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21 pages, 6545 KiB  
Article
Profiling of Breast Cancer Stem Cell Types/States Shows the Role of CD44hi/CD24lo-ALDH1hi as an Independent Prognostic Factor After Neoadjuvant Chemotherapy
by Hazem Ghebeh, Jumanah Y. Mirza, Taher Al-Tweigeri, Monther Al-Alwan and Asma Tulbah
Int. J. Mol. Sci. 2025, 26(17), 8219; https://doi.org/10.3390/ijms26178219 - 24 Aug 2025
Abstract
Multiple markers exist for breast cancer stem cells (CSCs), which are believed to represent the phenotypes of various CSC types and/or states. The relationship between each CSC subpopulation/state and the primary hallmarks of cancer has not been sufficiently clarified. In this study, six [...] Read more.
Multiple markers exist for breast cancer stem cells (CSCs), which are believed to represent the phenotypes of various CSC types and/or states. The relationship between each CSC subpopulation/state and the primary hallmarks of cancer has not been sufficiently clarified. In this study, six CSC markers (CD44hi/CD24lo, CD24, Ep-CAM, ALDH1, CD10, and BMI1) were assessed in a surgical cohort of 73 breast cancer patients. The expression of a single or multiple CSC markers was correlated with clinicopathological parameters, including markers of immune evasion, proliferation, epithelial–mesenchymal transition (EMT), and survival. All CSC phenotypes, except for CD10, correlated with markers indicative of higher proliferation. The CD44hi/CD24lo phenotype correlated with markers of EMT and PD-L1 expression, unlike ALDH1hi. Both Ep-CAMhi and CD24hi breast cancer were associated with indicators of immune evasion, including PD-L1 expression, and the infiltration of FOXP3+ and PD-1+ tumor-infiltrating lymphocytes (TIL). While the CD44hi/CD24lo, Ep-CAMhi, and ALDH1hi phenotypes correlated with shorter overall survival (OS), CD24hi correlated with reduced disease-free survival (DFS). Interestingly, among all tested CSC markers, the CD44hi/CD24lo-ALDH1hi combination phenotype correlated with the worst DFS (HR 2.8, p = 0.014 in univariate/multivariate analysis) and OS (p < 0.001, HR 6.4 in univariate and 5.4 in multivariate analysis). A side-by-side comparison of multiple CSC markers demonstrated the differential linkage of CSC phenotype/state with distinct features of breast cancer. This comparison demonstrates the advantage of the CD44hi/CD24lo-ALDH1hi combination marker for prognostication, especially after neoadjuvant chemotherapy. In the future, distinct markers of CSCs can hopefully be leveraged to trace/monitor different disease characteristics or treatment outcomes. Full article
(This article belongs to the Section Molecular Oncology)
25 pages, 7540 KiB  
Article
Data-Driven Digital Innovation Networks for Urban Sustainable Development: A Spatiotemporal Network Analysis in the Yellow River Basin, China
by Xuhong Zhang and Haiqing Hu
Buildings 2025, 15(17), 3006; https://doi.org/10.3390/buildings15173006 - 24 Aug 2025
Abstract
Digital city planning increasingly relies on data-driven approaches to address complex urban sustainability challenges through innovative network analysis methodologies. This study introduces a comprehensive spatiotemporal network framework to examine digital innovation networks as fundamental infrastructure for urban sustainable development, focusing on the Yellow [...] Read more.
Digital city planning increasingly relies on data-driven approaches to address complex urban sustainability challenges through innovative network analysis methodologies. This study introduces a comprehensive spatiotemporal network framework to examine digital innovation networks as fundamental infrastructure for urban sustainable development, focusing on the Yellow River Basin as a representative case study. Utilizing digital patent data as innovation indicators across 57 urban centers, we employ advanced network analysis techniques including Social Network Analysis (SNA) and the Quadratic Assignment Procedure (QAP) to investigate the spatiotemporal evolution patterns and underlying driving mechanisms of regional digital innovation networks. The methodology integrates big data analytics with urban planning applications to provide evidence-based insights for digital city planning strategies. Our empirical findings reveal three critical dimensions of urban sustainable development through digital innovation networks: First, the region demonstrated significant enhancement in digital innovation capacity from 2012 to 2022, with accelerated growth patterns post 2020, indicating robust urban resilience and adaptive capacity for sustainable transformation. Second, the spatial network configuration exhibited increasing interconnectivity characterized by strengthened urban–rural linkages and enhanced cross-regional innovation flows, forming a hierarchical centrality pattern where major metropolitan centers (Xi’an, Zhengzhou, Jinan, and Lanzhou) serve as innovation hubs driving coordinated regional development. Third, analysis of network formation mechanisms indicates that spatial proximity, market dynamics, and industrial foundations negatively correlate with network density, suggesting that regional heterogeneity in these characteristics promotes innovation diffusion and strengthens inter-urban connections, while technical human capital and governmental interventions show limited influence on network evolution. This research contributes to the digital city planning literature by demonstrating how data-driven network analysis can inform sustainable urban development strategies, providing valuable insights for policymakers and urban planners implementing AI technologies and big data applications in regional development planning. Full article
(This article belongs to the Section Architectural Design, Urban Science, and Real Estate)
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24 pages, 5906 KiB  
Article
Design and Framework of Non-Intrusive Spatial System for Child Behavior Support in Domestic Environments
by Da-Un Yoo, Jeannie Kang and Sung-Min Park
Sensors 2025, 25(17), 5257; https://doi.org/10.3390/s25175257 - 23 Aug 2025
Abstract
This paper proposes a structured design framework and system architecture for a non-intrusive spatial system aimed at supporting child behavior in everyday domestic environments. Rooted in ethical considerations, our approach defines four core behavior-guided design strategies: routine recovery, emotion-responsive adjustment, behavioral transition induction, [...] Read more.
This paper proposes a structured design framework and system architecture for a non-intrusive spatial system aimed at supporting child behavior in everyday domestic environments. Rooted in ethical considerations, our approach defines four core behavior-guided design strategies: routine recovery, emotion-responsive adjustment, behavioral transition induction, and external linkage. Each strategy is meticulously translated into a detailed system logic that outlines input conditions, trigger thresholds, and feedback outputs, designed for implementability with ambient sensing technologies. Through a comparative conceptual analysis of three sensing configurations—low-resolution LiDARs, mmWave radars, and environmental sensors—we evaluate their suitability based on technical feasibility, spatial integration, operationalized privacy metrics, and ethical alignment. Supported by preliminary technical observations from lab-based sensor tests, low-resolution LiDAR emerges as the most balanced option for its ability to offer sufficient behavioral insight while enabling edge-based local processing, robustly protecting privacy, and maintaining compatibility with compact residential settings. Based on this, we present a working three-layered system architecture emphasizing edge processing and minimal-intrusion feedback mechanisms. While this paper primarily focuses on the framework and design aspects, we also outline a concrete pilot implementation plan tailored for small-scale home environments, detailing future empirical validation steps for system effectiveness and user acceptance. This structured design logic and pilot framework lays a crucial foundation for future applications in diverse residential and care contexts, facilitating longitudinal observation of behavioral patterns and iterative refinement through lived feedback. Ultimately, this work contributes to the broader discourse on how technology can ethically and developmentally support children’s autonomy and well-being, moving beyond surveillance to enable subtle, ambient, and socially responsible spatial interactions attuned to children’s everyday lives. Full article
(This article belongs to the Special Issue Progress in LiDAR Technologies and Applications)
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25 pages, 2851 KiB  
Article
Pangenomic and Phenotypic Characterization of Colombian Capsicum Germplasm Reveals the Genetic Basis of Fruit Quality Traits
by Maira A. Vega-Muñoz, Felipe López-Hernández, Andrés J. Cortés, Federico Roda, Esteban Castaño, Guillermo Montoya and Juan Camilo Henao-Rojas
Int. J. Mol. Sci. 2025, 26(17), 8205; https://doi.org/10.3390/ijms26178205 - 23 Aug 2025
Abstract
Capsicum is one of the most economically significant vegetable crops worldwide, owing to its high content of bioactive compounds with nutritional, pharmacological, and industrial relevance. However, research has focused on C. annuum, often disregarding local diversity and secondary gene pools, which may [...] Read more.
Capsicum is one of the most economically significant vegetable crops worldwide, owing to its high content of bioactive compounds with nutritional, pharmacological, and industrial relevance. However, research has focused on C. annuum, often disregarding local diversity and secondary gene pools, which may contain hidden variation for quality traits. Therefore, this study evaluated the genetic and phenotypic diversity of 283 accessions from the Colombian germplasm collection in the agrobiodiversity hotspot of northwest South America, representing all five domesticated species of the genus. A total of 18 morphological, physicochemical, and biochemical fruit traits were assessed, including texture, color, capsaicinoid, and carotenoid content. The phenotypic data were integrated with genomic information obtained through genotyping-by-sequencing (GBS) using the C. annuum reference genome and a multispecies pangenome. Fixed-and-Random-Model-Circulating-Probability-Unification (FarmCPU) and Bayesian-information-and-Linkage-disequilibrium-Iteratively-Nested-Keyway (BLINK) genome-wide association studies (GWAS) were performed on both alignments, respectively, leading to the identification of complex polygenic architectures with 144 and 150 single nucleotide polymorphisms (SNPs) significantly associated with key fruit quality traits. Candidate genes involved in capsaicinoid biosynthesis were identified within associated genomic regions, terpenoid and sterol pathways, and cell wall modifiers. These findings highlight the potential of integrating pangenomic resources with multi-omics approaches to accelerate Capsicum improvement programs and facilitate the development of cultivars with enhanced quality traits and increased agro-industrial value. Full article
(This article belongs to the Special Issue Omics Technologies in Molecular Biology)
21 pages, 4010 KiB  
Article
Headwater Systems as Green Infrastructure: Prioritising Restoration Hotspots for Sustainable Rural Landscapes
by Selma B. Pena
Land 2025, 14(9), 1704; https://doi.org/10.3390/land14091704 - 23 Aug 2025
Abstract
This study aims to assess the role of headwater systems (HS) in enhancing ecological connectivity and supporting Green Infrastructure in the Centre Region of Portugal. Specifically, it identifies restoration opportunity areas within HS by analysing land-use changes over the past 70 years, modelling [...] Read more.
This study aims to assess the role of headwater systems (HS) in enhancing ecological connectivity and supporting Green Infrastructure in the Centre Region of Portugal. Specifically, it identifies restoration opportunity areas within HS by analysing land-use changes over the past 70 years, modelling land-use scenarios to promote ecological resilience, and evaluating connectivity between HS and Natura 2000 sites. The methodology integrates spatial analysis of historical land-use data with connectivity modelling using least-cost path approaches. Results show substantial transformation in HS areas, notably the expansion of eucalyptus plantations and a decline in agricultural land. Approximately 58% of the HS are identified as requiring restoration, including areas within the Natura 2000 network. The connectivity assessment reveals that HS can function as effective ecological corridors, contributing to improved water regulation, soil conservation, gene flow, and wildfire mitigation. A total of 61 potential ecological linkages between Natura 2000 sites were identified. These findings highlight the strategic importance of integrating HS into regional and national Green Infrastructure planning and supporting the implementation of the EU Biodiversity Strategy for 2030. The study recommends prioritising headwater restoration through multi-scale planning approaches and active involvement of local stakeholders to ensure sustainable land-use management. Full article
(This article belongs to the Special Issue Efficient Land Use and Sustainable Development in European Countries)
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20 pages, 2743 KiB  
Article
Extraction of Ficus carica Polysaccharide by Ultrasound-Assisted Deep Eutectic Solvent-Based Three-Phase Partitioning System: Process Optimization, Partial Structure Characterization, and Antioxidant Properties
by Qisen Sun, Zhubin Song, Fanghao Li, Xinyu Zhu, Xinyu Zhang and Hao Chen
Molecules 2025, 30(17), 3469; https://doi.org/10.3390/molecules30173469 - 23 Aug 2025
Abstract
An innovative ultrasound-assisted deep eutectic solvent-based three-phase partitioning (UA-DES-TPP) system was developed for the sustainable extraction of Ficus carica polysaccharide (FCP). Using a hydrophobic DES composed of dodecanoic acid and octanoic acid (1:1 molar ratio), a phase behavior-driven separation mechanism was established. The [...] Read more.
An innovative ultrasound-assisted deep eutectic solvent-based three-phase partitioning (UA-DES-TPP) system was developed for the sustainable extraction of Ficus carica polysaccharide (FCP). Using a hydrophobic DES composed of dodecanoic acid and octanoic acid (1:1 molar ratio), a phase behavior-driven separation mechanism was established. The system was systematically optimized through single-factor experiments and response surface methodology (RSM), achieving a maximum FCP yield of 9.22 ± 0.20% under optimal conditions (liquid–solid ratio 1:24.2 g/mL, top/bottom phase volume ratio 1:1.05 v/v, ammonium sulfate concentration 25.8%). Structural characterization revealed that FCP was a heteropolysaccharide primarily composed of glucose and mannose with α/β-glycosidic linkages and a loose fibrous network. Remarkably, the DESs demonstrated excellent recyclability over five cycles. Furthermore, FCP exhibited significant concentration-dependent antioxidant activities: 82.3 ± 3.8% DPPH radical scavenging at 8 mg/mL, 76.8 ± 0.8% ABTS+ scavenging, and ferric ion reducing power of 45.53 ± 1.07 μmol TE/g. This study provides a new path for the efficient and sustainable extraction of bioactive macromolecules. Full article
(This article belongs to the Special Issue Natural Antioxidants in Functional Food)
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26 pages, 4740 KiB  
Article
Development of a Powered Four-Bar Prosthetic Hip Joint Prototype
by Michael Botros, Hossein Gholizadeh, Farshad Golshan, David Langlois, Natalie Baddour and Edward D. Lemaire
Prosthesis 2025, 7(5), 105; https://doi.org/10.3390/prosthesis7050105 - 22 Aug 2025
Abstract
Background/Objectives: Hip-level amputees face ambulatory challenges due to the lack of a lower limb and prosthetic hip power. Some hip-level amputees restore mobility by using a prosthesis with hip, knee, and ankle joints. Powered prosthetic joints contain an actuator that provides external flexion-extension [...] Read more.
Background/Objectives: Hip-level amputees face ambulatory challenges due to the lack of a lower limb and prosthetic hip power. Some hip-level amputees restore mobility by using a prosthesis with hip, knee, and ankle joints. Powered prosthetic joints contain an actuator that provides external flexion-extension moments to assist with movement. Powered knee and powered ankle-foot units are on the market, but no viable powered hip unit is commercially available. This research details the development of a novel powered four-bar prosthetic hip joint that can be integrated into a full-leg prosthesis. Methods: The hip joint design consisted of a four-bar linkage with a harmonic drive DC motor placed in the inferior link and an additional linkage to transfer torque from the motor to the hip center of rotation. Link lengths were determined through engineering optimization. Device strength was demonstrated with force and finite element analysis and with ISO 15032:2000 A100 static compression tests. Walking tests with a wearable hip-knee-ankle-foot prosthesis simulator, containing the novel powered hip, were conducted with three able-bodied participants. Each participant walked back and forth on a level 10 m walkway. Custom hardware and software captured joint angles. Spatiotemporal parameters were determined from video clips processed in the Kinovea software (ver. 0.9.5). Results: The powered hip passed all force and finite element checks and ISO 15032:2000 A100 static compression tests. The participants, weighing 96 ± 2 kg, achieved steady gait at 0.45 ± 0.11 m/s with the powered hip. Participant kinematic gait profiles resembled those seen in transfemoral amputee gait. Some gait asymmetries occurred between the sound and prosthetic legs. No signs of mechanical failure were seen. Most design requirements were met. Areas for powered hip improvement include hip flexion range, mechanical advantage at high hip flexion, and device mass. Conclusions: The novel powered four-bar hip provides safe level-ground walking with a full-leg prosthesis simulator and is viable for future testing with hip-level amputees. Full article
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30 pages, 12874 KiB  
Article
Reservoir Properties of Lacustrine Deep-Water Gravity Flow Deposits in the Late Triassic–Early Jurassic Anyao Formation, Paleo-Ordos Basin, China
by Zhen He, Minfang Yang, Lei Wang, Lusheng Yin, Peixin Zhang, Kai Zhou, Peter Turner, Zhangxing Chen, Longyi Shao and Jing Lu
Minerals 2025, 15(9), 888; https://doi.org/10.3390/min15090888 - 22 Aug 2025
Abstract
The development of gravity flow sedimentology has improved our understanding of the physical properties of different types of gravity flow deposits, especially the advancement of various gravity flow models. Although studies of gravity flows have developed greatly, the linkage between different sub-facies and [...] Read more.
The development of gravity flow sedimentology has improved our understanding of the physical properties of different types of gravity flow deposits, especially the advancement of various gravity flow models. Although studies of gravity flows have developed greatly, the linkage between different sub-facies and their reservoir properties is hindered by a lack of detailed sedimentary records. Here, integrated test data (including thin-section petrology, high-pressure mercury injection experiments, capillary pressure curve analysis, and scanning electron microscopy) are used to evaluate links between different types of gravity flows and their reservoir properties from the Late Triassic–Early Jurassic Anyao Formation, southeastern Paleo-Ordos Basin, China. The petrological and sedimentological data reveal two types of deep-water gravity flow deposits comprising sandy debris flow (SDF) and turbidity current (TC) deposits. Both are fine-grained lithic sandstones and form low-porosity and ultra-low permeability reservoirs. Secondary porosity, formed by the dissolution of framework grains, including feldspars and lithic fragments, dominates the pore types. This secondary porosity is widely developed in the Anyao Formation and formed by reaction with organic acids during burial (early mesodiagenesis). The associated mud rocks have reached the early mature stage of the oil window with Tmax of 442–448 °C. Compared with the turbidites, the sandy debris flows have higher framework grain content (87.9 vs. 84.8%), framework grain size (0.091 vs. 0.008 mm), porosity (6.97 vs. 3.44%), pore throat radius (0.102 vs. 0.025 μm), and permeability (0.025 vs. 0.005 mD) but are relatively poor in the sorting of framework grains and pore throat radii. The most important petrological factors affecting porosity and permeability of the SDF reservoirs are framework grain size and feldspar grain content, respectively, but those of the TC reservoirs are feldspar grain content and the maximum pore throat radius. Diagenetic dissolution of framework grains is the most important porosity-affecting factor for both SDF and TC reservoirs. Our multi-proxy study provides new insights into the links between gravity flow sub-facies and reservoir properties in the lacustrine deep-water environment. Full article
(This article belongs to the Section Mineral Exploration Methods and Applications)
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25 pages, 7421 KiB  
Article
Analysis of Internal Explosion Vibration Characteristics of Explosion-Proof Equipment in Coal Mines Using Laser Doppler
by Xusheng Xue, Junbiao Qiu, Hongkui Zhang, Wenjuan Yang, Huahao Wan and Fandong Chen
Appl. Sci. 2025, 15(17), 9255; https://doi.org/10.3390/app15179255 - 22 Aug 2025
Abstract
Currently, there is a lack of methods for detecting the mechanism of gas explosion propagation within flameproof enclosures and the dynamic behavior of flameproof enclosures under explosion impact. Therefore, this paper studies a method for detecting the vibration characteristics of coal mine explosion-proof [...] Read more.
Currently, there is a lack of methods for detecting the mechanism of gas explosion propagation within flameproof enclosures and the dynamic behavior of flameproof enclosures under explosion impact. Therefore, this paper studies a method for detecting the vibration characteristics of coal mine explosion-proof equipment under internal gas explosions using laser Doppler. First, a model of gas explosion propagation and explosion transmission response in flameproof enclosures is established to reveal the mechanism of gas explosion transmission inside coal mine flameproof enclosures. Second, a laser Doppler measurement method for coal mine flameproof enclosures is proposed, along with a step-by-step progressive vibration characteristic analysis method. This begins with a single-frequency dimension analysis using the Fourier transform (FFT), extends to time–frequency joint analysis using the short-time Fourier transform (STFT) to incorporate a time scale, and then advances to a three-dimensional linkage of scale, time, and frequency using the wavelet transform (DWT) to solve the limitation of the fixed window length of the STFT, thereby achieving a dynamic characterization of the detonation response characteristics. Finally, a non-symmetric Gaussian impact load inversion model is constructed to validate the overall scheme. The experimental results show that the FFT analysis identified a 2000 Hz main frequency, along with the global frequency components of the flameproof enclosure vibration signal, the STFT analysis revealed the dynamic evolution of the 2000 Hz main frequency and global frequency over time, and the wavelet transform achieved higher accuracy positioning of the frequency amplitude in the time domain, with better time resolution. Finally, the experimental platform showed an error of less than 5% compared with the actual measured impact load, and the error between the inverted impact load and the actual load was less than 15%. The experimental platform is feasible, and the inversion model has good accuracy. The laser Doppler measurement method has significant advantages over traditional coal mine flameproof equipment measurement and analysis methods and can provide further failure analysis and prevention, design optimization, and safety performance evaluation of flameproof enclosures in the future. Full article
(This article belongs to the Special Issue Advanced Blasting Technology for Mining)
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21 pages, 16024 KiB  
Article
The Impact of Built Environment on Urban Vitality—A Multi-Scale Geographically Weighted Regression Analysis in the Case of Shenyang, China
by Xu Lu, Shan Huang, Wuqi Xie and Yuhang Sun
Buildings 2025, 15(17), 2989; https://doi.org/10.3390/buildings15172989 - 22 Aug 2025
Abstract
Urban vitality acts as a key driver of sustainable urban development, while the built environment serves as its physical foundation. However, spatial heterogeneity in urban landscapes leads to imbalanced impacts of economic, social, and environmental factors on vitality. Therefore, it is essential to [...] Read more.
Urban vitality acts as a key driver of sustainable urban development, while the built environment serves as its physical foundation. However, spatial heterogeneity in urban landscapes leads to imbalanced impacts of economic, social, and environmental factors on vitality. Therefore, it is essential to investigate the underlying principles governing vitality impacts imposed by diverse components of the built environment at the spatial level. This study synthesized multi-source remote sensing data alongside geospatial datasets aiming to quantify vitality and built environment indicators across Shenyang, China. We applied Ordinary Least Squares (OLS) regression for collinearity diagnosis and Multi-scale Geographically Weighted Regression (MGWR) to model spatial heterogeneity impacts at the planning-unit level. The regression factor analysis yielded three primary conclusions: (1) Functional Mixture Degree, Bus Stop Density, and Subway Station Density demonstrated a statistically significant positive correlation with urban vitality. (2) FAR (Floor Area Ratio), Vegetation Coverage, Commercial Facility Density, and Road Density exhibited differentiated effects in core areas versus peripheral areas. (3) Public Facility Density and Bus Stop Density showed a negative correlation trend with vitality levels in Industrial Functional Zones. We propose a geospatial analysis framework that leverages remote sensing to decode spatially heterogeneous built environment–vitality linkages. This approach supports precision urban renewal planning by identifying location-specific interventions. Geospatial big data and MGWR offer replicable tools for analyzing urban sustainability. Future work should integrate real-time sensor data to track vitality dynamics. Full article
26 pages, 1430 KiB  
Article
The Impact of Green Finance Policy on Environmental Performance: Evidence from China
by Xiaoling Yu and Kaitian Xiao
Sustainability 2025, 17(17), 7589; https://doi.org/10.3390/su17177589 - 22 Aug 2025
Abstract
We investigate whether and how the policy of establishing green finance pilot zones affects corporate environmental performance in China, by employing the DID model and taking 2324 Chinese A-share listed companies as the empirical sample. The main findings show that the green finance [...] Read more.
We investigate whether and how the policy of establishing green finance pilot zones affects corporate environmental performance in China, by employing the DID model and taking 2324 Chinese A-share listed companies as the empirical sample. The main findings show that the green finance policy can significantly improve corporate environmental performance in the green finance pilot zones. The policy effect varies according to enterprise ownership, sector, and degree of environmental supervision. In particular, compared with private enterprises and enterprises subject to key pollution monitoring, the environmental performance of state-owned firms and non-key pollution-monitored firms is more positively affected by the green finance policy. Through a mechanism analysis, we find that corporate innovation and financial constraints can play partially mediating roles in the linkage of green finance policy and corporate environmental performance. Among them, the mediating effects of green innovation and financial constraints are more prominent in private enterprises and key pollution-monitored enterprises. However, although the green finance policy can positively influence bank loans obtained by enterprises, there is no evidence to suggest that bank credit plays a significant mediating role between the green finance policy and corporate environmental performance. Our findings are helpful for understanding the effect of green finance policy on environmental sustainability and could provide some references for policymakers. In particular, we suggest that private and key pollution-monitored enterprises should actively respond to the green finance policy, broaden financing channels, and enhance capability of green innovation, thereby improving their environmental performance. Full article
13 pages, 696 KiB  
Article
A Lack of Complete Linkage Disequilibrium Between c.1236G>A and c.1129-5923C>G HapB3 Variants of DPYD: A Call to Revise European Pharmacogenetic Guidelines
by Almudena Gil-Rodriguez, Sheila Recarey-Rama, Ana Fernández Montes, Ana Rodríguez-Viyuela, Francisco Barros, Angel Carracedo and Olalla Maroñas
Int. J. Mol. Sci. 2025, 26(17), 8136; https://doi.org/10.3390/ijms26178136 - 22 Aug 2025
Viewed by 40
Abstract
Fluoropyrimidine derivatives can cause severe toxicity in patients with DPD deficiency. Regulatory agencies, such as the European Medicines Agency (EMA), recommend pre-emptive genotyping of the HapB3 haplotype, along with other variants. Historically, the two main HapB3 variants, the benign c.1236G>A and the pathogenic [...] Read more.
Fluoropyrimidine derivatives can cause severe toxicity in patients with DPD deficiency. Regulatory agencies, such as the European Medicines Agency (EMA), recommend pre-emptive genotyping of the HapB3 haplotype, along with other variants. Historically, the two main HapB3 variants, the benign c.1236G>A and the pathogenic c.1129-5923C>G, have been assumed to be in complete linkage disequilibrium. Recent findings contradict this assumption, questioning the reliability of the HapB3 analysis through c.1236G>A, which could directly impact patient safety. The aim of this study is to assess the linkage disequilibrium between the c.1236G>A and c.1129-5923C>G variants, with the ultimate goal of revising genotyping guidelines. A total of 46 patients already heterozygous for the c.1236G>A variant have been carefully reviewed for the c.1129-5923C>G variant. From the 46 patients analyzed, 45 maintain complete linkage disequilibrium between both variants. However, there is one patient where this linkage disequilibrium is not complete, being heterozygous for c.1236G>A and homozygous for c.1129-5923C>G. These findings challenge the validity of c.1236G>A as a surrogate marker for pathogenic variant c.1129-5923C>G. This article highlights the need for a review of the recommendations of the EMA and suggests laboratories to analyze both variants, or at least the pathogenic one, to ensure accurate therapeutic decisions. Full article
(This article belongs to the Special Issue Recent Advances in New Biomarkers for Cancers)
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14 pages, 1991 KiB  
Article
Construction of a Bin Genetic Map and QTL Mapping of Red Skin in Interspecific Pear Population
by Xiaojie Zhang, Mengyue Tang, Jianying Peng, Hui Ma and Yuxing Zhang
Horticulturae 2025, 11(8), 994; https://doi.org/10.3390/horticulturae11080994 - 21 Aug 2025
Viewed by 72
Abstract
Red epicarp in pears is an important trait for breeding. Exploring the genes regulating pear anthocyanin synthesis and developing molecular markers associated with these traits are important for obtaining new varieties of red pears. We performed whole-genome resequencing (WGS) on 127 ‘Yuluxiang ( [...] Read more.
Red epicarp in pears is an important trait for breeding. Exploring the genes regulating pear anthocyanin synthesis and developing molecular markers associated with these traits are important for obtaining new varieties of red pears. We performed whole-genome resequencing (WGS) on 127 ‘Yuluxiang (Pyrus bretschneideri)’ × ‘Xianghongli (Pyrus communis)’ F1 populations and identified a total of 510,179 single-nucleotide polymorphism (SNP) sites in the population. In total, 1972 bins were screened to form a high-density genetic map with a total map length of 815.507 cM, covering 17 linkage groups with an average genetic distance of 0.414 cM between markers. Three red skin quantitative trait loci (QTLs), located on LG4 and LG5, that explained 18.7% of the phenotypic variance, were detected. The QTL intervals contained 1658 genes, including 94 transcription factors (TF), subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Four key candidate genes (Pspp.Chr05.01969, Pspp.Chr05.01908, Pspp.Chr05.02419, and Pspp.Chr04.01087) that may play a role in promoting pear anthocyanin synthesis were screened and identified by a quantitative polymerase chain reaction (qPCR). Overall, our study deepens our understanding of the genetics of red peel traits in pears and accelerates pear breeding. Full article
(This article belongs to the Special Issue Color Formation and Regulation in Horticultural Plants)
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23 pages, 13081 KiB  
Article
Structural Characterization of a Novel Pectin Polysaccharide from Mango (Mangifera indica L.) Peel and Its Regulatory Effects on the Gut Microbiota in High-Fat Diet-Induced Obese Mice
by Ruyan Fan, Wenting Zhang, Lang Wang, Tao Fei, Jianbo Xiao and Lu Wang
Foods 2025, 14(16), 2910; https://doi.org/10.3390/foods14162910 - 21 Aug 2025
Viewed by 192
Abstract
The gut microbiota plays a significant role in metabolic diseases such as obesity. We extracted and purified a new type of pectin polysaccharide (mango peel pectin, MPP) from mango (Mangifera indica L.) peel. The structural analysis results reveal that MPP has a [...] Read more.
The gut microbiota plays a significant role in metabolic diseases such as obesity. We extracted and purified a new type of pectin polysaccharide (mango peel pectin, MPP) from mango (Mangifera indica L.) peel. The structural analysis results reveal that MPP has a molecular weight (Mw) of 6.76 × 105 Da and the mass fractions of the main components were galacturonic acid (21.36%), glucose (8.85%), and arabinose (5.97%). The results of methylation and NMR analyses reveal that the backbone of MPP consisted of →6)-α-D-GalpAOMe-(1→ and →4)-β-D-Glcp-(1→ linkages. Based on the above structural analysis, we further explored the therapeutic effect of MPP on high-fat diet-induced obese mice. The results demonstrate that MPP significantly suppressed body weight and dyslipidemia, reduced liver damage and lipid accumulation, attenuated changes in adipocyte hypertrophy, and improved glucose homeostasis and insulin resistance, with fasting blood glucose (FBG) levels decreasing by more than 12.8%. Furthermore, the modulatory impact of MPP on gut microbiota composition was investigated. MPP treatment significantly enhanced the levels of short-chain fatty acids (SCFAs) by decreasing the amount of Bacillota and reducing the Bacillota/Bacteroidota ratio, especially with an increase in the total SCFA content of over 64%. Meanwhile, MPP treatment encouraged beneficial bacteria to grow (e.g., Bacteroidota, Akkermansia, and Nanasyncoccus), altered the gut microbiome profiles in mice, and decreased the abundance of harmful bacteria (e.g., Paralachnospira, Coproplasma, Pseudoflavonifractor, Parabacteroides, Acetatifactor, and Phocaeicola). Overall, the findings demonstrate for the first time that MPP treats obesity by alleviating dyslipidemia, improving insulin resistance, and regulating gut microbiota to improve the intestinal environment. Full article
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Article
Dietary Fiber Intake Was Inversely Associated with All-Cause Mortality but Not with Cancer and Cardiovascular Disease Mortalities in the US
by Zoha Akbar, Sundus Fituri, Zumin Shi and Vijay Ganji
Diseases 2025, 13(8), 272; https://doi.org/10.3390/diseases13080272 - 21 Aug 2025
Viewed by 164
Abstract
Background: Evidence linking dietary fiber intake with cancer risk and mortality is equivocal. Objective: We investigated the relationship between dietary fiber intake and all-cause, cancer, and cardiovascular disease (CVD) mortalities in US adults ≥ 20 years. Methods: Data from the National Health and [...] Read more.
Background: Evidence linking dietary fiber intake with cancer risk and mortality is equivocal. Objective: We investigated the relationship between dietary fiber intake and all-cause, cancer, and cardiovascular disease (CVD) mortalities in US adults ≥ 20 years. Methods: Data from the National Health and Nutrition Examination Surveys (NHANES) from 2003 to 2016 were used. Seven two-year cycles were concatenated into one analytic data file, NHANES 2003–2016 (n = 25,868; age ≥ 20 years). Dietary fiber intakes were collected from one 24-h dietary recall. Fiber intakes were categorized into quartiles. Mortality information was obtained from data linkage. To determine mortality, subjects were followed up for 6.4 years. Association between dietary fiber and mortality from all causes, cancer, and CVD was determined with multivariable-adjusted Cox proportional hazards models. Multivariate-adjusted Cox proportional hazard regression was used to generate mortality survival rates. Results: During the follow-up period, out of 2520 deaths, 561 and 511 deaths were from cancer and CVD, respectively. Dietary fiber intake was inversely associated with all-cause mortality [RR (95% CI), 0.67 (0.56–0.80); p ≤ 0.001]. No relationship was observed between fiber intake and cancer mortality [RR (95% CI), 0.8 (0.55–1.17); p = 0.51] and CVD mortality [RR (95% CI), 0.84 (0.53–1.33); p = 0.67]. Conclusions: In the US population, dietary fiber intake was associated with decreased all-cause mortality, but not with cancer and CVD mortality. Full article
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