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17 pages, 4370 KiB  
Article
PSG and Other Candidate Genes as Potential Biomarkers of Therapy Resistance in B-ALL: Insights from Chromosomal Microarray Analysis and Machine Learning
by Valeriya Surimova, Natalya Risinskaya, Ekaterina Kotova, Abdulpatakh Abdulpatakhov, Anastasia Vasileva, Yulia Chabaeva, Sofia Starchenko, Olga Aleshina, Nikolay Kapranov, Irina Galtseva, Alina Ponomareva, Ilya Kanivets, Sergey Korostelev, Sergey Kulikov, Andrey Sudarikov and Elena Parovichnikova
Int. J. Mol. Sci. 2025, 26(15), 7437; https://doi.org/10.3390/ijms26157437 (registering DOI) - 1 Aug 2025
Abstract
Chromosomal microarray analysis (CMA) was performed for 40 patients with B-ALL undergoing treatment according to the ALL-2016 protocol to investigate the copy number alterations (CNAs) and copy neutral loss of heterozygosity (cnLOH) associated with minimal residual disease (MRD)-positive remission. Aberrations involving over 20,000 [...] Read more.
Chromosomal microarray analysis (CMA) was performed for 40 patients with B-ALL undergoing treatment according to the ALL-2016 protocol to investigate the copy number alterations (CNAs) and copy neutral loss of heterozygosity (cnLOH) associated with minimal residual disease (MRD)-positive remission. Aberrations involving over 20,000 genes were identified, and a random forest approach was applied to isolate a subset of genes whose CNAs and cnLOH are significantly associated with poor therapeutic response. We have assembled the triple matched healthy population data and used that data as a reference, but not as a matched control. We identified a recurrent cluster of cnLOH in the 19q13.2–19q13.31 region, significantly enriched in MRD-positive patients (70% vs. 47% in the reference group vs. 16% in MRD-negative patients). This region includes the pregnancy-specific glycoprotein (PSG) gene family and the oncogene ERF, suggesting a potential role in leukemic persistence and treatment resistance. Additionally, we observed significant deletions involving 7p22.3 and 16q13, often as part of large-scale losses affecting almost the entire chromosomes 7 and 16, indicative of global chromosomal instability. These findings highlight specific genomic regions potentially involved in therapy resistance and may contribute to improved risk stratification in B-ALL. Our findings emphasize the value of high-resolution CMA in diagnostics and risk stratification and suggest that PSG genes and other candidate genes could serve as biomarkers for predicting treatment outcomes. Full article
(This article belongs to the Special Issue Cancer Genomics)
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23 pages, 20334 KiB  
Article
Transient Stability Analysis for the Wind Power Grid-Connected System: A Manifold Topology Perspective on the Global Stability Domain
by Jinhao Yuan, Meiling Ma and Yanbing Jia
Electricity 2025, 6(3), 44; https://doi.org/10.3390/electricity6030044 (registering DOI) - 1 Aug 2025
Abstract
Large-scale wind power grid-connected systems can trigger the risk of power system instability. In order to enhance the stability margin of grid-connected systems, this paper accurately characterizes the topology of the global boundary of stability domain (BSD) of the grid-connected system based on [...] Read more.
Large-scale wind power grid-connected systems can trigger the risk of power system instability. In order to enhance the stability margin of grid-connected systems, this paper accurately characterizes the topology of the global boundary of stability domain (BSD) of the grid-connected system based on BSD theory, using the method of combining the manifold topologies and singularities at infinity. On this basis, the effect of large-scale doubly fed induction generators (DFIGs) replacing synchronous units on the BSD of the system is analyzed. Simulation results based on the IEEE 39-bus system indicate that the negative impedance characteristics and low inertia of DFIGs lead to a contraction of the stability domain. The principle of singularity invariance (PSI) proposed in this paper can effectively expand the BSD by adjusting the inertia and damping, thereby increasing the critical clearing time by about 5.16% and decreasing the dynamic response time by about 6.22% (inertia increases by about 5.56%). PSI is superior and applicable compared to traditional energy functions, and can be used to study the power angle stability of power systems with a high proportion of renewable energy. Full article
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31 pages, 2032 KiB  
Review
Leflunomide Applicability in Rheumatoid Arthritis: Drug Delivery Challenges and Emerging Formulation Strategies
by Ashish Dhiman and Kalpna Garkhal
Drugs Drug Candidates 2025, 4(3), 36; https://doi.org/10.3390/ddc4030036 (registering DOI) - 1 Aug 2025
Abstract
Rheumatoid arthritis (RA) is a chronic systemic inflammatory disorder primarily targeting joints, leading to pain, swelling, and stiffness. RA results from the body’s own immune system attacking its own tissues. Currently, there are various treatments available for RA including disease-modifying antirheumatic drugs (DMARDs) [...] Read more.
Rheumatoid arthritis (RA) is a chronic systemic inflammatory disorder primarily targeting joints, leading to pain, swelling, and stiffness. RA results from the body’s own immune system attacking its own tissues. Currently, there are various treatments available for RA including disease-modifying antirheumatic drugs (DMARDs) and NSAIDs. Leflunomide (LEF) is a USFDA-approved synthetic DMARD which is being widely prescribed for the management of RA; however, it faces several challenges such as prolonged drug elimination, hepatotoxicity, and others. LEF exerts its therapeutic effects by inhibiting dihydroorotate dehydrogenase (DHODH), thereby suppressing pyrimidine synthesis and modulating immune responses. Emerging nanotechnology-based therapies help in encountering the current challenges faced in LEF delivery to RA patients. This review enlists the LEF’s pharmacokinetics, mechanism of action, and clinical efficacy in RA management. A comparative analysis with methotrexate, biologics, and other targeted therapies, highlighting its role in monotherapy and combination regimens and the safety concerns, including hepatotoxicity, gastrointestinal effects, and teratogenicity, is discussed alongside recommended monitoring strategies. Additionally, emerging trends in novel formulations and drug delivery approaches are explored to enhance efficacy and minimize adverse effects. Overall, LEF remains a perfect remedy for RA patients, specifically individuals contraindicated with drugs like methotrexate. The therapeutic applicability of LEF could be enhanced by developing more customized treatments and advanced drug delivery approaches. Full article
(This article belongs to the Section Marketed Drugs)
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16 pages, 4891 KiB  
Article
Effects of Performance Variations in Key Components of CRTS I Slab Ballastless Track on Structural Response Following Slab-Replacement Operations
by Wentao Wu, Hongyao Lu, Yuelei He and Haitao Xia
Materials 2025, 18(15), 3621; https://doi.org/10.3390/ma18153621 (registering DOI) - 1 Aug 2025
Abstract
Slab-replacement operations are crucial for restoring deteriorated CRTS I slab ballastless tracks to operational standards. This study investigates the structural implications of the operation by evaluating the strength characteristics and material properties of track components both prior to and following replacement. Apparent strength [...] Read more.
Slab-replacement operations are crucial for restoring deteriorated CRTS I slab ballastless tracks to operational standards. This study investigates the structural implications of the operation by evaluating the strength characteristics and material properties of track components both prior to and following replacement. Apparent strength was measured using rebound hammer tests on three categories of slabs: retained, deteriorated, and newly installed track slabs. In addition, samples of old and new filling resins were collected and tested to determine their elastic moduli. These empirical data were subsequently used to develop a refined finite-element model that captures both pre- and post-replacement conditions. Under varying temperature loads, disparities in component performance were found to significantly affect stress distribution. Specifically, before replacement, deteriorated track slabs exhibited 10.74% lower strength compared to adjacent retained slabs, whereas, after replacement, new slabs showed a 25.26% increase in strength over retained ones. The elastic modulus of old filling resin was measured at 5.19 kN/mm, 35.13% below the minimum design requirement, while the new resin reached 10.48 kN/mm, exceeding the minimum by 31.00%. Although the slab-replacement operation enhances safety by addressing structural deficiencies, it may also create new weak points in adjacent areas, where insufficient stiffness results in stress concentrations and potential damage. This study offers critical insights for optimizing maintenance strategies and improving the long-term performance of ballastless track systems. Full article
(This article belongs to the Section Construction and Building Materials)
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26 pages, 89199 KiB  
Article
Light-Responsive PLGA Microparticles for On-Demand Vancomycin Release and Enhanced Antibacterial Efficiency
by Mishal Pokharel, Abid Neron, Amit Kumar Dey, Aishwarya Raksha Siddharthan, Menaka Konara, Md Mainuddin Sagar, Tracie Ferreira and Kihan Park
Pharmaceutics 2025, 17(8), 1007; https://doi.org/10.3390/pharmaceutics17081007 (registering DOI) - 1 Aug 2025
Abstract
Background: A precise drug delivery system enables the optimization of treatments with minimal side effects if it can deliver medication only when activated by a specific light source. This study presents a controlled drug delivery system based on poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs) [...] Read more.
Background: A precise drug delivery system enables the optimization of treatments with minimal side effects if it can deliver medication only when activated by a specific light source. This study presents a controlled drug delivery system based on poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs) designed for the sustained release of vancomycin hydrochloride. Methods: The MPs were co-loaded with indocyanine green (ICG), a near-infrared (NIR) responsive agent, and fabricated via the double emulsion method.They were characterized for stability, surface modification, biocompatibility, and antibacterial efficacy. Results: Dynamic light scattering and zeta potential analyses confirmed significant increases in particle size and surface charge reversal following chitosan coating. Scanning electron microscopy revealed uniform morphology in uncoated MPs (1–10 μm) and irregular surfaces post-coating. Stability tests demonstrated drug retention for up to 180 days. Among formulations, PVI1 exhibited the highest yield (76.67 ± 1.3%) and encapsulation efficiency (56.2 ± 1.95%). NIR irradiation (808 nm) enhanced drug release kinetics, with formulation PVI4 achieving over 48.9% release, resulting in improved antibacterial activity. Chitosan-coated MPs (e.g., PVI4-C) effectively suppressed drug release without NIR light for up to 8 h, with cumulative release reaching only 10.89%. Without NIR light, bacterial colonies exceeded 1000 CFU; NIR-triggered release reduced them below 120 CFU. Drug release data fitted best with the zero-order and Korsmeyer–Peppas models, suggesting a combination of diffusion-controlled and constant-rate release behavior. Conclusions: These results demonstrate the promise of chitosan-coated NIR-responsive PLGA MPs for precise, on-demand antibiotic delivery and improved antibacterial performance. Full article
(This article belongs to the Special Issue Nano-Based Delivery Systems for Topical Applications)
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22 pages, 3527 KiB  
Review
Applications of Organoids and Spheroids in Anaplastic and Papillary Thyroid Cancer Research: A Comprehensive Review
by Deepak Gulwani, Neha Singh, Manisha Gupta, Ridhima Goel and Thoudam Debraj Singh
Organoids 2025, 4(3), 18; https://doi.org/10.3390/organoids4030018 (registering DOI) - 1 Aug 2025
Abstract
Organoid and spheroid technologies have rapidly become pivotal in thyroid cancer research, offering models that are more physiologically relevant than traditional two-dimensional culture. In the study of papillary and anaplastic thyroid carcinomas, two subtypes that differ both histologically and clinically, three-dimensional (3D) models [...] Read more.
Organoid and spheroid technologies have rapidly become pivotal in thyroid cancer research, offering models that are more physiologically relevant than traditional two-dimensional culture. In the study of papillary and anaplastic thyroid carcinomas, two subtypes that differ both histologically and clinically, three-dimensional (3D) models offer unparalleled insights into tumor biology, therapeutic vulnerabilities, and resistance mechanisms. These models maintain essential tumor characteristics such as cellular diversity, spatial structure, and interactions with the microenvironment, making them extremely valuable for disease modeling and drug testing. This review emphasizes recent progress in the development and use of thyroid cancer organoids and spheroids, focusing on their role in replicating disease features, evaluating targeted therapies, and investigating epithelial–mesenchymal transition (EMT), cancer stem cell behavior, and treatment resistance. Patient-derived organoids have shown potential in capturing individualized drug responses, supporting precision oncology strategies for both differentiated and aggressive subtypes. Additionally, new platforms, such as thyroid organoid-on-a-chip systems, provide dynamic, high-fidelity models for functional studies and assessments of endocrine disruption. Despite ongoing challenges, such as standardization, limited inclusion of immune and stromal components, and culture reproducibility, advancements in microfluidics, biomaterials, and machine learning have enhanced the clinical and translational potential of these systems. Organoids and spheroids are expected to become essential in the future of thyroid cancer research, particularly in bridging the gap between laboratory discoveries and patient-focused therapies. Full article
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15 pages, 3291 KiB  
Article
Organelle Genome Characteristics and Phylogenetic Analysis of a Warm-Season Turfgrass Eremochloa ophiuroides (Poaceae)
by Junming Zhao, Yanli Xiong, Maotao Xu, Wenlong Gou, Tingyong Yang, Yi Xiong, Zhixiao Dong, Ling Pan, Lina Sha, Hong Luo and Xiao Ma
Biology 2025, 14(8), 975; https://doi.org/10.3390/biology14080975 (registering DOI) - 1 Aug 2025
Abstract
Plant mitochondrial genomes are characterized by their complex compositions and structures, large genomes, rapid recombination and evolution rates, and frequent intracellular gene transfer events. Centipedegrass, known as “Chinese turfgrass”, is a warm-season turfgrass that exhibits excellent tolerance to both biotic and abiotic stresses. [...] Read more.
Plant mitochondrial genomes are characterized by their complex compositions and structures, large genomes, rapid recombination and evolution rates, and frequent intracellular gene transfer events. Centipedegrass, known as “Chinese turfgrass”, is a warm-season turfgrass that exhibits excellent tolerance to both biotic and abiotic stresses. The chloroplast genome, with 139,107 bp, and the mitochondrial genome, with 564,432 bp, were both assembled into a single circular structure. We identified 44 gene transfer events between the chloroplast and mitochondrial genomes. The mitochondrial gene cox1 could serve as a marker for distinguishing accessions found at different altitudes. The unique features of the centipedegrass mitochondrial genome, coupled with the comparative genomic analysis of both chloroplast and mitochondrial genomes, have the potential to enrich the Poaceae database and provide crucial perspectives on plant evolution, energy metabolism, and responses to environmental conditions. The markers developed could facilitate the analysis of the genetic diversity of centipedegrass. Full article
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25 pages, 2451 KiB  
Article
Complexation and Thermal Stabilization of Protein–Polyelectrolyte Systems via Experiments and Molecular Simulations: The Poly(Acrylic Acid)/Lysozyme Case
by Sokratis N. Tegopoulos, Sisem Ektirici, Vagelis Harmandaris, Apostolos Kyritsis, Anastassia N. Rissanou and Aristeidis Papagiannopoulos
Polymers 2025, 17(15), 2125; https://doi.org/10.3390/polym17152125 (registering DOI) - 1 Aug 2025
Abstract
Protein–polyelectrolyte nanostructures assembled via electrostatic interactions offer versatile applications in biomedicine, tissue engineering, and food science. However, several open questions remain regarding their intermolecular interactions and the influence of external conditions—such as temperature and pH—on their assembly, stability, and responsiveness. This study explores [...] Read more.
Protein–polyelectrolyte nanostructures assembled via electrostatic interactions offer versatile applications in biomedicine, tissue engineering, and food science. However, several open questions remain regarding their intermolecular interactions and the influence of external conditions—such as temperature and pH—on their assembly, stability, and responsiveness. This study explores the formation and stability of networks between poly(acrylic acid) (PAA) and lysozyme (LYZ) at the nanoscale upon thermal treatment, using a combination of experimental and simulation measures. Experimental techniques of static and dynamic light scattering (SLS and DLS), Fourier transform infrared spectroscopy (FTIR), and circular dichroism (CD) are combined with all-atom molecular dynamics simulations. Model systems consisting of multiple PAA and LYZ molecules explore collective assembly and complexation in aqueous solution. Experimental results indicate that electrostatic complexation occurs between PAA and LYZ at pH values below LYZ’s isoelectric point. This leads to the formation of nanoparticles (NPs) with radii ranging from 100 to 200 nm, most pronounced at a PAA/LYZ mass ratio of 0.1. These complexes disassemble at pH 12, where both LYZ and PAA are negatively charged. However, when complexes are thermally treated (TT), they remain stable, which is consistent with earlier findings. Atomistic simulations demonstrate that thermal treatment induces partially reversible structural changes, revealing key microscopic features involved in the stabilization of the formed network. Although electrostatic interactions dominate under all pH and temperature conditions, thermally induced conformational changes reorganize the binding pattern, resulting in an increased number of contacts between LYZ and PAA upon thermal treatment. The altered hydration associated with conformational rearrangements emerges as a key contributor to the stability of the thermally treated complexes, particularly under conditions of strong electrostatic repulsion at pH 12. Moreover, enhanced polymer chain associations within the network are observed, which play a crucial role in complex stabilization. These insights contribute to the rational design of protein–polyelectrolyte materials, revealing the origins of association under thermally induced structural rearrangements. Full article
(This article belongs to the Section Polymer Physics and Theory)
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15 pages, 5769 KiB  
Article
Higher Winter Precipitation and Temperature Are Associated with Smaller Earlywood Vessel Size but Wider Latewood Width in Quercus faginea Lam.
by Ignacio García-González, Filipe Campelo, Joana Vieira and Cristina Nabais
Forests 2025, 16(8), 1252; https://doi.org/10.3390/f16081252 (registering DOI) - 1 Aug 2025
Abstract
Quercus faginea Lam., a winter-deciduous oak native to the Iberian Peninsula, typically grows under a Mediterranean climate. To identify the main drivers influencing radial wood increment, we analyzed the climatic signals in tree-ring width and wood anatomical traits using increment cores. Winter conditions [...] Read more.
Quercus faginea Lam., a winter-deciduous oak native to the Iberian Peninsula, typically grows under a Mediterranean climate. To identify the main drivers influencing radial wood increment, we analyzed the climatic signals in tree-ring width and wood anatomical traits using increment cores. Winter conditions influenced both latewood width and earlywood vessel size in the first row. Latewood was positively correlated with precipitation and temperature, with the long-term positive effect of winter water supply supported by SPEI. In contrast, vessel size showed negative correlations, also reflecting a long-term negative effect of winter precipitation. Consequently, conditions that enhanced latewood width and overall tree-ring growth appear to be associated with the formation of smaller earlywood vessels. Although ample winter precipitation replenishes soil water reserves and supports prolonged wood formation, it may also induce anaerobic soil conditions that promote root fermentation, depleting carbohydrates needed for cell turgor and expansion, and ultimately regulating earlywood vessel size. This physiological decoupling may help explain the lack of a significant correlation between latewood width and earlywood vessel size, underscoring their independent responses to environmental influences. Our findings highlighted the complex interplay between various climatic conditions affecting Q. faginea, with implications for understanding its adaptive capacity in changing climates. Full article
(This article belongs to the Section Forest Ecophysiology and Biology)
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13 pages, 733 KiB  
Proceeding Paper
AI-Based Assistant for SORA: Approach, Interaction Logic, and Perspectives for Cybersecurity Integration
by Anton Puliyski and Vladimir Serbezov
Eng. Proc. 2025, 100(1), 65; https://doi.org/10.3390/engproc2025100065 - 1 Aug 2025
Abstract
This article presents the design, development, and evaluation of an AI-based assistant tailored to support users in the application of the Specific Operations Risk Assessment (SORA) methodology for unmanned aircraft systems. Built on a customized language model, the assistant was trained using system-level [...] Read more.
This article presents the design, development, and evaluation of an AI-based assistant tailored to support users in the application of the Specific Operations Risk Assessment (SORA) methodology for unmanned aircraft systems. Built on a customized language model, the assistant was trained using system-level instructions with the goal of translating complex regulatory concepts into clear and actionable guidance. The approach combines structured definitions, contextualized examples, constrained response behavior, and references to authoritative sources such as JARUS and EASA. Rather than substituting expert or regulatory roles, the assistant provides process-oriented support, helping users understand and complete the various stages of risk assessment. The model’s effectiveness is illustrated through practical interaction scenarios, demonstrating its value across educational, operational, and advisory use cases, and its potential to contribute to the digital transformation of safety and compliance processes in the drone ecosystem. Full article
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19 pages, 851 KiB  
Review
The Multifaceted Role of Regulatory T Cells in Sepsis: Mechanisms, Heterogeneity, and Pathogen-Tailored Therapies
by Yingyu Qin and Jingli Zhang
Int. J. Mol. Sci. 2025, 26(15), 7436; https://doi.org/10.3390/ijms26157436 (registering DOI) - 1 Aug 2025
Abstract
Sepsis is a life-threatening condition caused by a dysregulated immune response to infection, characterized by an initial hyperinflammatory phase frequently followed by compensatory immunosuppression (CARS). Regulatory T cells (Tregs) play a critical, biphasic role: inadequate suppression during early hyperinflammation fails to control cytokine [...] Read more.
Sepsis is a life-threatening condition caused by a dysregulated immune response to infection, characterized by an initial hyperinflammatory phase frequently followed by compensatory immunosuppression (CARS). Regulatory T cells (Tregs) play a critical, biphasic role: inadequate suppression during early hyperinflammation fails to control cytokine storms, while excessive/persistent activity in late-phase immunosuppression drives immune paralysis and secondary infection susceptibility. This review explores advances in targeting Treg immunoregulation across bacterial, viral, and fungal sepsis, where pathogenic type critically influenced the types of immunoresponses, shaping Treg heterogeneity in terms of phenotype, survival, and function. Understanding this multifaceted Treg biology offers novel therapeutic avenues, highlighting the need to decipher functional heterogeneity and develop precisely timed, pathogen-tailored immunomodulation to safely harness beneficial Treg roles while mitigating detrimental immunosuppression. Full article
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14 pages, 31608 KiB  
Article
Primary Metabolic Variations in Maize Plants Affected by Different Levels of Nitrogen Supply
by The Ngoc Phuong Nguyen, Rose Nimoh Serwaa and Jwakyung Sung
Metabolites 2025, 15(8), 519; https://doi.org/10.3390/metabo15080519 (registering DOI) - 1 Aug 2025
Abstract
Background/Objectives: Nitrogen (N) is an essential macronutrient that strongly influences maize growth and metabolism. While many studies have focused on nitrogen responses during later developmental stages, early-stage physiological and metabolic responses remain less explored. This study investigated the effect of different nitrogen-deficient [...] Read more.
Background/Objectives: Nitrogen (N) is an essential macronutrient that strongly influences maize growth and metabolism. While many studies have focused on nitrogen responses during later developmental stages, early-stage physiological and metabolic responses remain less explored. This study investigated the effect of different nitrogen-deficient levels on maize seedling growth and primary metabolite profiles. Methods: Seedlings were treated with N-modified nutrient solution, which contained 0% to 120% of the standard nitrogen level (8.5 mM). Results: Nitrogen starvation (N0) significantly reduced plant height (by 11–14%), shoot fresh weight (over 30%) compared to the optimal N supply (N100). Total leaf nitrogen content under N0–N20 was less than half of that in N100, whereas moderate N deficiency resulted in moderate reductions in growth and nitrogen content. Metabolite analysis revealed that N deficiency induced the accumulation of soluble sugars and organic acids (up to threefold), while sufficient N promoted the synthesis of amino acids related to nitrogen assimilation and protein biosynthesis. Statistical analyses (PCA and ANOVA) showed that both genotypes (MB and TYC) and tissue type (upper vs. lower leaves) influenced the metabolic response to nitrogen, with MB displaying more consistent shifts and TYC exhibiting greater variability under moderate stress. Conclusions: These findings highlight the sensitivity of maize seedlings to early nitrogen deficiency, with severity influenced by nitrogen level, tissue-specific position, and genotype; thus underscore the close coordination between physiological growth and primary metabolic pathways in response to nitrogen availability. These findings expand current knowledge of nitrogen response mechanisms and offer practical insights for improving nitrogen use efficiency in maize cultivation. Full article
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16 pages, 19172 KiB  
Communication
DEAD-Box Helicase 3 Modulates the Non-Coding RNA Pool in Ribonucleoprotein Condensates During Stress Granule Formation
by Elizaveta Korunova, B. Celia Cui, Hao Ji, Aliaksandra Sikirzhytskaya, Srestha Samaddar, Mengqian Chen, Vitali Sikirzhytski and Michael Shtutman
Non-Coding RNA 2025, 11(4), 59; https://doi.org/10.3390/ncrna11040059 (registering DOI) - 1 Aug 2025
Abstract
Stress granule formation is a type of liquid–liquid phase separation in the cytoplasm, leading to RNA–protein condensates that are associated with various cellular stress responses and implicated in numerous pathologies, including cancer, neurodegeneration, inflammation, and cellular senescence. One of the key components of [...] Read more.
Stress granule formation is a type of liquid–liquid phase separation in the cytoplasm, leading to RNA–protein condensates that are associated with various cellular stress responses and implicated in numerous pathologies, including cancer, neurodegeneration, inflammation, and cellular senescence. One of the key components of mammalian stress granules is the DEAD-box RNA helicase DDX3, which unwinds RNA in an ATP-dependent manner. DDX3 is involved in multiple steps of RNA metabolism, facilitating gene transcription, splicing, and nuclear export and regulating cytoplasmic translation. In this study, we investigate the role of the RNA helicase DDX3’s enzymatic activity in shaping the RNA content of ribonucleoprotein (RNP) condensates formed during arsenite-induced stress by inhibiting DDX3 activity with RK-33, a small molecule previously shown to be effective in cancer clinical studies. Using the human osteosarcoma U2OS cell line, we purified the RNP granule fraction and performed RNA sequencing to assess changes in the RNA pool. Our results reveal that RK-33 treatment alters the composition of non-coding RNAs within the RNP granule fraction. We observed a DDX3-dependent increase in circular RNA (circRNA) content and alterations in the granule-associated intronic RNAs, suggesting a novel role for DDX3 in regulating the cytoplasmic redistribution of non-coding RNAs. Full article
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16 pages, 3753 KiB  
Article
Elevational Patterns and Seasonal Dynamics of Soil Organic Carbon Fractions and Content in Rice Paddies of Yuanyang Terrace, Southwest China
by Haitao Li, Linxi Chang, Yonglin Wu, Yang Li, Xinran Liang, Fangdong Zhan and Yongmei He
Agronomy 2025, 15(8), 1868; https://doi.org/10.3390/agronomy15081868 (registering DOI) - 1 Aug 2025
Abstract
Soil organic carbon (SOC) is an important part of the global C pool and is sensitive to climate change. The SOC content and fractions of rice paddies along four elevations (250, 1150, 1600 and 1800 m) on the same slope in four seasons [...] Read more.
Soil organic carbon (SOC) is an important part of the global C pool and is sensitive to climate change. The SOC content and fractions of rice paddies along four elevations (250, 1150, 1600 and 1800 m) on the same slope in four seasons (spring, summer, autumn and winter) at Yuanyang Terrace in southwest China were investigated, and their relationship with environmental factors was analyzed. The contents of SOC, unprotected SOC (uPOM), physically protected SOC (pPOM) and biochemically protected SOC (bcPOM) in rice paddies at a low elevation (250 m), were significantly lower by 49–51% than those at relatively high elevations (1600 m and 1800 m). Among the SOC fractions, the highest proportion (33–50%) was uPOM, followed by pPOM and bcPOM (accounting for 17–40%), and the lowest proportion was chemically protected SOC (cPOM). In addition, there were interseasonal differences among the contents of SOC fractions, with a significantly higher content of SOC, uPOM and pPOM at an elevation of 1600 m in summer than in the other three seasons, whereas the cPOM content at an elevation of 250 m in spring was significantly higher than in the other three higher elevations. According to the redundancy analysis (RDA), total nitrogen was the key environmental factor, with an explanatory degree of 56% affecting the contents of SOC and its fractions. Thus, the SOC content increased with increasing elevation, and physical and biochemical protection were potential stabilization mechanisms responsible for their stability in the rice paddy of Yuanyang Terrace. These results provides empirical evidence for the elevational distribution patterns and seasonal dynamics of SOC fractions in rice paddies across Yuanyang Terrace. These findings highlight the importance of physical and biochemical protection mechanisms in stabilizing SOC in rice paddies, which could enhance long-term C sequestration and contribute to climate change mitigation in terraced agroecosystems. Full article
(This article belongs to the Section Soil and Plant Nutrition)
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17 pages, 5703 KiB  
Review
IFN γ and the IFN γ Signaling Pathways in Merkel Cell Carcinoma
by Lina Song, Jinye Guan, Qunmei Zhou, Wenshang Liu, Jürgen C. Becker and Dan Deng
Cancers 2025, 17(15), 2547; https://doi.org/10.3390/cancers17152547 (registering DOI) - 1 Aug 2025
Abstract
Recent preclinical and clinical studies have confirmed the essential role of interferons in the host’s immune response against malignant cells. Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer strongly associated with Merkel cell polyomavirus (MCPyV). Despite progress in understanding MCC pathogenesis, [...] Read more.
Recent preclinical and clinical studies have confirmed the essential role of interferons in the host’s immune response against malignant cells. Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer strongly associated with Merkel cell polyomavirus (MCPyV). Despite progress in understanding MCC pathogenesis, the role of innate immune signaling, particularly interferon-γ (IFN γ) and its downstream pathways, remains underexplored. This review summarizes recent findings on IFN-γ in MCC, highlighting its dual role in promoting both antitumor immunity and immune evasion. IFN-γ enhances cytotoxic T cell responses, upregulates MHC class I/II expression, and induces tumor cell apoptosis. Transcriptomic studies have shown that IFN-γ treatment upregulates immune-regulatory genes including PD-L1, HLA-A/B/C, and IDO1 by over threefold; it also activates APOBEC3B and 3G, contributing to antiviral defense and tumor editing. Clinically, immune checkpoint inhibitors (ICIs) such as pembrolizumab and avelumab yield objective response rates of 30–56% and two-year overall survival rates exceeding 60% in advanced MCC. However, approximately 50% of patients do not respond, in part due to IFN-γ signaling deficiencies. This review further discusses IFN-γ’s crosstalk with the STAT1/3/5 pathways and emerging combination strategies aimed at restoring immune sensitivity. Understanding these mechanisms may inform personalized immunotherapeutic approaches and guide the development of IFN-γ–based interventions in MCC. Full article
(This article belongs to the Special Issue Histopathology and Pathogenesis of Skin Cancer)
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