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18 pages, 795 KiB  
Article
The Golden Year? Early Intervention Yields Superior Outcomes in Chronic Pelvic Pain with Pudendal Neuralgia: A Comparative Analysis of Early vs. Delayed Treatment
by Alexandru Ciudin, Albert Carrion, Rosa Regue, Alfredo Rodriguez, Eduardo Garcia-Cruz, Diana Finkelstein, Claudia Mercader, Cristian Toma, Razvan Popescu, Cristian Persu, Sergi Colom, Narcis Camps, Ramon Serrate and María José Ribal
Life 2025, 15(3), 376; https://doi.org/10.3390/life15030376 (registering DOI) - 27 Feb 2025
Abstract
Background: Chronic pelvic pain (CPP) associated with pudendal neuralgia (PN) significantly impacts quality of life (QoL). Pudendal nerve infiltration is a recognized treatment, but the optimal timing of intervention remains unclear. Methods: This prospective study included 81 patients diagnosed with PN and treated [...] Read more.
Background: Chronic pelvic pain (CPP) associated with pudendal neuralgia (PN) significantly impacts quality of life (QoL). Pudendal nerve infiltration is a recognized treatment, but the optimal timing of intervention remains unclear. Methods: This prospective study included 81 patients diagnosed with PN and treated with pudendal nerve infiltrations. Outcomes were assessed using the Visual Analog Scale (VAS), Spanish Pain Questionnaire (CDE–McGill), and the SF-12 health survey. Significant improvement was defined as a VAS reduction > 4 points and a QoL increase > 15 points. An ROC curve analysis identified a 13-month time-to-treatment threshold (sensitivity 78%, specificity 72%), categorizing patients into early (n = 27) and delayed treatment groups (n = 54). Results: The early treatment group showed significantly greater reductions in VAS scores (5.4 vs. 3.4 points, p < 0.01) and QoL improvements (18 vs. 8 points, p < 0.01) compared to the delayed group. Early intervention reduced reinfiltration rates (10% vs. 35%, p < 0.05) and decreased medication use, with 81% discontinuing gabapentin compared to 41% in the delayed group. Similar trends were observed for tryptizol (44% vs. 35%) and tramadol (74% vs. 30%). Multivariate analysis confirmed time to treatment as the strongest predictor of outcomes, with each additional month delaying treatment associated with a 0.18-point increase in final VAS scores (p < 0.001). Delayed treatment was linked to higher final doses of gabapentin (p = 0.01), dexketoprofen (p < 0.001), and tramadol (p = 0.012). Minimal complications were reported (15%, Clavien I). Conclusions: Early intervention in PN significantly improves pain, QoL, and reduces reinfiltration and medication reliance, supporting timely treatment for optimal outcomes. Full article
(This article belongs to the Special Issue Innovative Technologies in Pain Management)
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15 pages, 887 KiB  
Article
Natural Appetite Control: Food-Derived Aromas as Appetite Decreasing Agents—A Proof-of-Concept Study
by Michaela Godyla-Jabłoński, Natalia Pachura, Marta Klemens, Julia Wolska and Jacek Łyczko
Nutrients 2025, 17(5), 819; https://doi.org/10.3390/nu17050819 (registering DOI) - 27 Feb 2025
Abstract
Background and Objective: The global population is struggling with significant health challenges, among which overweight and obesity stand out. Currently, 61% of adults and 7.5% of children and adolescents are affected, underscoring the urgent need for effective solutions. This study evaluated appetite-reducing prototypes [...] Read more.
Background and Objective: The global population is struggling with significant health challenges, among which overweight and obesity stand out. Currently, 61% of adults and 7.5% of children and adolescents are affected, underscoring the urgent need for effective solutions. This study evaluated appetite-reducing prototypes related with food products, focusing on their ability to influence appetite through the sense of smell. The objective was to determine the effectiveness of these prototypes and identify the most promising candidates for further research. Methods: A questionnaire-based consumer survey was performed for six appetite-reducing agents. Forty-five participants with elevated body mass index values (BMI ≥ 25) were asked to verify the samples in terms of aroma intensity, pleasure, and potential for appetite reduction. Also, qualitative parameters such as the identification of the samples’ food associations was performed within the questionnaire. The questionnaire results were further compared with headspace solid-phase microextraction (HS-SPME Arrow) analysis results to identify volatile organic compounds associated with appetite-reducing properties. Results: The proof-of-concept study revealed that prototypes with unpleasant and irritating aromas demonstrated the highest appetite-reducing potential, scoring approximately 24 out of 35 points. Conversely, prototypes with pleasant, dessert-like aromas showed lower effectiveness, scoring between 14 and 18 points. Conclusions: By linking consumer perceptions to chemical analyses, we identified effective prototypes for further investigation, including studies measuring actual food intake. These findings contribute to developing innovative, non-invasive strategies to address overweight and obesity, offering a new dimension to appetite control through sensory modulation. Full article
(This article belongs to the Section Nutrition and Obesity)
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19 pages, 3546 KiB  
Article
A Comparative Assessment of Reynolds Averaged Navier–Stokes and Large-Eddy Simulation Models: Choosing the Best for Pool-Type Fishway Flow Simulations
by Ana L. Quaresma, Filipe Romão and António N. Pinheiro
Water 2025, 17(5), 686; https://doi.org/10.3390/w17050686 (registering DOI) - 27 Feb 2025
Abstract
Fishways are an important solution for mitigating the ecological impacts of river barriers, with their hydrodynamics playing a key role in their effectiveness. Computational fluid dynamics (CFD) is now one of the main tools to predict and characterize flow hydrodynamics, but choosing the [...] Read more.
Fishways are an important solution for mitigating the ecological impacts of river barriers, with their hydrodynamics playing a key role in their effectiveness. Computational fluid dynamics (CFD) is now one of the main tools to predict and characterize flow hydrodynamics, but choosing the most suitable turbulence model is considered one of its main challenges. Although substantial research has been carried out on vertical slot fishways, where the flow is predominantly two-dimensional, studies on pool-type fishways with bottom orifices remain scarce. In this study, three Reynolds averaged Navier–Stokes (RANS) turbulence models (the standard k-ε model, the renormalized group k-ε (RNG) model, and the standard k-ω model) and the large-eddy simulation (LES) model performances were compared to simulating the flow in a pool-type fishway with bottom orifices. ADV and PIV experimental data were used to assess model performance. While all the turbulence models accurately predicted the discharges and flow depths, the LES model outperformed the others in reproducing flow patterns, velocities, and turbulent kinetic energy. The RNG model also showed reasonable agreement with the experimental data. By contrast, the k-ε model delivered the poorest performance, failing to accurately predict the sizes of the recirculation zones and the locations of the recirculation axis and presenting the weakest agreement with the experimental observations. The value of the LES model in studying and characterizing fishway hydrodynamics, particularly concerning turbulence parameters, is highlighted. Full article
(This article belongs to the Special Issue Fishway Design and Development: New Challenges, Tools and Applications)
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22 pages, 4732 KiB  
Article
Rapid Impedance Measurement of Lithium-Ion Batteries Under Pulse Ex-Citation and Analysis of Impedance Characteristics of the Regularization Distributed Relaxation Time
by Haisen Chen, Jinghan Bai, Zhengpu Wu, Ziang Song, Bin Zuo, Chunxia Fu, Yunbin Zhang and Lujun Wang
Batteries 2025, 11(3), 91; https://doi.org/10.3390/batteries11030091 (registering DOI) - 27 Feb 2025
Abstract
To address the limitations of conventional electrochemical impedance spectroscopy (EIS) testing, we propose an efficient rapid EIS testing system. This system utilizes an AC pulse excitation signal combined with an “intelligent fast fourier transform (IFFT) optimization algorithm” to achieve rapid “one-to-many” impedance data [...] Read more.
To address the limitations of conventional electrochemical impedance spectroscopy (EIS) testing, we propose an efficient rapid EIS testing system. This system utilizes an AC pulse excitation signal combined with an “intelligent fast fourier transform (IFFT) optimization algorithm” to achieve rapid “one-to-many” impedance data measurements. This significantly enhances the speed, flexibility, and practicality of EIS testing. Furthermore, the conventional model-fitting approach for EIS data often struggles to resolve the issue of overlapping impedance arcs within a limited frequency range. To address this, the present study employs the Regularization Distributed Relaxation Time (RDRT) method to process EIS data obtained under AC pulse conditions. This approach avoids the workload and analytical uncertainties associated with assuming equivalent circuit models. Finally, the practical utility of the proposed testing system and the RDRT impedance analysis method is demonstrated through the estimation of battery state of health (SOH). In summary, the method proposed in this study not only addresses the issues associated with conventional EIS data acquisition and analysis but also broadens the methodologies and application scope of EIS impedance testing. This opens up new possibilities for its application in fields such as lithium-ion batteries (LIBs) energy storage. Full article
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21 pages, 7423 KiB  
Article
Cytosolic and Nucleosolic Calcium-Regulated Long Non-Coding RNAs and Their Target Protein-Coding Genes in Response to Hyperosmolarity and Salt Stresses in Arabidopsis thaliana
by Doudou Wang, Kaifeng Zheng, Wenfen Long, Liang Zhao, Wanjie Li, Xiuhua Xue and Shengcheng Han
Int. J. Mol. Sci. 2025, 26(5), 2086; https://doi.org/10.3390/ijms26052086 (registering DOI) - 27 Feb 2025
Abstract
Long non-coding RNAs (lncRNAs) are involved in plant biotic and abiotic stress responses, in which Ca2+ also plays a significant role. There is diversity in the regulation of different gene expressions by cytosolic Ca2+ ([Ca2+]cyt) and nucleosolic [...] Read more.
Long non-coding RNAs (lncRNAs) are involved in plant biotic and abiotic stress responses, in which Ca2+ also plays a significant role. There is diversity in the regulation of different gene expressions by cytosolic Ca2+ ([Ca2+]cyt) and nucleosolic Ca2+ ([Ca2+]nuc). However, no studies have yet explored the interrelationship between lncRNAs and calcium signaling, nor how calcium signaling regulates the expression of lncRNAs. Here, we use transgenic materials PV-NES and NLS-PV, which simulate [Ca2+]cyt- and [Ca2+]nuc-deficient mutants, respectively, and wild type (WT) materials in response to hyperosmolarity (250 mM sorbitol) or salt stresses (125 mM NaCl) at different time points to obtain RNA-seq data, respectively. Then, we proceed with the screening of lncRNAs, adding 688 new lncRNAs to the known Arabidopsis lncRNA database. Subsequently, through the analysis of differentially expressed lncRNA genes, it was found that cytosolic or nucleosolic calcium signals have distinct regulatory effects on differentially expressed lncRNAs (DElncRNAs) and differentially expressed protein-coding genes (DEPCGs) treated with high-concentration NaCl and sorbitol at different times. Furthermore, through weighted correlation network analysis (WGCNA), it is discovered that under hyperosmolarity and salt stresses, lncRNA-associated PCGs are related to the cell wall structure, the plasma membrane component, and osmotic substances through trans-regulation. In addition, by screening for cis-regulatory target PCGs of Ca2+-regulated lncRNAs related to osmotic stress, we obtain a series of lncRNA-PCG pairs related to water transport, cell wall components, and lateral root formation. Therefore, we expand the existing Arabidopsis lncRNA database and obtain a series of lncRNAs and PCGs regulated by [Ca2+]cyt or [Ca2+]nuc in response to salt and hyperosmolarity stress, providing a new perspective for subsequent research on lncRNAs. We also explore the trans- and cis-regulated target PCGs of lncRNAs regulated by calcium signaling, providing new insights for further studying salt stress and osmotic stress. Full article
(This article belongs to the Special Issue Advanced Plant Molecular Responses to Abiotic Stresses)
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18 pages, 5456 KiB  
Article
SJB2-043, a USP1 Inhibitor, Suppresses A549 Cell Proliferation, Migration, and EMT via Modulation of PI3K/AKT/mTOR, MAPK, and Wnt Signaling Pathways
by Lipeng Wu, Meng Yu, Huosheng Liang, Long Lin, Huajian Li, Guangyang Chen, Halimulati Muhetaer, Jingjing Li, Bo Wu, Xuejing Jia, Yuanye Dang, Guodong Zheng and Chuwen Li
Curr. Issues Mol. Biol. 2025, 47(3), 155; https://doi.org/10.3390/cimb47030155 (registering DOI) - 27 Feb 2025
Abstract
Objective: Non-small cell lung cancer (NSCLC) remains one of the most significant contributors to cancer-related mortality. This investigation explores the influence and underlying mechanisms of the USP1 inhibitor SJB2-043 on A549 cells, with the aim of advancing the development of anti-NSCLC therapeutics. Methods: [...] Read more.
Objective: Non-small cell lung cancer (NSCLC) remains one of the most significant contributors to cancer-related mortality. This investigation explores the influence and underlying mechanisms of the USP1 inhibitor SJB2-043 on A549 cells, with the aim of advancing the development of anti-NSCLC therapeutics. Methods: Publicly available databases were utilized to assess USP1 expression and its association with the progression of NSCLC. Gene expression variations were ascertained through RNA sequencing, followed by the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology pathway enrichment evaluations. Various doses of SJB2-043 were administered to A549 cells to evaluate its impact on cell multiplication, motility, apoptosis, and the cell cycle using CCK-8 assays, colony formation, wound healing, flow cytometry, and Western blotting (WB). Results: USP1 was found to be overexpressed in NSCLC specimens and linked to adverse prognosis. Treatment with SJB2-043 markedly inhibited A549 cell proliferation and migration, diminished clonogenic potential, and triggered apoptosis in a dose-dependent manner. Modifications in the cell cycle were observed, showing an elevated percentage of cells in the G2 phase while exhibiting a parallel decline in the G1 phase. WB examination demonstrated diminished protein levels of N-cadherin, CyclinB1, CDK1, C-myc, Bcl-2, p-ERK/ERK, p-p38/p38, p-JNK/JNK, p-AKT/AKT, and p-mTOR/mTOR, alongside an upregulation of E-cadherin, ZO-1, occludin, p53, Bax, p-β-catenin/β-catenin, and GSK3β. Conclusions: SJB2-043 exerts a suppressive effect on A549 cell proliferation, migration, and epithelial–mesenchymal transition while enhancing apoptosis. These cellular effects appear to be mediated through the inhibition of the MAPK, Wnt/β-catenin, and PI3K/AKT/mTOR signaling cascades, in addition to modulation of the cell cycle. Full article
(This article belongs to the Special Issue Linking Genomic Changes with Cancer in the NGS Era, 2nd Edition)
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17 pages, 1876 KiB  
Review
Advancements in the Esterification of Phytosterols Catalyzed by Immobilized Lipase
by Yuyang Zhang, Yan Yan, Zhiyuan Lin, Fanzhuo Kong, Xing Ni, Xue Zhang, Yani Zhao, Qiongya Lu and Bin Zou
Catalysts 2025, 15(3), 225; https://doi.org/10.3390/catal15030225 (registering DOI) - 27 Feb 2025
Abstract
Phytosterol exhibits cholesterol-lowering, cardiovascular-protecting, anti-inflammatory, and anticancer efficacies but has low bioavailability due to its high melting point and poor solubility. Esterification with fatty acids enhances liposolubility, improving absorption and utilization fivefold. Industrial production of phytosterol esters mainly relies on chemical synthesis, which [...] Read more.
Phytosterol exhibits cholesterol-lowering, cardiovascular-protecting, anti-inflammatory, and anticancer efficacies but has low bioavailability due to its high melting point and poor solubility. Esterification with fatty acids enhances liposolubility, improving absorption and utilization fivefold. Industrial production of phytosterol esters mainly relies on chemical synthesis, which faces challenges in separation, purification, and quality assurance due to side reactions. Enzymatic synthesis, featuring mild conditions, environmental friendliness, and high selectivity, has gained attention from academia and industry. Candida rugosa lipase (CRL) is widely utilized due to its high efficiency in catalyzing the esterification of phytosterol. Natural lipases are highly sensitive to changes in temperature and pH and are difficult to reuse in continuous cycles; however, certain immobilization techniques can improve their catalytic activity and stability. Furthermore, the application of immobilized lipases in the synthesis of phytosterol esters can be combined with ultrasonic treatment to enhance the efficiency of enzymatic catalysis. This paper reviews the research progress on the catalytic esterification of phytosterol by immobilized lipases, highlighting the current challenges and future research directions, thereby fostering further advancements in the field of preparing phytosterol esters through immobilized lipase catalysis. Full article
(This article belongs to the Special Issue Enzyme Catalysis: Innovations and Applications in Sustainable Chemistry)
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12 pages, 2054 KiB  
Article
Type I Interferon Modulates the Function of Ly6C High-Expressing Naïve CD8+ T Cells to Promote an Antitumor Response
by Hsin-Fang Tu, Julia Tao, Ming-Hung Hu, Darrell Fan, Ya-Chea Tsai, Tzyy-Choou Wu and Chien-Fu Hung
Vaccines 2025, 13(3), 246; https://doi.org/10.3390/vaccines13030246 (registering DOI) - 27 Feb 2025
Abstract
Background: Ly6C expression in naïve CD8+ T cells plays a crucial role in enhancing their effector activity, suggesting potential implications for cancer immunotherapy. This study investigates the functional impact of Ly6C expression on CD8+ T cells and explores albumin-conjugated IFNβ (Alb-IFNβ) as [...] Read more.
Background: Ly6C expression in naïve CD8+ T cells plays a crucial role in enhancing their effector activity, suggesting potential implications for cancer immunotherapy. This study investigates the functional impact of Ly6C expression on CD8+ T cells and explores albumin-conjugated IFNβ (Alb-IFNβ) as a strategy to modulate Ly6C expression and improve cancer vaccine efficacy. Methods: We analyzed the functional differences between Ly6C high-expressing (Ly6Chi) and Ly6C low-expressing (Ly6Clo) naïve CD8+ T cells in tumor suppression. To assess the role of type I interferon signaling, we administered Alb-IFNβ in C57BL/6J and IFNAR−/− mice and measured Ly6C expression in CD8+ T cells. The therapeutic potential of Alb-IFNβ was further evaluated in combination with a vaccinia virus encoding the HPV-16 E7 antigen (CRT-E7 vaccine) in a syngeneic TC-1 tumor model, assessing tumor growth, survival, and antigen-specific CD8+ T cell responses. Results: Naïve CD8+ T cells with elevated Ly6C expression exhibited enhanced tumor-suppressive capacity and required lower activation thresholds for effector function. Alb-IFNβ treatment selectively increased Ly6Chi naïve CD8+ T cells in C57BL/6J mice but not in IFNAR−/− mice, confirming type I interferon’s role in Ly6C regulation. Combining Alb-IFNβ pretreatment with the CRT-E7 vaccine significantly enhanced antigen-specific CD8+ T cell immunity, reducing tumor growth and prolonging survival in TC-1 tumor-bearing mice. Conclusions: Our findings suggest that Alb-IFNβ may enhance the antitumor activity of naïve CD8+ T cells by modulating Ly6C expression. Alb-IFNβ could potentially improve the efficacy of HPV vaccinia-based cancer vaccines, warranting further investigation as an adjuvant strategy in cancer immunotherapy. Full article
(This article belongs to the Special Issue Advances in Cancer Immunotherapy and Vaccines Research: 2nd Edition)
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16 pages, 15174 KiB  
Article
Numerical Study of Slamming Loads on Bow Flare of FPSO Model by Irregular Waves
by Young Jun Kim, Kyong-Hwan Kim, Bo Woo Nam, Sa Young Hong and Yoon-Jin Ha
J. Mar. Sci. Eng. 2025, 13(3), 455; https://doi.org/10.3390/jmse13030455 (registering DOI) - 27 Feb 2025
Abstract
Numerical studies were performed to investigate bow flare slamming loads under irregular waves. To estimate the slamming forces in the simulations, two time windows were selected based on existing experimental data. This study examined horizontal and vertical slamming phenomena by analyzing the relationship [...] Read more.
Numerical studies were performed to investigate bow flare slamming loads under irregular waves. To estimate the slamming forces in the simulations, two time windows were selected based on existing experimental data. This study examined horizontal and vertical slamming phenomena by analyzing the relationship between the motions and the resulting slamming forces. The horizontal and vertical slamming forces from the simulations were directly compared with the experimental data. Furthermore, the experiment and simulation results were compared against a representative classification code for additional validation. The findings provide insights into the physical phenomena of horizontal and vertical slamming and confirm that the formulation suggested by classification societies provides a reasonable estimation of slamming loads. Finally, the results emphasize that both horizontal and vertical slamming forces are significant design parameters. Full article
(This article belongs to the Section Ocean Engineering)
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19 pages, 1582 KiB  
Article
Designing Digital Escape Rooms with Generative AI in University Contexts: A Qualitative Study
by Paula Rodríguez-Rivera, José M. Rodríguez-Ferrer and Ana Manzano-León
Multimodal Technol. Interact. 2025, 9(3), 20; https://doi.org/10.3390/mti9030020 (registering DOI) - 27 Feb 2025
Abstract
The rapid evolution of technology in education highlights the need for methodologies that enhance student engagement and skill development. This study examines students’ perceptions of designing educational escape rooms using ICT tools and generative AI (GenAI) as a learning methodology. A total of [...] Read more.
The rapid evolution of technology in education highlights the need for methodologies that enhance student engagement and skill development. This study examines students’ perceptions of designing educational escape rooms using ICT tools and generative AI (GenAI) as a learning methodology. A total of 47 students participated in creating digital escape rooms with GenAI, Genially, and HeroForge in the course “Mediation in Conflicts and Situations of Violence” within a Social Education degree. A qualitative approach was used, analyzing focus group discussions conducted after the activity. Results indicate that students valued the experience, emphasizing its impact on digital competence, creativity, and problem-solving skills. Collaborative learning helped overcome initial technical challenges, and students recognized the practical applicability of escape room design in mediation contexts. However, they identified areas for improvement, such as the need for more initial training, extended development time, and better access to digital tools. This study contributes to game-based learning and AI-enhanced education research, positioning students as active designers rather than passive users. Future research should explore the long-term impact on knowledge retention and transferable skills in professional settings. Full article
(This article belongs to the Special Issue Innovative Theories and Practices for Designing and Evaluating Inclusive Educational Technology and Online Learning)
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17 pages, 1314 KiB  
Article
A Systems Biology Approach for Prioritizing ASD Genes in Large or Noisy Datasets
by Veronica Remori, Heather Bondi, Manuel Airoldi, Lisa Pavinato, Giulia Borini, Diana Carli, Alfredo Brusco and Mauro Fasano
Int. J. Mol. Sci. 2025, 26(5), 2078; https://doi.org/10.3390/ijms26052078 (registering DOI) - 27 Feb 2025
Abstract
Autism spectrum disorder (ASD) is a complex multifactorial neurodevelopmental disorder. Despite extensive research involving genome-wide association studies, copy number variant (CNV) testing, and genome sequencing, the comprehensive genetic landscape remains incomplete. In this context, we developed a systems biology approach to prioritize genes [...] Read more.
Autism spectrum disorder (ASD) is a complex multifactorial neurodevelopmental disorder. Despite extensive research involving genome-wide association studies, copy number variant (CNV) testing, and genome sequencing, the comprehensive genetic landscape remains incomplete. In this context, we developed a systems biology approach to prioritize genes associated with ASD and uncover potential new candidates. A Protein–Protein Interaction (PPI) network was generated from genes associated to ASD in a public database. Leveraging gene topological properties, particularly betweenness centrality, we prioritized genes and unveiled potential novel candidates (e.g., CDC5L, RYBP, and MEOX2). To test this approach, a list of genes within CNVs of unknown significance, identified through array comparative genomic hybridization analysis in 135 ASD patients, was mapped onto the PPI network. A prioritized gene list was obtained through ranking by betweenness centrality score. Intriguingly, by over-representation analysis, significant enrichments emerged in pathways not strictly linked to ASD, including ubiquitin-mediated proteolysis and cannabinoid receptor signaling, suggesting their potential perturbation in ASD. Our systems biology approach provides a promising strategy for identifying ASD risk genes, especially in large and noisy datasets, and contributes to a deeper understanding of the disorder’s complex genetic basis. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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15 pages, 3171 KiB  
Article
Genome-Wide Identification, Expression, and Protein Interaction of GRAS Family Genes During Arbuscular Mycorrhizal Symbiosis in Poncirus trifoliata
by Fang Song, Chuanya Ji, Tingting Wang, Zelu Zhang, Yaoyuan Duan, Miao Yu, Xin Song, Yingchun Jiang, Ligang He, Zhijing Wang, Xiaofang Ma, Yu Zhang, Zhiyong Pan and Liming Wu
Int. J. Mol. Sci. 2025, 26(5), 2082; https://doi.org/10.3390/ijms26052082 (registering DOI) - 27 Feb 2025
Abstract
Arbuscular mycorrhizal (AM) fungi establish mutualistic symbiosis with most land plants, facilitating mineral nutrient uptake in exchange for photosynthates. As one of the most commercially used rootstocks in citrus, Poncirus trifoliata heavily depends on AM fungi for nutrient absorption. The GRAS gene family [...] Read more.
Arbuscular mycorrhizal (AM) fungi establish mutualistic symbiosis with most land plants, facilitating mineral nutrient uptake in exchange for photosynthates. As one of the most commercially used rootstocks in citrus, Poncirus trifoliata heavily depends on AM fungi for nutrient absorption. The GRAS gene family plays essential roles in plant growth and development, signaling transduction, and responses to biotic and abiotic stresses. However, the identification and functional characterization of GRAS family genes in P. trifoliata remains largely unexplored. In this study, a comprehensive genome-wide analysis of PtGRAS family genes was conducted, including their identification, physicochemical properties, phylogenetic relationships, gene structures, conserved domains, chromosome localization, and collinear relationships. Additionally, the expression profiles and protein interaction of these genes under AM symbiosis were systematically investigated. As a result, 41 GRAS genes were identified in the P. trifoliata genome, and classified into nine distinct clades. Collinearity analysis revealed seven segmental duplications but no tandem duplications, suggesting that segmental duplication played a more important role in the expansion of the PtGRAS gene family compared to tandem duplication. Additionally, 18 PtGRAS genes were differentially expressed in response to AM symbiosis, including orthologs of RAD1, RAM1, and DELLA3 in P. trifoliata. Yeast two-hybrid (Y2H) screening further revealed that PtGRAS6 and PtGRAS20 interacted with both PtGRAS12 and PtGRAS18, respectively. The interactions were subsequently validated through bimolecular fluorescence complementation (BiFC) assays. These findings underscored the crucial role of GRAS genes in AM symbiosis in P. trifoliata, and provided valuable candidate genes for improving nutrient uptake and stress resistance in citrus rootstocks through molecular breeding approaches. Full article
(This article belongs to the Special Issue Molecular Research of Tropical Fruit (2nd Edition))
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17 pages, 4709 KiB  
Article
Defining the Protein Phosphatase 2A (PP2A) Subcomplexes That Regulate FoxO Transcription Factor Localization
by Adeline M. Luperchio and Daniel J. Salamango
Cells 2025, 14(5), 342; https://doi.org/10.3390/cells14050342 (registering DOI) - 27 Feb 2025
Abstract
The family of forkhead box O (FoxO) transcription factors regulate cellular processes involved in glucose metabolism, stress resistance, DNA damage repair, and tumor suppression. FoxO transactivation activity is tightly regulated by a complex network of signaling pathways and post-translational modifications. While it has [...] Read more.
The family of forkhead box O (FoxO) transcription factors regulate cellular processes involved in glucose metabolism, stress resistance, DNA damage repair, and tumor suppression. FoxO transactivation activity is tightly regulated by a complex network of signaling pathways and post-translational modifications. While it has been well established that phosphorylation promotes FoxO cytoplasmic retention and inactivation, the mechanism underlying dephosphorylation and nuclear translocation is less clear. Here, we investigate the role of protein phosphatase 2A (PP2A) in regulating this process. We demonstrate that PP2A and AMP-activated protein kinase (AMPK) combine to regulate nuclear translocation of multiple FoxO family members following inhibition of metabolic signaling or induction of oxidative stress. Moreover, chemical inhibitor studies indicate that nuclear accumulation of FoxO proteins occurs through inhibition of nuclear export as opposed to promoting nuclear import as previously speculated. Functional, genetic, and biochemical studies combine to identify the PP2A complexes that regulate FoxO nuclear translocation, and the binding motif required. Mutating the FoxO-PP2A interface to enhance or diminish PP2A binding alters nuclear translocation kinetics accordingly. Together, these studies shed light on the molecular mechanisms regulating FoxO nuclear translocation and provide insights into how FoxO regulation is integrated with metabolic and stress-related stimuli. Full article
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18 pages, 924 KiB  
Review
Biomarkers in Atopic Dermatitis in Children: A Comprehensive Review
by Cristiana Indolfi, Carolina Grella, Angela Klain, Giulio Dinardo, Simone Colosimo, Dario Piatto, Claudia Nespoli, Alessandra Perrotta and Michele Miraglia del Giudice
Life 2025, 15(3), 375; https://doi.org/10.3390/life15030375 (registering DOI) - 27 Feb 2025
Abstract
Atopic dermatitis (AD) is a chronic inflammatory skin disorder with significant implications for patient quality of life and a well-documented association with the atopic march. Recent advancements in biomarker research have unveiled critical insights into AD pathogenesis, diagnosis, prognosis, and therapeutic monitoring. This [...] Read more.
Atopic dermatitis (AD) is a chronic inflammatory skin disorder with significant implications for patient quality of life and a well-documented association with the atopic march. Recent advancements in biomarker research have unveiled critical insights into AD pathogenesis, diagnosis, prognosis, and therapeutic monitoring. This comprehensive review evaluates the utility of emerging biomarkers, including cytokines, chemokines, genetic markers, and microbiome-related components, in understanding the disease mechanisms and stratifying patient care. The role of minimally invasive diagnostic techniques, such as tape stripping and RNA monitoring, is highlighted, offering innovative approaches to pediatric populations. Furthermore, this review explores the biomarkers that predict disease progression, therapeutic response, and comorbidities, including food allergies and asthma. Personalized treatment strategies based on endotype-specific biomarkers are discussed as a future direction for improving clinical outcomes. Despite promising findings, the integration of biomarkers into routine practice necessitates further validation through large-scale studies. This work underscores the transformative potential of biomarker-driven approaches in enhancing the management of AD in children and its associated conditions. Full article
(This article belongs to the Special Issue Common and Novel Markers of Inflammation and Tissue Damage in Various Pathological Conditions)
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20 pages, 2789 KiB  
Article
Evaluating Interlaboratory Variability in Wastewater-Based COVID-19 Surveillance
by Arianna Azzellino, Laura Pellegrinelli, Ramon Pedrini, Andrea Turolla, Barbara Bertasi, Sandro Binda, Sara Castiglioni, Clementina E. Cocuzza, Fabio Ferrari, Andrea Franzetti, Maria Giovanna Guiso, Marina Nadia Losio, Marianna Martinelli, Antonino Martines, Rosario Musumeci, Desdemona Oliva, Laura Sandri, Valeria Primache, Francesco Righi, Annalisa Scarazzato, Silvia Schiarea, Elena Pariani, Emanuela Ammoni, Danilo Cereda and Francesca Malpeiadd Show full author list remove Hide full author list
Microorganisms 2025, 13(3), 526; https://doi.org/10.3390/microorganisms13030526 (registering DOI) - 27 Feb 2025
Abstract
Wastewater-based environmental surveillance enables the monitoring of SARS-CoV-2 dynamics within populations, offering critical epidemiological insights. Numerous workflows for tracking SARS-CoV-2 have been developed globally, underscoring the need for interlaboratory comparisons to ensure data consistency and comparability. An inter-calibration test was conducted among laboratories [...] Read more.
Wastewater-based environmental surveillance enables the monitoring of SARS-CoV-2 dynamics within populations, offering critical epidemiological insights. Numerous workflows for tracking SARS-CoV-2 have been developed globally, underscoring the need for interlaboratory comparisons to ensure data consistency and comparability. An inter-calibration test was conducted among laboratories within the network monitoring SARS-CoV-2 in wastewater samples across the Lombardy region (Italy). The test aimed to evaluate data reliability and identify potential sources of variability using robust statistical approaches. Three wastewater samples were analyzed in parallel by four laboratories using identical pre-analytical (PEG-8000-based centrifugation) and analytical processes (qPCR targeting N1/N3 and Orf-1ab). A two-way ANOVA framework within Generalized Linear Models was applied, and multiple pairwise comparisons among laboratories were performed using the Bonferroni post hoc test. The statistical analysis revealed that the primary source of variability in the results was associated with the analytical phase. This variability was likely influenced by differences in the standard curves used by the laboratories to quantify SARS-CoV-2 concentrations, as well as the size of the wastewater treatment plants. The findings of this study highlight the importance of interlaboratory testing in verifying the consistency of analytical determinations and in identifying the key sources of variation. Full article
(This article belongs to the Special Issue Surveillance of SARS-CoV-2 Employing Wastewater)
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25 pages, 863 KiB  
Review
Inhibition of Thioredoxin-Reductase by Auranofin as a Pro-Oxidant Anticancer Strategy for Glioblastoma: In Vitro and In Vivo Studies
by Nelly Chmelyuk, Maria Kordyukova, Maria Sorokina, Semyon Sinyavskiy, Valeriya Meshcheryakova, Vsevolod Belousov and Tatiana Abakumova
Int. J. Mol. Sci. 2025, 26(5), 2084; https://doi.org/10.3390/ijms26052084 (registering DOI) - 27 Feb 2025
Abstract
Reactive oxygen species (ROS) play a key role in cancer progression and antitumor therapy. Glioblastoma is a highly heterogeneous tumor with different cell populations exhibiting various redox statuses. Elevated ROS levels in cancer cells promote tumor growth and simultaneously make them more sensitive [...] Read more.
Reactive oxygen species (ROS) play a key role in cancer progression and antitumor therapy. Glioblastoma is a highly heterogeneous tumor with different cell populations exhibiting various redox statuses. Elevated ROS levels in cancer cells promote tumor growth and simultaneously make them more sensitive to anticancer drugs, but further elevation leads to cell death and apoptosis. Meanwhile, various subsets of tumor cells, such a glioblastoma stem cells (GSC) or the cells in tumor microenvironment (TME), demonstrate adaptive mechanisms to excessive ROS production by developing effective antioxidant systems such as glutathione- and thioredoxin-dependent. GSCs demonstrate higher chemoresistance and lower ROS levels than other glioma cells, while TME cells create a pro-oxidative environment and have immunosuppressive effects. Both subpopulations have become an attractive target for developing therapies. Increased expression of thioredoxin reductase (TrxR) is often associated with tumor progression and poor patient survival. Various TrxR inhibitors have been investigated as potential anticancer therapies, including nitrosoureas, flavonoids and metallic complexes. Gold derivatives are irreversible inhibitors of TrxR. Among them, auranofin (AF), a selective TrxR inhibitor, has proven its effectiveness as a drug for the treatment of rheumatoid arthritis and its efficacy as an anticancer agent has been demonstrated in preclinical studies in vitro and in vivo. However, further clinical application of AF could be challenging due to the low solubility and insufficient delivery to glioblastoma. Different delivery strategies for hydrophobic drugs could be used to increase the concentration of AF in the brain. Combining different therapeutic approaches that affect the redox status of various glioma cell populations could become a new strategy for treating brain tumor diseases. Full article
(This article belongs to the Special Issue Redox Homeostasis and Oxidative Stress in Human Metabolism and Disease)
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14 pages, 9022 KiB  
Article
Enhanced Pathogenic Consequences Induced by a Seven-Amino-Acid Extension in the G Protein of the HRSV BA9 Genotype
by Na Wang, Jingjing Song, Lei Cao, Naiying Mao, Yuqing Shi, Jie Jiang, Wuyang Zhu and Yan Zhang
Int. J. Mol. Sci. 2025, 26(5), 2081; https://doi.org/10.3390/ijms26052081 (registering DOI) - 27 Feb 2025
Abstract
In a previous outbreak of the human respiratory syncytial virus (HRSV), we identified a variant strain of genotype BA9 with a seven-amino-acid extension (Q-R-L-Q-S-Y-A) at the C-terminus of the attachment protein (G). To assess the impact of this extension on the virulence of [...] Read more.
In a previous outbreak of the human respiratory syncytial virus (HRSV), we identified a variant strain of genotype BA9 with a seven-amino-acid extension (Q-R-L-Q-S-Y-A) at the C-terminus of the attachment protein (G). To assess the impact of this extension on the virulence of HRSV, two full-length infectious clones using the wild strain of genotype BA9 as a backbone, one containing the seven-amino-acid extension (rRSV BA9 WT), and the other deleting this extension (rRSV BA9 Δ7AA), were successfully rescued using a reverse genetics system. The biological properties and virulence of the two rescued viruses were then compared and analyzed in vitro and in vivo. Compared to the rRSV BA9 Δ7AA, the rRSV BA9 WT exhibited a larger plaque size and a more pronounced suppression of the host cell innate immune response in vitro (IFN-β levels: 154.33 pg/mL vs. 11.27 pg/mL). The rRSV BA9 WT demonstrated increased adaptability in mice, with a 10-fold higher lung viral load and a stronger inflammatory response following intranasal exposure. Our study primarily demonstrated that the C-terminal extension of the G protein of the HRSV can enhance viral virulence, underscoring the importance of virological surveillance in the prevention and treatment of severe HRSV-related disease. Full article
(This article belongs to the Special Issue The Interaction Between Cell and Virus, 2nd Edition)
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12 pages, 2430 KiB  
Article
High Electrochemical Performance of Sodium-Ion Gel Polymer Electrolytes Achieved Through a Sandwich Design Strategy Combining Soft Polymers with a Rigid MOF
by Hanjiao Huang, Zongyou Li, Yanjun Gao, Tianqi Wang, Zihan Chen, Songjie Gan, Caizhen Yang, Qiyao Yu and Jian-Guo Zhang
Energies 2025, 18(5), 1160; https://doi.org/10.3390/en18051160 (registering DOI) - 27 Feb 2025
Abstract
Sodium-ion batteries (SIBs) are considered the next-generation candidates for partially substituting for commercial lithium-ion batteries in future energy storage systems because of the abundant sodium/potassium reserves and these batteries’ cost-effectiveness and high safety. Gel polymer electrolytes (GPEs) have become a popular research focus [...] Read more.
Sodium-ion batteries (SIBs) are considered the next-generation candidates for partially substituting for commercial lithium-ion batteries in future energy storage systems because of the abundant sodium/potassium reserves and these batteries’ cost-effectiveness and high safety. Gel polymer electrolytes (GPEs) have become a popular research focus due to their advantages in terms of safety and performance in research on quasi-solid-state sodium-ion batteries (QSSIBs). Building on previous studies that incorporated MOF fillers into polymer-based gel electrolytes, we propose a 3D sandwich structure in which MOF materials are first pressed into thin films and then coated and protected by polymer materials. Using this approach, we achieved an ion conductivity of 1.75 × 10−4 S cm−1 at room temperature and an ion transference number of 0.69. Solid-state sodium-ion batteries using this gel film electrolyte exhibited long cycling stability at a 2 C current density, retaining 75.2% of their specific capacity after 500 cycles. Full article
(This article belongs to the Section D2: Electrochem: Batteries, Fuel Cells, Capacitors)
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14 pages, 520 KiB  
Review
The Role of Adenogenesis Factors in the Pathogenesis of Endometriosis
by Pietro G. Signorile, Alfonso Baldi, Rosa Viceconte and Mariarosaria Boccellino
Int. J. Mol. Sci. 2025, 26(5), 2076; https://doi.org/10.3390/ijms26052076 (registering DOI) - 27 Feb 2025
Abstract
Endometriosis is a pathological condition characterized by the presence of the endometrial tissue, outside the uterine cavity. It affects nearly 10% of women of reproductive age and is responsible for infertility, chronic pain, and the weakening of the quality of life. Various pathogenetic [...] Read more.
Endometriosis is a pathological condition characterized by the presence of the endometrial tissue, outside the uterine cavity. It affects nearly 10% of women of reproductive age and is responsible for infertility, chronic pain, and the weakening of the quality of life. Various pathogenetic mechanisms have been suggested; however, the essential pathogenesis of endometriosis remains insufficiently comprehended. A comprehensive literature search was conducted in databases such as PubMed, Scopus, and Web of Science up to December 2024. Inclusion criteria encompassed studies investigating the pathogenetic mechanisms of endometriosis, while exclusion criteria included reviews, case reports, and studies lacking primary data. The analyzed studies explored multiple pathogenetic mechanisms, including retrograde menstruation, coelomic metaplasia, embryological defects, stem cell involvement, and epigenetic modifications. Special emphasis was placed on the role of uterine adenogenesis factors in the development and progression of endometriosis. A deeper understanding of the various pathogenetic mechanisms underlying endometriosis is crucial for advancing targeted therapeutic strategies. Further research into uterine adenogenesis factors may provide new insights into the disease’s pathophysiology and pave the way for novel treatment approaches. Full article
(This article belongs to the Special Issue Endometriosis: Focusing on Molecular and Cellular Research)
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18 pages, 3336 KiB  
Article
Marine-Derived COS-diDA for Sensitive Skin Treatment: Synthesis, Traits, and Anti-Inflammatory Effects
by Yue Su, Jinhua Hou, Yuanxi Zheng, Shanshan Zhang, Lixin Liu, Wenhui Wu and Chunling Bao
Cosmetics 2025, 12(2), 35; https://doi.org/10.3390/cosmetics12020035 (registering DOI) - 27 Feb 2025
Abstract
Due to environmental pollution, unhealthy lifestyles, and autoimmunity, many individuals frequently encounter skin problems, such as sensitive skin, caused by the activation of the TRPV1 pathway and immune-inflammatory reactions. This study aims to synthesize compounds with soothing effects using β-chitooligosaccharides (COS) derived from [...] Read more.
Due to environmental pollution, unhealthy lifestyles, and autoimmunity, many individuals frequently encounter skin problems, such as sensitive skin, caused by the activation of the TRPV1 pathway and immune-inflammatory reactions. This study aims to synthesize compounds with soothing effects using β-chitooligosaccharides (COS) derived from marine Sargassum, which is investigated for its regulating inflammatory responses and activating of TRPV1 pathways. Dopamine is used as the hydroxyl donor in this process. COS-diDA, a compound that binds two dopamine amines, is synthesized using Michael additions and Schiff base reactions under alkaline circumstances, with a pH of 8.5. This work investigates the soothing effects of COS-diDA using a HaCaT cell model activated with capsaicin (CAP). ELISA and immunofluorescence experiments provide evidence that COS-diDA efficiently inhibits the activation of the TRPV1 protein in HaCaT cells by reducing its levels when stimulated with CAP. In addition, ELISA analysis demonstrates that COS-diDA reduces the secretion of IL-1α, IL-6, and IL-8 from HaCaT cells stimulated with CAP, indicating an interaction between the TRPV1 protein and interleukins. Additional research on in vitro pain models generated by CAP confirms the anti-inflammatory and soothing properties of COS-diDA. The study indicates that COS-diDA exhibits favorable adhesion qualities and possesses anti-inflammatory action, making it a viable candidate for inclusion as an anti-inflammatory component of cosmetic formulations. Full article
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15 pages, 250 KiB  
Article
Metacognitive Monitoring in Written Communication: Improving Reflective Practice
by István Zsigmond, Panagiota Metallidou, Plousia Misailidi, Kalypso Iordanou and Eleonora Papaleontiou-Louca
Educ. Sci. 2025, 15(3), 299; https://doi.org/10.3390/educsci15030299 (registering DOI) - 27 Feb 2025
Abstract
Educational programs aimed at developing metacognitive skills usually focus on students, neglecting the development of teachers by teaching metacognitively aware instructional methods. The effectiveness of such development programs is well-established, but there is a gap between research findings and their application in schools. [...] Read more.
Educational programs aimed at developing metacognitive skills usually focus on students, neglecting the development of teachers by teaching metacognitively aware instructional methods. The effectiveness of such development programs is well-established, but there is a gap between research findings and their application in schools. A framework for a training program was developed in the context of an international partnership project aimed at enhancing the metacognitive abilities of both children and teachers. The final form of classroom activities was developed at the country level using action research methods with the involvement of teachers. After implementing a 3-week educational program involving 35 experimental and 19 control groups from Romanian public schools, a comparison of pre- and post-test scores indicated a significant increase in the number of children in the experimental group with improved efficiency in metacognitive monitoring in reading. Teachers’ metacognitive awareness significantly improved after the Teacher Training Program, as indicated by a comparison of the pre- and post-training results of the Metacognitive Awareness Inventory for Teachers (MAIT). No correlation was found between teachers’ development scores (as expressed by differences between pre- and post-intervention MAIT results) and the number of students from their classes whose progress in metacognitive monitoring significantly increased. The cyclical process of the action research methodology proved to be useful for increasing the efficiency of the intervention program. However, due to methodological limitations, the results are primarily interpretable within a local context. The results confirm expert recommendations aimed at integrating the targeted development of metacognitive teaching skills into both pre-service and in-service teacher training programs. Full article
(This article belongs to the Special Issue Enhancing Teaching through Reflective Practice: Strategies and Insights for Educators on Reflective Learning and Reflection)
17 pages, 7862 KiB  
Article
Two-Dimensional Simulation on the Critical Diameter of Particles in Asymmetric I-Shaped DLD Arrays
by Jiangbo Wu, Zihan Yan, Yongqing He, Jie Liu and Yao Lv
Micromachines 2025, 16(3), 270; https://doi.org/10.3390/mi16030270 (registering DOI) - 27 Feb 2025
Abstract
Deterministic lateral displacement (DLD) is a passive particle separation method based on microfluidic technology, with its separation mechanism primarily relying on particle size differences. Therefore, the critical separation size is of great significance in the design of DLD devices. The geometric asymmetry of [...] Read more.
Deterministic lateral displacement (DLD) is a passive particle separation method based on microfluidic technology, with its separation mechanism primarily relying on particle size differences. Therefore, the critical separation size is of great significance in the design of DLD devices. The geometric asymmetry of the pillar array design significantly influences fluid behavior and critical particle size variations. This study first analyzed particle motion characteristics through particle trajectory observation experiments within asymmetric microfluidic chips. Subsequently, a two-dimensional numerical simulation method was employed to investigate the effects of three different ratios of lateral gap size to downstream gap size (Gx:Gy) on particle trajectories and flow field distribution. The results indicate that as Gx:Gy decreases, the upward flow rate gradually reduces, accompanied by changes in the flow field velocity distribution, causing particles to favor displacement mode. This study provides new theoretical foundations for the precise regulation of particle motion behavior and introduces novel insights for optimizing DLD device design. Full article
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17 pages, 6988 KiB  
Article
Structural and Energetic Evidence Supports the Non-Covalent Phosphate Cyclization by the Class II Phospholipase D from Loxosceles intermedia
by Carolina Gismene, José Fernando Ruggiero Bachega, Daniel Z. Doherty, Silvio Sanches Veiga, Raghuvir K. Arni and Jorge Enrique Hernández González
Toxins 2025, 17(3), 111; https://doi.org/10.3390/toxins17030111 (registering DOI) - 27 Feb 2025
Abstract
Phospholipase D (PLD) enzymes from Loxosceles spider venom mediate envenomation pathology by cleaving phospholipid headgroups. We revisited the crystal structure of Loxosceles intermedia PLD (PDB: 3RLH) to evaluate two alternative mechanisms—covalent and non-covalent—for headgroup cleavage. The covalent mechanism involves a nucleophilic attack on [...] Read more.
Phospholipase D (PLD) enzymes from Loxosceles spider venom mediate envenomation pathology by cleaving phospholipid headgroups. We revisited the crystal structure of Loxosceles intermedia PLD (PDB: 3RLH) to evaluate two alternative mechanisms—covalent and non-covalent—for headgroup cleavage. The covalent mechanism involves a nucleophilic attack on the substrate’s P atom by catalytic histidine, forming a phosphohistidine intermediate. It was originally suggested that this intermediate hydrolyzes, leading to linear phosphates. The non-covalent mechanism relies on the substrate’s hydroxyl group performing an intramolecular attack on the P atom, thereby generating a cyclic phosphate. Structural refinement of the crystal structure revealed a cyclic phosphate bound at the active site, replacing previously assigned PEG molecules. This cyclic product, stabilized by His12, His47, and Mg2+, provides structural evidence that supports phosphate cyclization. The results of computational analyses, including molecular dynamics and quantum mechanics/molecular mechanics simulations, further support the non-covalent mechanism as the energetically preferred pathway, with a significantly lower activation barrier. Our findings highlight the role of substrate orientation and of the catalytic His residues in transphosphatidylation, advancing our understanding of PLD enzymology and providing insights for the design of inhibitors against Loxosceles envenomation. Full article
(This article belongs to the Special Issue From Animal Venoms to Solutions: In Honor of Professor Lourival D. Possani on the Occasion of His 85th Birthday)
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26 pages, 2304 KiB  
Review
Single-Cell Sequencing: Genomic and Transcriptomic Approaches in Cancer Cell Biology
by Ana Ortega-Batista, Yanelys Jaén-Alvarado, Dilan Moreno-Labrador, Natasha Gómez, Gabriela García and Erika N. Guerrero
Int. J. Mol. Sci. 2025, 26(5), 2074; https://doi.org/10.3390/ijms26052074 (registering DOI) - 27 Feb 2025
Abstract
This article reviews the impact of single-cell sequencing (SCS) on cancer biology research. SCS has revolutionized our understanding of cancer and tumor heterogeneity, clonal evolution, and the complex interplay between cancer cells and tumor microenvironment. SCS provides high-resolution profiling of individual cells in [...] Read more.
This article reviews the impact of single-cell sequencing (SCS) on cancer biology research. SCS has revolutionized our understanding of cancer and tumor heterogeneity, clonal evolution, and the complex interplay between cancer cells and tumor microenvironment. SCS provides high-resolution profiling of individual cells in genomic, transcriptomic, and epigenomic landscapes, facilitating the detection of rare mutations, the characterization of cellular diversity, and the integration of molecular data with phenotypic traits. The integration of SCS with multi-omics has provided a multidimensional view of cellular states and regulatory mechanisms in cancer, uncovering novel regulatory mechanisms and therapeutic targets. Advances in computational tools, artificial intelligence (AI), and machine learning have been crucial in interpreting the vast amounts of data generated, leading to the identification of new biomarkers and the development of predictive models for patient stratification. Furthermore, there have been emerging technologies such as spatial transcriptomics and in situ sequencing, which promise to further enhance our understanding of tumor microenvironment organization and cellular interactions. As SCS and its related technologies continue to advance, they are expected to drive significant advances in personalized cancer diagnostics, prognosis, and therapy, ultimately improving patient outcomes in the era of precision oncology. Full article
(This article belongs to the Special Issue Cancer Biology: From Genetic Aspects to Treatment)
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24 pages, 3892 KiB  
Article
Rotenone Induces Parkinsonism with Constipation Symptoms in Mice by Disrupting the Gut Microecosystem, Inhibiting the PI3K-AKT Signaling Pathway and Gastrointestinal Motility
by Li Liu, Yan Zhao, Weixing Yang, Yuqin Fan, Lixiang Han, Jun Sheng, Yang Tian and Xiaoyu Gao
Int. J. Mol. Sci. 2025, 26(5), 2079; https://doi.org/10.3390/ijms26052079 (registering DOI) - 27 Feb 2025
Abstract
Parkinson’s disease (PD) is one of the most common neurodegenerative diseases. Constipation is a prodromal symptom of PD. It is important to investigate the pathogenesis of constipation symptoms in PD. Rotenone has been successfully used to establish PD animal models. However, the specific [...] Read more.
Parkinson’s disease (PD) is one of the most common neurodegenerative diseases. Constipation is a prodromal symptom of PD. It is important to investigate the pathogenesis of constipation symptoms in PD. Rotenone has been successfully used to establish PD animal models. However, the specific mechanism of rotenone-induced constipation symptoms is not well understood. In this work, we found that constipation symptoms appeared earlier than motor impairment in mice gavaged with a low dose of rotenone (30 mg/kg·BW). Rotenone not only caused loss of dopaminergic neurons and accumulation of α-synuclein, but also significantly reduced serum 5-HT levels and 5-HTR4 in the striatum and colon. The mRNA expression of aquaporins, gastrointestinal motility factors (c-Kit, Cx43, smMLCK and MLC-3) in mouse colon was also significantly regulated by rotenone. In addition, both colon and brain showed rotenone-induced inflammation and barrier dysfunction; the PI3K/AKT pathway in the substantia nigra and colon was also significantly inhibited by rotenone. Importantly, the structure, composition and function of the gut microbiota were also significantly altered by rotenone. Some specific taxa were closely associated with motor and constipation symptoms, inflammation, and gut and brain barrier status in PD mice. Akkermansia, Staphylococcus and Lachnospiraceae_UCG—006 may play a role in exacerbating constipation symptoms, whereas Acinetobacter, Lactobacillus, Bifidobacterium, Solibacillus and Eubacterium_xylanophilum_groups may be beneficial in stimulating gastrointestinal peristalsis, maintaining motor function and alleviating inflammation and barrier damage in mice. In conclusion, low-dose rotenone can cause parkinsonism with constipation symptoms in mice by disrupting the intestinal microecosystem and inhibiting the PI3K-AKT pathway and gastrointestinal motility. Full article
(This article belongs to the Special Issue Advances and Challenges of Molecular Research on Disease in Animal Models in Biomedicine)
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