categories: (i) mechanistic insights, differentiating in vitro (liposome, reconstituted membrane systems) and in vivo evidence for HSP-PM recruitment; (ii) functional outputs, spanning how ion channels are affected, changes in membrane fluidity, transcytosis, and the process of endocytosis and exosome release; and (iii) pathological effects, focusing on how rewired lipid–chaperone crosstalk in cancer drives resistance to drugs through altered membrane composition and signaling. Finally, we highlight Membrane Lipid Therapy (MLT) strategies, such as nanocarriers targeting specific PM compartments or small molecules that inhibit HSP recruitment, as promising approaches to modulate the functional stability of epichaperome assembly and membrane functionality, with profound implications for tumorigenesis. Full article
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10 pages, 891 KB  
Case Report
The Rehabilitation of a Patient with Acute Transverse Myelitis After HPV Vaccination—A Case Report
by Kornelia Kowalik, Piotr Niebrzydowski, Julia Kropidłowska, Alexandra Kvinen, Małgorzata Kusiak-Kaczmarek and Dominika Szalewska
Diseases 2025, 13(9), 281; https://doi.org/10.3390/diseases13090281 - 1 Sep 2025
Cited by 1 | Viewed by 890
Abstract
Acute transverse myelitis (ATM) is a rare, immune-mediated disorder of the spinal cord characterized by sensory, motor, and autonomic dysfunction. Although the human papillomavirus (HPV) vaccine is widely regarded as safe, isolated reports have suggested a potential temporal association with autoimmune neurological events, [...] Read more.
Acute transverse myelitis (ATM) is a rare, immune-mediated disorder of the spinal cord characterized by sensory, motor, and autonomic dysfunction. Although the human papillomavirus (HPV) vaccine is widely regarded as safe, isolated reports have suggested a potential temporal association with autoimmune neurological events, including ATM. We present a case of a 21-year-old woman who developed ATM two weeks following administration of the first dose of the HPV vaccine (Cervarix). The clinical presentation included rapid-onset paraparesis, sensory deficits, and sphincter dysfunction. An MRI revealed a T2-hyperintense lesion at the Th10–Th12 level. A cerebrospinal fluid analysis showed elevated protein levels. The patient underwent corticosteroid therapy, plasmapheresis, and IVIG, followed by a comprehensive, individualized rehabilitation program. This included balance and stability training, Redcord-based neuromuscular activation, electrostimulation, and pelvic floor therapy. Although no causal link between HPV vaccination and ATM has been established, this case emphasizes the importance of considering post-vaccinal autoimmune phenomena. More importantly, it illustrates the critical role of early, targeted rehabilitation—particularly pelvic floor re-education and neuromodulation—in improving outcomes in patients with significant motor and autonomic deficits. Full article
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24 pages, 11100 KB  
Article
ATRX Promotes Transcription Initiation of HSV-1 Immediate Early Genes During Early Lytic Infection
by Laura E. M. Dunn, Mackenzie M. Clark and Joel D. Baines
Viruses 2025, 17(9), 1169; https://doi.org/10.3390/v17091169 - 27 Aug 2025
Viewed by 1229
Abstract
Herpes simplex virus 1 (HSV-1) transcribes its genome using host RNA polymerase II (Pol II) in a temporally regulated cascade. We previously proposed a model of Transient Immediate Early gene Mediated Repression (TIEMR), in which early repression of immediate early (IE) genes is [...] Read more.
Herpes simplex virus 1 (HSV-1) transcribes its genome using host RNA polymerase II (Pol II) in a temporally regulated cascade. We previously proposed a model of Transient Immediate Early gene Mediated Repression (TIEMR), in which early repression of immediate early (IE) genes is relieved to initiate the cascade. Given the rapid association of promyelocytic leukaemia nuclear body (PML-NB) components with incoming HSV-1 genomes, we sought to investigate their roles in TIEMR. siRNA knockdown revealed that depletion of ATRX, but not PML, significantly reduced nascent transcription from viral IE promoters at 1.5 hpi, while DAXX knockdown increased transcription. ChIP-Seq showed ATRX localizes to both transcriptionally active IE genes and restricted non-IE genes, suggesting diverse functions. Notably, ATRX occupancy at active IE promoters correlated with G-quadruplex (G4) motifs, and G4 stabilization mimicked ATRX knockdown by reducing transcription initiation. These findings uncover a previously unrecognized pro-transcriptional role for ATRX at IE genes and suggest that ATRX promotes escape from TIEMR by facilitating transcription initiation and preventing G4-mediated repression. Full article
(This article belongs to the Special Issue Herpesvirus Transcriptional Control)
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44 pages, 1023 KB  
Review
Systemic Neurodegeneration and Brain Aging: Multi-Omics Disintegration, Proteostatic Collapse, and Network Failure Across the CNS
by Victor Voicu, Corneliu Toader, Matei Șerban, Răzvan-Adrian Covache-Busuioc and Alexandru Vlad Ciurea
Biomedicines 2025, 13(8), 2025; https://doi.org/10.3390/biomedicines13082025 - 20 Aug 2025
Cited by 3 | Viewed by 3209
Abstract
Neurodegeneration is increasingly recognized not as a linear trajectory of protein accumulation, but as a multidimensional collapse of biological organization—spanning intracellular signaling, transcriptional identity, proteostatic integrity, organelle communication, and network-level computation. This review intends to synthesize emerging frameworks that reposition neurodegenerative diseases (ND) [...] Read more.
Neurodegeneration is increasingly recognized not as a linear trajectory of protein accumulation, but as a multidimensional collapse of biological organization—spanning intracellular signaling, transcriptional identity, proteostatic integrity, organelle communication, and network-level computation. This review intends to synthesize emerging frameworks that reposition neurodegenerative diseases (ND) as progressive breakdowns of interpretive cellular logic, rather than mere terminal consequences of protein aggregation or synaptic attrition. The discussion aims to provide a detailed mapping of how critical signaling pathways—including PI3K–AKT–mTOR, MAPK, Wnt/β-catenin, and integrated stress response cascades—undergo spatial and temporal disintegration. Special attention is directed toward the roles of RNA-binding proteins (e.g., TDP-43, FUS, ELAVL2), m6A epitranscriptomic modifiers (METTL3, YTHDF1, IGF2BP1), and non-canonical post-translational modifications (SUMOylation, crotonylation) in disrupting translation fidelity, proteostasis, and subcellular targeting. At the organelle level, the review seeks to highlight how the failure of ribosome-associated quality control (RQC), autophagosome–lysosome fusion machinery (STX17, SNAP29), and mitochondrial import/export systems (TIM/TOM complexes) generates cumulative stress and impairs neuronal triage. These dysfunctions are compounded by mitochondrial protease overload (LONP1, CLPP), UPR maladaptation, and phase-transitioned stress granules that sequester nucleocytoplasmic transport proteins and ribosomal subunits, especially in ALS and FTD contexts. Synaptic disassembly is treated not only as a downstream event, but as an early tipping point, driven by impaired PSD scaffolding, aberrant endosomal recycling (Rab5, Rab11), complement-mediated pruning (C1q/C3–CR3 axis), and excitatory–inhibitory imbalance linked to parvalbumin interneuron decay. Using insights from single-cell and spatial transcriptomics, the review illustrates how regional vulnerability to proteostatic and metabolic stress converges with signaling noise to produce entropic attractor collapse within core networks such as the DMN, SN, and FPCN. By framing neurodegeneration as an active loss of cellular and network “meaning-making”—a collapse of coordinated signal interpretation, triage prioritization, and adaptive response—the review aims to support a more integrative conceptual model. In this context, therapeutic direction may shift from damage containment toward restoring high-dimensional neuronal agency, via strategies that include the following elements: reprogrammable proteome-targeting agents (e.g., PROTACs), engineered autophagy adaptors, CRISPR-based BDNF enhancers, mitochondrial gatekeeping stabilizers, and glial-exosome neuroengineering. This synthesis intends to offer a translational scaffold for viewing neurodegeneration as not only a disorder of accumulation but as a systems-level failure of cellular reasoning—a perspective that may inform future efforts in resilience-based intervention and precision neurorestoration. Full article
(This article belongs to the Special Issue Cell Signaling and Molecular Regulation in Neurodegenerative Disease)
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31 pages, 2141 KB  
Review
Climate, Soil, and Microbes: Interactions Shaping Organic Matter Decomposition in Croplands
by Muhammad Tahir Khan, Skaidrė Supronienė, Renata Žvirdauskienė and Jūratė Aleinikovienė
Agronomy 2025, 15(8), 1928; https://doi.org/10.3390/agronomy15081928 - 10 Aug 2025
Cited by 4 | Viewed by 2498
Abstract
Soil organic matter (SOM) decomposition is a critical biogeochemical process that regulates the carbon cycle, nutrient availability, and agricultural sustainability of cropland systems. Recent progress in multi-omics and microbial network analyses has provided us with a better understanding of the decomposition process at [...] Read more.
Soil organic matter (SOM) decomposition is a critical biogeochemical process that regulates the carbon cycle, nutrient availability, and agricultural sustainability of cropland systems. Recent progress in multi-omics and microbial network analyses has provided us with a better understanding of the decomposition process at different spatial and temporal scales. Climate factors, such as temperature and seasonal variations in moisture, play a critical role in microbial activity and enzyme kinetics, and their impacts are mediated by soil physical and chemical properties. Soil mineralogy, texture, and structure create different soil microenvironments, affecting the connectivity of microbial habitats, substrate availability, and protective mechanisms of organic matter. Moreover, different microbial groups (bacteria, fungi, and archaea) contribute differently to the decomposition of plant residues and SOM. Recent findings suggest the paramount importance of living microbial communities as well as necromass in forming soil organic carbon pools. Microbial functional traits such as carbon use efficiency, dormancy, and stress tolerance are essential drivers of decomposition in the soil. Furthermore, the role of microbial necromass, alongside live microbial communities, in the formation and stabilization of persistent SOM fractions is increasingly recognized. Based on this microbial perspective, feedback between local microbial processes and landscape-scale carbon dynamics illustrates the cross-scale interactions that drive agricultural productivity and regulate soil climate. Understanding these dynamics also highlights the potential for incorporating microbial functioning into sustainable agricultural management, which offers promising avenues for increasing carbon sequestration without jeopardizing soil nutrient cycling. This review explores current developments in intricate relationships between climate, soil characteristics, and microbial communities determining SOM decomposition, serving as a promising resource in organic fertilization and regenerative agriculture. Specifically, we examine how nutrient availability, pH, and oxygen levels critically influence these microbial contributions to SOM stability and turnover. Full article
(This article belongs to the Section Farming Sustainability)
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20 pages, 14292 KB  
Article
Non-Fourier Thermoelastic Peridynamic Modeling of Cracked Thin Films Under Short-Pulse Laser Irradiation
by Tao Wu, Tao Xue, Yazhou Wang and Kumar Tamma
Modelling 2025, 6(3), 68; https://doi.org/10.3390/modelling6030068 - 15 Jul 2025
Cited by 1 | Viewed by 2582
Abstract
In this paper, we develop a peridynamic computational framework to analyze thermomechanical interactions in fractured thin films subjected to ultrashort-pulsed laser excitation, employing nonlocal discrete material point discretization to eliminate mesh dependency artifacts. The generalized Cattaneo–Fourier thermal flux formulation uncovers contrasting dynamic responses: [...] Read more.
In this paper, we develop a peridynamic computational framework to analyze thermomechanical interactions in fractured thin films subjected to ultrashort-pulsed laser excitation, employing nonlocal discrete material point discretization to eliminate mesh dependency artifacts. The generalized Cattaneo–Fourier thermal flux formulation uncovers contrasting dynamic responses: hyperbolic heat propagation (FT=0) generates intensified temperature localization and elevates transient crack-tip stress concentrations relative to classical Fourier diffusion (FT=1). A GSSSS (Generalized Single Step Single Solve) i-Integration temporal scheme achieves oscillation-free numerical solutions across picosecond-level laser–matter interactions, effectively resolving steep thermal fronts through adaptive stabilization. These findings underscore hyperbolic conduction’s essential influence on stress-mediated fracture evolution during ultrafast laser processing, providing critical guidelines for thermal management in micro-/nano-electromechanical systems. Full article
(This article belongs to the Special Issue The 5th Anniversary of Modelling)
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25 pages, 1560 KB  
Review
Integrating Hyperspectral Imaging, Plant Functional Diversity, and Soil-Lithology to Uncover Mountainscape Disturbance Dynamics Induced by Landsliding
by Ana Kilgore and Carla Restrepo
Remote Sens. 2025, 17(11), 1806; https://doi.org/10.3390/rs17111806 - 22 May 2025
Cited by 1 | Viewed by 1655
Abstract
The global biodiversity crisis has emphasized the unique contribution of functional diversity to ecosystem function, stability, and resilience. In this regard, the increasing availability of remotely sensed data together with the development of new sensors and approaches has the potential to improve our [...] Read more.
The global biodiversity crisis has emphasized the unique contribution of functional diversity to ecosystem function, stability, and resilience. In this regard, the increasing availability of remotely sensed data together with the development of new sensors and approaches has the potential to improve our ability to quantify and monitor ecosystem traits and functions at unprecedented spatial, temporal, and spectral scales. In particular, air- and spaceborne hyperspectral data are making possible the measurement of plant-level functional traits to investigate ecosystem function and functional diversity in novel ways. In this review, we posit that these developments, together with similar ones on soils and lithologies, can help us understand relationships between functional diversity, ecosystem processes, and landsliding, and more broadly the disturbance dynamics of mountainscapes. Acknowledging the challenges associated with mountainous regions, this review aims to (1) synthesize broad established methods to retrieve functional traits from remotely sensed data, (2) summarize approaches to characterize functional diversity derived from remotely sensed functional traits, (3) review work addressing functional diversity, ecosystem functioning, and dynamics of mountainscapes, and (4) elaborate on how these methods and approaches can help develop a needed “ecosystem-centered” view of landslides. This view acknowledges that ecosystem diversity influences both slope resistance and susceptibility to failure and landslide recovery, that interactions between ecosystem and geomorphic processes drive the dynamics of mountainscapes mediated by landslides at multiple scales, and that the variability in landslide size represents a source of diversity while also playing a fundamental role in landslide recovery and landscape memory. Full article
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23 pages, 16916 KB  
Article
High-Temporal-Resolution Modeling of Land Surface Temperature and Groundwater Level Impacts on Shallow Aquifer Thermal Regimes
by Yulong Wei, De Wang, Fubin Luo, Xinpeng Tian, Xiaoli Bi, Zixiang Zhou and Wenjing Hu
Water 2025, 17(7), 1107; https://doi.org/10.3390/w17071107 - 7 Apr 2025
Viewed by 995
Abstract
Climate change is recognized to directly and indirectly affect groundwater systems. However, the mechanisms through which climate change influences groundwater temperature (GWT), particularly how seasonal variations mediate these effects, remain incompletely understood. This study utilized high-temporal-resolution (hourly) data by parameterizing groundwater levels (GWLs) [...] Read more.
Climate change is recognized to directly and indirectly affect groundwater systems. However, the mechanisms through which climate change influences groundwater temperature (GWT), particularly how seasonal variations mediate these effects, remain incompletely understood. This study utilized high-temporal-resolution (hourly) data by parameterizing groundwater levels (GWLs) and instantaneous temperature gradients to model GWT, establishing the Seasonally Adaptive Thermal Diffusivity Numerical Model (SATDNM). Through scenario analyses, the potential impacts of climate change on GWT were simulated. The results indicate that our model captures seasonal and interannual variations more precisely compared to classical models, revealing the seasonal influence of GWLs and instantaneous temperature gradients on subsurface thermal properties such as advents and wet-season rainfall, as well as long-term surface warming and GWL decline. The key findings include (1) a greater sensitivity to extreme heat during winter, (2) wet-season rainfall potentially stabilizing groundwater temperature, and (3) declining GWLs amplifying GWT fluctuations. By 2100, the projected mean GWT increases under four Shared Socioeconomic Pathway (SSP) scenarios are approximately 0.51 °C (SSP1-2.6), 1.25 °C (SSP2-4.5), 2.19 °C (SSP3-7.0), and 2.87 °C (SSP5-8.5). Under four scenarios of annual GWL decline rates, GWT fluctuations increased by approximately 0.094 °C (0.01 m/year), 0.27 °C (0.02 m/year), 0.44 °C (0.03 m/year), and 0.67 °C (0.04 m/year), respectively. These findings enhance the mechanistic understanding of climate–groundwater thermal interactions and provide new insights for adaptive groundwater management under climate change. Full article
(This article belongs to the Section Water and Climate Change)
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18 pages, 3385 KB  
Article
Impact of Rural Ageing on Non-Grain Agricultural Production in China: An Analysis Based on Food Security Strategy
by Yuanzhi Guo and Yuan Tian
Foods 2025, 14(7), 1214; https://doi.org/10.3390/foods14071214 - 30 Mar 2025
Viewed by 690
Abstract
The increasing population ageing in rural China has had a far-reaching impact on agricultural production structures. However, most of the existing studies on the impact of rural ageing on NGAP are based on a micro-farmer perspective and lack consideration under macro policies. This [...] Read more.
The increasing population ageing in rural China has had a far-reaching impact on agricultural production structures. However, most of the existing studies on the impact of rural ageing on NGAP are based on a micro-farmer perspective and lack consideration under macro policies. This study analyses the impact of rural ageing on NGAP within the framework of food security strategy and examines this relationship using provincial panel data based on revealing the spatial-temporal characteristics of the two. The results show that the ageing level in rural China from 2005 to 2021 exhibited a rapidly rising trend and an unbalanced distribution pattern with decreasing spatial agglomeration, while the evolution of NGAP followed an upward and then downward trend, with an increasing degree of spatial agglomeration. Under the food security strategy, rural ageing has a significant dampening effect on NGAP, which mainly stems from the partial mediating roles of the increase in the area of farmland per labourer and agricultural-related fiscal investment. In light of the future trend of population ageing in rural China, targeted measures are needed to stabilize grain production and guarantee national food security. Full article
(This article belongs to the Section Food Security and Sustainability)
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11 pages, 2270 KB  
Article
Effects of Temperature and Time on the Denaturation of Transforming Growth Factor Beta-1 and Cytokines from Bovine Platelet-Rich Gel Supernatants
by Jorge U. Carmona and Catalina López
Gels 2024, 10(9), 583; https://doi.org/10.3390/gels10090583 - 11 Sep 2024
Viewed by 1973
Abstract
There is a lack of information about transforming growth factor beta-1 (TGF-β1) and cytokines contained in pure platelet-rich plasma (P-PRP) and release from pure-platelet-rich gel supernatants (P-PRGS) might be affected by the temperature and time factors; P-PRP from 6 heifers was [...] Read more.
There is a lack of information about transforming growth factor beta-1 (TGF-β1) and cytokines contained in pure platelet-rich plasma (P-PRP) and release from pure-platelet-rich gel supernatants (P-PRGS) might be affected by the temperature and time factors; P-PRP from 6 heifers was activated with calcium gluconate. Thereafter, P-PRG and their supernatants (P-PRGS) were maintained at −80, −20, 4, 21, and 37 °C and collected at 3, 6, 12, 24, 48, 96, 144, 192, 240, and 280 h for subsequent determination of TGF-β1, tumor necrosis factor alfa (TNF-α), interleukin (IL)-2, and IL-6; TGF-β1 concentrations were significantly (p < 0.05) higher in PRGS maintained at 21 and 37 °C when compared to PRGS maintained at 4, −20, and −80 °C; PRGS TNF-α concentrations were not influenced by temperature and time factors. However, PRGS maintained at 4 °C showed significantly (p < 0.05) higher concentrations when compared to PRGS maintained at −20, and −80 °C at 144, and 192 h. IL-6 concentrations were significantly (p < 0.05) higher in PRGS stored at −20, and −80 over the first 48 h and at 10 days when compared to PRGS stored at 4, 21, and 37 °C. These results could suggest that P-PRP/P-PRGS could be maintained and well preserved for at least 12 days at room temperature for clinical use in bovine therapeutic massive protocols. Full article
(This article belongs to the Special Issue Synthesis, Characterization and Pharmaceutical Applications of Gels)
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17 pages, 2658 KB  
Communication
Effect of Levetiracetam on Oxidant–Antioxidant Activity during Long-Term Temporal Lobe Epilepsy in Rats
by Iván Ignacio-Mejía, Itzel Jatziri Contreras-García, Luz Adriana Pichardo-Macías, Mercedes Edna García-Cruz, Blanca Alcira Ramírez Mendiola, Cindy Bandala, Omar Noel Medina-Campos, José Pedraza-Chaverri, Noemí Cárdenas-Rodríguez and Julieta Griselda Mendoza-Torreblanca
Int. J. Mol. Sci. 2024, 25(17), 9313; https://doi.org/10.3390/ijms25179313 - 28 Aug 2024
Cited by 1 | Viewed by 1779
Abstract
Epilepsy is a disorder characterized by a predisposition to generate seizures. Levetiracetam (LEV) is an antiseizure drug that has demonstrated oxidant–antioxidant effects during the early stages of epilepsy in several animal models. However, the effect of LEV on oxidant–antioxidant activity during long-term epilepsy [...] Read more.
Epilepsy is a disorder characterized by a predisposition to generate seizures. Levetiracetam (LEV) is an antiseizure drug that has demonstrated oxidant–antioxidant effects during the early stages of epilepsy in several animal models. However, the effect of LEV on oxidant–antioxidant activity during long-term epilepsy has not been studied. Therefore, the objective of the present study was to determine the effects of LEV on the concentrations of five antioxidant enzymes and on the levels of four oxidant stress markers in the hippocampus of rats with temporal lobe epilepsy at 5.7 months after status epilepticus (SE). The results revealed that superoxide dismutase (SOD) activity was significantly greater in the epileptic group (EPI) than in the control (CTRL), CTRL + LEV and EPI + LEV groups. No significant differences were found among the groups’ oxidant markers. However, the ratios of SOD/hydrogen peroxide (H2O2), SOD/glutathione peroxidase (GPx) and SOD/GPx + catalase (CAT) were greater in the EPI group than in the CTRL and EPI + LEV groups. Additionally, there was a positive correlation between SOD activity and GPx activity in the EPI + LEV group. LEV-mediated modulation of the antioxidant system appears to be time dependent; at 5.7 months after SE, the role of LEV may be as a stabilizer of the redox state. Full article
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18 pages, 2000 KB  
Article
GSK3α Regulates Temporally Dynamic Changes in Ribosomal Proteins upon Amino Acid Starvation in Cancer Cells
by Lorent Loxha, Nurul Khalida Ibrahim, Anna Sophie Stasche, Büsra Cinar, Tim Dolgner, Julia Niessen, Sabine Schreek, Beate Fehlhaber, Michael Forster, Martin Stanulla and Laura Hinze
Int. J. Mol. Sci. 2023, 24(17), 13260; https://doi.org/10.3390/ijms241713260 - 26 Aug 2023
Cited by 4 | Viewed by 2785
Abstract
Amino acid availability is crucial for cancer cells’ survivability. Leukemia and colorectal cancer cells have been shown to resist asparagine depletion by utilizing GSK3-dependent proteasomal degradation, termed the Wnt-dependent stabilization of proteins (Wnt/STOP), to replenish their amino acid pool. The inhibition of GSK3α [...] Read more.
Amino acid availability is crucial for cancer cells’ survivability. Leukemia and colorectal cancer cells have been shown to resist asparagine depletion by utilizing GSK3-dependent proteasomal degradation, termed the Wnt-dependent stabilization of proteins (Wnt/STOP), to replenish their amino acid pool. The inhibition of GSK3α halts the sourcing of amino acids, which subsequently leads to cancer cell vulnerability toward asparaginase therapy. However, resistance toward GSK3α-mediated protein breakdown can occur, whose underlying mechanism is poorly understood. Here, we set out to define the mechanisms driving dependence toward this degradation machinery upon asparagine starvation in cancer cells. We show the independence of known stress response pathways including the integrated stress response mediated with GCN2. Additionally, we demonstrate the independence of changes in cell cycle progression and expression levels of the asparagine-synthesizing enzyme ASNS. Instead, RNA sequencing revealed that GSK3α inhibition and asparagine starvation leads to the temporally dynamic downregulation of distinct ribosomal proteins, which have been shown to display anti-proliferative functions. Using a CRISPR/Cas9 viability screen, we demonstrate that the downregulation of these specific ribosomal proteins can rescue cell death upon GSK3α inhibition and asparagine starvation. Thus, our findings suggest the vital role of the previously unrecognized regulation of ribosomal proteins in bridging GSK3α activity and tolerance of asparagine starvation. Full article
(This article belongs to the Special Issue GSK3 as a Master Regulator of Cellular Processes)
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22 pages, 1779 KB  
Review
RNA-Binding Proteins in Bladder Cancer
by Yuanhui Gao, Hui Cao, Denggao Huang, Linlin Zheng, Zhenyu Nie and Shufang Zhang
Cancers 2023, 15(4), 1150; https://doi.org/10.3390/cancers15041150 - 10 Feb 2023
Cited by 7 | Viewed by 3395
Abstract
RNA-binding proteins (RBPs) are key regulators of transcription and translation, with highly dynamic spatio-temporal regulation. They are usually involved in the regulation of RNA splicing, polyadenylation, and mRNA stability and mediate processes such as mRNA localization and translation, thereby affecting the RNA life [...] Read more.
RNA-binding proteins (RBPs) are key regulators of transcription and translation, with highly dynamic spatio-temporal regulation. They are usually involved in the regulation of RNA splicing, polyadenylation, and mRNA stability and mediate processes such as mRNA localization and translation, thereby affecting the RNA life cycle and causing the production of abnormal protein phenotypes that lead to tumorigenesis and development. Accumulating evidence supports that RBPs play critical roles in vital life processes, such as bladder cancer initiation, progression, metastasis, and drug resistance. Uncovering the regulatory mechanisms of RBPs in bladder cancer is aimed at addressing the occurrence and progression of bladder cancer and finding new therapies for cancer treatment. This article reviews the effects and mechanisms of several RBPs on bladder cancer and summarizes the different types of RBPs involved in the progression of bladder cancer and the potential molecular mechanisms by which they are regulated, with a view to providing information for basic and clinical researchers. Full article
(This article belongs to the Special Issue The Role and Therapeutic Target Potential of RBPs in Cancer)
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