Advancing Open Science
Supporting academic communities
since 1996
 
14 pages, 2214 KB  
Article
Evaluation of the Role of AID-Induced Mutagenesis in Resistance to B-Cell Receptor Pathway Inhibitors in Chronic Lymphocytic Leukemia
by Chiara Pighi, Alessandro Gasparetto, Elisa Genuardi, Jianli Tao, Qi Wang, Candida Vitale, Valentina Griggio, Rocco Piazza, Sabino Ciavarella, Marta Coscia, Simone Ferrero, Alberto Zamò, Claudia Voena and Roberto Chiarle
Curr. Issues Mol. Biol. 2025, 47(12), 1031; https://doi.org/10.3390/cimb47121031 (registering DOI) - 10 Dec 2025
Abstract
Chronic lymphocytic leukemia (CLL) is the most common leukemia in Western countries, and B-cell receptor (BCR) pathway inhibitors such as idelalisib and ibrutinib are currently established therapies for CLL. Although effective, these drugs frequently lead to resistance, but the mechanisms are still not [...] Read more.
Chronic lymphocytic leukemia (CLL) is the most common leukemia in Western countries, and B-cell receptor (BCR) pathway inhibitors such as idelalisib and ibrutinib are currently established therapies for CLL. Although effective, these drugs frequently lead to resistance, but the mechanisms are still not fully understood. Activation-induced cytidine deaminase (AID) is a B-cell enzyme essential for antibody diversification. However, it can also introduce off-target mutations, leading to genomic instability. This study investigates whether treatment with BCR pathway inhibitors increases AID activity in CLL and whether this activity contributes to the development of drug resistance. Peripheral blood samples from CLL patients were collected before and after treatment with idelalisib or ibrutinib. Targeted sequencing was used to identify mutations in known AID off-target genes. Concurrently, AID-wild type (AID-WT) and AID-knockout (AID-KO) CLL cell lines were established and subsequently exposed to escalating doses of BCR pathway inhibitors to develop drug-resistant models. In patient samples, treatment with BCR pathway inhibitors was associated with an increase in AID-dependent mutations in off-target genes, including BCL2, MYC, and IRF8. The in vitro models efficiently recapitulated the patients’ data, as only AID-WT CLL cells accumulated mutations in the same AID off-target genes after drug exposure. However, no mutations were detected in genes that could mediate drug resistance. We conclude that BCR pathway inhibitors enhance AID mutational activity in CLL, but this does not appear to be directly involved in driving drug resistance. AID-targeted loci may nonetheless serve as biomarkers for monitoring genomic instability during treatment and inform further study. Full article
(This article belongs to the Section Molecular Medicine)
Show Figures

Figure 1

15 pages, 2322 KB  
Article
Establishment and Biological Characteristics Analysis of a Hybrid Culter Lineage from Megalobrama amblycephala (♀) and Culter alburnus (♂)
by Jinhui Huang, Yingying Yang, Jiawang Huang, Xiaoyu Huang, Jiaxuan Zhu, Yanran Xiong, Lang Qin, Hongxuan Liang, Ming Wen, Yuxiang Wang, Xu Huang, Fangzhou Hu, Shi Wang, Chang Wu and Shaojun Liu
Animals 2025, 15(24), 3555; https://doi.org/10.3390/ani15243555 (registering DOI) - 10 Dec 2025
Abstract
Culter alburnus (topmouth culter, TC) is extensively distributed in various rivers and lakes in China. As a widely adaptive fish species, they have significant economic value and special ecological roles. Intergeneric hybridization is a pivotal strategy for generating novel hybrid lineages and species. [...] Read more.
Culter alburnus (topmouth culter, TC) is extensively distributed in various rivers and lakes in China. As a widely adaptive fish species, they have significant economic value and special ecological roles. Intergeneric hybridization is a pivotal strategy for generating novel hybrid lineages and species. In a previous study, we obtained an improved bisexual hybrid culter, BTBTF1, derived from the hybrid lineage of Megalobrama amblycephala (blunt snout bream, BSB, 2n = 48, ♀) × Culter alburnus (2n = 48, ♂). In this study, we established an improved hybrid culter lineage by the self-crossing of BTBTF1 and evaluated the biological characteristics regarding cytology, morphology, and genetics. DNA content and chromosome analyses confirmed that BTBTF1-F2 was a diploid lineage (2n = 48), with morphological traits exhibiting intermediate values between parental species, except for significantly TC-biased full-length-to-body length (FL/BL) and body length-to-head length (BL/HL) ratios (p < 0.05). ITS sequencing analysis revealed that BTBTF1-F2 inherited ITS1 sequences from BSB and TC. The global methylation level in BTBTF1-F2 was substantially reduced compared to progenitors, characterized by elevated full and diminished hemimethylation states. Transcriptomic analysis identified 7877 differentially expressed genes (DEGs), displaying 9.05%/8.30% maternal (BSB)-dominant and 17.01%/18.95% paternal (TC)-dominant expression patterns in BTBTF1 and F2. Remarkable intergenerational similarity in phenotypic and molecular profiles, coupled with bidirectional inheritance of progenitor characteristics, confirmed BTBTF1-F2 as a genetically stable allodiploid lineage. Remarkably, ITS sequencing analysis, methylation patterns, and DEG expression collectively demonstrated significant TC-oriented bias (p < 0.05). This study reports a novel stabilized allodiploid culter lineage after a comprehensive assessment at cytology, morphology, and genetic levels, and provides new insights into genetic bias in hybrid progeny. Full article
(This article belongs to the Special Issue Genetics, Breeding, and Farming of Aquatic Animals)
Show Figures

Figure 1

23 pages, 4907 KB  
Article
A Conjugate Heat Transfer Approach to Analyze the Thermal Performance of a 1MW Synchronous Motor–Generator
by ByungKon Kim and Jun Su Park
Electronics 2025, 14(24), 4867; https://doi.org/10.3390/electronics14244867 (registering DOI) - 10 Dec 2025
Abstract
This study used a 3D numerical model to investigate the heat-flow behavior of a 1 MW synchronous motor–generator by creating a conjugate heat transfer model that included the rotating parts. The computational model involved complex solid/fluid interfaces, a rotor–stator gap, and a fan-driven [...] Read more.
This study used a 3D numerical model to investigate the heat-flow behavior of a 1 MW synchronous motor–generator by creating a conjugate heat transfer model that included the rotating parts. The computational model involved complex solid/fluid interfaces, a rotor–stator gap, and a fan-driven cooling path that passes through a stator’s external flow path in order to identify local temperature fields and flow distributions. Under design conditions, localized high-temperature regions were observed in the rotor coil because the cooling air was heated, and the airflow then diverged through the stator’s internal channels. On the contrary, periodic low-temperature areas were formed around the stator’s circumference as a result of conductive heat diffusion into the outer casing. A correlation was derived describing a relationship where the peak temperature decreased in a clear logarithmic manner as the cooling air mass flow rate increased. We confirmed that a cooling flow rate of at least 2.0 kg/s is needed to keep the rotor coil temperature below 120 °C within its operational limit under design points. Furthermore, the functional form of the temperature–flow rate relationship remained logarithmic, and the correlation coefficients in this relationship changed linearly with heat generation, even under off-design conditions, where the total heat generation was reduced to 88% of the design value and the ambient temperature was lowered. The study results will provide a practical basis for swiftly estimating peak temperature for various operating scenarios and for determining cooling paths and fan geometry to avoid repeating expensive simulations. Full article
(This article belongs to the Section Power Electronics)
23 pages, 1356 KB  
Article
Equilibrium Pricing and Power Design in Hybrid Supply Chains: A Stackelberg Game Approach
by Bingyan Yang and Xiaomo Yu
Mathematics 2025, 13(24), 3939; https://doi.org/10.3390/math13243939 (registering DOI) - 10 Dec 2025
Abstract
This paper investigates a service-oriented hybrid supply chain involving a manufacturer, a service provider, and an integrator, where product demand is jointly influenced by service level and retail price. To address the increasing dominance of service providers in value creation, we construct two [...] Read more.
This paper investigates a service-oriented hybrid supply chain involving a manufacturer, a service provider, and an integrator, where product demand is jointly influenced by service level and retail price. To address the increasing dominance of service providers in value creation, we construct two Stackelberg game models under different power structures: manufacturer-dominant and service-provider dominant. The models characterize the equilibrium pricing and service decisions across supply chain members considering service sensitivity. Analytical results indicate that the service-provider dominant structure outperforms in high-sensitivity markets, resulting in higher service levels, demand, and overall supply chain profits. Numerical experiments further validate the theoretical findings and offer managerial insights into the design of power structures in service-integrated supply chains. The results offer guidance for optimizing pricing and service strategies in complex, service-sensitive environments. Full article
(This article belongs to the Section D: Statistics and Operational Research)
14 pages, 1100 KB  
Article
High-Quality Agar Polysaccharide from Unexplored Gelidium micropterum Kützing Biomass
by Anurag A. K. Sharma, Ravi S. Baghel, S. V. Sandhya, Rahul Kaushik, Ashok S. Jagtap and Balaji Vaishnavi
Polymers 2025, 17(24), 3278; https://doi.org/10.3390/polym17243278 (registering DOI) - 10 Dec 2025
Abstract
The agar is an important polysaccharide widely used in the food industry, pharmaceuticals, cosmetics, microbiology, and molecular biology applications. The global demand for agar polysaccharide is steadily rising, but its production is limited due to shortage of good raw material. This research investigates [...] Read more.
The agar is an important polysaccharide widely used in the food industry, pharmaceuticals, cosmetics, microbiology, and molecular biology applications. The global demand for agar polysaccharide is steadily rising, but its production is limited due to shortage of good raw material. This research investigates the potential of Gelidium micropterum as an alternative and sustainable source of high-quality agar. Agar was extracted using different concentrations of NaOH (4, 6, 8, and 10% w/v) and without NaOH treatment. The resulting agar yields ranged from 16.97% to 26.03%, with corresponding gel strengths between 855 ± 51 and 2078 ± 55 g/cm2. Notably, 8% and 10% NaOH pre-treatments yielded agar with superior gel strength and thermal properties, surpassing those reported for other Gelidiales species under similar conditions. Structural characterisation was performed using FT-IR, 13C-NMR, and 1H-NMR spectroscopy, confirming similarities with standard agar. The extracted agar’s molecular weights were in the range of 5704–7276 kDa. Sulphate content varied from 0.175 ± 0.082% to 6.197 ± 0.446% across treatments. The agar also supported microbial growth at lower concentrations than commercial agar, indicating promising application potential. These findings highlight G. micropterum as a promising, sustainable option for expanding agar resources. Full article
(This article belongs to the Section Biobased and Biodegradable Polymers)
18 pages, 2023 KB  
Article
Development of Mono-Material Multilayer Light Barrier Films
by Rocío Ayelén Fuentes, Giacomo Foli, Roberta Di Carlo, Yanela Natalyn Alonso, Luciana Andrea Castillo and Matteo Minelli
Polymers 2025, 17(24), 3279; https://doi.org/10.3390/polym17243279 (registering DOI) - 10 Dec 2025
Abstract
Mono-material multilayer polypropylene films were developed as light barrier structures through the incorporation of mineral-filled composite layers. Trilayer films with different layer arrangements were fabricated by thermocompression from polypropylene-based films containing 0, 1 and 5 wt.% of talc and kaolinite. A monolayer polypropylene [...] Read more.
Mono-material multilayer polypropylene films were developed as light barrier structures through the incorporation of mineral-filled composite layers. Trilayer films with different layer arrangements were fabricated by thermocompression from polypropylene-based films containing 0, 1 and 5 wt.% of talc and kaolinite. A monolayer polypropylene film of equivalent total thickness was used as a control. Structural, thermal, mechanical, optical, and gas barrier properties were evaluated for all films fabricated. A well-defined trilayer structure was confirmed by SEM. FTIR analysis demonstrated negligible thermo-oxidation, with no thermal-degradation during processing. Improved thermal stability and a slight modification in crystallinity were evidenced by TGA and DSC, respectively. XRD revealed the predominance of the α-form crystalline phase and a preferential polymer crystal orientation associated with the particle presence. Regarding mechanical behavior, enhanced stiffness and tensile strength without loss of sealability or puncture resistance were observed. Trilayer films exhibited significantly reduced UV and visible light transmittance, while maintaining adequate translucency, making them suitable for photosensitive packaging applications. Gas permeabilities remained nearly unchanged, confirming that the barrier performances were preserved. Overall, these mono-material multilayer composites films offer a promising and recyclable alternative to conventional multi-material light barrier packaging, combining improved UV protection, mechanical robustness, and environmental compatibility. Full article
(This article belongs to the Section Polymer Composites and Nanocomposites)
Show Figures

Figure 1

30 pages, 966 KB  
Article
Technology-Enhanced STEM Physics Instruction: Self-Efficacy of Adult Learners in Second Chance Schools
by Despina Radiopoulou, Charalampos Karagiannidis and Paraskevi Zacharia
Appl. Sci. 2025, 15(24), 13019; https://doi.org/10.3390/app152413019 (registering DOI) - 10 Dec 2025
Abstract
This study explores the impact of two teaching methods on the Self-Efficacy in Physics of adult learners in Greek Second Chance Schools (SCSs), an institution designed to promote Lifelong Learning. The participants were divided into two groups. The experimental group was taught selected [...] Read more.
This study explores the impact of two teaching methods on the Self-Efficacy in Physics of adult learners in Greek Second Chance Schools (SCSs), an institution designed to promote Lifelong Learning. The participants were divided into two groups. The experimental group was taught selected Physics topics using a STEM-based approach, while the control group received instruction through traditional lectures. Quantitative data were collected using two reliable and validated structured questionnaires to assess the self-efficacy of adult learners prior to and following the instructional intervention. Findings reveal that the STEM-based approach led to a statistically significant improvement in self-efficacy beliefs among adult learners, with no differences observed by gender or age. This study highlights the value of integrating technology-enhanced STEM education into alternative education frameworks and provides a foundation for future investigations in adult education contexts through the application of innovative, learner-focused methodologies. Full article
(This article belongs to the Special Issue Challenges and Trends in Technology-Enhanced Learning)
15 pages, 916 KB  
Article
Optimal Determination of Synchronous Condenser Placement and Voltage Setting for Enhancing Power System Stability
by Juseong Lee, Hyeongjun Jo and Soobae Kim
Energies 2025, 18(24), 6474; https://doi.org/10.3390/en18246474 (registering DOI) - 10 Dec 2025
Abstract
With the increasing share of renewable energy in power systems, the instability of the power systems is becoming increasingly significant. Consequently, power system stability has become a critical issue, and non-transmission alternatives have been examined as potential solutions. Among non-transmission alternatives, the synchronous [...] Read more.
With the increasing share of renewable energy in power systems, the instability of the power systems is becoming increasingly significant. Consequently, power system stability has become a critical issue, and non-transmission alternatives have been examined as potential solutions. Among non-transmission alternatives, the synchronous condenser can enhance power system stability by providing inertia support and reactive power compensation, especially in systems with a high share of renewable energy. The placement and voltage settings of synchronous condensers significantly impact system stability. This paper proposes a methodology for determining the optimal placement and optimal voltage setting of synchronous condensers for enhancing their voltage stability and transient stability; the improved voltage stability index and synchronizing torque coefficient are used for enhancing the voltage stability and transient stability, respectively. A case study with a focus on specific stability aspects and involving scenarios where the size and number of synchronous capacitors are varied while maintaining a constant inertia energy is presented. The results of the case study show that strategically optimizing the placement and voltage setting of synchronous condensers can enhance the stability of a power system significantly. Full article
(This article belongs to the Special Issue Advanced Electric Power Systems, 2nd Edition)
40 pages, 1187 KB  
Review
Inborn Errors of Amino Acid Metabolism Revisited: Clinical Implications and Insights into Current Therapies
by Abdul L. Shakerdi, Darragh Nerney, Eleanor J. Molloy and Ina Knerr
J. Clin. Med. 2025, 14(24), 8749; https://doi.org/10.3390/jcm14248749 (registering DOI) - 10 Dec 2025
Abstract
Background/Objectives: Inborn errors of amino acid metabolism (IEAAMs) are inherited disorders caused by defects in amino acid catabolism, biosynthesis, or transport. In this review, we aimed to synthesise recent evidence on the clinical manifestations and current and future therapeutic strategies for major IEAAMs. [...] Read more.
Background/Objectives: Inborn errors of amino acid metabolism (IEAAMs) are inherited disorders caused by defects in amino acid catabolism, biosynthesis, or transport. In this review, we aimed to synthesise recent evidence on the clinical manifestations and current and future therapeutic strategies for major IEAAMs. Methods: A narrative review was undertaken on studies published up to November 2025. No fixed start date was set. Instead, earlier studies were included if historically significant or frequently cited in contemporary guidelines, and emphasis was placed on recent developments over the last 5–10 years. Evidence was identified through structured searches of PubMed, clinical trial registries, and public communications on selected IEAAMs, which were synthesised in textual and tabular form. Results: Management across IEAAMs involves the restriction of amino acids or natural proteins, disease-specific dietary formulations, micronutrient optimisation, cofactor or enzyme replacement, and pharmacological chaperones. This is supported by structured monitoring and emergency regimens to prevent catabolic crises. Organ transplantation remains crucial for select indications, such as liver transplantation in hereditary tyrosinaemia with liver disease. Novel approaches include substrate reduction, the pharmacological targeting of upstream pathways, viral vector gene transfer, and liver-directed mRNA therapy. Several of these novel approaches have entered clinical trials, but many remain in the preclinical stage. Conclusions: Despite advances in the treatment of IEAAMs, many patients still experience significant morbidity. Future focus should be on further refining emerging molecular and gene-based treatments and optimising neuroprotective and metabolic targets. The equitable implementation of personalised, life-spanning treatments within multidisciplinary rare disease services will be essential. Full article
(This article belongs to the Section Clinical Pediatrics)
19 pages, 570 KB  
Article
Immediate Effects of Biomimetic Hydroxyapatite Toothpaste and Mouthwash on Dentin Hypersensitivity: A Randomized Controlled Trial
by Andrea Scribante, Matteo Pellegrini, Alessandro Chiesa, Stefania Crea and Andrea Butera
Oral 2025, 5(4), 100; https://doi.org/10.3390/oral5040100 (registering DOI) - 10 Dec 2025
Abstract
Background/Objectives: Dentin hypersensitivity (DH) is associated with gingival recession and dentin exposure. Biomimetic hydroxyapatite (HAp) reduces DH by occluding dentinal tubules, with conventional toothpaste formulations showing benefits. High-density HAp mouthwashes may enhance bioavailability, but comparative evidence is scarce. This trial assessed the immediate [...] Read more.
Background/Objectives: Dentin hypersensitivity (DH) is associated with gingival recession and dentin exposure. Biomimetic hydroxyapatite (HAp) reduces DH by occluding dentinal tubules, with conventional toothpaste formulations showing benefits. High-density HAp mouthwashes may enhance bioavailability, but comparative evidence is scarce. This trial assessed the immediate desensitizing efficacy of a conventional HAp toothpaste and a high-density HAp mouthwash after professional oral hygiene. Methods: One hundred participants were randomized 1:1 to Biorepair® (Coswell S.p.A., Funo, BO, Italy) Total Protection Toothpaste (Control) or Biorepair® (Coswell S.p.A., Funo, BO, Italy) High-Density Mouthwash (Test). Assessments were performed at baseline (T0), post-debridement (T1), and after product use (T2). The primary endpoint was patient-level Schiff Air Index (SAI). Secondary endpoints included tooth-level SAI, Visual Analog Scale (VAS) scores, and gingival recession (GR). The trial was registered at ClinicalTrials.gov (NCT07057141) and followed CONSORT 2025 guidelines. Friedman and Dunn’s tests and regression models were applied. Results: Both groups showed significant reductions in hypersensitivity. Patient-level mean SAI decreased from 1.47 to 0.66 in the Control and from 1.48 to 0.45 in the Test group, while VAS declined from 3.66 to 1.57 (Control) and from 4.15 to 1.37 (Test). Post hoc analyses showed significant intragroup reductions between T0/T1 and T2 in both groups, with no significant differences between groups at any timepoint. GR remained stable across the study. Regression analyses identified follow-up time and GR as significant predictors, whereas treatment allocation was not, indicating that the acute advantage of the mouthwash at T2 did not persist once longitudinal trends were considered. Conclusions: Both HAp formulations effectively reduced dentin hypersensitivity 30 s after application. The high-density mouthwash exhibited slightly lower mean values at T2, although these differences were not statistically significant. Full article
Show Figures

Figure 1

27 pages, 850 KB  
Review
Sexual Dimorphisms in Neurodevelopment May Affect TBI Recovery in Pediatric Patients
by Moira F. Taber, Franklin D. West and Erin E. Kaiser
Biomedicines 2025, 13(12), 3033; https://doi.org/10.3390/biomedicines13123033 (registering DOI) - 10 Dec 2025
Abstract
Traumatic brain injury (TBI) is a leading cause of death and disability, with broad heterogeneity in recovery outcomes particularly noted in pediatric patients. Children post-TBI are vulnerable to aberrant neurodevelopment, specifically in structural and functional neural networks as they correlate with cognitive, behavioral, [...] Read more.
Traumatic brain injury (TBI) is a leading cause of death and disability, with broad heterogeneity in recovery outcomes particularly noted in pediatric patients. Children post-TBI are vulnerable to aberrant neurodevelopment, specifically in structural and functional neural networks as they correlate with cognitive, behavioral, and motor function outcomes. Consideration for sex as a biological variable which innately influences neuroanatomy, neurodevelopment, and functional organization may elucidate risk factors for negative outcomes in pediatric TBI. For example, TBI damage in sexually dimorphic neural structures and networks may explain deficits in social cognition, working memory, as well as internalizing and externalizing behaviors, which differentially impact the quality of life in male versus female TBI patients. However, characterization of sex in conjunction with developmental patterns in normal and injured pediatric populations is limited due to small sample sizes, the low representation of females, a lack of longitudinal data, and the utilization of analyses that are not sensitive enough to detect subtle differences in TBI pathologies and recovery between the sexes. This review aims to analyze and synthesize the existing evidence regarding the influence of sex on the developmental trajectories of neuroanatomical structures, white and gray matter compartments, and the network disruptions that align with sex-specific functional recovery outcomes following pediatric TBI. The delineation of these sex influences will facilitate better precision-based medicine approaches to improve patient outcomes. Full article
22 pages, 1229 KB  
Article
Orthogonal Experiment on the Mechanical Properties of Tuff Mechanism Sand Concrete
by Haitao Zhang, Zhiguo Liu, Zhaoen Wang, Caiqian Yang, Zhentian Zhang, Diwei Lang, Peng Hou, Junjie Luo and Yuanhang Zhang
Buildings 2025, 15(24), 4465; https://doi.org/10.3390/buildings15244465 (registering DOI) - 10 Dec 2025
Abstract
Against the backdrop of global natural sand scarcity and stringent ecological protection policies, tuff mechanism sand has emerged as a promising alternative fine aggregate for concrete, especially in coastal infrastructure hubs like Ningbo, where abundant tuff resources coexist with acute natural sand shortages. [...] Read more.
Against the backdrop of global natural sand scarcity and stringent ecological protection policies, tuff mechanism sand has emerged as a promising alternative fine aggregate for concrete, especially in coastal infrastructure hubs like Ningbo, where abundant tuff resources coexist with acute natural sand shortages. However, existing research on TMS concrete lacks systematic multi-factor optimization, while the performance regulation mechanism of TMS remains unclear, hindering its application in large-scale engineering. To address this gap, this study employed a L16(45) orthogonal experimental design to systematically investigate the effects of five key factors, including fineness modulus, sand ratio, fly ash-to-ground granulated blast-furnace slag ratio, stone powder content, and water–binder ratio, on the 3 d, 7 d, and 28 d compressive, splitting tensile, and flexural strengths of TMS concrete from Ningbo. The results indicate that all three strengths exhibit rapid growth from 3 d to 7 d and stable growth from 7 d to 28 d, with the 3 d compressive strength accounting for 72.5% of the 28 d value, while flexural strength shows the lowest 3 d proportion (63.1%) and highest late-stage growth rate. Range analysis reveals that water–binder ratio is the dominant factor controlling compressive strength and splitting tensile strength, whereas fineness modulus dominates flexural strength. The optimal fineness modulus values for compressive, splitting tensile, and flexural strengths are 2.60, 2.90, and 2.30, respectively; a stone powder content of 0% optimizes compressive and flexural strengths, while 6% is optimal for splitting tensile strength. Notably, the interaction between fineness modulus and water–binder ratio exerts a statistically significant effect on compressive strength (p = 0.008), while the other interactions are negligible. This study fills the gap in research on multi-factor synergistic optimization of TMS concrete and provides targeted mix proportion designs for different engineering requirements. The findings not only enrich the theoretical system of manufactured-sand concrete but also offer practical technical support for the resource utilization of TMS in medium-to-high-strength concrete engineering, aligning with the sustainable development goals of the construction industry. Full article
(This article belongs to the Section Building Materials, and Repair & Renovation)
22 pages, 2846 KB  
Review
Prediction of Esterification and Antioxidant Properties of Food-Derived Fatty Acids and Ascorbic Acid Based on Machine Learning: A Review
by Xinyu Wang, Jianyi Wang, Xiaoyu Zhang, Tiantong Lan, Jingsheng Liu and Hao Zhang
Foods 2025, 14(24), 4255; https://doi.org/10.3390/foods14244255 (registering DOI) - 10 Dec 2025
Abstract
This study is dedicated to summarizing and performing an in-depth analysis of the antioxidant properties of ascorbic acid fatty acid esters. The esterification reaction mechanism of ascorbic acid with palmitic acid, lauric acid, and oleic acid in food systems was elaborated in detail, [...] Read more.
This study is dedicated to summarizing and performing an in-depth analysis of the antioxidant properties of ascorbic acid fatty acid esters. The esterification reaction mechanism of ascorbic acid with palmitic acid, lauric acid, and oleic acid in food systems was elaborated in detail, and its antioxidant mechanism was discussed in depth. The free radical scavenging mechanism and oxidative inhibition effect of two mainstream determination methods, DPPH and ABTS, were analyzed. Esterification, as a core organic synthesis reaction, is widely used in the production of food antioxidants, pharmaceutical ingredients, chemical polymers, and cosmetic oil-based matrices. At the same time, in view of the wide application of machine learning as a multidisciplinary core technology, this paper selects free radical scavenging rate and esterification yield as characteristic parameters and normalizes the offspring into random forest model training to achieve accurate prediction of antioxidant performance. Finally, in the future, it is necessary to expand the data set, optimize the model structure, explore multi-model fusion to improve the prediction effect, and promote the application of machine learning in the screening design of new antioxidants and the optimization of green synthesis processes to promote the intelligent and sustainable development of food antioxidant research. Full article
(This article belongs to the Section Food Physics and (Bio)Chemistry)
Show Figures

Figure 1

21 pages, 3491 KB  
Article
Urban Roadside Forests as Green Infrastructure: Multifunctional Ecosystem Services in a Coastal City of China
by Wenjing Niu, Xiang Yu and Lu Ding
Forests 2025, 16(12), 1841; https://doi.org/10.3390/f16121841 (registering DOI) - 10 Dec 2025
Abstract
Urban roadside forests are vital components of green infrastructure that provide multiple ecosystem services, contributing to climate regulation, environmental quality, and urban resilience. This study assessed the multifunctional ecosystem services of roadside tree communities along four representative road types—Coastal Scenic, Commercial Arterial, Residential [...] Read more.
Urban roadside forests are vital components of green infrastructure that provide multiple ecosystem services, contributing to climate regulation, environmental quality, and urban resilience. This study assessed the multifunctional ecosystem services of roadside tree communities along four representative road types—Coastal Scenic, Commercial Arterial, Residential Secondary, and Industrial Park Roads—in Weihai, a coastal city in eastern China. Based on a complete tree inventory (6742 individuals from 38 species) integrated with the i-Tree Eco model, we quantified three key ecosystem services, carbon storage and annual sequestration, air-pollutant removal, and stormwater interception, and monetized their benefits. Results indicate that roadside forests stored approximately 1120 tons of carbon and sequestered 78 tons annually (≈USD 0.53 million; CNY 3.85 million), removed 1.28 tons of air pollutants per year (≈USD 9370; CNY 68,400), and intercepted 1560 m3 of stormwater (≈USD 5560; CNY 40,600). Commercial Arterial and Coastal Scenic Roads yielded the highest total ecosystem-service values, while Residential Secondary Roads achieved the greatest per-area efficiency. These findings highlight the significant contribution of urban roadside forests to sustainable and climate-resilient city development and underscore their potential role in urban forest planning and management. Full article
(This article belongs to the Special Issue Growth, Maintenance, and Function of Urban Trees)
Show Figures

Figure 1

23 pages, 2861 KB  
Article
Metaheuristic-Optimized Cassava Starch/CNF/SiO2 Bio-Nanocomposite Films for Sustainable Food Packaging: A Data-Driven Approach
by Mei Bie, Ting Wang, Zhichao Yang, Shiwei Yuan, Yinghui Gu, Chong Liu, Wei Zhao and Kai Song
Sustainability 2025, 17(24), 11070; https://doi.org/10.3390/su172411070 (registering DOI) - 10 Dec 2025
Abstract
Addressing the urgent challenges of plastic pollution and food waste, this study develops a high-performance, fully biodegradable bio-nanocomposite film from renewable agricultural resources through a data-driven optimization approach. The ternary system combines cassava starch (matrix), cellulose nanofibrils (CNFs for reinforcement), and nano-silica materials [...] Read more.
Addressing the urgent challenges of plastic pollution and food waste, this study develops a high-performance, fully biodegradable bio-nanocomposite film from renewable agricultural resources through a data-driven optimization approach. The ternary system combines cassava starch (matrix), cellulose nanofibrils (CNFs for reinforcement), and nano-silica materials (SiO2-NPs as barrier enhancer). Response Surface Methodology synergistically coupled with the Firefly Algorithm—a metaheuristic optimization technique—systematically determined the optimal formulation (1.99% w/v starch, 1.38% w/v CNF, 0.30% w/v SiO2-NPs). The optimized film achieved exceptional performance: tensile strength of 5.813 MPa, elongation at break of 12.37%, and water vapor permeability of 5.395 × 10−6 g·cm−1·s−1·Pa−1. Critically, the film demonstrated over 80% biodegradation within 60 days and superior UV-shielding capabilities (>90%), effectively extending food shelf-life while minimizing environmental impact. This work establishes a robust strategy for designing sustainable packaging materials through intelligent optimization, valorizing agricultural by-products, and contributing to circular economy principles and UN Sustainable Development Goals. The integration of renewable resources with metaheuristic algorithms represents a significant advancement toward sustainable food packaging solutions. Full article
(This article belongs to the Special Issue Sustainable Food Processing and Food Packaging Technologies)
Show Figures

Figure 1

28 pages, 1660 KB  
Article
Adaptive Reinforcement Learning-Based Framework for Energy-Efficient Task Offloading in a Fog–Cloud Environment
by Branka Mikavica and Aleksandra Kostic-Ljubisavljevic
Sensors 2025, 25(24), 7516; https://doi.org/10.3390/s25247516 (registering DOI) - 10 Dec 2025
Abstract
Ever-increasing computational demand introduced by the expanding scale of Internet of Things (IoT) devices poses significant concerns in terms of energy consumption in a fog–cloud environment. Due to the limited resources of IoT devices, energy-efficient task offloading becomes even more challenging for time-sensitive [...] Read more.
Ever-increasing computational demand introduced by the expanding scale of Internet of Things (IoT) devices poses significant concerns in terms of energy consumption in a fog–cloud environment. Due to the limited resources of IoT devices, energy-efficient task offloading becomes even more challenging for time-sensitive tasks. In this paper, we propose a reinforcement learning-based framework, namely Adaptive Q-learning-based Energy-aware Task Offloading (AQETO), that dynamically manages the energy consumption of fog nodes in a fog–cloud network. Concurrently, it considers IoT task delay tolerance and allocates computational resources while satisfying deadline requirements. The proposed approach dynamically determines energy states of each fog node using Q-learning depending on workload fluctuations. Moreover, AQETO prioritizes allocation of the most urgent tasks to minimize delays. Extensive experiments demonstrate the effectiveness of AQETO in terms of the minimization of fog node energy consumption and delay and the maximization of system efficiency. Full article
(This article belongs to the Section Intelligent Sensors)
19 pages, 2085 KB  
Article
Personalized Robotic-Assisted Total Knee Arthroplasty with Anatomo-Functional Implant Positioning for Varus Knees: A Minimum Follow-Up of 5 Years
by Zakee Azmi, Aymen Alqazzaz, Cécile Batailler and Sébastien Parratte
J. Pers. Med. 2025, 15(12), 617; https://doi.org/10.3390/jpm15120617 (registering DOI) - 10 Dec 2025
Abstract
Background/Objectives: Some personalized alignment (PA) concepts have been described with symmetrical gaps in extension and flexion. However, laxity in native knees was significantly greater laterally than medially with respect to both extension and flexion. We hypothesized that a personalized alignment can restore [...] Read more.
Background/Objectives: Some personalized alignment (PA) concepts have been described with symmetrical gaps in extension and flexion. However, laxity in native knees was significantly greater laterally than medially with respect to both extension and flexion. We hypothesized that a personalized alignment can restore the native knee alignment, keep a satisfying patellar tracking, and obtain physiological ligament balancing, that is, a symmetric gap in extension and an asymmetric gap in flexion. We aimed to assess: (1) the postoperative alignment of TKA and postoperative patellar tracking (primary outcome); (2) the ligament balancing at the end of the surgery; and (3) clinical outcomes and complication rates. Methods: In this single-center, retrospective case series, we evaluated 45 patients in a consecutive series who underwent robotic-assisted primary TKA using PA between January and September 2020 with a minimum follow-up of 5 years. Complication was defined as grade ≥3 according to the Clavien-Dindo classification. Data assessed were: TKA alignment and implant positioning on postoperative radiographs, patellar tracking on the merchant view, and ligament balancing in extension and flexion upon completion of surgery. Results: Mean follow-up was 62.1 ± 2.5 months. The postoperative mean HKA angle was 177.4° ± 2.2. The medial distal femoral angle was restored (91.1° ± 1.5 postoperatively versus 91.3° ± 2). A total of four TKAs had a patellar tilt superior to 5° (8.9%). No significant difference was found in the medial gap laxity—both in extension and in flexion—and the lateral gap laxity in extension. The lateral gap laxity in flexion was significantly higher than extension or medial gap laxity (+2.9 mm). One patient was readmitted for delayed wound healing. Average improvements in Knee Society knee and function scores were 55.86 and 51.84 points, respectively. Conclusions: This personalized alignment technique using anatomo-functional implant positioning allowed restoration of native knee alignment with a “safe zone” (3° varus/valgus) for the tibial implant, maintained satisfying patellar tracking, and restituted the asymmetrical gap laxity in flexion with a higher laxity in the lateral compartment. Being the longest system-specific study to date, the results are encouraging at 5 years with no major complications. However, longer follow-up will be required to confirm the use of this technique. Full article
(This article belongs to the Special Issue Cutting-Edge Innovations in Hip and Knee Joint Replacement)
Show Figures

Figure 1

33 pages, 1135 KB  
Review
Refining Mouse Models of Gaucher Disease: Advancing Mechanistic Insights, Biomarker Discovery, and Therapeutic Strategies
by Nima Fattahi, Jiapeng Ruan, Glenn Belinsky, Shu Xing, Pramod K. Mistry and Shiny Nair
Int. J. Mol. Sci. 2025, 26(24), 11915; https://doi.org/10.3390/ijms262411915 (registering DOI) - 10 Dec 2025
Abstract
Gaucher disease (GD), caused by biallelic pathogenic variants in GBA1, has evolved from being understood as a macrophage-restricted lysosomal disorder to a multisystem condition involving neuroinflammation, immune dysregulation, and cell-type-specific lipid toxicity. This expanded view has driven a parallel progression in GD mouse [...] Read more.
Gaucher disease (GD), caused by biallelic pathogenic variants in GBA1, has evolved from being understood as a macrophage-restricted lysosomal disorder to a multisystem condition involving neuroinflammation, immune dysregulation, and cell-type-specific lipid toxicity. This expanded view has driven a parallel progression in GD mouse model development. Early chemically induced and germline knockout models provided foundational insights but were limited by perinatal lethality or incomplete phenotypic fidelity. Subsequent generations of conditional, inducible, and lineage-specific models enabled dissection of visceral and neuronopathic manifestations and clarified the contributions of macrophages, B cells, neurons, microglia, osteoblasts, and endothelial cells to disease pathogenesis. More recent humanized immune and gene-edited platforms, together with multi-omics integration, now allow modeling of genotype-specific biology and therapeutic response with greater translational precision. In this review, we synthesize the evolution of GD mouse models across these eras, evaluate their strengths and limitations, and highlight species-specific challenges including differences in lipid metabolism, immune architecture, and the absence of the GBAP1 pseudogene in mice that influence interpretation and clinical translation. We outline emerging strategies for incorporating patient-derived mutations, modifier pathways, and clinically meaningful endpoints into future models. Our aim is to provide a coherent framework that bridges murine and human GD biology and supports the development of more predictive platforms to accelerate mechanistic discovery, biomarker development, and therapeutic innovation across all subtypes of GD. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
29 pages, 8141 KB  
Article
Optimized Explainable Machine Learning Protocol for Battery State-of-Health Prediction Based on Electrochemical Impedance Spectra
by Lamia Akther, Md Shafiul Alam, Mohammad Ali, Mohammed A. AlAqil, Tahmida Khanam and Md. Feroz Ali
Electronics 2025, 14(24), 4869; https://doi.org/10.3390/electronics14244869 (registering DOI) - 10 Dec 2025
Abstract
Monitoring the battery state of health (SOH) has become increasingly important for electric vehicles (EVs), renewable storage systems, and consumer gadgets. It indicates the residual usable capacity and performance of a battery in relation to its original specifications. This information is crucial for [...] Read more.
Monitoring the battery state of health (SOH) has become increasingly important for electric vehicles (EVs), renewable storage systems, and consumer gadgets. It indicates the residual usable capacity and performance of a battery in relation to its original specifications. This information is crucial for the safety and performance enhancement of the overall system. This paper develops an explainable machine learning protocol with Bayesian optimization techniques trained on electrochemical impedance spectroscopy (EIS) data to predict battery SOH. Various robust ensemble algorithms, including HistGradientBoosting (HGB), Random Forest, AdaBoost, Extra Trees, Bagging, CatBoost, Decision Tree, LightGBM, Gradient Boost, and XGB, have been developed and fine-tuned for predicting battery health. Eight comprehensive metrics are employed to estimate the model’s performance rigorously: coefficient of determination (R2), mean squared error (MSE), median absolute error (medae), mean absolute error (MAE), correlation coefficient (R), Nash–Sutcliffe efficiency (NSE), Kling–Gupta efficiency (KGE), and root mean squared error (RMSE). Bayesian optimization techniques were developed to optimize hyperparameters across all models, ensuring optimal implementation of each algorithm. Feature importance analysis was performed to thoroughly evaluate the models and assess the features with the most influence on battery health degradation. The comparison indicated that the GradientBoosting model outperformed others, achieving an MAE of 0.1041 and an R2 of 0.9996. The findings suggest that Bayesian-optimized tree-based ensemble methods, particularly gradient boosting, excel at forecasting battery health status from electrochemical impedance spectroscopy data. This result offers an excellent opportunity for practical use in battery management systems that employ diverse industrial state-of-health assessment techniques to enhance battery longevity, contributing to sustainability initiatives for second-life lithium-ion batteries. This capability enables the recycling of vehicle batteries for application in static storage systems, which is environmentally advantageous and ensures continuity. Full article
(This article belongs to the Special Issue Advanced Control and Power Electronics for Electric Vehicles)
22 pages, 525 KB  
Article
On Triangle-Free v3 Configurations
by Abdullah Alazemi and Anton Betten
Mathematics 2025, 13(24), 3938; https://doi.org/10.3390/math13243938 (registering DOI) - 10 Dec 2025
Abstract
We describe a classification algorithm of combinatorial triangle-free v3-configurations. The (non-isomorphic) triangle-free v3 configurations are classified for v{23,24}. We conclude that there is no triangle-free v3 configuration that is blocking set free [...] Read more.
We describe a classification algorithm of combinatorial triangle-free v3-configurations. The (non-isomorphic) triangle-free v3 configurations are classified for v{23,24}. We conclude that there is no triangle-free v3 configuration that is blocking set free for v24. We also give some statistics on some properties of the structures, like transitivity, self-duality, and self-polarity. Full article
(This article belongs to the Section E1: Mathematics and Computer Science)
17 pages, 2953 KB  
Article
AWJ Cutting Process Quality Modeling and Optimization Based on Footprint Angle
by Andrzej Perec, Elzbieta Kawecka and Wojciech Zajac
Materials 2025, 18(24), 5548; https://doi.org/10.3390/ma18245548 (registering DOI) - 10 Dec 2025
Abstract
Various materials may be machined using the abrasive water jet (AWJ) cutting method. Many control factors, such as abrasive flow, operating pressure, and traverse speed, influence the efficiency and surface quality of AWJ-cut components. The common distinguishing factor of process efficiency and quality [...] Read more.
Various materials may be machined using the abrasive water jet (AWJ) cutting method. Many control factors, such as abrasive flow, operating pressure, and traverse speed, influence the efficiency and surface quality of AWJ-cut components. The common distinguishing factor of process efficiency and quality is the angle of machining footprints (striation angle). This paper presents research results on the control parameters as a method of influencing the striation angle through the angle level of machining footprints to achieve high efficiency and quality, for example, the high-impact and abrasive-resistant steel. This will enable quality control of the AWJ cutting process by continuously measuring the jet deflection angle in an online mode and adjusting these parameters in real-time to maintain high efficiency and the required surface quality. The particular interest in utilizing this basis is the possibility of setting cutting parameters for new materials not included in the implemented model of the AWJ cutting machine. Full article
(This article belongs to the Special Issue High-Pressure Water Jet Machining in Materials Engineering)
20 pages, 4564 KB  
Article
On-Ground Photovoltaic Plants Designed to Recharge Aircraft Batteries
by Musab Hammas Khan, Patrizia Lamberti, Elisabetta Sieni and Vincenzo Tucci
Energies 2025, 18(24), 6473; https://doi.org/10.3390/en18246473 (registering DOI) - 10 Dec 2025
Abstract
To explore the potential of solar energy in the pursuit of a more sustainable aviation sector, this research examines the feasibility of solar photovoltaic systems for battery recharge of electric or electric hybrid aircraft deployed at four airports in North Africa and North, [...] Read more.
To explore the potential of solar energy in the pursuit of a more sustainable aviation sector, this research examines the feasibility of solar photovoltaic systems for battery recharge of electric or electric hybrid aircraft deployed at four airports in North Africa and North, Central, and South Europe, respectively: Cairo International, London Heathrow, Milan Malpensa, and Rome Fiumicino. Employing PVGIS software with Google Maps, a site-specific photovoltaic array can be designed, optimizing module tilt and orientation to maximize solar energy collection across various climatic conditions. The energy production of the photovoltaic systems at the selected airports is compared to the energy demand required for the annual recharge of the batteries (28 MWh each) used in a widely popular medium-range aircraft, the Airbus A320. Although the calculated amount of energy, allowing for daily capacities ranging from 6 to 10 batteries on average, is insufficient to support the extensive demand associated with the typical air traffic in such airports, the potential of solar energy to decarbonize aircraft seems an appropriate approach to be pursued. Locations with limited solar access necessitate hybrid solutions, especially in sunny regions. Full article
Show Figures

Figure 1

16 pages, 639 KB  
Systematic Review
Efficacy and Safety of Placental Extract on Menopausal Symptoms: A Systematic Review
by Sára Papp, László Tűű, Katalin Nas, Zsófia Telkes, Lotti Keszthelyi, Márton Keszthelyi, Nándor Ács, Szabolcs Várbíró and Marianna Török
Nutrients 2025, 17(24), 3857; https://doi.org/10.3390/nu17243857 (registering DOI) - 10 Dec 2025
Abstract
Background: Menopause affects every woman worldwide, with varying degrees of severity. In addition to traditional treatments such as hormone replacement therapy, there is also a growing interest in alternative treatments. One possible way to address this need is through the use of placenta [...] Read more.
Background: Menopause affects every woman worldwide, with varying degrees of severity. In addition to traditional treatments such as hormone replacement therapy, there is also a growing interest in alternative treatments. One possible way to address this need is through the use of placenta extracts. This systematic review is the first to evaluate the efficacy of placental extracts in randomized controlled trials (RCTs). Methods: A systematic search of three databases (MEDLINE, Scopus, Embase) identified studies on placental extract treatment of menopausal symptoms in women, yielding 272 records, with 11 eligible studies. Results: Menopausal severity scores (Kupperman Menopausal Index, Simplified Menopausal Index, Menopausal Rating Scale), somatic and vasomotor symptoms, skin conditions, and certain psychological indicators were significantly improved in the 11 enrolled randomized controlled trials, including perimenopausal and postmenopausal women treated with porcine or human dried, purified placental extract. Placental extract was well tolerated in all studies; no significant side effects or clinically significant laboratory abnormalities were recorded. Conclusions: Porcine and human placental extracts appear to offer potential benefits for alleviating menopausal symptoms. Full article
(This article belongs to the Special Issue Exploring the Role of Bioactive Compounds in Immunonutrition)
18 pages, 484 KB  
Article
A High-Throughput, BRAM-Efficient NTT/INTT Accelerator for ML-KEM
by Xianwei Gao, Yitong Li, Tianyao Li, Xuemei Li and Jianxin Wang
Electronics 2025, 14(24), 4868; https://doi.org/10.3390/electronics14244868 (registering DOI) - 10 Dec 2025
Abstract
The Number-Theoretic Transform is the primary performance bottleneck in hardware accelerators for post-quantum cryptography schemes like the Module-Lattice-based Key-Encapsulation Mechanism. A key design challenge is the trade-off between the massive parallelism required for low-latency computation and the prohibitive on-chip Block RAM consumption this [...] Read more.
The Number-Theoretic Transform is the primary performance bottleneck in hardware accelerators for post-quantum cryptography schemes like the Module-Lattice-based Key-Encapsulation Mechanism. A key design challenge is the trade-off between the massive parallelism required for low-latency computation and the prohibitive on-chip Block RAM consumption this typically entails. This paper introduces an NTT/INTT accelerator architecture that resolves this conflict, achieving a state-of-the-art latency of 40 clock cycles for a 256-point transform while utilizing only 5 BRAM blocks. Our architecture achieves this by pairing a 32-way parallel streaming datapath with a hybrid memory subsystem that strategically allocates on-chip storage resources. The core innovation is the use of distributed RAM instead of BRAM for high-bandwidth buffering of intermediate data between pipeline stages. This reserves the scarce BRAM resources for storing static twiddle factors and for system-level FIFO interfaces. By deliberately trading abundant logic fabric and dedicated DSP slices for BRAM efficiency, our work demonstrates a design point optimized for high-speed, BRAM-constrained System-on-Chip environments, proving that a focus on memory hierarchy is critical to developing PQC solutions that are both fast and practical for real-world integration. Full article
(This article belongs to the Section Electronic Materials, Devices and Applications)
Show Figures

Figure 1

21 pages, 2862 KB  
Article
Preparation of Acid-Modified Biochar and Remediation Mechanisms on Soda–Saline–Alkali Soil
by Luwen Zhang, Zhichen Liu, Zhenke Liu, Yuxiang Chen and Zunhao Zhang
Agronomy 2025, 15(12), 2836; https://doi.org/10.3390/agronomy15122836 (registering DOI) - 10 Dec 2025
Abstract
Soil salinization poses significant threats to food security and ecosystem functions, while acid-modified biochar functions as an effective carbon-based material for the reclamation of saline–alkali soils. In this study, acid-modified biochars prepared using boric (BC), sulfuric (SC), hydrochloric (HC), acetic (AC), phosphoric (PC), [...] Read more.
Soil salinization poses significant threats to food security and ecosystem functions, while acid-modified biochar functions as an effective carbon-based material for the reclamation of saline–alkali soils. In this study, acid-modified biochars prepared using boric (BC), sulfuric (SC), hydrochloric (HC), acetic (AC), phosphoric (PC), and oxalic (OC) acids were analyzed. The ameliorative effects of acid-modified biochar on soda–saline–alkaline soils were evaluated through adsorption and pot experiments, with preliminary insights into its mechanism of action. The results indicated that the specific surface area and maximum adsorption capacities (Qm) of conventional biochar and OC were 5.91, 35.39 m2 g−1 and 21.62, 41.00 mg g−1, respectively. After the addition of conventional biochar, OC and SC in pot experiments, soil pH, (CO32− + HCO3) content, and exchangeable sodium percentage (ESP) were significantly reduced. Compared to conventional biochar, SC increased the relative abundance of Bacillus, Adhaeribacter, and Preussia, while OC increased the relative abundance of Antarcticbacterium, Diezia, and Peziza. OC and SC maximally increased both the aboveground and belowground biomass of Medicago falcata L., while simultaneously reducing sodium content. This study demonstrated that biochar modified with SC and OC significantly reduced soda–saline–alkali stress. SC and OC exhibited greater potential in remediating soda–saline–alkali soils. Full article
(This article belongs to the Section Soil and Plant Nutrition)
19 pages, 3633 KB  
Article
Single-Cell Mapping of Genetic Risk Across Ten Respiratory Diseases
by Miao Zhou and Chao Xue
Biology 2025, 14(12), 1765; https://doi.org/10.3390/biology14121765 (registering DOI) - 10 Dec 2025
Abstract
Understanding how genetic risk variants contribute to respiratory diseases requires mapping genome-wide association study (GWAS) signals to disease-relevant cell types and states within the human lung. Here, we integrated GWAS summary statistics for ten major respiratory diseases, including asthma, COPD, idiopathic pulmonary fibrosis [...] Read more.
Understanding how genetic risk variants contribute to respiratory diseases requires mapping genome-wide association study (GWAS) signals to disease-relevant cell types and states within the human lung. Here, we integrated GWAS summary statistics for ten major respiratory diseases, including asthma, COPD, idiopathic pulmonary fibrosis (IPF), COVID-19, and lung cancer, using a large-scale single-cell transcriptomic dataset of more than 523,000 cells from the Human Lung Cell Atlas. Applying the single-cell Disease Relevance Score (scDRS) framework, we systematically identified shared and disease-specific cellular associations across four major compartments, namely epithelial, immune, endothelial, and stromal. We found that alveolar type II (AT2) cells represent a central susceptibility hub for asthma, COPD, and COVID-19, whereas disease-specific risk enrichment was observed in subpopulations such as CCL3+ alveolar macrophages in COVID-19 and adventitial fibroblasts in asthma. Importantly, subclustering revealed substantial heterogeneity within cell types, with distinct transcriptional programs underlying differential disease associations. For example, AT2 subclusters exhibited divergent susceptibility patterns to asthma versus COVID-19, reflecting immune-interacting versus antiviral states. Our results provide a systematic single-cell framework for linking genetic risk to the cellular architecture of the human lung and uncover both shared and disease-specific mechanisms underlying respiratory disease susceptibility. Full article
Show Figures

Figure 1

Open Access Journals

Browse by Indexing Browse by Subject Selected Journals
Back to TopTop