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18 pages, 684 KB

Open AccessArticle

A New Goodness-of-Fit Test for Azzalini’s Skew-t Distribution Based on the Energy Distance Framework with Applications

by Joseph Njuki and Abeer M. Hasan

Mathematics 2025, 13(23), 3833; https://doi.org/10.3390/math13233833 (registering DOI) - 29 Nov 2025

In response to the growing need for flexible parametric models for skewed and heavy-tailed data, this paper introduces a novel goodness-of-fit test for the Skew-t distribution, a widely used flexible parametric probability distribution. Traditional methods often fail to capture the complex behavior [...] Read more.

In response to the growing need for flexible parametric models for skewed and heavy-tailed data, this paper introduces a novel goodness-of-fit test for the Skew-t distribution, a widely used flexible parametric probability distribution. Traditional methods often fail to capture the complex behavior of data in fields such as engineering, public health, and the social sciences. Our proposed test, based on energy statistics, provides practitioners with a robust and powerful tool for assessing the suitability of the Skew-t distribution for their data. We present a comprehensive methodological evaluation, including a comparative study that highlights the advantages of our approach over traditional tests. The results of our simulation studies demonstrate a significant improvement in power, leading to more reliable inference. To further showcase the practical utility of our method, we apply the proposed test to three real-world datasets, offering a valuable contribution to both the theoretical and applied aspects of statistical modeling for non-normal data. Full article

(This article belongs to the Special Issue Advances in Flexible Parametric Distributions for Modeling Skewness and Kurtosis)

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30 pages, 4746 KB

Open AccessArticle

Bioinformatic Approach to Identify Positive Prognostic TGFB2-Dependent and Negative Prognostic TGFB2-Independent Biomarkers for Breast Cancers

by Sanjive Qazi, Stephen Richardson, Mike Potts, Scott Myers and Vuong Trieu

Int. J. Mol. Sci. 2025, 26(23), 11580; https://doi.org/10.3390/ijms262311580 (registering DOI) - 29 Nov 2025

Abstract

Breast cancer is highly heterogeneous, with multiple subtypes that differ in molecular and clinical characteristics. It remains the most common cancer among women worldwide. We conducted a hypothesis-generating study using a bioinformatics approach in order to identify potential prognostic biomarkers for breast cancer [...] Read more.

Breast cancer is highly heterogeneous, with multiple subtypes that differ in molecular and clinical characteristics. It remains the most common cancer among women worldwide. We conducted a hypothesis-generating study using a bioinformatics approach in order to identify potential prognostic biomarkers for breast cancer patients across multiple molecular subtypes. Given the influential role of the transforming growth factor beta (TGFB) pathway in shaping the immune microenvironment, we focused on the isoform, transforming growth factor beta 2 (TGFB2), which is upregulated in tumors, to identify TGFB2-dependent and -independent biomarkers for breast cancer patients’ overall survival (OS) responses. We evaluated the impact of TGFB2 mRNA expression, in conjunction with other potential prognostic markers, on overall survival (OS) in breast cancer patients using The Cancer Genome Atlas (TCGA) and KMplotter databases. We employed a multivariate Cox proportional hazards model to compute hazard ratios (HRs) for TGFB2 mRNA expression, integrating an interaction term that accounts for the multiplicative relationship between TGFB2 and marker gene expressions while controlling age at diagnosis and cancer subtype and differentiating between patients receiving chemotherapy alone and those undergoing alternative therapeutic interventions. We used the KMplotter database to confirm TGFB2-independent prognostic markers from TCGA data. In cases dependent on TGFB2, increased mRNA expression of TGFB2 alongside higher levels of GDAP1, TBL1XR1, RNFT1, HACL1, SLC27A2, NLE1, or TXNDC16 was correlated with improved OS among breast cancer patients, of which four genes were upregulated in tumor tissues (SLC27A2, TXNDC16, TBL1XR1, GDAP1). Future studies will be required to confirm breast cancer patients could improve OS outcomes for patients expressing high levels of TGFB2 and the marker genes in prospective clinical trials. Additionally, multivariate analysis revealed that the elevated expression of six genes (ENO1, GLRX2, PLOD1, PRDX4, TAGLN2, TMED9) were correlated with increases in HR, independent of TGFB2 mRNA expression; all except GLRX2 were identified as druggable targets. Future investigations assessing protein expression in breast cancer tumors to confirm the results of our retrospective analysis of mRNA levels will determine whether the protein products of these genes represent viable therapeutic targets. Protein–protein interaction (STRING) analysis indicated that TGFB2 is associated with EGFR and MYC from the PAM50 breast cancer gene signature. These findings suggest that correlation of TGFB2-related markers could potentially complement the PAM50 signature in the assessment of OS prognosis in breast cancer patients, but further validation of the TGFB2/EGFR/MYC proteins in tumors is warranted. Full article

(This article belongs to the Section Molecular Oncology)

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24 pages, 7480 KB

Open AccessArticle

Interference of Pseudomonas aeruginosa Virulence Factors by Different Extracts from Inula Species

by Tsvetelina Paunova-Krasteva, Petya D. Dimitrova, Tsvetozara Damyanova, Dayana Borisova, Milena Leseva, Iveta Uzunova, Petya A. Dimitrova, Viktoria Ivanova, Antoaneta Trendafilova, Ralitsa Veleva and Tanya Topouzova-Hristova

Pharmaceuticals 2025, 18(12), 1824; https://doi.org/10.3390/ph18121824 (registering DOI) - 29 Nov 2025

Abstract

Objectives: Pseudomonas aeruginosa is an opportunistic pathogen of high clinical relevance due to its ability to form biofilms, its inherent virulence regulated by quorum-sensing systems, and its multidrug resistance. In the present study, we evaluated the inhibitory potential of nine extracts from [...] Read more.

Objectives: Pseudomonas aeruginosa is an opportunistic pathogen of high clinical relevance due to its ability to form biofilms, its inherent virulence regulated by quorum-sensing systems, and its multidrug resistance. In the present study, we evaluated the inhibitory potential of nine extracts from Inula species (chloroform and methanolic fractions, including a sesquiterpene lactone-enriched fraction) against biofilm formation and virulence-associated traits of P. aeruginosa PAO1 and three multidrug-resistant clinical isolates, as well as their cytotoxicity, biocompatibility, and ability to affect cytokine and nitric oxide production in infected skin explants. Methods: The following methods were applied: fractionation and extraction of plant extracts; cytotoxicity assessment on HFF cells; crystal violet assay for determining antibiofilm activity; fluorescence microscopy for evaluating biofilm viability; electron microscopy for assessing the 3D structure of biofilms and morphological alterations; inhibition assays of pyocyanin pigment, protease activity, bacterial motility, interleukin-17, and nitric oxide production; histological analysis of mouse skin explants. Results: Quantitative analyses of antibiofilm activity revealed that five of the tested extracts inhibited biofilm formation by more than 50%. Structural and functional analyses using confocal laser scanning microscopy and scanning electron microscopy demonstrated a substantial reduction in biofilm thickness, exfoliation of biofilm biomass, the presence of isolated bacterial clusters, metabolically inactive cell populations, and morphological abnormalities associated with cell elongation, invaginations, and polar deformations as a consequence of treatment. In addition, the plant extracts strongly affected virulence factors regulated by quorum sensing. The methanolic fractions from I. britannica and I. bifrons significantly suppressed pyocyanin synthesis. In contrast, the chloroform fractions from I. helenium and I. spiraeifolia produced the largest inhibition zones in assays for extracellular protease activity. Furthermore, all chloroform extracts suppressed bacterial motility, with the lowest swarming diameter observed for the chloroform and lactone-enriched fractions from I. britannica. The chloroform extracts of I. helenium and I. bifrons, methanolic extracts of I. britannica, and chloroform and methanolic extracts of I. spiraeifolia showed relatively low toxicity to normal diploid human fibroblasts. Methanolic and chloroform fractions from I. britannica disrupted biofilm integrity and reduced IL-17A and nitric oxide production in infected skin explants. Conclusions: All these findings indicate a possible synergistic action of the chemical constituents within the fractions on quorum-sensing regulation, biofilm formation, cellular viability, and modulation of host inflammatory responses. Full article

(This article belongs to the Special Issue Challenges in Discovering Innovations Related to Biofilms: Virulence, Spread, Control Strategies and Treatment)

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13 pages, 1835 KB

Open AccessArticle

Thykamine™: A New Player in the Field of Anti-Inflammatory Drugs

by Charles Lynde, Louis Flamand, Vincent McCarty and John Sampalis

Biomedicines 2025, 13(12), 2938; https://doi.org/10.3390/biomedicines13122938 (registering DOI) - 29 Nov 2025

Abstract

Background/Objectives: Persistent inflammation driven by cytokines/chemokines plays a crucial role in the pathogenesis of numerous chronic inflammatory and autoimmune conditions, including rheumatoid arthritis, atopic dermatitis, and ulcerative colitis. Current therapeutic agents often present limitations due to adverse effects. Thykamine™, a new plant-derived [...] Read more.

Background/Objectives: Persistent inflammation driven by cytokines/chemokines plays a crucial role in the pathogenesis of numerous chronic inflammatory and autoimmune conditions, including rheumatoid arthritis, atopic dermatitis, and ulcerative colitis. Current therapeutic agents often present limitations due to adverse effects. Thykamine™, a new plant-derived multi-target drug, has demonstrated promising anti-inflammatory effects and a favorable safety profile in clinical settings. This study aimed to compare the in vitro chemokine-inhibitory potency of Thykamine™, a novel plant-derived anti-inflammatory compound, with that of six marketed corticosteroid and non-steroidal agents. Methods: This study compared the in vitro potency of Thykamine™ against widely prescribed anti-inflammatory agents, including corticosteroids (betamethasone, clobetasol, hydrocortisone, prednisone) and non-steroidal therapies (crisaborole, pimecrolimus). Potency was assessed by measuring the inhibition of key pro-inflammatory chemokines: MCP-1, MIP-1α, MIP-1β, and RANTES in lipopolysaccharide-stimulated U937 cells. Results: Area-under-the-curve (AUC) analyses confirmed that Thykamine™ inhibited secretion of the chemokines MCP-1, MIP-1α, and MIP-1β with significantly greater potency than all other agents tested. Thykamine™ also suppressed secretion of RANTES similarly to prednisone and significantly more than betamethasone, clobetasol, hydrocortisone, and pimecrolimus but less than crisaborole due to crisaborole’s elevated potency when administered at high concentration. Conclusions: Overall, Thykamine™ showed significantly greater or comparable inhibitory potency, particularly at lower concentrations, without evidence of cytotoxicity. These findings underscore the potential of Thykamine™ as a potent, multi-target anti-inflammatory therapy, which could offer substantial clinical advantages by effectively controlling chemokine-mediated inflammation with potentially fewer adverse effects. The results of this study support the need for evaluation of the clinical therapeutic efficacy of Thykamine™ in a wide range of autoimmune conditions. Full article

(This article belongs to the Special Issue Advances in Pharmacology of Pain and Inflammation)

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11 pages, 1618 KB

Open AccessArticle

Demolding Simulation of Propagation Phase Metasurfaces via Roll-to-Plate Nanoimprint

by Bowen Hu, Hao Chen, Dizhi Sun and Liangui Deng

Micromachines 2025, 16(12), 1360; https://doi.org/10.3390/mi16121360 (registering DOI) - 29 Nov 2025

Abstract

Propagation phase metasurfaces have excellent electromagnetic regulation and polarization-insensitive properties, while roll-to-plate nanoimprint lithography (R2P-NIL) is ideal for their large-scale low-cost fabrication. Existing demolding simulations for R2P-NIL are limited to 2D analysis, ignore elastomeric roller impacts, and cannot handle the discrete pillar/hole structures [...] Read more.

Propagation phase metasurfaces have excellent electromagnetic regulation and polarization-insensitive properties, while roll-to-plate nanoimprint lithography (R2P-NIL) is ideal for their large-scale low-cost fabrication. Existing demolding simulations for R2P-NIL are limited to 2D analysis, ignore elastomeric roller impacts, and cannot handle the discrete pillar/hole structures of such metasurfaces. This study establishes a 3D multiscale simulation model using a finite element method combining a macroscopic elastomeric roller deformation model and a microscopic demolding stress model with motion equation-based parameter transfer. Simulation results show macroscopically that zero elastomeric layer thickness minimizes stress, while stress rises and then stabilizes with increasing thickness; a moderately larger roller radius disperses stress; excessive pressure amplifies stress; a microscopically higher resist elastic modulus lowers stress; cylindrical structures have less stress than cuboids; and the limit aspect ratio peaks at a 100 nm line width. This work provides theoretical support for R2P-NIL parameter optimization and promotes the stable large-scale production of propagation phase metasurfaces. Full article

(This article belongs to the Special Issue Fabrication of Functional Surface Microstructures)

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23 pages, 1752 KB

Open AccessArticle

Economics of Renewables Versus Fossil Fuels 2022–2036: Case Study of an Individual House Applying Investment Project Evaluation Methods

by Robert Uberman and Wojciech Naworyta

Energies 2025, 18(23), 6282; https://doi.org/10.3390/en18236282 (registering DOI) - 29 Nov 2025

Abstract

This paper presents a comprehensive economic comparison between renewable and fossil-fuel-based heating systems for a newly constructed residential building in Kraków, Poland, over the period 2022–2030. The analysis introduces the concept of Corrected Final Energy Consumption (CFEC) as a harmonized measure for comparing [...] Read more.

This paper presents a comprehensive economic comparison between renewable and fossil-fuel-based heating systems for a newly constructed residential building in Kraków, Poland, over the period 2022–2030. The analysis introduces the concept of Corrected Final Energy Consumption (CFEC) as a harmonized measure for comparing various energy sources and applies the Present Value of Total Lifecycle Cost (PVTLC) as an appropriate financial metric for non-commercial residential investments. Four heating options were examined: district heating system (DHS), gas boiler, air-to-water heat pump, and heat pump combined with photovoltaic (PV) panels. Based on real tariffs and standardized data from the Energy Performance Certificate (EPC), the DHS option demonstrated the lowest lifecycle cost, while the air-to-water heat pump—despite environmental advantages—proved the most expensive without substantial subsidies. Sensitivity analyses confirmed the strong influence of investment subsidies and fuel price fluctuations on the competitiveness of alternative systems. The findings highlight the methodological shortcomings of conventional annual-cost approaches and propose PVTLC as a more reliable decision-making tool for residential energy planning. The study also discusses regulatory, climatic, and behavioral factors affecting investment outcomes and emphasizes the need to integrate financial, environmental, and social criteria when evaluating household-level energy solutions. Full article

(This article belongs to the Special Issue From Consumer Behavior to Business Innovation: Paths to a Sustainable Energy Future)

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16 pages, 4097 KB

Open AccessArticle

Transcriptome Analysis of Paeonia ostii ‘Fengdan’ Seeds Uncovers Starch and Sucrose Metabolism Conferring High Yield Under Brassinosteroid Treatment

by Shixi Yu, Ruixue Xiao, Xiaopeng Li, Renjie Li, Chengwei Song, Yuying Li, Jingyi Zhao and Xiaogai Hou

Genes 2025, 16(12), 1424; https://doi.org/10.3390/genes16121424 (registering DOI) - 29 Nov 2025

Abstract

Background: Tree peony (Paeonia section Moutan DC.) seeds, renowned for their rich content of unsaturated fatty acids, hold significant medicinal and nutritional value. Despite their potential, their yield is relatively low, which constrains economic gains and health benefits. Brassinosteroids (BRs), emerging [...] Read more.

Background: Tree peony (Paeonia section Moutan DC.) seeds, renowned for their rich content of unsaturated fatty acids, hold significant medicinal and nutritional value. Despite their potential, their yield is relatively low, which constrains economic gains and health benefits. Brassinosteroids (BRs), emerging as potent plant growth regulators, have demonstrated efficacy in boosting plant productivity. Methods: This study employed Paeonia ostii ‘Fengdan’ and administered either water (control group, CKs) or 0.05 mg/L BRs through foliar application during the seed enrichment and conversion phase to assess the effects of BR treatment on seed yield. Results: The BR treatment notably enhanced the protein, starch, and sugar content and yield of P. ostii ‘Fengdan’ seeds, surpassing those of the CKs. Transcriptome profiling identified a plethora of differentially expressed genes in P. ostii ‘Fengdan’ in response to BR treatment, which are implicated in biological processes associated with nutrient reservoir activity. KEGG analysis highlighted the pivotal role of starch and sucrose metabolism in the BR treatment response. WGCNA revealed key gene expression modules that correlate with physiological traits in P. ostii ‘Fengdan’. Furthermore, the quantitative real-time PCR (qRT-PCR) validation of key genes in this pathway revealed that BR treatment enhances yield through a dual mechanism: accelerating the seed-filling process and optimizing developmental timing for earlier maturation. Conclusions: Collectively, these findings offer inaugural comprehensive genomic resources delineating the transcriptional regulatory mechanisms of BRs in P. ostii ‘Fengdan’ seeds. Full article

(This article belongs to the Section Plant Genetics and Genomics)

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16 pages, 1600 KB

Open AccessArticle

A Transformer-Based Multi-Task Learning Model for Vehicle Traffic Surveillance

by Fernando Hermosillo-Reynoso, Juan-Carlos López-Pimentel, Erica Ruiz-Ibarra, Armando García-Berumen, José A. Del-Puerto-Flores, H. E. Gilardi-Velazquez, Vinoth Babu Kumaravelu and L. A. Luna-Rodriguez

Mathematics 2025, 13(23), 3832; https://doi.org/10.3390/math13233832 (registering DOI) - 29 Nov 2025

Abstract

Vehicle traffic surveillance (VTS) systems are based on the automatic analysis of video sequences to detect, classify, and track vehicles in urban environments. The design of new VTS systems requires computationally efficient architectures with high performance in accuracy. Conventional approaches based on multi-stage [...] Read more.

Vehicle traffic surveillance (VTS) systems are based on the automatic analysis of video sequences to detect, classify, and track vehicles in urban environments. The design of new VTS systems requires computationally efficient architectures with high performance in accuracy. Conventional approaches based on multi-stage pipelines have been successfully used during the last decade. However, these systems need to be improved to face the challenges of complex, high-mobility traffic environments. This article proposes an efficient system based on transformer architectures for VTS channels. The proposed analysis system is evaluated in scenarios with high vehicle density and occlusions. The results demonstrate that the proposed scheme reduces the computational complexity required for multi-object detection and tracking and exhibits a Multiple Object Tracking Accuracy (MOTA) of 0.757 and an identity F1 score (IDF1) of 0.832 when compared to conventional multi-stage systems under the same conditions and parameters, along with achieving a high detection precision of 0.934. The results show the viability of implementing the proposed system in practical applications for high-density vehicle VTS channels. Full article

(This article belongs to the Special Issue Data-Driven Decentralized Learning for Future Communication Networks)

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15 pages, 3255 KB

Open AccessArticle

Engineering Glutathione Peroxidase-Loaded Polymeric Nanogels Through a Grafting-To Route for Enhanced Enzyme Stability and Activity

by Suman Basak

Polymers 2025, 17(23), 3180; https://doi.org/10.3390/polym17233180 (registering DOI) - 29 Nov 2025

Abstract

Nanogels provide unique opportunities for stabilizing fragile enzymes through soft, hydrated polymer networks. Here, we report the development of a glutathione peroxidase (GPx)-loaded nanogel (GPxNG) engineered via a mild “grafting-to” epoxy–amine coupling strategy to enhance enzyme stability and antioxidant function. An amphiphilic copolymer [...] Read more.

Nanogels provide unique opportunities for stabilizing fragile enzymes through soft, hydrated polymer networks. Here, we report the development of a glutathione peroxidase (GPx)-loaded nanogel (GPxNG) engineered via a mild “grafting-to” epoxy–amine coupling strategy to enhance enzyme stability and antioxidant function. An amphiphilic copolymer composed of methacrylated 2,2,6,6-tetramethyl-4-piperidyl (PMA) and glycidyl methacrylate (GMA) was synthesized by controlled reversible addition–fragmentation chain-transfer (RAFT) polymerization using a poly(ethylene glycol) (PEG) macro-chain transfer agent (macro-CTA), yielding well-defined polymer chains with reactive epoxy groups. Covalent conjugation between polymer epoxides and GPx enzyme surface amines generated soft, PEGylated nanogels with high coupling efficiency, uniform particle sizes, and excellent colloidal stability. The engineered nanogels exhibited shear-thinning injectability, robust storage stability, and non-cytotoxic behavior in RAW 264.7 macrophages. Compared with native GPx enzyme, GPxNGs demonstrated significantly enhanced reactive oxygen species (ROS) scavenging activity, including strong inhibition of lipid peroxidation and copper-induced low-density lipoprotein (LDL) oxidation. Importantly, the nanogels preserved GPx enzyme activity after extended storage, freeze–thaw cycles, and repeated catalytic use, whereas the free enzyme rapidly lost function. This protective effect arises from the nanoscale confinement of the GPx enzyme within the flexible PEG-based network, which limits unfolding and aggregation. Overall, this work introduces a simple and biocompatible “grafting-to” nanogel platform capable of stabilizing redox-active enzymes without harsh conditions. The GPx nanogels combine high enzymatic preservation, potent antioxidant activity, and excellent handling properties, highlighting their potential as a therapeutic nanoplatform for mitigating oxidative stress-associated disorders such as atherosclerosis. Full article

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23 pages, 16512 KB

Open AccessArticle

Exploring the Relationship Between the Built Environment and Spatiotemporal Heterogeneity of Urban Traffic Congestion During Tourism Peaks: A Case Study of Harbin, China

by Renyue Cui and Jun Zhang

ISPRS Int. J. Geo-Inf. 2025, 14(12), 470; https://doi.org/10.3390/ijgi14120470 (registering DOI) - 29 Nov 2025

Abstract

Understanding the spatial heterogeneity of traffic congestion drivers is crucial for data-informed urban planning in tourist cities. This study investigates the spatiotemporal relationship between built environment characteristics and traffic congestion in the central urban area of a major northern Chinese tourist city. We [...] Read more.

Understanding the spatial heterogeneity of traffic congestion drivers is crucial for data-informed urban planning in tourist cities. This study investigates the spatiotemporal relationship between built environment characteristics and traffic congestion in the central urban area of a major northern Chinese tourist city. We apply a Multiscale Geographically Weighted Regression (MGWR) model to geospatial data across four typical peak periods and benchmark the results against Ordinary Least Squares (OLS) and Geographically Weighted Regression (GWR). The MGWR model demonstrates superior capability in capturing spatial non-stationarity and multiscale effects. The results reveal strong spatiotemporal heterogeneity in the effects of built environment factors on congestion. Intersection density demonstrates a stronger mitigating effect during weekday evening peaks. Catering facilities significantly exacerbate congestion in tourist hotspots. Tourism-related facilities such as hotels and attractions intensify congestion during weekend peaks. Parking availability shows dual impacts, with peripheral parking reducing pressure and central clustering worsening congestion. Our geospatially disaggregated results provide empirical evidence for location-sensitive and temporally adaptive traffic management and urban design strategies. This study highlights the value of MGWR-based spatial modeling in supporting geoinformation-driven urban mobility planning. Full article

15 pages, 3367 KB

Open AccessArticle

Brain Changes in Alcohol Induced Liver Cirrhosis Patients: Insights from Quantitative Susceptibility Mapping

by Andrej Vovk, Stefan Ropele, Sebastian Stefanovic, Borut Stabuc, Dusan Suput, Marjana Turk Jerovsek and Gasper Zupan

Biomedicines 2025, 13(12), 2937; https://doi.org/10.3390/biomedicines13122937 (registering DOI) - 29 Nov 2025

Abstract

Background and Purpose: Hepatic encephalopathy (HE) is a neuropsychiatric syndrome associated with liver cirrhosis (LC) that often results in cognitive impairment. Minimal HE (mHE), a subtle form of the condition, significantly affects patients’ quality of life. Advanced imaging techniques, such as quantitative susceptibility [...] Read more.

Background and Purpose: Hepatic encephalopathy (HE) is a neuropsychiatric syndrome associated with liver cirrhosis (LC) that often results in cognitive impairment. Minimal HE (mHE), a subtle form of the condition, significantly affects patients’ quality of life. Advanced imaging techniques, such as quantitative susceptibility mapping (QSM), provide new insights into the brain changes associated with HE. Materials and Methods: The study included 28 patients (17 with mHE and 11 without) with alcohol-induced LC and 25 healthy controls. MR imaging, including QSM, was utilized to assess microstructural tissue changes and iron deposition in the brain. Cognitive function was assessed through a neuropsychological test battery. QSM quantified magnetic susceptibility in deep gray matter, while enlarged perivascular spaces (EPVS) were evaluated using T2-weighted images. Statistical analyses, including non-parametric tests and linear regression, assessed differences in susceptibility and their correlation with cognitive performance and EPVS. Results: Significant differences in cognitive performance and brain susceptibility were observed between patients and controls. Patients exhibited lower susceptibility in the caudate nucleus with the accumbens (CNA); mHE patients, in particular, had a significant reduction in CNA susceptibility. Additionally, EPVS grade correlated positively with cognitive decline, suggesting that EPVS may play an essential role in the pathophysiology of mHE. Conclusions: This study demonstrates that QSM can detect subtle brain changes in LC patients, with decreased susceptibility in the CN (caudate nucleus) linked to cognitive impairment in mHE. The role of EPVS in HE warrants further investigation, as it may affect the efficacy of current diagnostic and therapeutic approaches. These findings highlight the potential of QSM to improve HE assessment. Full article

(This article belongs to the Section Neurobiology and Clinical Neuroscience)

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17 pages, 1632 KB

Open AccessArticle

Adsorption of Imidazolium-Based ILs Combined on Activated Carbon Obtained from Grape Seeds

by Ismael F. Mena, Elena Diaz, Jose Palomar and Angel F. Mohedano

Molecules 2025, 30(23), 4595; https://doi.org/10.3390/molecules30234595 (registering DOI) - 29 Nov 2025

Abstract

In this work, the adsorption of imidazolium-based ionic liquids containing the bis(trifluoromethanesulfonyl) imide anion (NTf₂⁻) from aqueous phase was evaluated using different activated carbons (ACs). Three commercial Acs and two Acs prepared from grape seeds (one produced by pyrolysis and [...] Read more.

In this work, the adsorption of imidazolium-based ionic liquids containing the bis(trifluoromethanesulfonyl) imide anion (NTf₂⁻) from aqueous phase was evaluated using different activated carbons (ACs). Three commercial Acs and two Acs prepared from grape seeds (one produced by pyrolysis and the other by hydrothermal carbonization (HTC), both activated with potassium hydroxide) were tested, assessing the adsorption of both the cation and the anion. For commercial ACs, similar adsorption performances were observed, with maximum adsorption capacities ranging from 0.85 to 1.08 mmol g⁻¹. These values increased under acidic conditions (pH 4), reaching 1.74 mmol g⁻¹ for the 1-butyl-3-methylimidazolium cation (Bmim⁺) and 1.87 mmol g⁻¹ for NTf₂⁻. Among the prepared ACs, the HTC-derived AC showed slightly higher capacities than the commercial samples, while the pyrolysis-derived AC exhibited the highest adsorption capacity for BmimNTf₂ (3.36 mmol g⁻¹ at pH 4). In terms of reusability, the pyrolysis-derived AC maintained 84% of its initial adsorption capacity between the third and fifth regeneration cycles. These results highlight the high adsorption performance and recyclability of grape-seed-derived activated carbons, demonstrating their potential for the removal of ionic liquids from aqueous environments. Full article

(This article belongs to the Special Issue Ionic Liquids and Deep Eutectic Solvents in Catalysis: Current Status and Future Outlook)

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18 pages, 534 KB

Open AccessArticle

Dopaminergic Genetic Variation and Trait Impulsivity: The Role of COMT rs4680 in Mixed Behavioral and Substance Addictions

by Gabriela Zdunek, Remigiusz Recław, Aleksandra Suchanecka, Krzysztof Chmielowiec, Dariusz Larysz, Marta Kuczak-Wójtowicz, Kinga Łosińska, Jolanta Chmielowiec and Anna Grzywacz

Life 2025, 15(12), 1836; https://doi.org/10.3390/life15121836 (registering DOI) - 29 Nov 2025

Abstract

Background: Impulsivity is a multidimensional trait associated with the development and maintenance of behavioral and substance addictions. Genetic polymorphisms, particularly within the dopaminergic system, are thought to modulate individual differences in impulsivity. The COMT rs4680 (Val158Met) polymorphism influences enzymatic activity of catechol-O-methyltransferase [...] Read more.

Background: Impulsivity is a multidimensional trait associated with the development and maintenance of behavioral and substance addictions. Genetic polymorphisms, particularly within the dopaminergic system, are thought to modulate individual differences in impulsivity. The COMT rs4680 (Val158Met) polymorphism influences enzymatic activity of catechol-O-methyltransferase and may alter dopaminergic tone in the prefrontal cortex. This study investigated whether COMT rs4680 genotype interacts with addiction status (behavioral and substance addictions) to influence trait impulsivity. Methods: The study included 309 Polish men: 128 with mixed behavioral and substance addictions and 181 healthy controls. All participants completed the Barratt Impulsiveness Scale (BIS-11) and were genotyped for COMT rs4680. A two-way ANOVA was used to assess main and interaction effects of genotype and group on total and subscale BIS-11 scores. Results: Individuals with mixed addictions scored significantly higher on all BIS-11 subscales (p < 0.01). A significant interaction effect was observed for the Non-Planning (F_2,303 = 4.40, p = 0.0131, η² = 0.028) and Total BIS-11 scale (F_2,303 = 5.77, p = 0.0035, η² = 0.037), with the A/A genotype associated with increased impulsivity, especially among the clinical group. Conclusions: These findings support a gene-by-environment interaction in impulsivity, where COMT rs4680 Met/Met homozygotes may be more susceptible to heightened impulsivity in addiction contexts. The results highlight the potential utility of COMT genotyping in personalizing therapeutic strategies for impulse-related disorders such as addictive disorders. This study extends evidence on dopaminergic modulation of impulsivity to behavioral and substance addictions. Full article

(This article belongs to the Section Genetics and Genomics)

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20 pages, 815 KB

Open AccessArticle

Automotive Scratch Detection: A Lightweight Convolutional Network Approach Augmented by Generative Adversarial Learning

by Guojie Qu, Jiaying Liao, Kai Liu, Bin Xu and Yuwen Qian

Machines 2025, 13(12), 1107; https://doi.org/10.3390/machines13121107 (registering DOI) - 29 Nov 2025

Abstract

The growing demand for high-precision machining and inspection in modern manufacturing has positioned machine vision as a key technology for surface defect detection. However, identifying subtle surface scratches on automotive components remains a challenging task due to the stringent requirements on sensitivity, precision, [...] Read more.

The growing demand for high-precision machining and inspection in modern manufacturing has positioned machine vision as a key technology for surface defect detection. However, identifying subtle surface scratches on automotive components remains a challenging task due to the stringent requirements on sensitivity, precision, and robustness against complex background interference. In this paper, we propose an automated detection system with a Convolutional Neural Network (CNN) architecture. To address data scarcity, we construct a large-scale, high-quality dataset using both data augmentation and Generative Adversarial Network (GAN)-based synthesis. Furthermore, the proposed lightweight CNN replaces traditional fully connected layers with one-dimensional convolutional layers to reduce parameter complexity and model size, while a Dropout mechanism is incorporated to mitigate overfitting and enhance generalization. Experimental results demonstrate that the proposed model achieves superior detection accuracy and robustness across diverse imaging conditions. Moreover, the developed system effectively addresses the limitations of data insufficiency and model complexity, offering an efficient and automated solution for surface quality inspection in industrial manufacturing. Full article

(This article belongs to the Section Machines Testing and Maintenance)

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11 pages, 221 KB

Open AccessArticle

Validation of the Greek Version of the Colorado Learning Difficulties Questionnaire

by Eleni Panagiota Fefe, Xanthi Tigani, Maria Michou, Vasiliki Efthymiou, Antonios I. Christou, Christina Darviri, Maria Charalampopoulou, Emmanouil Apostolakis, Stavroula Papadodima, Christina Kanaka-Gantenbein and Flora Bacopoulou

Children 2025, 12(12), 1623; https://doi.org/10.3390/children12121623 (registering DOI) - 29 Nov 2025

Abstract

Background: Learning disabilities have a significant impact on children’s and adolescents’ academic progress; thus, early detection is of great importance. Parents play a key role, as they can provide valuable and unique information regarding their offspring’s learning challenges. The Colorado Learning Difficulties Questionnaire [...] Read more.

Background: Learning disabilities have a significant impact on children’s and adolescents’ academic progress; thus, early detection is of great importance. Parents play a key role, as they can provide valuable and unique information regarding their offspring’s learning challenges. The Colorado Learning Difficulties Questionnaire (CLDQ) is a quick and easy-to-use parent-report rating questionnaire evaluating specific areas of functioning that are most affected in children and adolescents with learning difficulties, such as reading, mathematics, social cognition, spatial abilities, and memory. This study aimed to examine the validity and reliability of the Greek version of the CLDQ. Methods: A cross-sectional design was employed in a sample of Greek parents and caregivers to test the Greek version of the CLDQ. The 20-item questionnaire was translated into Greek using the appropriate forward-backward translation. Results: The final sample consisted of 303 parents/caregivers of children and adolescents aged 11–17 years with learning difficulties. Analysis was consistent with the original scale and revealed five major factors labeled Reading, Mathematics, Social Cognition, Social Anxiety, and Spatial Problems. Contrary to the original version, two items loaded on two separate factors. Conclusions: The Greek version of the CLDQ demonstrated acceptable reliability and good validity. Consistent with the original version, exploratory factor analysis identified five distinct factors. These findings support the Greek version of the CLDQ as a valid and reliable tool for assessing and screening students with learning difficulties in Greece. Full article

(This article belongs to the Section Global Pediatric Health)

16 pages, 645 KB

Open AccessArticle

Evaluation of Carnitine Status in Postnatal Piglets from Sows Fed Clofibrate

by Brandon Pike, Jinan Zhao, Julie A. Hicks, Tim Boston, Hsiao-Ching Liu, Jack Odle and Xi Lin

Curr. Issues Mol. Biol. 2025, 47(12), 1004; https://doi.org/10.3390/cimb47121004 (registering DOI) - 29 Nov 2025

Abstract

Milk carnitine content decreases quickly with lactation days and is accompanied by PPARα downregulation. This study aimed to investigate the effects of the maternal supplementation of the PPARα agonist, clofibrate, on milk carnitine content and carnitine status in neonates during lactation. Pregnant sows [...] Read more.

Milk carnitine content decreases quickly with lactation days and is accompanied by PPARα downregulation. This study aimed to investigate the effects of the maternal supplementation of the PPARα agonist, clofibrate, on milk carnitine content and carnitine status in neonates during lactation. Pregnant sows (n = 27) were fed diets containing either 0, 0.25, or 0.5% clofibrate from d107 gestation to d7 of lactation. Carnitines were determined in milk on d1, 3, 5, 7, 10, 14, and 19 post farrowing and in the plasma, intestine, and liver of piglets on d1, 7, 14, and 19. Milk carnitine decreased quadratically with lactation days (p < 0.0001). Hepatic and intestinal carnitines increased with postnatal age (p < 0.05). Correlations between levels were detected between milk and plasma (R² = 0.5, p < 0.0001) and milk and intestine (R² = 0.23; p < 0.05). Clofibrate increased BBH expression (p < 0.05) and tended to increase OCTN2 expression (p = 0.055) in intestine and TMLH in liver (p = 0.059). Hepatic ALD and TMLH increased (p < 0.0005) with postnatal age. However, gene modification had no effect on plasma and mucosa carnitine concentrations. We conclude that changes in carnitines within plasma and mucosa are mostly driven by milk carnitines during postnatal development. Full article

(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)

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20 pages, 13220 KB

Open AccessArticle

Prioritization Model for the Location of Temporary Points of Distribution for Disaster Response

by María Fernanda Carnero Quispe, Miguel Antonio Daza Moscoso, Jose Manuel Cardenas Medina, Ana Ysabel Polanco Aguilar, Irineu de Brito Junior and Hugo Tsugunobu Yoshida Yoshizaki

Logistics 2025, 9(4), 174; https://doi.org/10.3390/logistics9040174 (registering DOI) - 29 Nov 2025

Abstract

Background: Disasters generate abrupt surges in humanitarian demand, requiring response strategies that balance operational performance with vulnerability considerations. This study examines how temporary Points of Distribution (PODs) can be planned and activated to support timely and equitable resource distribution after a high-magnitude earthquake. [...] Read more.

Background: Disasters generate abrupt surges in humanitarian demand, requiring response strategies that balance operational performance with vulnerability considerations. This study examines how temporary Points of Distribution (PODs) can be planned and activated to support timely and equitable resource distribution after a high-magnitude earthquake. Methods: A two-stage framework is proposed. First, a modular p-median model identifies POD locations and allocates modular capacity to minimize population-weighted distance under capacity constraints; travel-distance percentiles guide the selection of p. Second, a SMART-based multi-criteria model ranks facilities using operational metrics and vulnerability indicators, including seismic and economic conditions and the presence of at-risk groups. Results: Evaluation of p values from 3 to 30 shows substantial reductions in travel distances as PODs increase, with an elbow at

p = 12

, where 50% of the residents are within 500 m, 75% within 675 m, and 95% within 1200 m. The SMART analysis forms three priority clusters: facilities 24 and 9 as highest priority; 23, 4, 12, and 22 as medium priority; and the remaining sites as lower priority. Sensitivity analysis shows that rankings are responsive to vulnerability weights, although clusters remain stable. Conclusions: The framework integrates optimization and multi-criteria decision analysis without increasing model complexity, enabling meaningful decision-maker involvement throughout the modeling process. Full article

(This article belongs to the Section Humanitarian and Healthcare Logistics)

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24 pages, 2834 KB

Open AccessArticle

From Laboratory Screening to Greenhouse Flight Bioassay: Development of a Plant-Based Attractant for Tomicus brevipilosus

by Ying Wang, Dan Feng, Genying Zhao, Haoran Li and Peng Chen

Forests 2025, 16(12), 1797; https://doi.org/10.3390/f16121797 (registering DOI) - 29 Nov 2025

Abstract

Tomicus brevipilosus Eggers is a major forest pest affecting Pinus yunnanensis Franch and Pinus kesiya var. Langbianensis (A.Chev.) Gaussen ex Bui in Southwest China. While attractants exist for related species, this study aimed to develop a more effective, tailored attractant for T. brevipilosus [...] Read more.

Tomicus brevipilosus Eggers is a major forest pest affecting Pinus yunnanensis Franch and Pinus kesiya var. Langbianensis (A.Chev.) Gaussen ex Bui in Southwest China. While attractants exist for related species, this study aimed to develop a more effective, tailored attractant for T. brevipilosus. We assessed the activity of host plant volatiles using electroantennography (EAG). Female and male beetles showed strong responses to different compounds: females to β-pinene, terpinolene, (+)-3-carene, and (R)-(+)-limonene; males to (+)-3-carene, 2-isopropyl-5-methylanisole, and D(+)-camphor. An optimized blend of these compounds achieved a high selection rate (57 ± 20%) in olfactory assays. This study represents a crucial preliminary investigation. The concentrations and release systems (rubber septa and centrifuge tubes) were optimized under controlled conditions to identify the most promising candidate for future scaling, rather than for immediate large-scale application. In semi-field cage bioassays, trap catch was highest at mid-canopy height (1.5 times branch-free height), under the cage canopy, and in treatments with low-to-moderate canopy density. This work provides a foundation for developing improved monitoring and management tools for T. brevipilosus. Full article

(This article belongs to the Section Forest Health)

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4 pages, 224 KB

Open AccessEditorial

Current Issues in Vietnamese Linguistics: An Introduction

by Trang Phan, Nigel Duffield and Chao-Ting Tim Chou

Languages 2025, 10(12), 293; https://doi.org/10.3390/languages10120293 (registering DOI) - 29 Nov 2025

Abstract

This Special Issue of Languages, part of the ISVL (International Symposium on Vietnamese Linguistics) series, presents revised papers from the 4th and 5th ISVL workshops, hosted by National Yang Ming Chiao Tung University in 2024 and Ca’ Foscari University of Venice in [...] Read more.

This Special Issue of Languages, part of the ISVL (International Symposium on Vietnamese Linguistics) series, presents revised papers from the 4th and 5th ISVL workshops, hosted by National Yang Ming Chiao Tung University in 2024 and Ca’ Foscari University of Venice in 2025 [...] Full article

(This article belongs to the Special Issue Current Issues in Vietnamese Linguistics)

13 pages, 3986 KB

Open AccessArticle

Effects of Disinfectant Solutions Against COVID-19 on Surface Roughness, Gloss, and Color of Removable Denture Materials

by Aikaterini Mikeli, Nick Polychronakis, Xanthippi Barmpagadaki, Gregory Polyzois, Panagiotis Lagouvardos and Spiros Zinelis

J. Funct. Biomater. 2025, 16(12), 446; https://doi.org/10.3390/jfb16120446 (registering DOI) - 29 Nov 2025

Abstract

The objective of this study was to investigate the effect of surface disinfectant solutions against COVID-19 on the surface roughness, gloss, and color of removable denture materials. Fifty rectangular metallic specimens made of Co-Cr alloy and fifty disk-shaped specimens made of PMMA were [...] Read more.

The objective of this study was to investigate the effect of surface disinfectant solutions against COVID-19 on the surface roughness, gloss, and color of removable denture materials. Fifty rectangular metallic specimens made of Co-Cr alloy and fifty disk-shaped specimens made of PMMA were prepared according to the manufacturers’ instructions. Fifty maxillary right central incisors were also included in the study. The above-mentioned specimens were equally divided into five groups (n = 10). Four disinfectant solutions were tested (0.1 wt% NaOCl, 0.5 wt% H₂O₂, 78 wt% ethanol, and 1 wt% Povidone Iodine), and freshly distilled water was used as the control. To simulate clinical practice, each specimen was immersed in the disinfectant solution 15 times. All specimens were marked, and surface roughness, gloss, and color were measured before and after immersion. All roughness parameters (Sa, Sq, Sz, Sc, and Sv) and gloss values before and after immersion were statistically compared. ΔE*ab values were statistically compared with perception and acceptability thresholds according to ISO/TR 28642. No significant differences were identified for surface roughness parameters for all groups tested. All materials demonstrated a significant increase in gloss after aging regime, while only the metallic specimens illustrated ΔE*ab values higher than the acceptability threshold after disinfection with H₂O₂. None of the surface properties deteriorated after exposure to tested disinfectants, and thus, all of them can be effectively implemented in everyday practice. Full article

(This article belongs to the Special Issue Biomaterials in Conservative Dentistry and Prosthodontics (2nd Edition))

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14 pages, 2531 KB

Open AccessArticle

Reestablishment and Conservation Implications of the Milu Deer Population in Poyang Lake

by Zhibin Cheng, Zhenyu Zhong, Bin Xiong, Xinghua Zhong, Jialiang Ma, Daoli Liu, Chenmiao Feng, Qingyun Guo, Qingxun Zhang, Jiade Bai and Kun Cheng

Animals 2025, 15(23), 3446; https://doi.org/10.3390/ani15233446 (registering DOI) - 29 Nov 2025

Abstract

Reintroduction has been recognized as a vital approach to protecting and restoring wild populations of rare and endangered species. Although numerous reintroduction programs have been launched worldwide, in-depth studies on population establishment, dynamics, distribution patterns, and challenges remain limited. The Milu (Elaphurus [...] Read more.

Reintroduction has been recognized as a vital approach to protecting and restoring wild populations of rare and endangered species. Although numerous reintroduction programs have been launched worldwide, in-depth studies on population establishment, dynamics, distribution patterns, and challenges remain limited. The Milu (Elaphurus davidianus), endemic to China and once declared Extinct in the Wild by the IUCN, has become one of the most successful examples of global endangered species reintroduction since the initiation of its recovery program in 1985. Focusing on the reintroduction project in the Poyang Lake basin—China’s largest freshwater lake—this study analyzed 14 years of monitoring data to examine the processes of population re-establishment, demographic trends, and spatiotemporal distribution of the species, while also identifying major ongoing challenges. Findings reveal the following: (1) the acclimatization process was essential for 10 individuals first reintroduced in 2013, and then 30 individuals joined to the growing population, followed by the largest-scale release of 47 in 2018, which finally led to eight consecutive years of natural reproduction, with a theoretically estimated population of 89 individuals until August 2025; (2) among 1697 individual sightings in 238 monitoring events, 952 records can be distinguished between male and female individuals (sex ratio = 1:1.63), yielding a mean herd size of 7.28 ± 0.68 individuals per sighting event—although numbers rose slightly in 2024, a declining trend was observed from 2019 to 2023 (from 11.26 to 5.13); (3) the Milu have expanded their range across eastern Poyang Lake, demonstrating a behavioral patterns of migrating out of the lake zone during flood seasons and returning in dry season; (4) the restoration of the Milu population is a systematic endeavor, in which government support and the participation of conservation professionals, scientists, volunteers, media, and the public are critical factors; and (5) ongoing threats such as human disturbance (e.g., habitat degradation) and climate change continue to jeopardize long-term population viability. This study offers important scientific insights into the recovery of endangered wildlife globally and underscores the essential role of governmental commitment, long-term monitoring, and multi-stakeholder collaboration in species reintroduction efforts. Full article

(This article belongs to the Special Issue Advances in Ungulate Science: Behavior, Physiology, Reproduction and Conservation)

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20 pages, 2213 KB

Open AccessArticle

Regional Rural Transformation Pathways: A Spatial–Temporal Comparison of Bangladesh, China, Indonesia, and Pakistan

by Pengfei Shi, Dong Wang, David Shearer, Abedullah, Mohammad Jahangir Alam, Chunlai Chen, Jikun Huang, Abid Hussian, Nunung Nuryartono and Tahlim Sudaryanto

Land 2025, 14(12), 2344; https://doi.org/10.3390/land14122344 (registering DOI) - 29 Nov 2025

Abstract

This paper examines the historical evolution and pathways of rural transformation (RT) at the regional level in four Asian countries—Bangladesh, China, Indonesia, and Pakistan. We conduct a comparative spatial analysis of regional level changes in high-value agricultural production (HVAP) and non-farm rural employment [...] Read more.

This paper examines the historical evolution and pathways of rural transformation (RT) at the regional level in four Asian countries—Bangladesh, China, Indonesia, and Pakistan. We conduct a comparative spatial analysis of regional level changes in high-value agricultural production (HVAP) and non-farm rural employment (NFRE). Using long-run data and bivariate mapping, we trace how rural economies have evolved over the past four decades and identify multiple transformation pathways. The results reveal both common upward trends and stark regional contrasts. China demonstrates the most rapid and synergic rise, integrating agricultural upgrading with widespread non-farm rural expansion. Bangladesh and Indonesia show more diverse trajectories, shaped by migration, urbanization, and agro-industrial linkages. Pakistan’s transformation is slower and more fragmented, marked by strong progress in some regions but persistent lags in others. The findings underscore that RT is not linear and can follow diverse pathways—synergic, HVAP-driven, NFRE-driven, remittance-based, or stagnant—depending on geography, natural endowments, policy, and local resource endowments. Our research highlights the need for regionally tailored strategies that link agricultural upgrading with rural labor diversification, strengthen rural–urban connectivity, and ensure that lagging regions are not left further behind. Full article

(This article belongs to the Section Land Socio-Economic and Political Issues)

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30 pages, 1076 KB

Open AccessReview

IoT Applications and Challenges in Global Healthcare Systems: A Comprehensive Review

by Fadele Ayotunde Alaba, Alvaro Rocha, Hakeem Adewale Sulaimon and Owamoyo Najeem

Future Internet 2025, 17(12), 549; https://doi.org/10.3390/fi17120549 (registering DOI) - 29 Nov 2025

Abstract

The Internet of Things (IoT) has influenced the healthcare industry by enabling real-time monitoring, data-driven decision-making, and automation of medical activities. IoT in healthcare comprises a network of interconnected medical devices, sensors, and software systems that gather, analyse, and transmit patient data, enhancing [...] Read more.

The Internet of Things (IoT) has influenced the healthcare industry by enabling real-time monitoring, data-driven decision-making, and automation of medical activities. IoT in healthcare comprises a network of interconnected medical devices, sensors, and software systems that gather, analyse, and transmit patient data, enhancing the efficiency, accuracy, and accessibility of healthcare services. Despite its benefits, the deployment and impact of IoT in healthcare vary between countries due to differences in healthcare infrastructure, regulatory frameworks, and technical advancements. This review highlights how IoT technologies underpin the efficiency of EHR and HIE systems by enabling continuous data flow, interoperability, and real-time patient care. It also addresses the problems involved with IoT adoption, including data privacy concerns, interoperability issues, high implementation costs, and cybersecurity dangers. Additionally, the paper examines future trends in IoT healthcare, including 5G integration, AI-enhanced healthcare analytics, blockchain-based security solutions, and the creation of energy-efficient IoT medical equipment. Through an analysis of worldwide trends and obstacles, this research offers suggestions for policies, methods, and best practices to close the digital healthcare gap and make sure that healthcare solutions powered by the IoT are available, safe, and effective everywhere. Full article

(This article belongs to the Special Issue Artificial Intelligence (AI) in Healthcare: Technologies, Applications, Challenges)

25 pages, 2734 KB

Open AccessArticle

Mathematical Modeling and Optimization of AI-Driven Virtual Game Data Center Storage System

by Sijin Zhu, Xuebo Yan, Xiaolin Zhang, Mengyao Guo and Ze Gao

Mathematics 2025, 13(23), 3831; https://doi.org/10.3390/math13233831 (registering DOI) - 29 Nov 2025

Abstract

Frequent fluctuations in virtual item transactions make data access in virtual games highly dynamic. These heat changes denote temporal variations in data popularity driven by trading activity, which in turn cause traditional storage systems to struggle with timely heat adaptation, increased latency, and [...] Read more.

Frequent fluctuations in virtual item transactions make data access in virtual games highly dynamic. These heat changes denote temporal variations in data popularity driven by trading activity, which in turn cause traditional storage systems to struggle with timely heat adaptation, increased latency, and energy waste. This study proposes an AI-driven modeling framework for virtual game data centers. The heat feature vector composed of transaction frequency, price fluctuation, and scarcity forms the state space of a Markov decision process, while data migration between multi-layer storage structures constitutes the action space. The model captures temporal locality and spatial clustering in transaction behaviors, applies a sliding-window prediction mechanism to estimate access intensity, and enhances load perception. A scheduling mechanism combining an R2D3 (Recurrent Replay Distributed DQN from Demonstrations) policy network with temporal attention and mixed integer programming jointly optimizes latency, energy consumption, and resource constraints to achieve global data allocation tuning. Experiments on a simulated high-frequency trading dataset show that the system reduces access delay to 420 ms at a transaction intensity of 1000 per second and controls the total migration energy consumption to 85.7 Wh. The Edge layer achieves a peak hit rate of 63%, demonstrating that the proposed method enables accurate heat identification and energy-efficient multi-layer scheduling under highly dynamic environments. Full article

(This article belongs to the Special Issue New Advances in Distributed Systems, Edge Intelligence, and Artificial Intelligence)

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12 pages, 1192 KB

Open AccessArticle

Simulation of Residual Stress Around Nano-Perforations in Elastic Media: Insights for Porous Material Design

by Shuang Wang, Xin Jia, Kun Song, Haibing Yang, Shichao Xing, Hongyuan Li and Ming Cheng

Materials 2025, 18(23), 5388; https://doi.org/10.3390/ma18235388 (registering DOI) - 29 Nov 2025

Abstract

The mechanical integrity of advanced porous materials and perforated structures at the nanoscale is critically governed by the interaction of surface effects and stress concentration around pore architectures. This paper investigates the residual stress field induced by surface tension around two arbitrarily shaped [...] Read more.

The mechanical integrity of advanced porous materials and perforated structures at the nanoscale is critically governed by the interaction of surface effects and stress concentration around pore architectures. This paper investigates the residual stress field induced by surface tension around two arbitrarily shaped nano-perforations within an infinite elastic matrix, a configuration highly relevant to nanoporous metals and functional composites. By leveraging the complex variable method and conformal mapping techniques, the physical domains of the perforations (approximated as triangular and square shapes, paired with an elliptical perforation) are transformed into unit circles. This transformation allows for the derivation of semi-analytical solutions for the complex potentials and the subsequent stress field. Systematic numerical case studies reveal that a reduced inter-perforation distance dramatically intensifies the hoop stress concentration at the adjacent vertices, identifying these sites as potential initiation points for mechanical failure. Conversely, an increase in the size of one perforation can effectively shield its neighbor and reduce the overall stress level. These findings provide quantitative, physics-based guidelines for the microstructural design of nanoporous materials. By consciously tailoring the spatial distribution, size, and shape of perforations, the mechanical reliability of nanomaterials can be rationally optimized for applications in nanoscale systems. Full article

(This article belongs to the Special Issue Recent Developments in Elasticity of Advanced Composites, Porous Materials and Perforated Structures)

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22 pages, 2846 KB

Open AccessReview

From Cells to Organoids: Approaches, Regulatory Mechanisms, Applications, and Challenges of Organoids

by Lihong Wang, Anqi Chen, Dong Zhang and Zuping He

Cells 2025, 14(23), 1898; https://doi.org/10.3390/cells14231898 (registering DOI) - 29 Nov 2025

Abstract

Organoids refer to three-dimensional (3D) multicellular tissues derived from stem cells or single cells through their self-assembly capacity, and significantly, they mimic structural and functional characteristics of the organ from which they are derived. Organoids can maintain the gene expression profiles and mutational [...] Read more.

Organoids refer to three-dimensional (3D) multicellular tissues derived from stem cells or single cells through their self-assembly capacity, and significantly, they mimic structural and functional characteristics of the organ from which they are derived. Organoids can maintain the gene expression profiles and mutational features of parental cells during long-term culture. This makes organoids more relevant to the human bodies than gene knockout or overexpression animal models. Consequently, organoids have been widely used in various kinds of fields, including studies on organ developmental mechanisms, regenerative medicine, organ repair, the construction of disease models, high-throughput drug screening, and personalized medicine. Notably, significant progress has recently been made in organoid construction methodologies and regulatory mechanisms. These include the selections of starting cell sources, optimizing matrix materials, and the related cell signaling pathways. The rapid development of organoid technologies has provided new opportunities for their applications in organ transplantation, drug and toxicity screening, and molecular mechanisms for cell and tissue development. In this review, we discuss organoid construction methods involving the starting cell selection and spatiotemporal mediation, regulatory mechanisms with signaling molecules and pathways, and their applications in unveiling organogenesis mechanisms and disease etiology, drug screening, toxicity testing, personalized medicine, regenerative medicine, and alternatives to animal experiments. We also address the perspectives and challenges in this field with an aim to promote the development of organoids in basic research and translational medicine. Full article

(This article belongs to the Special Issue Organ Regeneration: Cells, Organoids and Organs)

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12 pages, 8928 KB

Open AccessArticle

Clinical and Molecular Characterization of KRAS-Mutated Renal Cell Carcinoma

by Andrea Lopez Sanmiguel, Yash S. Khandwala, Kuo Fengshen, Mark Dawidek, Ethan Tse, Daniel Barbakoff, Lina Posada Calderon, Maria I. Carlo, Jonathan Coleman, Paul Russo, Satish K. Tickoo, Victor E. Reuter, Ed Reznik, Ying-Bei Chen and A. Ari Hakimi

Cancers 2025, 17(23), 3832; https://doi.org/10.3390/cancers17233832 (registering DOI) - 29 Nov 2025

Abstract

Background/Objectives: KRAS mutations in renal cell carcinoma (RCC) are uncommon and most frequently described in papillary renal neoplasm with reverse polarity (PRNRP). Beyond this entity, the broader clinicopathologic and molecular features of KRAS-mutated RCC remain insufficiently characterized. This study aimed to provide [...] Read more.

Background/Objectives: KRAS mutations in renal cell carcinoma (RCC) are uncommon and most frequently described in papillary renal neoplasm with reverse polarity (PRNRP). Beyond this entity, the broader clinicopathologic and molecular features of KRAS-mutated RCC remain insufficiently characterized. This study aimed to provide a descriptive assessment of KRAS-mutated RCC. Methods: KRAS-mutant RCC patients were identified from the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) and The Cancer Genome Atlas Kidney Renal Papillary Cell Carcinoma (TCGA-KIRP) cohorts. Copy-number alterations were evaluated using Fraction and allele-specific copy number estimates from tumor sequencing (FACETS). Available samples were used for immunohistochemistry and RNA-sequencing analysis. Results: Seventeen patients were included. Three distinct KRAS-mutant RCC subtypes were identified: KRAS-mutant PRCC (35%), KRAS-mutant URCC (35%), and PRNRP (29%). Seven patients (41%) had metastatic disease; none were PRNRP. RNA-based deconvolution analysis revealed that PRNRP had enrichment in distal nephron components, whereas KRAS-mutant PRCC was enriched in proximal tubule cells (p = 0.02). IHC staining of L1CAM was positive in PRNRP but negative in KRAS-mutant PRCC, supporting their distinct cell-of-origin phenotypes. This study is limited by its cohort size, which influences the availability of tissue samples. Conclusions: PRNRP represents a distinct KRAS-mutant RCC subtype with unique metabolic and genomic features linked to its distal nephron origin. This contrasts with the genomic complexity and aggressive clinical behavior observed in KRAS-mutant PRCC and URCC, highlighting the need for subtype-specific diagnostic criteria and therapeutic strategies. Full article

(This article belongs to the Section Molecular Cancer Biology)

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