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33 pages, 8117 KiB  
Article
Induced Microglial-like Cells Derived from Familial and Sporadic Alzheimer’s Disease Peripheral Blood Monocytes Show Abnormal Phagocytosis and Inflammatory Response to PSEN1 E280A Cholinergic-like Neurons
by Viviana Soto-Mercado, Miguel Mendivil-Perez, Carlos Velez-Pardo and Marlene Jimenez-Del-Rio
Int. J. Mol. Sci. 2025, 26(15), 7162; https://doi.org/10.3390/ijms26157162 - 24 Jul 2025
Abstract
In familial Alzheimer’s disease (FAD), presenilin 1 (PSEN1) E280A cholinergic-like neurons (ChLNs) induce aberrant secretion of extracellular amyloid beta (eAβ). How PSEN1 E280A ChLNs-eAβ affects microglial activity is still unknown. We obtained induced microglia-like cells (iMG) from human peripheral blood cells (hPBCs) in [...] Read more.
In familial Alzheimer’s disease (FAD), presenilin 1 (PSEN1) E280A cholinergic-like neurons (ChLNs) induce aberrant secretion of extracellular amyloid beta (eAβ). How PSEN1 E280A ChLNs-eAβ affects microglial activity is still unknown. We obtained induced microglia-like cells (iMG) from human peripheral blood cells (hPBCs) in a 15-day differentiation process to investigate the effect of bolus addition of Aβ42, PSEN1 E280A cholinergic-like neuron (ChLN)-derived culture supernatants, and PSEN1 E280A ChLNs on wild type (WT) iMG, PSEN1 E280A iMG, and sporadic Alzheimer’s disease (SAD) iMG. We found that WT iMG cells, when challenged with non-cellular (e.g., lipopolysaccharide, LPS) or cellular (e.g., Aβ42, PSEN1 E280A ChLN-derived culture supernatants) microenvironments, closely resemble primary human microglia in terms of morphology (resembling an “amoeboid-like phenotype”), expression of surface markers (Ionized calcium-binding adapter molecule 1, IBA-1; transmembrane protein 119, TMEM119), phagocytic ability (high pHrodo™ Red E. coli BioParticles™ phagocytic activity), immune metabolism (i.e., high generation of reactive oxygen species, ROS), increase in mitochondrial membrane potential (ΔΨm), response to ATP-induced transient intracellular Ca2+ influx, cell polarization (cluster of differentiation 68 (CD68)/CD206 ratio: M1 phenotype), cell migration activity according to the scratch wound assay, and especially in their inflammatory response (secretion of cytokine interleukin-6, IL-6; Tumor necrosis factor alpha, TNF-α). We also found that PSEN1 E280A and SAD iMG are physiologically unresponsive to ATP-induced Ca2+ influx, have reduced phagocytic activity, and diminished expression of Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) protein, but when co-cultured with PSEN1 E280A ChLNs, iMG shows an increase in pro-inflammatory phenotype (M1) and secretes high levels of cytokines IL-6 and TNF-α. As a result, PSEN1 E280A and SAD iMG induce apoptosis in PSEN1 E280A ChLNs as evidenced by abnormal phosphorylation of protein TAU at residue T205 and cleaved caspase 3 (CC3). Taken together, these results suggest that PSEN1 E280A ChLNs initiate a vicious cycle between damaged neurons and M1 phenotype microglia, resulting in excessive ChLN death. Our findings provide a suitable platform for the exploration of novel therapeutic approaches for the fight against FAD. Full article
(This article belongs to the Special Issue Role of Glia in Human Health and Disease)
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13 pages, 1401 KiB  
Article
Cost-Effectiveness of Endoscopic Stricturotomy Versus Resection Surgery for Crohn’s Disease Strictures
by Kate Lee Karlin, Grace Kim, Francesca Lim, Adam S. Faye, Chin Hur and Bo Shen
Healthcare 2025, 13(15), 1801; https://doi.org/10.3390/healthcare13151801 - 24 Jul 2025
Abstract
Background: Endoscopic therapies for Crohn’s disease (CD) strictures, including endoscopic balloon dilation (EBD) and endoscopic stricturotomy (ESt), are less invasive interventions compared to surgery. ESt is advantageous for strictures that are longer, more fibrotic, or adjacent to anatomic structures requiring precision, and it [...] Read more.
Background: Endoscopic therapies for Crohn’s disease (CD) strictures, including endoscopic balloon dilation (EBD) and endoscopic stricturotomy (ESt), are less invasive interventions compared to surgery. ESt is advantageous for strictures that are longer, more fibrotic, or adjacent to anatomic structures requiring precision, and it has shown a high rate of surgery-free survival. Methods: We designed a microsimulation state-transition model comparing ESt to surgical resection for CD strictures. We calculated quality-adjusted life years (QALYs) over a 10-year time horizon; secondary outcomes included costs (in 2022 USD) and incremental cost-effectiveness ratios (ICERs). We used a societal perspective to compare our strategies at a willingness-to-pay (WTP) threshold of 100,000 USD/QALY. Sensitivity analyses, both deterministic and probabilistic, were performed. Results: The surgery strategy cost more than 2.5 times the ESt strategy, but resulted in nine more QALYs per 100 persons. The ICER for the surgery strategy was 308,787 USD/QALY; thus, the ESt strategy was determined more cost-effective. One-way sensitivity analyses showed that quality of life after ESt as compared to that after surgery, the likelihood of repeat intervention, and surgical mortality and cost were the most influential parameters shifting cost-effectiveness. Probabilistic sensitivity analyses favored ESt in most (65.5%) iterations. Conclusions: Our study finds endoscopic stricturotomy to be a cost-effective strategy to manage primary or anastomotic Crohn’s disease strictures. Post-intervention quality of life and probabilities of requiring repeated interventions exert most influence on cost-effectiveness. The decision between ESt and surgery should be made considering patient and stricture characteristics, preferences, and cost-effectiveness. Full article
(This article belongs to the Section Healthcare Quality and Patient Safety)
24 pages, 3701 KiB  
Article
Multifunctional REE Selective Hybrid Membranes Based on Ion-Imprinted Polymers and Modified Multiwalled Carbon Nanotubes: A Physicochemical Characterization
by Aleksandra Rybak, Aurelia Rybak, Sławomir Boncel, Anna Kolanowska, Waldemar Kaszuwara, Mariusz Nyc, Rafał Molak, Jakub Jaroszewicz and Spas D. Kolev
Int. J. Mol. Sci. 2025, 26(15), 7136; https://doi.org/10.3390/ijms26157136 - 24 Jul 2025
Abstract
A novel type of multifunctional hybrid membranes combining modified chitosan, functionalized multi-walled carbon nanotubes (MWCNTs), and rare earth element ion-imprinted polymers (REEIIPs) were designed and characterized. The synthesized materials were characterized by thermogravimetric analysis (TGA), scanning electron microscopy (SEM), vibrating sample magnetometry (VSM), [...] Read more.
A novel type of multifunctional hybrid membranes combining modified chitosan, functionalized multi-walled carbon nanotubes (MWCNTs), and rare earth element ion-imprinted polymers (REEIIPs) were designed and characterized. The synthesized materials were characterized by thermogravimetric analysis (TGA), scanning electron microscopy (SEM), vibrating sample magnetometry (VSM), X-ray diffraction (XRD), X-ray micro-tomography, and Fourier transform infrared spectroscopy (FTIR). The hybrid membranes were also studied in terms of their mechanical and rheological properties. The key element of the proper preparation of hybrid membranes using the casting method in an external magnetic field was to synthesize membrane components with appropriate magnetic properties. It was found that they showed tunable weak ferromagnetic properties, and the increase in modified nanotube addition caused the rise in the membrane’s saturation magnetization, which for Nd-selective hybrid membranes reached 0.44 emu/g. Also, the increase in thermooxidative stability was noted after introducing functionalized nanotubes into polymer matrices, which, in the case of Gd-selective membranes, were stable even up to 730 °C. The rise in the modified MWCNT addition and selection of appropriate REE ion-imprinted polymers improved mechanical (Rm and E values increase even twice) and rheological parameters (almost double growth of E′ and E″ values) of the tested membranes. Synthesized hybrid membranes showed a high rejection of matrix components and an increase in retention ratio with rising MWCNT-REEIIP addition, ultimately reaching 94.35%, 92.12%, and 90.11% for Nd, Pr, and Gd, respectively. The performed analysis confirmed homogeneous dispersion, phase compatibility, network integration, formation of a complex 3D microstructure, and improved operational stability of created hybrid membranes, which is significant for their future applications in Nd, Pr, and Gd recovery from coal fly ash extracts. Full article
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12 pages, 11599 KiB  
Article
Dual pH- and Temperature-Responsive Fluorescent Hybrid Materials Based on Carbon Dot-Grafted Triamino-Tetraphenylethylene/N-Isopropylacrylamide Copolymers
by Huan Liu, Yuxin Ding, Longping Zhou, Shirui Xu and Bo Liao
C 2025, 11(3), 53; https://doi.org/10.3390/c11030053 - 22 Jul 2025
Abstract
Carbon dots (CDs), a class of carbon-based fluorescent nanomaterials, have garnered significant attention due to their tunable optical properties and functional versatility. In this study, we developed a hybrid material by grafting pH- and temperature-responsive copolymers onto CDs via reversible addition-fragmentation chain-transfer (RAFT) [...] Read more.
Carbon dots (CDs), a class of carbon-based fluorescent nanomaterials, have garnered significant attention due to their tunable optical properties and functional versatility. In this study, we developed a hybrid material by grafting pH- and temperature-responsive copolymers onto CDs via reversible addition-fragmentation chain-transfer (RAFT) polymerization. Triamino-tetraphenylethylene (ATPE) and N-isopropylacrylamide (NIPAM) were copolymerized at varying ratios and covalently linked to CDs, forming a dual-responsive system. Structural characterization using FTIR, 1H NMR, and TEM confirmed the successful grafting of the copolymers onto CDs. The hybrid material exhibited pH-dependent fluorescence changes in acidic aqueous solutions, with emission shifting from 450 nm (attributed to CDs) to 500 nm (aggregation-induced emission, AIE, from ATPE) above a critical pH threshold. Solid films of the hybrid material demonstrated reversible fluorescence quenching under HCl vapor and recovery/enhancement under NH3 vapor, showing excellent fatigue resistance over multiple cycles. Temperature responsiveness was attributed to the thermosensitive poly(NIPAM) segments, with fluorescence intensity increasing above 35 °C due to polymer chain collapse and ATPE aggregation. This work provides a strategy for designing multifunctional hybrid materials with potential applications in recyclable optical pH/temperature sensors. Full article
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20 pages, 2494 KiB  
Article
Effect of Environmental Exposure to Zearalenone on the Metabolic Profile of Patients with Sigmoid Colorectal Cancer or Colorectal Cancer on the Day of Hospital Admission
by Sylwia Lisieska-Żołnierczyk, Magdalena Gajęcka, Łukasz Zielonka, Katarzyna E. Przybyłowicz and Maciej T. Gajęcki
Int. J. Mol. Sci. 2025, 26(14), 6967; https://doi.org/10.3390/ijms26146967 - 20 Jul 2025
Viewed by 190
Abstract
Colorectal cancer is one of the most commonly diagnosed types of cancer and constitutes the second most frequent cancer in women (W) and the third most frequent cancer in men (M). The aim of the study was to determine if environmental exposure to [...] Read more.
Colorectal cancer is one of the most commonly diagnosed types of cancer and constitutes the second most frequent cancer in women (W) and the third most frequent cancer in men (M). The aim of the study was to determine if environmental exposure to zearalenone (ZEN) (a mycoestrogen) affects the metabolic profile of patients diagnosed with sigmoid colorectal cancer (SCC) and colorectal cancer (CRC) (division based on their location) at hospital admission. Male and female patients who were diagnosed with SCC or CRC and whose blood samples tested positive or negative for ZEN participated in a year-long study. Seventeen patients with symptoms of SCC and CRC, in whom ZEN and its metabolites were not detected in peripheral blood, constituted the patients without ZEN (PWZ) group. The experimental groups comprised a total of 16 patients who were diagnosed with SCC or CRC and tested positive for ZEN but negative for ZEN metabolites. Patients exposed to ZEN were characterized by increased levels of liver enzymes (alanine aminotransferase (ALT) from 5.8 to 18.1 IU/L; aspartate aminotransferase (AST) from 2.8 to 10.7 IU/L) and decrease in the value of the De Ritis ratio (below 1.0), different gamma glutamyl transpeptidase and AST activity, lower albumin (from 0.24 g/dL in M to 0.67 g/dL in W) and total protein levels (from 0.75 to 1.76 g/dL), a decrease in total cholesterol (from 21.6 to 40.3 mg/dL) and triglyceride levels (from 7.8 to 37.2 mg/dL), and lower activity of lipase C (from 28.72 to 64.75 IU/L). The metabolic profile of M and W patients diagnosed with SCC and CRC and exposed to ZEN revealed intensified biotransformation processes in the liver, liver damage, and a predominance of catabolic processes. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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22 pages, 840 KiB  
Article
Relationship Between Family Support, C-Reactive Protein and Body Mass Index Among Outpatients with Schizophrenia
by Argyro Pachi, Athanasios Tselebis, Evgenia Kavourgia, Nikolaos Soultanis, Dimitrios Kasimis, Christos Sikaras, Spyros Baras and Ioannis Ilias
Healthcare 2025, 13(14), 1754; https://doi.org/10.3390/healthcare13141754 - 20 Jul 2025
Viewed by 264
Abstract
Background/Objectives: Schizophrenia has been associated with increased inflammatory and metabolic disturbances. Perceived family support potentially affects inflammatory and metabolic biomarkers. The aim of this study was to determine the interrelations between family support, C-reactive protein (CRP) and Body Mass Index (BMI) in a [...] Read more.
Background/Objectives: Schizophrenia has been associated with increased inflammatory and metabolic disturbances. Perceived family support potentially affects inflammatory and metabolic biomarkers. The aim of this study was to determine the interrelations between family support, C-reactive protein (CRP) and Body Mass Index (BMI) in a sample of outpatients with schizophrenia. Importantly, this study sought to elucidate the effect of perceived family support on inflammatory processes among patients with schizophrenia. Methods: In this cross-sectional correlation study, 206 outpatients with schizophrenia in clinical remission completed a standardized self-report questionnaire that assessed family support (Family Support Scale—FSS). Sociodemographic, clinical and laboratory data were also recorded. Results: Among the participants, 49.5% had detectable CRP values (≥0.11 mg/dL), whereas 14.6% had positive CRP levels (>0.6 mg/dL). There was a significant difference in CRP levels among the different BMI groups (normal weight/overweight vs. obese). For obese patients, the crude odds ratios (ORs) for detectable and positive CRP values were 1.980 (95% confidence interval (CI) [1.056, 3.713]) and 27.818 (95% CI [6.300, 122.838]), respectively. Significant positive correlations were observed among CRP, BMI and illness duration, while scores on the FSS were negatively associated with these variables. The results of binary logistic regression analysis indicated that both BMI and family support were significant factors in determining the likelihood of having positive CRP levels, with each unit increase in the BMI associated with a 17% (95% CI [0.025, 0.337]) increase in the odds, and with each unit increase in family support leading to an 8.6% (95% CI [0.018, 0.15]) decrease. A moderation analysis revealed that the association between family support and the probability of having positive CRP levels depends on the BMI value, but only for obese patients did the protective effect of family support significantly decrease the magnitude of the risk of having positive CRP (b = −0.1972, SE = 0.053, OR = 0.821, p = 0.000, 95% CI [−0.3010, −0.0934]). Conclusions: The effect of perceived family support on inflammatory responses becomes evident in cases where beyond metabolic complications, inflammatory processes have already been established. Increased perceived family support seems to protect against inflammation and, notably, the association between low perceived family support and increased inflammation is even stronger. Establishing the role of family involvement during the treatment of patients with schizophrenia through inflammatory processes is a novelty of this study, emphasizing the need to incorporate family therapy into psychiatric treatment plans. However, primary interventions are considered necessary for patients with schizophrenia in order to maintain their BMI within normal limits and avoid the subsequent nosological sequelae. Full article
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27 pages, 1036 KiB  
Review
Outcomes in Adults with Celiac Disease Following a Gluten-Free Diet
by Daniel Vasile Balaban, Iulia Enache, Marina Balaban, Răzvan Andrei David, Andreea-Diana Vasile, Alina Popp and Mariana Jinga
J. Clin. Med. 2025, 14(14), 5144; https://doi.org/10.3390/jcm14145144 - 20 Jul 2025
Viewed by 280
Abstract
Background/Objectives: Histological follow-up still lacks consensus in the long-term management of adult patients with celiac disease (CD) adhering to a gluten-free diet (GFD). Despite clinical and serological improvement, a significant proportion of patients continue to have persistent villous atrophy. We aimed to [...] Read more.
Background/Objectives: Histological follow-up still lacks consensus in the long-term management of adult patients with celiac disease (CD) adhering to a gluten-free diet (GFD). Despite clinical and serological improvement, a significant proportion of patients continue to have persistent villous atrophy. We aimed to synthesize current evidence regarding histological outcomes after GFD treatment in adult CD, focusing on mucosal healing rates, assessment methods, and remission criteria. Methods: We conducted a literature search with extraction and analysis of published cohort studies that included adult patients with CD on GFD with follow-up biopsy data. Extracted parameters included demographic details, baseline histology, GFD duration and adherence, serologic status, and histologic recovery rates with corresponding remission criteria. Results: Data from 46 studies comprising 15,530 patients were analyzed. The overall mean age was 41 years, and 73.3% were female. Mean histologic remission across cohorts was 58.8%, with considerable interstudy variation. Remission criteria also varied widely, ranging from strict Marsh 0 control histology to more inclusive definitions that considered Marsh 1 or even non-atrophic mucosa (Marsh < 3) as indicative of recovery, while some studies relied on quantitative villous height-to-crypt depth ratio thresholds, substantially influencing reported remission rates. Longer GFD duration and rigorous diet adherence assessment using validated questionnaires and accurate laboratory tools were associated with higher remission rates. Conclusions: Histologic remission in GFD-treated adult patients with CD is highly variable and strongly influenced by remission definitions and adherence assessment methods. Standardized reporting using validated metrics for histologic outcome and dietary compliance is essential for harmonizing follow-up strategies in adult CD. Full article
(This article belongs to the Special Issue Future Trends in the Diagnosis and Management of Celiac Disease)
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16 pages, 2268 KiB  
Article
Epichloë Endophyte Alters Bacterial Nitrogen-Cycling Gene Abundance in the Rhizosphere Soil of Perennial Ryegrass
by Munire Maimaitiyiming, Yanxiang Huang, Letian Jia, Mofan Wu and Zhenjiang Chen
Biology 2025, 14(7), 879; https://doi.org/10.3390/biology14070879 - 18 Jul 2025
Viewed by 158
Abstract
Perennial ryegrass (Lolium perenne), an important forage and turfgrass species, can establish a mutualistic symbiosis with the fungal endophyte Epichloë festucae var. lolii. Although the physiological and ecological impacts of endophyte infection on ryegrass have been extensively investigated, the response of [...] Read more.
Perennial ryegrass (Lolium perenne), an important forage and turfgrass species, can establish a mutualistic symbiosis with the fungal endophyte Epichloë festucae var. lolii. Although the physiological and ecological impacts of endophyte infection on ryegrass have been extensively investigated, the response of the soil microbial community and nitrogen-cycling gene to this relationship has received much less attention. The present study emphasized abundance and diversity variation in the AOB-amoA, nirK and nosZ functional genes in the rhizosphere soil of the endophyte–ryegrass symbiosis following litter addition. We sampled four times: at T0 (prior to first litter addition), T1 (post 120 d of 1st litter addition), T2 (post 120 d of 2nd litter addition) and T3 (post 120 d of 3rd litter addition) times. Real-time fluorescence quantitative PCR (qPCR) and PCR amplification and sequencing were used to characterize the abundance and diversity of the AOB-amoA, nirK and nosZ genes in rhizosphere soils of endophyte-infected (E+) plants and endophyte-free (E−) plants. A significant enhancement of total Phosphorus (P), Soil Organic Carbon (SOC), Ammonium ion (NH4+) and Nitrate ion (NO3) contents in the rhizosphere soil was recorded in endophyte-infected plants at different sampling times compared to endophyte-free plants (p ≤ 0.05). The absolute abundance of the AOB-amoA gene at T0 and T1 times was higher, as was the absolute abundance of the nosZ gene at T0, T1 and T3 times in the E+ plant rhizophere soils relative to E− plant rhizosphere soils. A significant change in relative abundance of the AOB-amoA and nosZ genes in the host rhizophere soils of endophyte-infected plants at T1 and T3 times was observed. The experiment failed to show any significant alteration in abundance and diversity of the nirK gene, and diversity of the AOB-amoA and nosZ genes. Analysis of the abundance and diversity of the nirK gene indicated that changes in soil properties accounted for approximately 70.38% of the variation along the first axis and 16.69% along the second axis, and soil NH4+ (p = 0.002, 50.4%) and soil C/P ratio (p = 0.012, 15.8%) had a strong effect. The changes in community abundance and diversity of the AOB-amoA and nosZ genes were mainly related to soil pH, N/P ratio and NH4+ content. The results demonstrate that the existence of tripartite interactions among the foliar endophyte E. festucae var. Lolii, L. perenne and soil nitrogen-cycling gene has important implications for reducing soil losses on N. Full article
(This article belongs to the Collection Plant Growth-Promoting Bacteria: Mechanisms and Applications)
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20 pages, 10915 KiB  
Article
Combination Therapy with Human Chorionic Villi MSCs and Secretory Factors Enhances Cutaneous Wound Healing in a Rat Model
by Qingwen Deng, Jiawei Huang, Lai Ling Tsang, Jinghui Guo, Chi Chiu Wang, Xiaohu Zhang and Xiaohua Jiang
Int. J. Mol. Sci. 2025, 26(14), 6888; https://doi.org/10.3390/ijms26146888 - 17 Jul 2025
Viewed by 233
Abstract
Cutaneous wound healing is a complex process involving multiple cellular and molecular events, and current treatments often face limitations in efficacy and safety. Stem-cell therapy, particularly using mesenchymal stem cells (MSCs), has emerged as a promising approach to enhance wound repair through both [...] Read more.
Cutaneous wound healing is a complex process involving multiple cellular and molecular events, and current treatments often face limitations in efficacy and safety. Stem-cell therapy, particularly using mesenchymal stem cells (MSCs), has emerged as a promising approach to enhance wound repair through both direct cell replacement and paracrine signaling. This study investigates the therapeutic potential of human chorionic villus mesenchymal stem cells (hCV-MSCs) and their secretory factors in enhancing cutaneous wound healing. Utilizing a rat model, we combined the local administration of hCV-MSC-laden PEGDA/SA/Col-I hydrogel with the systemic delivery of their secretome, aiming to leverage the complementary mechanisms of cellular and cell-free therapies. Our findings demonstrate that hCV-MSCs delivered via PEGDA/SA/Col-I hydrogel significantly accelerated wound closure compared to controls, with near-complete closure observed by day 20. Histological analysis revealed enhanced keratinocyte maturation (increased KRT10/KRT14 ratio) and a higher density of CD31+ blood vessels, indicating improved re-epithelialization and angiogenesis. A mass spectrometry analysis of the hCV-MSC secretome identified 849 proteins, with enrichment in pathways related to ECM organization, cell adhesion, and immune regulation. Key proteins such as ANXA1, SERPINE1, and WNT5A were implicated in wound-healing processes. Combination therapy with systemic secretome administration further accelerated wound closure and enhanced collagen deposition, keratinocyte maturation, and vascularization compared to hCV-MSCs alone. Our results highlight the promising application of hCV-MSCs and their secretome in cutaneous wound healing, paving the way for innovative therapeutic strategies that integrate both local and systemic regenerative approaches. Full article
(This article belongs to the Special Issue Recent Advances in Adult Stem Cell Research)
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40 pages, 4846 KiB  
Article
Comparative Analysis of Some Methods and Algorithms for Traffic Optimization in Urban Environments Based on Maximum Flow and Deep Reinforcement Learning
by Silvia Baeva, Nikolay Hinov and Plamen Nakov
Mathematics 2025, 13(14), 2296; https://doi.org/10.3390/math13142296 - 17 Jul 2025
Viewed by 159
Abstract
This paper presents a comparative analysis between classical maximum flow algorithms and modern deep Reinforcement Learning (RL) algorithms applied to traffic optimization in urban environments. Through SUMO simulations and statistical tests, algorithms such as Ford–Fulkerson, Edmonds–Karp, Dinitz, Preflow–Push, Boykov–Kolmogorov and Double [...] Read more.
This paper presents a comparative analysis between classical maximum flow algorithms and modern deep Reinforcement Learning (RL) algorithms applied to traffic optimization in urban environments. Through SUMO simulations and statistical tests, algorithms such as Ford–Fulkerson, Edmonds–Karp, Dinitz, Preflow–Push, Boykov–Kolmogorov and Double DQN are compared. Their efficiency and stability are evaluated in terms of metrics such as cumulative vehicle dispersion and the ratio of waiting time to vehicle number. The results show that classical algorithms such as Edmonds–Karp and Dinitz perform stably under deterministic conditions, while Double DQN suffers from high variation. Recommendations are made regarding the selection of an appropriate algorithm based on the characteristics of the environment, and opportunities for improvement using DRL techniques such as PPO and A2C are indicated. Full article
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14 pages, 415 KiB  
Article
Cellular Recovery and Body Composition Changes in Pediatric Celiac Disease After the Start of a Gluten-Free Diet: A Prospective Cohort Study
by Teresa Nestares, María Jiménez-Muñoz, Encarnación Torcuato-Rubio, Laura Tamayo Pérez, Marta de la Flor Alemany, Marta Herrador-López, Víctor Navas-López and Rafael Martín-Masot
J. Clin. Med. 2025, 14(14), 5061; https://doi.org/10.3390/jcm14145061 - 17 Jul 2025
Viewed by 335
Abstract
Background/Objectives: Celiac disease (CD) alters nutrient absorption and body composition, especially during childhood. Although adherence to a gluten-free diet (GFD) promotes mucosal recovery, its impact on cellular functionality and metabolic balance remains underexplored. This study aims to evaluate the utility of bioelectrical impedance [...] Read more.
Background/Objectives: Celiac disease (CD) alters nutrient absorption and body composition, especially during childhood. Although adherence to a gluten-free diet (GFD) promotes mucosal recovery, its impact on cellular functionality and metabolic balance remains underexplored. This study aims to evaluate the utility of bioelectrical impedance vector analysis (BIVA) in assessing nutritional status, inflammatory improvement, and body composition changes in pediatric patients with CD following a GFD. Methods: Seventy-nine children aged 5–14 years were studied. Three groups were analyzed: (1) 25 children with newly diagnosed CD, evaluated at diagnosis and after 12 months of GFD (prospective cohort); (2) 25 CD patients on a GFD for over 24 months (cross-sectional); and (3) 29 healthy controls. Body composition (fat mass (FM), fat-free mass (FFM), body cell mass (BCM), phase angle (PhA), and Na+/K+ ratio) was measured. GFD adherence was assessed and a dietary assessment was also performed. Results: After 12 months on a GFD, newly diagnosed CD patients showed significant increases in FM (from 8.2 to 10.1 kg, p = 0.001), FFM (p = 0.001), and BCM (p = 0.0001), along with a significant decrease in the Na+/K+ ratio (p = 0.015). Compared to healthy controls, CD children on GFD for more than 24 months had higher FM (12.2 vs. 8.8 kg, p = 0.013) and lower Na+/K+ ratios (p = 0.006). PhA increased slightly over time but did not reach statistical significance. Conclusions: Our study suggests that the adherence to a GFD leads to improved body composition and cellular homeostasis in children with CD, as reflected by increases in BCM and reductions in Na+/K+ ratio, making it a promising biomarker for monitoring inflammation and cellular recovery. Full article
(This article belongs to the Special Issue Future Trends in the Diagnosis and Management of Celiac Disease)
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14 pages, 1222 KiB  
Article
The Role of Endothelial Progenitor Cells (EPCs) and Circulating Endothelial Cells (CECs) as Early Biomarkers of Endothelial Dysfunction in Children with Newly Diagnosed Type 1 Diabetes
by Milena Jamiołkowska-Sztabkowska, Sebastian Ciężki, Aleksandra Starosz, Kamil Grubczak, Marcin Moniuszko, Artur Bossowski and Barbara Głowińska-Olszewska
Cells 2025, 14(14), 1095; https://doi.org/10.3390/cells14141095 - 17 Jul 2025
Viewed by 220
Abstract
The aim of this study is to assess endothelial progenitor cells (EPCs) and circulating endothelial cells (CECs) at the time of type 1 diabetes (T1D) recognition concerning patients’ clinical state, remaining insulin secretion, and further partial remission (PR) occurrence. We recruited 45 children [...] Read more.
The aim of this study is to assess endothelial progenitor cells (EPCs) and circulating endothelial cells (CECs) at the time of type 1 diabetes (T1D) recognition concerning patients’ clinical state, remaining insulin secretion, and further partial remission (PR) occurrence. We recruited 45 children that were admitted to hospital due to newly diagnosed T1D (median age 10.8 yrs), and 20 healthy peers as a control group. EPC and CEC levels were measured at disease onset in PBMC isolated from whole peripheral blood with the use of flow cytometry. Clinical data regarding patients’ condition, C-peptide secretion, and further PR prevalence were analyzed. T1D-diagnosed patients presented higher EPC levels than the control group (p = 0.026), while no statistical differences in CEC levels and EPC/CEC ratio were observed. Considering only T1D patients, those with better clinical conditions presented lower EPCs (p = 0.021) and lower EPC/CEC ratios (p = 0.0002). Patients with C-peptide secretion within a normal range at disease onset presented lower EPC/CEC ratios (p = 0.027). Higher levels of EPCs were observed more frequently in patients with higher glucose, decreased fasting C-peptide, and lower stimulated C-peptide (all p < 0.05). The presence of DKA was related to higher EPC/CEC ratios (p = 0.034). Significantly higher levels of CECs were observed in patients who presented partial remission of the disease at 6 months after diagnosis (p = 0.03) only. In the study group, positive correlations of CECs with age, BMI at onset, and BMI in following years were observed. EPC/CEC ratios correlated positively with glucose levels at hospital admission and negatively with age, BMI, pH, and stimulated C-peptide level. We reveal a new potential for the application of EPCs and CECs as biomarkers, reflecting both endothelial injury and reconstruction processes in children with T1D. There is a need for further research in order to reduce cardiovascular risk in children with T1D. Full article
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28 pages, 9709 KiB  
Article
Simulating Effects of Continuous and Intermittent Water Flow on Soil Water Distribution Under Subsurface Point Source Using HYDRUS Program
by Mohamed Shaban and A A Alazba
Water 2025, 17(14), 2117; https://doi.org/10.3390/w17142117 - 16 Jul 2025
Viewed by 237
Abstract
Optimizing water resource utilization is a critical challenge to meet the dramatic increase in food demand. Therefore, continuous studies to minimize water demand for plants are highly needed. This study aims to employ HYDRUS (2D/3D) software to simulate the effects of continuous and [...] Read more.
Optimizing water resource utilization is a critical challenge to meet the dramatic increase in food demand. Therefore, continuous studies to minimize water demand for plants are highly needed. This study aims to employ HYDRUS (2D/3D) software to simulate the effects of continuous and intermittent water flow on soil water distribution under a subsurface point source. The constant parameters included loamy sand soil, a water application time of 30 min, and an emitter discharge of 3.41 L/h. The variable parameters consisted are two pipe depths (25 cm and 35 cm), three ratios of ON:OFF times (1ON:1OFF, 1ON:3OFF, and 1ON:5OFF), and five water application cycles (WF1C, WF2C, WF3C, WF4C, and WF5C, with WF1C as for the continuous water flow). The results revealed that, in 30 min of water application, continuous water flow and ON:OFF ratios of 1ON:1OFF and 1ON:3OFF achieved maximum water retention in the vicinity of the emitter. In 60 min, increasing cycles enhanced retention for 1ON:1OFF and 1ON:3OFF, yet the 1ON:5OFF time ratio achieved the highest water content near the emitter. In 120 min, the 1ON:1OFF ratio showed an insignificant effect with cycle variations, but 1ON:3OFF and 1ON:5OFF exhibited increased retention. Similarly, in 180 min, 1ON:1OFF was unaffected by cycles, whereas 1ON:3OFF and 1ON:5OFF significantly improved retention. After 360 min, all treatments displayed equal water retention relative to the emitter position. Also, the results revealed that increasing water application cycles and ON:OFF time ratios lead to more holding soil water content, especially at soil levels of 20, 30, and 40 cm. These results affirm that positioning the emitters line at 25 cm enhances water retention more effectively than at 35 cm. Ultimately, statistical analysis confirmed that the combination of pipe depth, water application cycles, and ON:OFF ratios significantly affects the retention of soil water content in the vicinity of the emitter. Full article
(This article belongs to the Section Soil and Water)
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11 pages, 3627 KiB  
Article
The Influence of Traps on the Self-Heating Effect and THz Response of GaN HEMTs
by Huichuan Fan, Xiaoyun Wang, Xiaofang Wang and Lin Wang
Photonics 2025, 12(7), 719; https://doi.org/10.3390/photonics12070719 - 16 Jul 2025
Viewed by 183
Abstract
This study systematically investigates the effects of trap concentration on self-heating and terahertz (THz) responses in GaN HEMTs using Sentaurus TCAD. Traps, inherently unavoidable in semiconductors, can be strategically introduced to engineer specific energy levels that establish competitive dynamics between the electron momentum [...] Read more.
This study systematically investigates the effects of trap concentration on self-heating and terahertz (THz) responses in GaN HEMTs using Sentaurus TCAD. Traps, inherently unavoidable in semiconductors, can be strategically introduced to engineer specific energy levels that establish competitive dynamics between the electron momentum relaxation time and the carrier lifetime. A simulation-based exploration of this mechanism provides significant scientific value for enhancing device performance through self-heating mitigation and THz response optimization. An AlGaN/GaN heterojunction HEMT model was established, with trap concentrations ranging from 0 to 5×1017 cm3. The analysis reveals that traps significantly enhance channel current (achieving 3× gain at 1×1017 cm3) via new energy levels that prolong carrier lifetime. However, elevated trap concentrations (>1×1016 cm3) exacerbate self-heating-induced current collapse, reducing the min-to-max current ratio to 0.9158. In THz response characterization, devices exhibit a distinct DC component (Udc) under non-resonant detection (ωτ1). At a trap concentration of 1×1015 cm3, Udc peaks at 0.12 V when VgDC=7.8 V. Compared to trap-free devices, a maximum response attenuation of 64.89% occurs at VgDC=4.9 V. Furthermore, Udc demonstrates non-monotonic behavior with concentration, showing local maxima at 4×1015 cm3 and 7×1015 cm3, attributed to plasma wave damping and temperature-gradient-induced electric field variations. This research establishes trap engineering guidelines for GaN HEMTs: a concentration of 4×1015 cm3 optimally enhances conductivity while minimizing adverse impacts on both self-heating and the THz response, making it particularly suitable for high-sensitivity terahertz detectors. Full article
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14 pages, 2100 KiB  
Article
Response of Han River Estuary Discharge to Hydrological Process Changes in the Tributary–Mainstem Confluence Zone
by Shuo Ouyang, Changjiang Xu, Weifeng Xu, Junhong Zhang, Weiya Huang, Cuiping Yang and Yao Yue
Sustainability 2025, 17(14), 6507; https://doi.org/10.3390/su17146507 - 16 Jul 2025
Viewed by 204
Abstract
This study investigates the dynamic response mechanisms of discharge capacity in the Han River Estuary to hydrological process changes at the Yangtze–Han River confluence. By constructing a one-dimensional hydrodynamic model for the 265 km Xinglong–Hankou reach, we quantitatively decouple the synergistic effects of [...] Read more.
This study investigates the dynamic response mechanisms of discharge capacity in the Han River Estuary to hydrological process changes at the Yangtze–Han River confluence. By constructing a one-dimensional hydrodynamic model for the 265 km Xinglong–Hankou reach, we quantitatively decouple the synergistic effects of riverbed scouring (mean annual incision rate: 0.12 m) and Three Gorges Dam (TGD) operation through four orthogonal scenarios. Key findings reveal: (1) Riverbed incision dominates discharge variation (annual mean contribution >84%), enhancing flood conveyance efficiency with a peak flow increase of 21.3 m3/s during July–September; (2) TGD regulation exhibits spatiotemporal intermittency, contributing 25–36% during impoundment periods (September–October) by reducing Yangtze backwater effects; (3) Nonlinear interactions between drivers reconfigure flow paths—antagonism occurs at low confluence ratios (R < 0.15, e.g., Cd increases to 45 under TGD but decreases to 8 under incision), while synergy at high ratios (R > 0.25) reduces Hanchuan Station flow by 13.84 m3/s; (4) The 180–265 km confluence-proximal zone is identified as a sensitive area, where coupled drivers amplify water surface gradients to −1.41 × 10−3 m/km (2.3× upstream) and velocity increments to 0.0027 m/s. The proposed “Natural/Anthropogenic Dual-Stressor Framework” elucidates estuary discharge mechanisms under intensive human interference, providing critical insights for flood control and trans-basin water resource management in tide-free estuaries globally. Full article
(This article belongs to the Special Issue Sediment Movement, Sustainable Water Conservancy and Water Transport)
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