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19 pages, 1614 KiB

Open AccessArticle

A Two-Layer User Energy Management Strategy for Virtual Power Plants Based on HG-Multi-Agent Reinforcement Learning

by Sen Tian, Qian Xiao, Tianxiang Li, Zibo Wang, Ji Qiao, Hong Zhu and Wenlu Ji

Appl. Sci. 2025, 15(12), 6713; https://doi.org/10.3390/app15126713 (registering DOI) - 15 Jun 2025

Household loads are becoming dominant in virtual power plants (VPP). However, their dispatch potential has not yet been explored due to the lack of detailed user power management. To solve this issue, a novel two-layer user energy management strategy based on HG-multi-agent reinforcement [...] Read more.

Household loads are becoming dominant in virtual power plants (VPP). However, their dispatch potential has not yet been explored due to the lack of detailed user power management. To solve this issue, a novel two-layer user energy management strategy based on HG-multi-agent reinforcement learning has been proposed in this paper. Firstly, a novel two-layer optimization framework is established, where the upper layer is applied to coordinate the scheduling and benefit allocation among various stakeholders and the lower layer is applied to execute intelligent decision-making for users. Secondly, the mathematical model for the framework is established, where a detailed household power management model is proposed in the lower layer, and the generated predicted power demands are used to replace the conventional aggregate model in the upper layer. As a result, the energy consumption behaviors of household users can be precisely described in the scheduling scheme. Furthermore, an HG-multi-agent reinforcement-based method is applied to accelerate the game-solving process. Case study results indicate that the proposed method leads to a reduction in user costs and an increase in VPP profit. Full article

(This article belongs to the Special Issue Emerging Trends in Energy Management: Techniques, Applications and Future Directions)

18 pages, 745 KiB

Open AccessArticle

The Impact of Trade with Border Effect on GDP per Capita: Global Evidence

by Hansen Tandra, I Gusti Ayu Putu Mahendri, Sujianto Sujianto, Bahtiar Rifai, Zamroni Salim, Helena da Silva and Yulia Pujiharti

Economies 2025, 13(6), 174; https://doi.org/10.3390/economies13060174 (registering DOI) - 15 Jun 2025

Abstract

Many countries worldwide share borders that offer several benefits, such as easier access, faster knowledge transfer, and more efficient trade diplomacy. However, reliance on land-border trade alone has not been consistently shown to increase GDP per capita or vice versa. This study investigates [...] Read more.

Many countries worldwide share borders that offer several benefits, such as easier access, faster knowledge transfer, and more efficient trade diplomacy. However, reliance on land-border trade alone has not been consistently shown to increase GDP per capita or vice versa. This study investigates the relationship between trade and GDP per capita by distinguishing trade between land-border countries and non-land-border countries. The analysis applied two-stage least squares (2SLS) estimation using data from 87 countries with land borders covering 2010 to 2021. The share of trade to land and non-land borders around the world was dominated by China, Germany, and the United States, with a share of more than 10%. The results revealed a negative relationship between trade with land-border countries and GDP per capita, while trade with non-land-border countries showed a positive effect. To enhance the benefits of land-border trade, improving governance and infrastructure are essential to sustain its impacts in the future. Full article

(This article belongs to the Section Economic Development)

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26 pages, 5832 KiB

Open AccessArticle

AGEN: Adaptive Error Control-Driven Cross-View Geo-Localization Under Extreme Weather Conditions

by Mengmeng Xu, Hongxiang Lv, Hai Zhu, Enlai Dong and Fei Wu

Sensors 2025, 25(12), 3749; https://doi.org/10.3390/s25123749 (registering DOI) - 15 Jun 2025

Abstract

Cross-view geo-localization is a task of matching the same geographic image from different views, e.g., drone and satellite. Due to its GPS-free advantage, cross-view geo-localization is gaining increasing research interest, especially in drone-based localization and navigation applications. In order to guarantee system accuracy, [...] Read more.

Cross-view geo-localization is a task of matching the same geographic image from different views, e.g., drone and satellite. Due to its GPS-free advantage, cross-view geo-localization is gaining increasing research interest, especially in drone-based localization and navigation applications. In order to guarantee system accuracy, existing methods mainly focused on image augmentation and denoising while still facing performance degradation when extreme weather conditions are considered. In this paper, we propose a robust end-to-end image retrieval framework, AGEN, serving for cross-view geo-localization under extreme weather conditions. Inspired by the strengths of the DINOv2 network, particularly its strong performance in global feature extraction, while acknowledging its limitations in capturing fine-grained details, we integrate the DINOv2 network with the Local Pattern Network (LPN) algorithm module to extract valuable classification features more efficiently. Additionally, to further enhance model robustness, we innovatively introduce an Adaptive Error Control (AEC) module based on fuzzy control to optimize the loss function dynamically. Specifically, by adjusting loss weights adaptively, the AEC module allows the model to better handle complex and challenging scenarios. Experimental results demonstrate that AGEN achieves a Recall@1 accuracy of 91.71% on the University160k-WX dataset under extreme weather conditions. Through extensive experiments on two well-known public datasets, i.e., University-1652 and SUES-200, AGEN achieves state-of-the-art Recall@1 accuracy in both drone-view target localization tasks and drone navigation tasks, outperforming existing models. In particular, on the University-1652 dataset, AGEN reaches 95.43% Recall@1 in the drone-view target localization task, showcasing its superior capability in handling challenging scenarios. Full article

(This article belongs to the Section Navigation and Positioning)

17 pages, 831 KiB

Open AccessArticle

Increased Frequency of the Non-Dipper Blood Pressure Pattern in Patients with Systemic Sclerosis: Insights from 24-Hour Ambulatory Monitoring

by Oğuzhan Zengin, Gülşah Soytürk, Burak Göre, Mustafa Yürümez, Ali Can Kurtipek, Emra Asfuroğlu Kalkan, Hatice Ecem Konak, Şükran Erten and Ihsan Ateş

J. Pers. Med. 2025, 15(6), 253; https://doi.org/10.3390/jpm15060253 (registering DOI) - 15 Jun 2025

Abstract

Background: In systemic sclerosis (SSc), endothelial dysfunction, inflammation, and reduced nitric oxide levels may disrupt circadian blood pressure (BP) regulation. There are studies showing that inflammatory and certain other cells in diseases like SSc exhibit diurnal rhythms. In our study, we examined the [...] Read more.

Background: In systemic sclerosis (SSc), endothelial dysfunction, inflammation, and reduced nitric oxide levels may disrupt circadian blood pressure (BP) regulation. There are studies showing that inflammatory and certain other cells in diseases like SSc exhibit diurnal rhythms. In our study, we examined the effect of SSc on BP. In particular, the frequency of the non-dipper pattern (lack of nighttime BP reduction) in SSc patients has not been adequately investigated. The aim of this study was to evaluate the 24 h BP profile in SSc patients and to compare the frequency of the non-dipper pattern with that of the non-scleroderma group. Additionally, the identification of disrupted circadian BP patterns in SSc patients aims to contribute to the development of personalized, time-sensitive BP monitoring strategies in the future and to support the applicability of personalized medicine in this context. Methods: A total of 31 SSc patients diagnosed according to the 2013 ACR/EULAR classification criteria and 30 age- and sex-matched individuals without SSc were included in this prospective study. BP changes between day and night were evaluated by measuring BP every 30 min with a 24 h ambulatory blood pressure monitoring (ABPM) device. The non-dipper pattern was defined as a decrease in BP of less than 10% during the night compared to the day. To better assess BP fluctuations during the night, nighttime measurements were divided into two time periods: first, 24:00–04:00, and then 04:00–08:00. Additionally, laboratory and clinical parameters and SSc subtypes were compared between the groups. Results: The ABPM findings were compared between the groups with and without SSc. The non-dipper pattern was significantly more common in the SSc group at all time intervals. The non-dipper pattern was observed in 25.8% of the non-SSc group and 83.9% of SSc patients (p < 0.001). In the period between 24:00 and 04:00, the prevalence was 25.8% in the control group and 71.0% in SSc patients (p < 0.001), and between 04:00 and 08:00, it was 35.5% in the control group and 80.6% in SSc patients (p < 0.001). No significant difference was found in non-dipper patterns between individuals with diffuse and limited cutaneous forms of systemic sclerosis. Conclusions: The non-dipper BP pattern is significantly more common in patients with SSc, indicating the disruption of the circadian rhythm affecting BP. Analysis performed by dividing the night into specific time periods revealed that this deterioration continued throughout the night. The findings highlight the importance of circadian BP monitoring in SSc patients and may contribute to future risk stratification and treatment strategies. Circadian BP analysis in SSc may help to develop strategies that are personalized for these patients and tailored to their physiological rhythm. Full article

(This article belongs to the Section Personalized Therapy and Drug Delivery)

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17 pages, 496 KiB

Open AccessReview

Analyzing Patterns and Predictive Models of Energy and Water Consumption in Schools

by Hana Begić Juričić and Hrvoje Krstić

Sustainability 2025, 17(12), 5514; https://doi.org/10.3390/su17125514 (registering DOI) - 15 Jun 2025

Abstract

Schools are major consumers of energy and water, significantly influencing environmental sustainability and operational budgets. This study presents a comprehensive review of global trends in energy and water consumption in school buildings, identifying key factors that shape usage patterns, such as the geographic [...] Read more.

Schools are major consumers of energy and water, significantly influencing environmental sustainability and operational budgets. This study presents a comprehensive review of global trends in energy and water consumption in school buildings, identifying key factors that shape usage patterns, such as the geographic location, climate, building characteristics, and occupancy levels. A particular focus is placed on the role of predictive models in enhancing resource efficiency. The review found that energy consumption in schools varies widely, with heating, lighting, and cooling systems being the primary contributors. In contrast, research on water consumption—especially predictive modeling—is notably scarce, with no studies found that focused specifically on school buildings. This highlights a critical gap in the literature. This study evaluated the existing predictive approaches, including regression analyses, machine learning algorithms, and statistical models, which offer valuable tools for forecasting consumption and guiding targeted efficiency interventions. The findings underscore the urgent need for data-driven strategies to support sustainable resource management in educational facilities. Full article

(This article belongs to the Special Issue Resilient Infrastructure Planning: Enhancing Sustainability in Construction)

20 pages, 1838 KiB

Open AccessArticle

Thermal Conductivity of Sustainable Earthen Materials Stabilized by Natural and Bio-Based Polymers: An Experimental and Statistical Analysis

by Rizwan Shoukat, Marta Cappai, Giorgio Pia, Tadeusz Kubaszek, Roberto Ricciu, Łukasz Kolek and Luca Pilia

Energies 2025, 18(12), 3144; https://doi.org/10.3390/en18123144 (registering DOI) - 15 Jun 2025

Abstract

The natural and sustainable ability of earthen building materials makes them highly valuable. Bio-stabilization involves using biological materials or processes in earthen construction to enhance the performance and characteristics of earthen materials. The main objective of bio-stabilization is to substitute high-energy-intensive building materials [...] Read more.

The natural and sustainable ability of earthen building materials makes them highly valuable. Bio-stabilization involves using biological materials or processes in earthen construction to enhance the performance and characteristics of earthen materials. The main objective of bio-stabilization is to substitute high-energy-intensive building materials with more green, thermally efficient substitutions, ultimately reducing indirect emissions. The large-scale use of earth presents a viable alternative due to its extensive availability and, more importantly, its low embodied energy. The aim of this work is to investigate the thermal conductivity of earth stabilized with Opuntia Ficus-Indica (OFI), a natural biopolymer, and to assess how these properties vary based on mix design. A comparative analysis is performed to evaluate the thermal performance of bio-based polymer-stabilized earthen materials (S-30, S-40, D-30, and D-40) alongside natural biopolymer-stabilized earth (OFI-30 and OFI-40) under dry conditions, employing an experimental method. A scanning electron microscope was employed to examine the microstructure of bio-stabilized earthen materials from the samples. Statistical analysis was conducted on the collected data using ANOVA with a significance level of 0.05. The Tukey test was applied to identify specific mean pairings that demonstrate significant differences in the characteristics of the mixtures at each replacement level, maintaining a confidence interval of 95%. The experimental and statistical findings reveal that the OFI-30, D-40, and S-40 mixtures exhibit strong bonding with earthen materials and high thermal performance compared to all other mix designs in environmental samples. Additionally, these mix designs show further improvement in thermal performance in the dry conditions. Full article

(This article belongs to the Special Issue Biomass and Municipal Solid Waste Thermal Conversion Technologies: 3rd Edition)

30 pages, 13022 KiB

Open AccessArticle

Dynamic Mechanical Characteristics and Fracture Size Effect of Coal Sandstone Under High-Temperature and High-Strain Rate Coupling Action

by Ming Li, Fuqiang Zhu, Yiwen Mao, Fangwei Fan, Boyuan Wu and Jishuo Deng

Fractal Fract. 2025, 9(6), 381; https://doi.org/10.3390/fractalfract9060381 (registering DOI) - 15 Jun 2025

Abstract

The deformation control of surrounding rock in the combustion air zone is crucial for the safety and efficiency of underground coal gasification (UCG) projects. Coal-bearing sandstone, a common surrounding rock in UCG chambers, features a brittle structure composed mainly of quartz, feldspar, and [...] Read more.

The deformation control of surrounding rock in the combustion air zone is crucial for the safety and efficiency of underground coal gasification (UCG) projects. Coal-bearing sandstone, a common surrounding rock in UCG chambers, features a brittle structure composed mainly of quartz, feldspar, and clay minerals. Its mechanical behavior under high-temperature and dynamic loading is complex and significantly affects rock stability. To investigate the deformation and failure mechanisms under thermal–dynamic coupling, this study conducted uniaxial impact compression tests using a high-temperature split Hopkinson pressure bar (HT-SHPB) system. The focus was on analyzing mechanical response, energy dissipation, and fragmentation characteristics under varying temperature and strain rate conditions. The results show that the dynamic elastic modulus, compressive strength, fractal dimension of fragments, energy dissipation density, and energy consumption rate all increase initially with temperature and then decrease, with inflection points observed at 400 °C. Conversely, dynamic peak strain first decreases and then increases with rising temperature, also showing a turning point at 400 °C. This indicates a shift in the deformation and failure mode of the material. The findings provide critical insights into the thermo-mechanical behavior of coal-bearing sandstone under extreme conditions and offer a theoretical basis for designing effective deformation control strategies in underground coal gasification projects. Full article

(This article belongs to the Section Engineering)

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33 pages, 5009 KiB

Open AccessArticle

Quercetin as a Therapeutic Option in a Rat Model of Aluminum Chloride- and D-Galactose-Induced Neurodegeneration

by Marina Kukolj, Nada Oršolić, Lea Langer Horvat, Barbara Nikolić, Tatjana Ocrt, Karmen Branović Čakanić, Romana Gračan, Ivana Zrinščak, Maja Jazvinšćak Jembrek and Goran Šimić

Int. J. Mol. Sci. 2025, 26(12), 5743; https://doi.org/10.3390/ijms26125743 (registering DOI) - 15 Jun 2025

Abstract

Aluminum (Al) is one of the most abundant metals on Earth and is well known as an environmental neurotoxic agent in the pathogenesis of Alzheimer’s disease. Aluminum toxicity is associated with oxidative stress, reduction of antioxidant enzymes, and disruption of the balance of [...] Read more.

Aluminum (Al) is one of the most abundant metals on Earth and is well known as an environmental neurotoxic agent in the pathogenesis of Alzheimer’s disease. Aluminum toxicity is associated with oxidative stress, reduction of antioxidant enzymes, and disruption of the balance of cellular metals, such as iron (Fe), calcium (Ca), and copper (Cu), which causes structural and functional changes in the nervous tissue of the brain or peripheral nervous system. The intake of functional foods, rich in antioxidants, such as quercetin, may be beneficial in combating oxidative stress and neurodegenerative changes in the brain. The aim of this study was to provide deeper insight into the cellular and molecular neuroprotective effects of quercetin in regulating amyloid-beta (Aβ) accumulation, tau pathology, and neuroinflammation in the Al/D-galactose-induced rat model (Al/D-gal) of AD. The results showed that quercetin successfully modulated the impaired homeostatic and neuropathological consequences of aluminum chloride and D-galactose administration over 28 days: it directly protected neurons by regulating the level of oxidative stress and antioxidants, reduced Aβ aggregation by inhibiting the activity of acetylcholinesterase (AChE), increased the survival, growth, and differentiation of nerve cells by maintaining the level of brain-derived neurotrophic factor (BDNF), and regulated microglial immunoreactivity and neuroinflammation by reducing the level of proinflammatory cytokines. The multiple effects confirm that quercetin can be applied as an alternative non-pharmaceutical approach in reducing Al-induced neurotoxicity and maintaining adaptive homeostasis, which consequently affects the functioning of the central nervous system and the whole organism. Full article

(This article belongs to the Special Issue Targeting Oxidative Stress for Disease: 2nd Edition)

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12 pages, 813 KiB

Open AccessArticle

Use of Colorimetry for the Measurement of Intradermally Injected Histamine-Induced Erythema in Healthy Dogs: A Proof-of-Concept Study

by Ana Petak, Elisa Samuel (Badulescu), Svetlina Aleksandrova, Evi I. Sofou, Manolis K. Chatzis and Manolis N. Saridomichelakis

Vet. Sci. 2025, 12(6), 590; https://doi.org/10.3390/vetsci12060590 (registering DOI) - 15 Jun 2025

Abstract

The interpretation of intradermal test results may improve if wheal erythema is measured objectively using colorimetry. Our aim was to find the necessary number of erythema colorimetric measurements, taken before and after intradermal injections of histamine 0.01% (H1), histamine 0.001% (H2), histamine 0.0001% [...] Read more.

The interpretation of intradermal test results may improve if wheal erythema is measured objectively using colorimetry. Our aim was to find the necessary number of erythema colorimetric measurements, taken before and after intradermal injections of histamine 0.01% (H1), histamine 0.001% (H2), histamine 0.0001% (H3) and a negative control (NC). We also aimed to assess whether erythema should be measured at the wheal center or border, and to investigate whether erythema appears beyond histamine wheals (flare), as observed in humans. Duplicate injections of the four solutions were administered on the lateral thorax of seven healthy dogs and erythema was measured by removing and repositioning the colorimeter probe. Colorimetry can differentiate the change in erythema (ΔE) at the center (ΔEc), but not at the border, of the H1 wheals from the ΔE of NC and H3 wheals. Reliable ways to calculate ΔEc were to use the first positive a* axis value of the colorimeter before and after the injection or to obtain the first seven positive a* axis values, excluding the highest and lowest, and calculated the mean of the remaining five. Unlike in humans, intradermal injection of histamine, even at a concentration of 0.01%, did not induce a flare reaction in healthy dogs. Full article

(This article belongs to the Special Issue Research in Small Animal Clinical Dermatology)

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14 pages, 1301 KiB

Open AccessArticle

Guarded Outcomes After Hip Hemiarthroplasty in Patients with Cerebral Palsy: Highlighting a Personalized Medicine Approach to Mitigate the Risk of Complications

by Ahmed Nageeb Mahmoud, Nicholas R. Brule, Juan D. Bernate, Mark A. Seeley, Michael Suk and Daniel S. Horwitz

J. Pers. Med. 2025, 15(6), 252; https://doi.org/10.3390/jpm15060252 (registering DOI) - 15 Jun 2025

Abstract

Background: The effectiveness of hip hemiarthroplasty in managing femoral neck fractures in individuals with cerebral palsy has seldom been reported. Objectives: Given the complex neuromuscular issues associated with cerebral palsy (CP), this retrospective study aims to document the outcomes and characterize the complications [...] Read more.

Background: The effectiveness of hip hemiarthroplasty in managing femoral neck fractures in individuals with cerebral palsy has seldom been reported. Objectives: Given the complex neuromuscular issues associated with cerebral palsy (CP), this retrospective study aims to document the outcomes and characterize the complications of hip hemiarthroplasty for fractures of the femoral neck in a series of patients with CP, emphasizing the role of precision medicine in management. Methods: Six cases of hip hemiarthroplasty in six male patients with cerebral palsy and displaced femoral neck fractures have been reviewed in this study. The patients’ mean age at the time of surgery was 55.6 ± 14.1 years (range, 33–71). All the patients were independent indoor ambulators before their femoral neck fracture and had various medical comorbidities. Five patients had intellectual disabilities. Results: The mean clinical and radiographic follow-ups for the patients included in this series were 91.5 and 71.3 months, respectively. All the patients developed significant heterotopic ossification (HO) around the operated hip, which was observed as early as the second week postoperatively on radiographs. HO progressed throughout the follow-up for all the patients. One patient had an early postoperative dislocation with femoral stem loosening, which was managed by implant revision. Another patient had an acetabular protrusion, leading to the loss of their weight-bearing ability and mobility due to pain. Four patients were deceased at a mean of 86.5 months after the index surgery. Conclusions: After considering the preliminary evidence provided with this small case series, this study suggests the overall guarded outcomes of hip hemiarthroplasty in patients with CP. Given the 100% rate of heterotopic ossification, a precision medicine framework with consideration for HO prophylaxis may be recommended after hip hemiarthroplasty in patients with CP. It may also be reasonable to scrutinize a personalized risk assessment approach in this patient subset regarding decision making, surgical approach, and rehabilitation program. The clinical outcomes and the risks of complications following hemiarthroplasty should be sensibly presented to patients with cerebral palsy and their caregivers to achieve reasonable postoperative expectations. Full article

(This article belongs to the Special Issue Orthopedic Diseases: Surgical Treatments and Personalized Rehabilitation Strategies)

14 pages, 523 KiB

Open AccessArticle

Effect of the Combined Use of Postbiotics and Oxalic Acid Against Varroa destructor Under Field Conditions

by Eduardo José García-Vicente, María Benito-Murcia, María Martín, Ana Pérez, Noelia Hermosilla, Salomé Martínez-Morcillo, Juan Manuel Alonso and David Risco

Agriculture 2025, 15(12), 1292; https://doi.org/10.3390/agriculture15121292 (registering DOI) - 15 Jun 2025

Abstract

Varroa destructor is a parasitic mite of honeybees that is considered one of the main problems in beekeeping today. The reduction in the efficacy of conventional miticides and the presence of residues in beehives highlight the need to investigate new organic products as [...] Read more.

Varroa destructor is a parasitic mite of honeybees that is considered one of the main problems in beekeeping today. The reduction in the efficacy of conventional miticides and the presence of residues in beehives highlight the need to investigate new organic products as alternative treatments. Postbiotic products have been shown to decrease mite viability in in vitro experiments. However, their use in beehives has not yet been assessed. The aim of this study was to test the efficacy of postbiotics and oxalic acid against V. destructor under field conditions. Two experiments were performed during the summer and autumn seasons, with four study groups: control (C), postbiotic (POS), oxalic acid (OX), and both combined (POX). Phoretic and brood V. destructor were determined at the beginning and end of the study to assess their evolution, as well as the percentage effectiveness of each treatment by registering the mite fall in beehive sanitary bottoms. Postbiotic alone did not show a significant effect on V. destructor under field conditions. However, the combined treatment of postbiotics and oxalic acid improved the results obtained with oxalic acid alone, resulting in greater effectiveness and reduction of phoretic and brood V. destructor. Full article

(This article belongs to the Special Issue Recent Advances in Bee Rearing and Production)

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11 pages, 982 KiB

Open AccessArticle

An Artificial Intelligence Algorithm for Early Detection of Left Ventricular Systolic Dysfunction in Patients with Normal Sinus Rhythm

by Seongjin Park, Hyo Jin Lee, Sung-Hee Song, KyungChang Woo, Jiwon Kim, Juwon Kim, Ju Youn Kim, Seung-Jung Park, Young Keun On and Kyoung-Min Park

J. Clin. Med. 2025, 14(12), 4257; https://doi.org/10.3390/jcm14124257 (registering DOI) - 15 Jun 2025

Abstract

Background/Objectives: Most previous studies using artificial intelligence (AI) to detect left ventricular systolic dysfunction (LVSD) from electrocardiograms (ECGs) relied on data obtained near the time of echocardiography or included patients with known cardiac disease, limiting their specificity for screening. We aimed to evaluate [...] Read more.

Background/Objectives: Most previous studies using artificial intelligence (AI) to detect left ventricular systolic dysfunction (LVSD) from electrocardiograms (ECGs) relied on data obtained near the time of echocardiography or included patients with known cardiac disease, limiting their specificity for screening. We aimed to evaluate whether AI models could predict future LVSD from ECGs interpreted as normal and recorded one to two years before echocardiography. Methods: We retrospectively analyzed 24,203 sinus rhythm ECGs from 11,131 patients. Two convolutional neural network models (DenseNet-121 and ResNet-101) were trained (70%), validated (10%), and tested (20%) to predict LVSD (defined as ejection fraction ≤50%). Survival analysis was performed using Kaplan–Meier curves and the log-rank test. Results: Of the total population, 2734 patients had LVSD and 8397 had preserved EF. DenseNet-121 and ResNet-101 demonstrated excellent discrimination for LVSD with AUROCs of 0.930 and 0.925, accuracies of 0.887 and 0.860, sensitivities of 0.821 and 0.856, and specificities of 0.908 and 0.861, respectively. In the test set, patients predicted to have LVSD showed a significantly higher risk of echocardiographic LVSD (hazard ratio 9.89, 95% CI 8.20–11.92, p = 0.005) and lower 24-month survival (log-rank p < 0.001). Conclusions: AI-enabled ECG models predicted future LVSD from clinically normal ECGs recorded up to two years prior to imaging. These findings suggest a potential role for AI-ECG in the early detection of subclinical LVSD and improved risk stratification in asymptomatic individuals. Full article

(This article belongs to the Special Issue Application of Artificial Intelligence in Cardiology)

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21 pages, 5307 KiB

Open AccessArticle

Increasing Ecosystem Fluxes Observed from Eddy Covariance and Solar-Induced Fluorescence Data

by Jiao Zheng, Hao Zhou, Xu Yue, Xichuan Liu, Zhuge Xia, Jun Wang, Jingfeng Xiao, Xing Li and Fangmin Zhang

Remote Sens. 2025, 17(12), 2064; https://doi.org/10.3390/rs17122064 (registering DOI) - 15 Jun 2025

Abstract

Ecosystems modulate Earth’s climate through the exchange of carbon and water fluxes. However, long-term trends in these terrestrial fluxes remain unclear due to the lack of continuous measurements on the global scale. This study combined flux data from 197 eddy covariance sites with [...] Read more.

Ecosystems modulate Earth’s climate through the exchange of carbon and water fluxes. However, long-term trends in these terrestrial fluxes remain unclear due to the lack of continuous measurements on the global scale. This study combined flux data from 197 eddy covariance sites with satellite-retrieved solar-induced chlorophyll fluorescence (SIF) to investigate spatiotemporal variations in gross primary productivity (GPP), evapotranspiration (ET), and their coupling via water use efficiency (WUE) from 2001 to 2020. We developed six global GPP and ET products at 0.05° spatial and 8-day temporal resolution, using two machine learning models and three SIF products, which integrate vegetation physiological parameters with data-driven approaches. These datasets provided mean estimates of 128 ± 2.3 Pg C yr⁻¹ for GPP, 522 ± 58.2 mm yr⁻¹ for ET, and 1.8 ± 0.21 g C kg⁻¹ H₂O yr⁻¹ for WUE, with upward trends of 0.22 ± 0.04 Pg C yr⁻² in GPP, 0.64 ± 0.14 mm yr⁻² in ET, and 0.0019 ± 0.0005 g C kg⁻¹ H₂O yr⁻² in WUE over the past two decades. These high-resolution datasets are valuable for exploring terrestrial carbon and water responses to climate change, as well as for benchmarking terrestrial biosphere models. Full article

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20 pages, 4522 KiB

Open AccessArticle

Establishment of a Stable BK Polyomavirus-Secreting Cell Line: Characterization of Viral Genome Integration and Replication Dynamics Through Comprehensive Analysis

by Tamara Löwenstern, David Vecsei, David Horner, Robert Strassl, Anil Bozdogan, Michael Eder, Franco Laccone, Markus Hengstschläger, Farsad Eskandary and Ludwig Wagner

Int. J. Mol. Sci. 2025, 26(12), 5745; https://doi.org/10.3390/ijms26125745 (registering DOI) - 15 Jun 2025

Abstract

Polyomaviruses have the potential to cause significant morbidity not only in transplant medicine, but also in other forms of disease or variants of immunosuppression. In kidney transplant recipients or recipients of human stem cell transplants, the BK-Virus is the major proponent of manifestations [...] Read more.

Polyomaviruses have the potential to cause significant morbidity not only in transplant medicine, but also in other forms of disease or variants of immunosuppression. In kidney transplant recipients or recipients of human stem cell transplants, the BK-Virus is the major proponent of manifestations such as BKPyV-associated nephropathy or hemorrhagic cystitis. As no polyomavirus-specific drug with proven in vivo effects has been developed so far, methods to screen for such drugs are important. This work describes the establishment of a virus-secreting cell line. By infecting a pre-established monkey kidney cell line (COS-1) with a non-rearranged human BK polyomavirus isolated from a kidney transplant patient suffering from BKPyV-associated nephropathy, a continuously replicating cell type with consistent virus secretion could be established and was termed COSSA. Measurements of BKPyV replication, virion production, and secretion were performed both intracellularly and in the cell supernatant. Viral proteins such as VP1 and LTAg were accurately tracked by confocal microscopy, as well as by immunoblot and qPCR. An intracellular flow cytometry (FACS) assay detecting VP1 protein was established and revealed an expanded range of positive intracellular signals. The viruses produced proved to be infectious in human tubular epithelial cell lines. Long-range sequencing of the COSSA genome using Oxford Nanopore Technology revealed a total of five distinct BKPyV integration events. One integration of a partial BKPyV genome was located upstream of the epidermal growth factor receptor gene. The second and third, both truncated forms of integration, were close to histocompatibility gene locuses, while the fourth was characterized by a ninefold and the fifth by a fourfold tandem repeat of the BKPyV genome. From both of the repeat forms, virus replicates were derived showing deletions/duplications on early and late genes and inversions within the non-coding control region (NCCR). This pattern of repetitive viral genome integration is a potential key driver of enhanced viral replication and increased virion assembly, ultimately supporting efficient virus egress. Quantitative PCR analysis confirmed the release of approximately 10⁸/mL viral units per 48 h from 2 × 10⁵ COSSA cells into the culture supernatant. Notably, the NCCR region of the most frequent copies of circular virus and the integrated tetrameric tandem repeat exhibited a rearranged configuration, which may contribute to the observed high replication dynamics. The establishment of a consistent methodology to generate and secrete BKPyV from a cell line is expected to significantly facilitate antiviral drug development. Full article

(This article belongs to the Special Issue Host Responses to Virus Infection)

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25 pages, 2655 KiB

Open AccessArticle

Recasting Antiquarianism as Confucian Orthodoxy: Wang Zuo’s Expanded Essential Criteria of Antiquities and the Moral Reinscription of Material Culture in the Ming Dynasty

by Ziming Chen and Hanwei Wang

Religions 2025, 16(6), 778; https://doi.org/10.3390/rel16060778 (registering DOI) - 15 Jun 2025

Abstract

This article examines Xinzeng Gegu yaolun 新增格古要論 (Expanded Essential Criteria of Antiquities), a connoisseurship manual compiled in 1460 by the mid-Ming official Wang Zuo 王佐. Drawing upon Cao Zhao’s 曹昭 early Ming Gegu yaolun 格古要論 (Essential Criteria of Antiquities), [...] Read more.

This article examines Xinzeng Gegu yaolun 新增格古要論 (Expanded Essential Criteria of Antiquities), a connoisseurship manual compiled in 1460 by the mid-Ming official Wang Zuo 王佐. Drawing upon Cao Zhao’s 曹昭 early Ming Gegu yaolun 格古要論 (Essential Criteria of Antiquities), Wang reconfigured a manual focused on authentication and appreciation into a text structured by Confucian values and political ethics. He added ritual-oriented entries in chapters four and ten through thirteen, such as “An Examination of Song Dynasty Attire and Rank Titles” 宋制服裝入銜考 and “An Inquiry into Gold and Silver Insignia” 佩金銀牌考, reinforcing Confucian ideology through commentary on ritual institutions and the inclusion of imperial edicts and commemorative inscriptions. He also reorganized the placement of guqin 古琴, calligraphy and painting, while redefining evaluative standards to integrate material objects into moral instruction and bureaucratic discipline. In doing so, Wang reinforced a shared community of scholar–officials, using ritual hierarchy, loyalist writings, and gift exchange to respond to the uncertainty of a fractured political order. This article argues that through a non-canonical text like Xinzeng Gegu yaolun, mid-Ming scholar–officials extended Confucian discourse into antiquities, transforming antiquarian writing into a visible enactment of ethical values and collective identity. Full article

(This article belongs to the Special Issue The Multiple Images and Forms of Classical Confucian and Daoist Ethics for Living)

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17 pages, 4436 KiB

Open AccessArticle

Influence of the Casein Genotype on Goat Milk Bioactivity: An In Silico Analysis of the Casein Peptidome

by Aram Y. Rubio-Reyes, Iván Delgado-Enciso, Eduardo Casas, Estela Garza-Brenner and Ana M. Sifuentes-Rincón

Molecules 2025, 30(12), 2601; https://doi.org/10.3390/molecules30122601 (registering DOI) - 15 Jun 2025

Abstract

Goat caseins are highly polymorphic proteins that affect milk functional properties. In this study, an in silico approach was employed to analyze the influence of goat casein allelic variants on the quantity and bioactivity potential of peptides released after enzymatic hydrolysis. The reported [...] Read more.

Goat caseins are highly polymorphic proteins that affect milk functional properties. In this study, an in silico approach was employed to analyze the influence of goat casein allelic variants on the quantity and bioactivity potential of peptides released after enzymatic hydrolysis. The reported protein sequences from the most frequent allelic variants in Capra hircus caseins (α-S1, β, α-S2, and κ-casein) were analyzed in the BIOPEP-UWM database to determine the frequency of occurrence of bioactive fragments from each casein. After specific hydrolysis with pepsin, trypsin, and chymotrypsin A, important differences in the peptide profile and bioactivity potential were observed within and between the casein allelic variants. The β-casein A and C alleles, α-S1-casein allele E, and α-S2-casein allele F presented the highest bioactivity potential, and some allele-specific peptides were also released, highlighting the impact of genotype on the predicted bioactivity. The inhibition of angiotensin-converting enzyme (ACE-I) and dipeptidyl peptidase IV (DPP-IV) activities was the most frequent bioactivity of the released peptides, suggesting possible antihypertensive and antidiabetic effects. Once confirmed by experimental studies, the use of goat casein genotyping could direct efforts to enhance the functional quality of goat milk. Full article

(This article belongs to the Special Issue Bioactive Compounds from Functional Foods, 2nd Edition)

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17 pages, 1168 KiB

Open AccessSystematic Review

Transforming Healthcare: A Comprehensive Review of Augmented and Virtual Reality Interventions

by Aristeidis Petrakis, Lefteris Koumakis, Eleni Kazantzaki and Haridimos Kondylakis

Sensors 2025, 25(12), 3748; https://doi.org/10.3390/s25123748 (registering DOI) - 15 Jun 2025

Abstract

Augmented reality (AR) and virtual reality (VR) technologies have rapidly expanded within healthcare due to their innovative capabilities for enhancing patient care, medical training, and health outcomes. This systematic review synthesizes quantitative studies published post-2020, explicitly investigating AR and VR healthcare interventions. The [...] Read more.

Augmented reality (AR) and virtual reality (VR) technologies have rapidly expanded within healthcare due to their innovative capabilities for enhancing patient care, medical training, and health outcomes. This systematic review synthesizes quantitative studies published post-2020, explicitly investigating AR and VR healthcare interventions. The review identifies, evaluates, and summarizes the effectiveness of these interventions, highlighting their clinical implications, outcomes, and implementation challenges. Twenty eligible studies were included, examining various health conditions such as cardiopulmonary resuscitation training, mental health disorders, stroke rehabilitation, and orthopedic recovery. Findings indicate generally positive outcomes from AR and VR interventions; however, issues including technology usability, adherence, and methodological limitations are noted. This review underscores the significant potential of AR and VR interventions in healthcare, but emphasizes the need for more rigorous research to address current gaps in the clinical effectiveness and application. Full article

(This article belongs to the Special Issue Feature Review Papers in Intelligent Sensors)

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15 pages, 253 KiB

Open AccessArticle

The Natural Environment and Investment in Economic Growth: From the Perspective of the Prosperity of Developed and Developing Countries

by Ximena Morales-Urrutia, Aracelly Núñez-Naranjo, Rubén Nogales-Portero and Evelin Yanez-Toapanta

Sustainability 2025, 17(12), 5513; https://doi.org/10.3390/su17125513 (registering DOI) - 15 Jun 2025

Abstract

This research aims to identify the environmental factors that affect economic growth in developed and developing countries using a panel data regression model. In advanced economies, restrictions on international investment, emissions, the use of natural resources, and environmental preservation efforts stand out as [...] Read more.

This research aims to identify the environmental factors that affect economic growth in developed and developing countries using a panel data regression model. In advanced economies, restrictions on international investment, emissions, the use of natural resources, and environmental preservation efforts stand out as influential variables. In contrast, in developing countries, contract enforcement, emissions, and exposure to air pollution are key determinants of economic performance. This study concludes that the natural environment plays a more significant role in the economic growth of developed countries, due to their greater capacity to implement sustainability policies. In developing countries, institutional conditions and environmental management are more relevant, highlighting the need to strengthen legal frameworks and invest in mitigation measures to achieve sustainable economic development. Full article

28 pages, 9170 KiB

Open AccessArticle

Electrical Characteristics and Desaturation Effectiveness During Horizontal Electrolysis in Calcareous Sand

by Yumin Chen, Ying Zhou, Runze Chen, Saeed Sarajpoor and Xiao Xie

Buildings 2025, 15(12), 2061; https://doi.org/10.3390/buildings15122061 (registering DOI) - 15 Jun 2025

Abstract

Electrolysis desaturation has emerged as an innovative technique to mitigate liquefaction risk by reducing soil saturation in liquefiable foundations. This study evaluated the effectiveness of horizontal electrolysis on calcareous sandy foundations in marine environments by employing 35‰ NaCl solution as pore fluid under [...] Read more.

Electrolysis desaturation has emerged as an innovative technique to mitigate liquefaction risk by reducing soil saturation in liquefiable foundations. This study evaluated the effectiveness of horizontal electrolysis on calcareous sandy foundations in marine environments by employing 35‰ NaCl solution as pore fluid under different current intensities (1A, 2A, and 4A). Experimental results demonstrated that hydrogen gas was generated at the cathode, while chlorine gas was produced at the anode, with peak gas retention rates of 100%, 90.83%, and 63.26% for 1A; 97.61%, 79.04%, and 60.94% for 2A; and 95.37%, 48.49%, and 42.81% for 4A over three electrolysis cycles. Three key findings emerged from our investigation: First, the resistivity of calcareous sand displayed a three-stage variation pattern, primarily governed by temperature and gas content evolution. Second, the temperature-corrected resistivity model provided reliable saturation data, revealing that electrode-adjacent soil layers exhibited significantly greater saturation reduction compared to intermediate layers. The average saturation variation during a single electrolysis cycle reached 3.2%, 2.6%, and 4.4% for 1A, 2A, and 4A, respectively, in the soil layers near the electrodes, compared to 2.1%, 1.7%, and 3.3% in the middle soil layers under the same current intensities. Third, upon stopping electrolysis, gas redistribution led to decreased saturation in upper soil layers, with lower current intensities more effective in retaining gases within the soil matrix. Based on these findings, an electrolytic influence coefficient for calcareous sand applicable to Archie’s formulation is proposed. This study enhances the understanding of the mechanism of electrolysis desaturation and provides a theoretical basis for the effectiveness of electrolysis desaturation on calcareous sand foundations. Full article

(This article belongs to the Special Issue Future Civil Engineering: Low-Carbon, High Performance and Strong Durability—2nd Edition)

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16 pages, 3742 KiB

Open AccessArticle

Redox Imbalance Is Associated with Neuronal Apoptosis in the Cortex of Neonates Gestated Under Chronic Hypoxia

by Esteban G. Figueroa, Rodrigo L. Castillo, Adolfo A. Paz, Matías Monsalves-Alvarez, Francisca Salas-Pérez, Ximena Calle, Tamara A. Jiménez, Emilio A. Herrera and Alejandro Gonzaléz-Candia

Antioxidants 2025, 14(6), 736; https://doi.org/10.3390/antiox14060736 (registering DOI) - 15 Jun 2025

Abstract

Gestational chronic hypoxia impacts prenatal development, leading to fetal growth restriction (FGR), defined as the fetus’s failure to reach its genetic growth potential. Postnatal hypoxia in the cerebral tissue can induce a redox imbalance and mitochondrial dysfunction, consequently increasing neuronal death. However, these [...] Read more.

Gestational chronic hypoxia impacts prenatal development, leading to fetal growth restriction (FGR), defined as the fetus’s failure to reach its genetic growth potential. Postnatal hypoxia in the cerebral tissue can induce a redox imbalance and mitochondrial dysfunction, consequently increasing neuronal death. However, these data cannot necessarily be extrapolated to prenatal hypoxia. In this regard, this study aims to describe the effect of gestational hypoxia on redox balance and apoptosis cell death mechanisms in the prefrontal cortex of guinea pigs. Ten Guinea pig (Cavia porcellus) pregnant dams were utilized in this study; five gestated in normoxia (Nx; three newborn males, and two females) and five gestated under chronic hypobaric hypoxia (Hx; two newborn males, and three females). We monitored the pregnancies by ultrasound examinations from gestational days 20 to 65 (term ~ 70). At birth, pups were euthanized, and the fetal brain was collected for cellular redox measurement, mitochondrial enzyme expression, and apoptosis assay. Gestation under hypoxia induced an imbalance in the expression of anti- and pro-oxidant enzymes, resulting in increased oxidative stress. Additionally, a decrease in cytochrome I and III expression and neuronal density in the neonatal prefrontal cortex was observed. Finally, DNA fragmentation was increased by the TUNEL assay in the brain tissue of newborns gestated under chronic hypoxia. Our findings demonstrate the association of gestational hypoxia with oxidative stress and neuronal death in newborns, which may predispose to neuronal dysfunction in adulthood. Full article

(This article belongs to the Special Issue Oxidative Stress and Antioxidants in Hypoxia and Human Pathophysiology Settings, 2nd Edition)

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Graphical abstract

21 pages, 4997 KiB

Open AccessSystematic Review

NOD2 Polymorphisms and Their Association with Colorectal Cancer Risk: An Updated Systematic Review and Meta-Analysis

by Mohamad Ayub Khan Sharzehan, Hilary Sito, Md Asiful Islam, Rahman Jamal and Shing Cheng Tan

Cancers 2025, 17(12), 1999; https://doi.org/10.3390/cancers17121999 (registering DOI) - 15 Jun 2025

Abstract

Background: Nucleotide-binding oligomerization domain-containing protein 2, encoded by NOD2, can trigger chronic gut inflammation that leads to colorectal cancer (CRC). However, studies that have investigated the association of NOD2 polymorphisms and CRC susceptibility have produced inconsistent findings. To clarify this relationship, a [...] Read more.

Background: Nucleotide-binding oligomerization domain-containing protein 2, encoded by NOD2, can trigger chronic gut inflammation that leads to colorectal cancer (CRC). However, studies that have investigated the association of NOD2 polymorphisms and CRC susceptibility have produced inconsistent findings. To clarify this relationship, a meta-analysis was conducted to integrate data from previous studies to achieve a more precise evaluation of the risk association. Methods: PubMed, Scopus, and Web of Science databases were systematically searched to identify relevant studies on the association of NOD2 polymorphisms with CRC risk. Genetic risk association was quantitatively assessed under five genetic models: homozygous, heterozygous, dominant, recessive, and allele. Thirteen studies, comprising 5,013 cases and 4,463 controls, were included in this study. Four NOD2 polymorphisms were investigated in these studies, namely rs2066842, rs2066844, rs2066845, and rs2066847. Results: Of these, only rs2066845 and rs2066847 were found to be significantly associated with increased CRC risk (rs2066845, heterozygous OR = 1.544, 95% CI = 1.014–2.349, P = 0.043; dominant OR = 1.561, 95% CI = 1.035–2.354, P = 0.034; allele OR = 1.572, 95% CI = 1.040–2.375, P = 0.032; rs2066847, heterozygous OR = 1.321, 95% CI = 1.060–1.647, P = 0.013; dominant OR = 1.402, 95% CI = 1.147–1.713, P = 0.001; allele OR = 1.345, 95% CI = 1.088–1.663, P = 0.006). Conclusions: In conclusion, the NOD2 rs2066845 and rs2066847 polymorphisms are associated with an increased risk of CRC and may potentially serve as predisposition biomarkers for the cancer. Full article

(This article belongs to the Special Issue Hereditary and Familial Colorectal Cancer)

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16 pages, 1628 KiB

Open AccessArticle

Anatomical Characteristics Predict Response to Transcranial Direct Current Stimulation (tDCS): Development of a Computational Pipeline for Optimizing tDCS Protocols

by Giulia Caiani, Emma Chiaramello, Marta Parazzini, Eleonora Arrigoni, Leonor J. Romero Lauro, Alberto Pisoni and Serena Fiocchi

Bioengineering 2025, 12(6), 656; https://doi.org/10.3390/bioengineering12060656 (registering DOI) - 15 Jun 2025

Abstract

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique promisingly used to treat neurological and psychological disorders. Nevertheless, the inter-subject heterogeneity in its after-effects frequently limits its efficacy. This can be attributed to fixed-dose methods, which do not consider inter-subject anatomical [...] Read more.

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique promisingly used to treat neurological and psychological disorders. Nevertheless, the inter-subject heterogeneity in its after-effects frequently limits its efficacy. This can be attributed to fixed-dose methods, which do not consider inter-subject anatomical variations. This work attempts to overcome this constraint by examining the effects of age and anatomical features, including the volume of cerebrospinal fluid (CSF), the thickness of the skull, and the composition of brain tissue, on electric field distribution and cortical excitability. A computational approach was used to map the electric field distribution over the brain tissues of realistic head models reconstructed from MRI images of twenty-three subjects, including adults and children of both genders. Significant negative correlations (p < 0.05) were found in the data between the maximum electric field strength and anatomical variable parameters. Furthermore, this study showed that the percentage of brain tissue exposed to an electric field amplitude above a pre-defined threshold (i.e., 0.227 V/m) was the main factor influencing the responsiveness to tDCS. In the end, the research suggests multiple regression models as useful tool to predict subjects’ responsiveness and to support a personalized approach that tailors the injected current to the morphology of the patient. Full article

(This article belongs to the Special Issue Electromagnetic Fields in Bioengineering: Advancing the OneHealth Paradigm)

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20 pages, 7968 KiB

Open AccessArticle

Horizontal PGA Estimates for Varying Deep Geological Conditions—A Case Study of Banja Luka

by Borko Bulajić, Silva Lozančić, Senka Bajić, Anka Starčev-Ćurčin, Miloš Šešlija, Miljan Kovačević and Marijana Hadzima-Nyarko

Appl. Sci. 2025, 15(12), 6712; https://doi.org/10.3390/app15126712 (registering DOI) - 15 Jun 2025

Abstract

In this study, the city of Banja Luka is used as a case study to evaluate horizontal PGA values in regions with a history of moderate to strong earthquakes and with different deep geological conditions. We present regional attenuation equations for PGA that [...] Read more.

In this study, the city of Banja Luka is used as a case study to evaluate horizontal PGA values in regions with a history of moderate to strong earthquakes and with different deep geological conditions. We present regional attenuation equations for PGA that can capture both the impacts of deep geology and local soil conditions. A PSHA study for a site in Banja Luka was carried out using the developed empirical scaling equations and compared to all previous seismic hazard estimations for the same region. The data indicate that variations in deep geological conditions may have a greater impact on PGA values than local soil effects. Given the scarcity of scaling equations that consider deep geology in addition to local soil conditions, we believe this case study is a step toward developing more accurate PGA estimates for comparable regions. Full article

(This article belongs to the Special Issue Intelligent Technologies in Geotechnical Engineering and Geological Hazards)

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19 pages, 3682 KiB

Open AccessArticle

Mulberry (Morus alba) Twig and Leaf Extracts Ameliorate Obesity-Related Metabolic Disorders via Gut Microbiota Modulation in High-Fat Diet-Fed Mice

by Wei Qian, Jinyan Han, Xiang Shi, Xiaoqing Qin, Feng Jiao, Minjuan Zhang, Lijun Bao and Chao Su

Animals 2025, 15(12), 1768; https://doi.org/10.3390/ani15121768 (registering DOI) - 15 Jun 2025

Abstract

Mulberry (Morus alba) twigs and leaves, rich in flavonoids, polyphenols, polysaccharides, and alkaloids with multi-target regulatory properties on glucose/lipid metabolism, were evaluated for their anti-obesity effects using methanol-extracted twigs (MTE) and aqueous-extracted leaves (MLE) in high-fat diet (HFD)-induced obese mice. Both [...] Read more.

Mulberry (Morus alba) twigs and leaves, rich in flavonoids, polyphenols, polysaccharides, and alkaloids with multi-target regulatory properties on glucose/lipid metabolism, were evaluated for their anti-obesity effects using methanol-extracted twigs (MTE) and aqueous-extracted leaves (MLE) in high-fat diet (HFD)-induced obese mice. Both extracts significantly ameliorated obesity-related metabolic dysregulation, as evidenced by attenuated body weight gain, visceral fat accumulation, serum lipid profiles, homeostatic model assessment of insulin resistance (HOMA-IR), and hepatic inflammation compared to HFD controls (p < 0.05). Concurrently, MTE and MLE enhanced systemic antioxidant capacity and elevated high-density lipoprotein cholesterol (HDL-C) levels. Notably, high-dose MTE (MTEH, 1000 mg/kg) markedly reduced perirenal adiposity while increasing brown adipose tissue mass (p < 0.05). Mechanistic investigations revealed that MTEH reshaped gut microbiota composition by suppressing Firmicutes and Enterococcus, while enriching beneficial Faecalibaculum and Bifidobacterium spp. (p < 0.05). Furthermore, cecal short-chain fatty acid (SCFA) profiling demonstrated MTEH and MLEH-mediated metabolic reprogramming, characterized by increased propionic acid and decreased butyric acid, suggesting microbiota-dependent modulation of host energy metabolism. These findings collectively highlight the potential of mulberry extracts as multi-targeted nutraceuticals for obesity intervention via gut microbiota–SCFA axis regulation. Full article

(This article belongs to the Section Animal Nutrition)

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51 pages, 1310 KiB

Open AccessReview

Ferritin in Acute Myeloid Leukemia: Not Only a Marker of Inflammation and Iron Overload, but Also a Regulator of Cellular Iron Metabolism, Signaling and Communication

by Håkon Reikvam, Magnus Gramstad Rolfsnes, Linn Rolsdorph, Miriam Sandnes, Frode Selheim, Maria Hernandez-Valladares and Øystein Bruserud

Int. J. Mol. Sci. 2025, 26(12), 5744; https://doi.org/10.3390/ijms26125744 (registering DOI) - 15 Jun 2025

Abstract

Ferritin is important for cellular iron storage and metabolism. It consists of 24 ferritin heavy- or light-chain subunits surrounding an iron-containing core, but it is also released as an extracellular molecule that shows increased systemic levels during acute-phase reactions. Furthermore, acute myeloid leukemia [...] Read more.

Ferritin is important for cellular iron storage and metabolism. It consists of 24 ferritin heavy- or light-chain subunits surrounding an iron-containing core, but it is also released as an extracellular molecule that shows increased systemic levels during acute-phase reactions. Furthermore, acute myeloid leukemia (AML) is an aggressive bone marrow malignancy that can be associated with increased ferritin levels both at the time of first diagnosis but also during/following anti-AML treatment due to an iron overload. Such high systemic ferritin levels at diagnosis or later allogeneic stem cell transplantation are associated with decreased long-term survival. Extracellular ferritin binds to several receptors expressed by AML cells (e.g., the transferrin receptor and CXCR4 chemokine receptor) and AML-supporting non-leukemic bone marrow cells (e.g., endothelial, mesenchymal or immunocompetent cells). Ferritin can thereby affect the AML cells directly as well as indirectly via AML-supporting neighboring cells. Finally, ferritin should be regarded as a regulator of the dysfunctional iron metabolism that causes increased iron levels in AML cells, and it is important for cell survival through its function during the initial steps of ferroptosis. Thus, ferritin is not only an adverse prognostic biomarker, but also an important regulator of AML cell proliferation, survival and chemosensitivity and the targeting of iron metabolism/ferroptosis is, therefore, a possible strategy in AML therapy. Full article

(This article belongs to the Special Issue Molecular Mechanism of Acute Myeloid Leukemia)

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16 pages, 1321 KiB

Open AccessSystematic Review

Occurrence Rates of Delirium in Brain Tumor Patients: A Systematic Review and Meta-Analysis

by Zachary Tentor, Alexander Finnemore, Paul J. Miller, Joshua Davis, Erika Juarez Martinez, Charlotta Lindvall, Eyal Y. Kimchi and John Y. Rhee

Cancers 2025, 17(12), 1998; https://doi.org/10.3390/cancers17121998 (registering DOI) - 15 Jun 2025

Abstract

Background: The occurrence (incidence or prevalence) of delirium in brain tumors is unknown, yet delirium is associated with increased morbidity and mortality and worse quality of life. We conducted a systematic review and meta-analysis to determine the occurrence of delirium in hospitalized [...] Read more.

Background: The occurrence (incidence or prevalence) of delirium in brain tumors is unknown, yet delirium is associated with increased morbidity and mortality and worse quality of life. We conducted a systematic review and meta-analysis to determine the occurrence of delirium in hospitalized patients with brain tumors. Methods: PubMed, Scopus, and Web of Science were systematically searched for papers from 1 January 1999 to 12 July 2024, including references from texts. Cross-sectional, prospective, and other cohort study designs were included, and individual case reports, case series, editorials, and reviews were excluded. The included papers were scored using a validated sensitivity analysis tool and tested for quality and bias using funnel plots and Egger’s test. We used random effects models for the summary estimates. We performed subgroup analyses by tumor type, tumor location, delirium subtype, and length of stay. Results: Of the 452 studies screened, 27 were included, representing 35,958 patients. The overall occurrence of delirium was 0.17 (95% CI [0.11–0.24]). Delirium occurrence in patients with low-grade gliomas, high-grade gliomas, and brain metastases was 0.10 [0.06–0.16], 0.21 [0.10–0.40], and 0.31 [0.16–0.50], respectively. Compared to the occipital lobe, there was a higher occurrence of delirium for tumors in the frontal (RR 3.08 [1.35–8.22]) and temporal lobes (RR 2.88 [1.22–7.93]). The patients were more likely to have hypoactive (RR 1.61 [1.30; 1.98]) than hyperactive delirium. Delirium was associated with 4.62 additional hospitalized days compared to those without delirium (CI [3.23–6.01]). Discussion: We confirmed high occurrence rates of delirium in patients hospitalized with brain tumors. Patients with brain metastases had a higher occurrence of delirium compared to patients with gliomas, and delirium occurrence rates were higher in patients with frontotemporal tumors. Delirium occurrence rates in the literature are very heterogeneous and point toward a need for tailored assessments in patients with brain tumors. Full article

(This article belongs to the Special Issue Quality of Life in Patients with Brain Tumors)

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