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22 pages, 3358 KB  
Article
MultiScaleSleepNet: A Hybrid CNN–BiLSTM–Transformer Architecture with Multi-Scale Feature Representation for Single-Channel EEG Sleep Stage Classification
by Cenyu Liu, Qinglin Guan, Wei Zhang, Liyang Sun, Mengyi Wang, Xue Dong and Shuogui Xu
Sensors 2025, 25(20), 6328; https://doi.org/10.3390/s25206328 (registering DOI) - 13 Oct 2025
Abstract
Accurate automatic sleep stage classification from single-channel EEG remains challenging due to the need for effective extraction of multiscale neurophysiological features and modeling of long-range temporal dependencies. This study aims to address these limitations by developing an efficient and compact deep learning architecture [...] Read more.
Accurate automatic sleep stage classification from single-channel EEG remains challenging due to the need for effective extraction of multiscale neurophysiological features and modeling of long-range temporal dependencies. This study aims to address these limitations by developing an efficient and compact deep learning architecture tailored for wearable and edge device applications. We propose MultiScaleSleepNet, a hybrid convolutional neural network–bidirectional long short-term memory–transformer architecture that extracts multiscale temporal and spectral features through parallel convolutional branches, followed by sequential modeling using a BiLSTM memory network and transformer-based attention mechanisms. The model obtained an accuracy, macro-averaged F1 score, and kappa coefficient of 88.6%, 0.833, and 0.84 on the Sleep-EDF dataset; 85.6%, 0.811, and 0.80 on the Sleep-EDF Expanded dataset; and 84.6%, 0.745, and 0.79 on the SHHS dataset. Ablation studies indicate that attention mechanisms and spectral fusion consistently improve performance, with the most notable gains observed for stages N1, N3, and rapid eye movement. MultiScaleSleepNet demonstrates competitive performance across multiple benchmark datasets while maintaining a compact size of 1.9 million parameters, suggesting robustness to variations in dataset size and class distribution. The study supports the feasibility of real-time, accurate sleep staging from single-channel EEG using parameter-efficient deep models suitable for portable systems. Full article
(This article belongs to the Special Issue AI on Biomedical Signal Sensing and Processing for Health Monitoring)
18 pages, 1340 KB  
Article
Genetic Characterization and Pathogenesis of Highly Pathogenic Avian Influenza Virus A (H5N1) Isolated in Egypt During 2021–2023
by Mina Nabil Kamel, Yassmin Moatasim, Basma Emad Aboulhoda, Mokhtar Gomaa, Ahmed El Taweel, Omnia Kutkat, Mohamed El Sayes, Mohamed GabAllah, Hend AbdAllah, Refaat M. Gabre, Maha M. AlKhazindar, Ahmed Kandeil, Pamela P. McKenzie, Richard J. Webby, Mohamed Ahmed Ali, Ghazi Kayali and Rabeh El-Shesheny
Viruses 2025, 17(10), 1370; https://doi.org/10.3390/v17101370 (registering DOI) - 13 Oct 2025
Abstract
Highly pathogenic avian influenza (HPAI) viruses have recently had a substantial impact on global poultry production and public health. In Egypt, clade 2.3.4.4b HPAI H5N1 viruses were first isolated from wild birds in 2021 and then became dominant in domestic poultry. In this [...] Read more.
Highly pathogenic avian influenza (HPAI) viruses have recently had a substantial impact on global poultry production and public health. In Egypt, clade 2.3.4.4b HPAI H5N1 viruses were first isolated from wild birds in 2021 and then became dominant in domestic poultry. In this study, we aimed to genetically characterize the H5N1 viruses isolated in Egypt during 2021–2023 and examine the pathogenicity and transmissibility of two H5N1 strains isolated from wild and domestic poultry in chickens. We collected 7588 specimens from live bird markets including poultry, wild birds, and environmental samples. Influenza A viruses were detected in 20.94% (484/2311) of tested samples, and 17 isolates were identified as H5N1 through complete genome sequencing. Phylogenetic analysis revealed that all H5N1 viruses were closely related to Eurasian viruses and classified into three distinct genetic groups, suggesting multiple introductions likely linked to migratory birds. Experimental infections of chickens with two H5N1 isolates, A/Pintail/Egypt/RA19853OP/2021 and A/duck/Egypt/BA20361C/2022, showed efficient replication, systemic infection, and transmission by direct contact. These findings underscore the need for continued surveillance of H5N1 at the poultry-wild bird interface to identify circulating strains, evaluate their biological characteristics, and assess their zoonotic potential. Full article
(This article belongs to the Section General Virology)
21 pages, 7564 KB  
Article
Spatio-Temporal Evolution and Zonal Control of Non-Grain Cultivated Land in Major Grain Producing Areas: A Case Study of Henan Province
by Aman Fang, Ziyi Xing, Weiqiang Chen, Yuanqing Shi, Lingfei Shi, Xinwei Feng and Yuehong Ma
Land 2025, 14(10), 2046; https://doi.org/10.3390/land14102046 (registering DOI) - 13 Oct 2025
Abstract
Ensuring food security amidst increasing non-grain utilization of cultivated land is a critical challenge in major grain-producing regions. This study analyzes the spatio-temporal evolution and driving mechanisms of non-grain cultivated land in Henan Province, China, from 2012 to 2023, using spatial autocorrelation, multiple [...] Read more.
Ensuring food security amidst increasing non-grain utilization of cultivated land is a critical challenge in major grain-producing regions. This study analyzes the spatio-temporal evolution and driving mechanisms of non-grain cultivated land in Henan Province, China, from 2012 to 2023, using spatial autocorrelation, multiple linear regression, geographically and temporally weighted regression model, and cluster analysis. Results show that the non-grain ratio exhibited a fluctuating yet overall increasing trend, from 27.47% in 2012 to 25.91% in 2017 and reaching 30.28% in 2023, with higher values in the northern and southwestern counties of the province. Spatial clustering patterns remained relatively stable, characterized by a “high–high clustering in the southwest and low–low clustering in the north,” which was further substantiated by significant Global Moran’s I values (0.362 in 2012 and 0.307 in 2023). Key drivers included per capita level of agricultural mechanization, labor force per unit of cultivated land area, output value per unit of cultivated land area, and per capita disposable income of rural residents. PCA and K-means clustering identified three zonal types: agricultural production support (45.10% of counties), agricultural production weakening (35.29% of counties), and economically location-guided (19.61% of counties). The findings underscore the need for differentiated policies—such as precision subsidies, land consolidation, and ecological farming practices. This study provides a scientific basis for zonal governance of non-grain cultivated land in grain-producing areas. Full article
(This article belongs to the Section Land Use, Impact Assessment and Sustainability)
20 pages, 652 KB  
Review
Short Peptides as Excipients in Parenteral Protein Formulations: A Mini Review
by Dorian Migoń, Zbigniew Jaremicz and Wojciech Kamysz
Pharmaceutics 2025, 17(10), 1328; https://doi.org/10.3390/pharmaceutics17101328 (registering DOI) - 13 Oct 2025
Abstract
Biopharmaceutical medicines represent one of the most dynamic sectors of the pharmaceutical industry, with therapeutic proteins forming the largest and most important group. Their structural complexity and inherent sensitivity to chemical and physical stressors, however, continue to pose major challenges for formulation development [...] Read more.
Biopharmaceutical medicines represent one of the most dynamic sectors of the pharmaceutical industry, with therapeutic proteins forming the largest and most important group. Their structural complexity and inherent sensitivity to chemical and physical stressors, however, continue to pose major challenges for formulation development and long-term stability. Short peptides have emerged as a promising yet underutilized class of excipients for protein-based drug products. Their modular architecture allows for precise tuning of physicochemical properties such as polarity, charge distribution, and hydrogen-bonding potential, thereby offering advantages over single amino acids. Experimental studies indicate that short peptides can serve multiple functions: stabilizers, antioxidants, viscosity-lowering agents, and as lyo/cryoprotectants or bulking agents in lyophilized formulations. Notably, the relatively small and chemically defined space of short peptides—approximately 400 possible dipeptides and 8000 tripeptides—makes them particularly amenable to systematic screening and computational modeling. This enables rational identification of candidates with tailored excipient functions. This review summarizes current knowledge on the use of short peptides as excipients in parenteral protein formulations, with a focus on their functional versatility and potential for rational design in future development. Full article
(This article belongs to the Section Biopharmaceutics)
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12 pages, 585 KB  
Article
Association between Osteoarthritis and the Triglyceride–Glucose Index in the Korean Population: A Large-Scale Cross-Sectional Study
by Jeong Hee Chi and Bum Ju Lee
J. Clin. Med. 2025, 14(20), 7226; https://doi.org/10.3390/jcm14207226 (registering DOI) - 13 Oct 2025
Abstract
Background: Osteoarthritis (OA) is associated with triglyceride‒glucose (TyG) index values. However, the evidence supporting this association remains controversial. This study explores the associations of OA with the TyG index and with a combination of the TyG index and obesity in the Korean population. [...] Read more.
Background: Osteoarthritis (OA) is associated with triglyceride‒glucose (TyG) index values. However, the evidence supporting this association remains controversial. This study explores the associations of OA with the TyG index and with a combination of the TyG index and obesity in the Korean population. Methods: A total of 15,128 subjects (including 6575 men and 8553 women) were included in this analysis. Complex sample binary logistic regression was used to analyze the associations of OA with TyG, TyG-body mass index (TyG-BMI), TyG-waist circumference (TyG-WC), and the TyG-waist-to-height ratio (TyG-WHtR). We applied the Bonferroni correction to account for multiple comparisons. Results: The prevalence of OA in the Korean population was 7.3% in men and 24.3% in women. The TyG was not associated with OA. In men, the odds ratio (OR) for the TyG was 0.89 (95% CI, 0.79–1.00; p = 0.315) per one standard deviation increase in the crude model, and the adjusted OR was 0.98 (95% CI, 0.86–1.11; adjusted p > 0.999) in the adjusted model. In women, the OR for the TyG was 1.27 (95% CI, 1.19–1.35; p < 0.001), whereas the adjusted OR was 1.08 (95% CI, 1.01–1.16; adjusted p = 0.236). In the adjusted models, TyG-BMI, TyG-WC, and TyG-WHtR were not associated with OA in men but strongly associated with OA in women. Conclusions: The TyG index was not associated with OA in the Korean population. The strength of the associations between OA and the TyG indices combined with obesity was lower than the that of the associations between OA and BMI, WC, and WHtR individually. Full article
(This article belongs to the Section Orthopedics)
14 pages, 942 KB  
Article
Diversity of Escherichia coli from Faecal Samples of Danish Calves with Diarrhoea
by Anna Luiza Farias Alencar, Abdurrahman Hassan Jibril, Birgitta Svensmark, Lene Agerskov, Henrik Læssøe Martin, Marc Stegger, André Becker Saidenberg, Gang Liu, Yaovi Mahuton Gildas Hounmanou, Annette Sønderholm Juel, John Elmerdahl Olsen and Rikke Heidemann Olsen
Vet. Sci. 2025, 12(10), 987; https://doi.org/10.3390/vetsci12100987 (registering DOI) - 13 Oct 2025
Abstract
Several different pathogens, including Escherichia coli, are strongly associated with calf diarrhoea. The population diversity of intestinal E. coli within each diarrhetic calf and between diarrhetic calves is not well understood. In the present study, 391 faecal samples were obtained during 2023–2024 [...] Read more.
Several different pathogens, including Escherichia coli, are strongly associated with calf diarrhoea. The population diversity of intestinal E. coli within each diarrhetic calf and between diarrhetic calves is not well understood. In the present study, 391 faecal samples were obtained during 2023–2024 from Danish dairy calves with diarrhoea. Semi-quantified growth estimates of E. coli after culturing did not reflect the diarrhetic grade nor whether E. coli was the only pathogen observed in the sample. From each sample, five isolates were subjected to multiple-locus variable-number tandem repeat analysis (MLVA) and revealed that 70% of faecal samples contained more than one type of E. coli. Genotyping, sequence typing and in silico serotyping showed a large diversity of E. coli between faecal samples. Surprisingly, isolates with a genotype representing mixed features of Diffusely adhering E. coli/Extraintestinal pathogenic E. coli were found in 25% of the isolates, while the classic Enterotoxigenic E. coli genotype was only observed in 5% of the isolates, and only 4% of the faecal samples were positive for E. coli F5 (K99) fimbriae, as determined by PCR. In conclusion, a diverse population of (non-F5) E. coli is associated with diarrhoea in calves. High genomic diversity of E. coli within samples needs to be considered when selecting only one isolate for antimicrobial resistance profiling and vaccination measurements. Full article
(This article belongs to the Section Veterinary Microbiology, Parasitology and Immunology)
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22 pages, 1565 KB  
Article
Double-Layer Optimal Configuration of Wind–Solar-Storage for Multi-Microgrid with Electricity–Hydrogen Coupling
by Dong Yang, Gangying Pan, Jianhua Zhang, Jun He, Yulin Zhang and Chuanliang Xiao
Processes 2025, 13(10), 3263; https://doi.org/10.3390/pr13103263 (registering DOI) - 13 Oct 2025
Abstract
To address the collaborative optimization challenge in multi-microgrid systems with significant renewable energy integration, this study presents a dual-layer optimization model incorporating power-hydrogen coupling. Firstly, a hydrogen energy system coupling framework including photovoltaics, storage batteries, and electrolysis hydrogen production/fuel cells was constructed at [...] Read more.
To address the collaborative optimization challenge in multi-microgrid systems with significant renewable energy integration, this study presents a dual-layer optimization model incorporating power-hydrogen coupling. Firstly, a hydrogen energy system coupling framework including photovoltaics, storage batteries, and electrolysis hydrogen production/fuel cells was constructed at the architecture level to realize the flexible conversion of multiple energy forms. From a modeling perspective, the upper-layer optimization aims to minimize lifecycle costs by determining the optimal sizing of distributed PV systems, battery storage, hydrogen tanks, fuel cells, and electrolyzers within the microgrid. At the lower level, a distributed optimization framework facilitates energy sharing (both electrical and hydrogen-based) across microgrids. This operational layer maximizes yearly system revenue while considering all energy transactions—both inter-microgrid and grid-to-microgrid exchanges. The resulting operational boundaries feed into the upper-layer capacity optimization, with the optimal equipment configuration emerging from the iterative convergence of both layers. Finally, the actual microgrid in a certain area is taken as an example to verify the effectiveness of the proposed method. Full article
(This article belongs to the Section Energy Systems)
18 pages, 5737 KB  
Article
Limestones in the Roman Architecture of Oderzo and Concordia Sagittaria (Italy): Petrography and Provenance
by Chiara Girotto and Claudio Mazzoli
Heritage 2025, 8(10), 429; https://doi.org/10.3390/heritage8100429 (registering DOI) - 13 Oct 2025
Abstract
This paper presents the results of a research project on the use of stone in Roman architecture in Oderzo and Concordia Sagittaria, located between the Tagliamento and the Piave rivers (Italy). The study involved a documental survey, material sampling and analysis, provenance identification, [...] Read more.
This paper presents the results of a research project on the use of stone in Roman architecture in Oderzo and Concordia Sagittaria, located between the Tagliamento and the Piave rivers (Italy). The study involved a documental survey, material sampling and analysis, provenance identification, and interpretation of results to reconstruct ancient stone trade routes. During sampling, 33 carbonate rock specimens were collected from archaeological sites and architectural elements in Oderzo, and 52 from Concordia Sagittaria. In both cities, these rocks were primarily used for architectural elements such as columns and capitals, whereas these lithotypes were less frequently employed in structures and infrastructures. The analysis revealed a significant reliance on regional limestones. Petrographic examinations (PLM-TL) identified six main limestone groups, many of which were linked to quarries located in the Aurisina and in the Triestine Karst region, as well as in the Prealps and Berici Hills. The study encountered several challenges: many analysed samples displayed petrographic characteristics consistent with multiple sources, complicating the precise identification of their extraction site. Despite a detailed understanding of the region’s geology, reference geological datasets often overlook outcrops that may have been exploited in antiquity. Consequently, when samples lacked distinctive features, tracing them to a particular quarrying basin proved difficult. In conclusion, the research underscores the extensive use of local limestones while acknowledging the challenges posed by limited petrographic reference data, which hinder the precise identification of the source basins of the materials used in Roman construction. Full article
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13 pages, 826 KB  
Article
Assessing the Stability of Polymer Inclusion Membranes: The Case of Aliquat 336-Based Membranes
by Kalina Velikova, Todor Dudev, Tsveta Sarafska, Lea Kukoc-Modun, Spas D. Kolev and Tony Spassov
Membranes 2025, 15(10), 309; https://doi.org/10.3390/membranes15100309 (registering DOI) - 13 Oct 2025
Abstract
Leaching of the extractant from polymer inclusion membranes (PIMs) into the feed and receiving aqueous solutions shortens their life. Therefore, when a particular PIM extractant has been selected, it is important to choose a base polymer that will minimize to the greatest extent [...] Read more.
Leaching of the extractant from polymer inclusion membranes (PIMs) into the feed and receiving aqueous solutions shortens their life. Therefore, when a particular PIM extractant has been selected, it is important to choose a base polymer that will minimize to the greatest extent extractant leaching compared to other base polymers, thus providing the best stability of the PIM. However, comparisons of the stability of PIMs composed of the same extractant and different base polymers is usually conducted by multiple cycles of extraction and back-extraction steps, which are time-consuming and labor-intensive. An alternative approach based on thermal analysis (thermogravimetric analysis (TGA) and differential thermal analysis (DTA)) was developed and applied to PIMs containing 40 wt.% Aliquat 336, one of the most frequently used PIM extractants, and the three most frequently used PIM base polymers, i.e., poly(vinyl chloride) (PVC), cellulose triacetate (CTA), and poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP). The temperatures and enthalpies associated with Aliquat 336 release were compared, with PVDF-HFP exhibiting the highest values, indicating the strongest interaction between the extractant and the polymer matrix and, thus, the highest stability. The PVC-based PIM was predicted to be the most prone to extractant leaching among the PIMs studied. This stability ranking was confirmed theoretically by quantum chemistry (DFT) calculations, which provided molecular-level insights into the likely interaction sites between Aliquat 336 and the polymer chains. An experimental validation of the above leaching order was also provided by PIM leaching experiments in aqueous 0.1 M and 0.05 M NaCl solutions, where membrane mass losses over a 24 h period were determined. The results of the current study demonstrated thermal analysis to be a fast and viable approach in comparing the stability of PIMs with the same extractant but different base polymers. Full article
21 pages, 5270 KB  
Article
Spatiotemporal Modeling of the Total Nitrogen Concentration Fields in a Semi-Enclosed Water Body Using a TCN-LSTM-Hybrid Model
by Xiaohui Yan, Hongyun Cheng, Shenshen Chi, Sidi Liu and Zuhao Zhu
Processes 2025, 13(10), 3262; https://doi.org/10.3390/pr13103262 (registering DOI) - 13 Oct 2025
Abstract
In the field of water process engineering, accurately predicting the total nitrogen (TN) concentration distribution in the Semi-Enclosed Bay area is of great importance for water quality assessment, pollution control, and scientific management. Due to the coupling of multiple influencing factors, the pollution [...] Read more.
In the field of water process engineering, accurately predicting the total nitrogen (TN) concentration distribution in the Semi-Enclosed Bay area is of great importance for water quality assessment, pollution control, and scientific management. Due to the coupling of multiple influencing factors, the pollution process is complex, and traditional monitoring methods struggle to achieve large-scale, long-term real-time observation. Although numerical simulations can reproduce TN transport processes, they are computationally expensive and have low prediction efficiency. To address this, this study develops a deep learning hybrid model that integrates a Temporal Convolutional Network (TCN) and a Long Short-Term Memory (LSTM) network, referred to as the TCN-LSTM-Hybrid Model, to predict the spatiotemporal distribution of TN concentration fields in Shenzhen Bay. Comparative experiments show that this model outperforms traditional models such as TCN, LSTM, GRU, and MLP in terms of prediction accuracy and spatial generalization, offering higher computational efficiency and breaking through the limitations of “point-based prediction” by achieving “field-based prediction,” thereby providing a new path for pollutant simulation in complex ocean environments, supporting more informed decision making in ocean and coastal management. Full article
(This article belongs to the Section Chemical Processes and Systems)
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24 pages, 662 KB  
Article
Hybrid Leadership Style in Kibbutz Industries to Promote Sustainability
by Yaffa Moskovich
Sustainability 2025, 17(20), 9070; https://doi.org/10.3390/su17209070 (registering DOI) - 13 Oct 2025
Abstract
This study investigates the use of a hybrid leadership style in three kibbutz factories—two in privatized communities and one in a cooperative community. The factory leaders integrate multiple leadership styles in managing their enterprises. This blended style reflects a hybrid approach to management [...] Read more.
This study investigates the use of a hybrid leadership style in three kibbutz factories—two in privatized communities and one in a cooperative community. The factory leaders integrate multiple leadership styles in managing their enterprises. This blended style reflects a hybrid approach to management that has democratic and autocratic elements as well as a transformational leadership style that is also community-oriented. The goals of the managers are to make the factory operations sustainable while remaining loyal to communal values. We conducted 75 interviews in the three kibbutzim with individuals from various ranks, ranging from senior leadership to production workers. In addition, to supplement the information, we analyzed organizational documents, including internal newsletters, reports, and booklets summarizing 50 years of activity, as well as news articles that provided up-to-date information on business transactions that contributed to the success of the kibbutz industries. The result identified a hybrid style that combines the communal, transformational, and democratic or autocratic styles. Many features of communal leadership were evident in the practices of kibbutz members rather than those of outsiders and by strategies focused on maintaining the industry for kibbutz members in the long run and an egalitarian communal style. The hybrid style contains democratic features such as transparent and open communication, and a transformational style was also found in key components of this leadership style, including innovation, professionalism, dynamism, adaptability to environmental changes, and human sensitivity. Full article
(This article belongs to the Special Issue Corporate Social Performance: Pathways to Sustainable Growth)
14 pages, 2654 KB  
Article
Microstructure and Hydrogen Storage Properties of Composites Derived from Oxidized Alloy Glass in the System of Zr-Pd-Pt
by Masakuni Ozawa, Naoya Katsuragawa, Masatomo Hattori and Hidemi Kato
J. Compos. Sci. 2025, 9(10), 563; https://doi.org/10.3390/jcs9100563 (registering DOI) - 13 Oct 2025
Abstract
A study on the hydrogen storage of composite materials derived from alloy glass in the system of Zr-Pd-Pt was conducted through the integration of multiple methodologies. The alloy following heat treatment in air at temperatures ranging from 280 °C to 800 °C showed [...] Read more.
A study on the hydrogen storage of composite materials derived from alloy glass in the system of Zr-Pd-Pt was conducted through the integration of multiple methodologies. The alloy following heat treatment in air at temperatures ranging from 280 °C to 800 °C showed a precipitated structure comprising metallic Pd-Pt particles and a ZrO2 matrix. In the sample treated at 280 °C, the spillover phenomenon of absorbed hydrogen was suggested. The plateau region of the hydrogen pressure–concentration (PCT) isotherm showed the gradient profiles for the samples oxidized at 400 °C, 600 °C, and 800 °C. In the equilibrium absorption process, the ΔH° of approximately 38 kJ/mol was proposed, and the highest storage of hydrogen was H/Pd = 0.61 by the sample oxidized in air at 600 °C. The temperature programmed reduction (TPR) results exhibited rapid hydrogen release behavior at temperatures ranging from 50 °C to 65 °C. The findings offer novel insights into the microstructure, fabrication process, and overall hydrogen absorption/desorption properties of the composites prepared from a Zr-Pd-Pt alloy glass. Full article
(This article belongs to the Special Issue Composite Materials for Hydrogen Storage)
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16 pages, 2463 KB  
Article
Thymopentin Enhances Antitumor Immunity Through Thymic Rejuvenation and T Cell Functional Reprogramming
by Md Amir Hossain, Ye Zhang, Li Ji, Yumei Chen, Yue Luan, Yaxuan Si, Yuqing Fang, Junlan Qiu, Zhuo Wang and Guilai Liu
Biomedicines 2025, 13(10), 2494; https://doi.org/10.3390/biomedicines13102494 (registering DOI) - 13 Oct 2025
Abstract
Background/Objectives: T cell dysfunction represents a fundamental barrier to effective cancer immunotherapy. Although immune checkpoint blockades and adoptive cell transfer have achieved clinical success, therapeutic resistance remains prevalent across cancer types. Thymopentin (TP5), a synthetic immunomodulatory pentapeptide (Arg-Lys-Asp-Val-Tyr), has demonstrated immunostimulatory properties, [...] Read more.
Background/Objectives: T cell dysfunction represents a fundamental barrier to effective cancer immunotherapy. Although immune checkpoint blockades and adoptive cell transfer have achieved clinical success, therapeutic resistance remains prevalent across cancer types. Thymopentin (TP5), a synthetic immunomodulatory pentapeptide (Arg-Lys-Asp-Val-Tyr), has demonstrated immunostimulatory properties, yet its anticancer potential remains unexplored. The aim of this study was to investigate TP5’s antitumor efficacy and underlying immunological mechanisms. Methods: We evaluated TP5’s therapeutic effects in multiple murine tumor models, including B16-F10 melanoma, MC38 colorectal carcinoma, Hepa 1-6, and LM3 hepatocellular carcinoma. Immune cell populations and functional states were characterized using flow cytometry, ELISAs, and immunofluorescence analyses. The potential of TP5 as an adjuvant for T cell-based therapies was also systematically assessed. Results: The TP5 treatment markedly suppressed tumor growth across caner models through strictly T cell-dependent mechanisms. Critically, TP5 promoted thymic rejuvenation under immunocompromised conditions, restoring the thymus–tumor immunological balance and revitalizing peripheral T cell immunity. TP5 functionally reprogrammed T cell states, preserving effector function while ameliorating exhaustion. Furthermore, TP5 demonstrated synergistic efficacy when combined with adoptive T cell therapies, enhancing both proliferation and effector functions. Conclusions: TP5 represents a promising immunomodulator that addresses fundamental limitations of current T cell therapies by simultaneously enhancing T cell function and reversing thymic involution under immunocompromised conditions. Our findings provide compelling evidence for TP5’s clinical translation in cancer treatment. Full article
15 pages, 301 KB  
Review
Endocrine-Disrupting Chemicals and Male Infertility: Mechanisms, Risks, and Regulatory Challenges
by Sofoklis Stavros, Nikolaos Kathopoulis, Efthalia Moustakli, Anastasios Potiris, Ismini Anagnostaki, Spyridon Topis, Nefeli Arkouli, Konstantinos Louis, Charalampos Theofanakis, Themos Grigoriadis, Nikolaos Thomakos and Athanasios Zikopoulos
J. Xenobiot. 2025, 15(5), 165; https://doi.org/10.3390/jox15050165 (registering DOI) - 13 Oct 2025
Abstract
Male reproductive health is increasingly threatened by endocrine-disrupting chemicals (EDCs), which interfere with hormonal homeostasis and reproductive physiology. Rising rates of male infertility have been linked to greater exposure to pollutants such as heavy metals, phthalates, pesticides, and bisphenol A. These compounds act [...] Read more.
Male reproductive health is increasingly threatened by endocrine-disrupting chemicals (EDCs), which interfere with hormonal homeostasis and reproductive physiology. Rising rates of male infertility have been linked to greater exposure to pollutants such as heavy metals, phthalates, pesticides, and bisphenol A. These compounds act through multiple mechanisms, including oxidative stress, apoptosis, receptor-mediated disruption of estrogenic and androgenic signaling, alterations in the hypothalamic–pituitary–gonadal (HPG) axis, and heritable epigenetic changes. Such disruptions impair key outcomes like sperm concentration, motility, morphology, DNA integrity, and steroidogenesis. Evidence from animal studies and human epidemiology consistently demonstrates these harmful effects, with biomarkers of EDC exposure correlating with reduced semen quality, hormonal imbalances, and infertility. Beyond individual health, infertility linked to EDCs carries significant social and economic costs. This review evaluates regulatory frameworks, highlights methodological challenges in risk assessment, and synthesizes mechanistic and clinical evidence. Particular attention is given to unresolved issues such as non-monotonic dose responses, mixture effects, low-dose exposures, and transgenerational impacts. Future priorities include refining biomonitoring, addressing mixture risks, and strengthening international regulation. By integrating mechanistic, clinical, and policy insights, this review underscores the urgent need for strategies to mitigate EDC-related threats to male reproductive health. Full article
17 pages, 1517 KB  
Article
Cytokine Profile and Oxidative Patterns in Murine Models of Disseminated Infection by Mucorales Species
by Hiram Villanueva-Lozano, Martín García-Juárez, Adrián G. Rosas-Taraco, Rogelio de J. Treviño-Rangel and Gloria M. González
Pathogens 2025, 14(10), 1036; https://doi.org/10.3390/pathogens14101036 (registering DOI) - 13 Oct 2025
Abstract
Mucormycosis is a life-threatening infection caused by fungi of the Mucorales order, typically associated with immunocompromised hosts, but increasingly reported in immunocompetent individuals. This study investigated fungal burden, Th1/Th17 inflammatory profiles, and organ-specific dynamics in immunocompetent BALB/c mice intravenously infected with Rhizopus oryzae [...] Read more.
Mucormycosis is a life-threatening infection caused by fungi of the Mucorales order, typically associated with immunocompromised hosts, but increasingly reported in immunocompetent individuals. This study investigated fungal burden, Th1/Th17 inflammatory profiles, and organ-specific dynamics in immunocompetent BALB/c mice intravenously infected with Rhizopus oryzae, Mucor circinelloides, or Rhizomucor pusillus. Colony-forming units were quantified in spleen, liver, and kidney at multiple time points, while serum cytokines and oxidative stress markers were analyzed. The results showed fungal persistence primarily in the spleen, accompanied by species-specific Th1/Th17 responses: R. oryzae induced the highest inflammatory response among all groups, with maximal cytokine production observed on day 7, particularly for IL-17A (352.58 pg/mL). In contrast, M. circinelloides exhibited its peak cytokine levels earlier, reaching the highest TNF-α concentration on day 3 (425.43 pg/mL). Meanwhile, R. pusillus triggered an early but moderate inflammatory response, with a maximum TNF-α value of 372.62 pg/mL detected on day 1, followed by clearance. Correlation analysis highlighted distinct immunological patterns, with IL-10 acting as a negative regulator of inflammation, while TNF-α and IL-17A reflected infection intensity depending on species and timing. The spleen emerged as a key organ coordinating immune responses during systemic infection. These findings reveal that mucormycosis in immunocompetent hosts triggers complex, species-dependent immune dynamics beyond classical immunosuppression, emphasizing the need to consider host–pathogen interactions when developing targeted antifungal strategies. Full article
(This article belongs to the Section Fungal Pathogens)
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