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Search Results (3,305)

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12 pages, 2095 KiB  
Article
Exploring the Role of Guilt in Eating Disorders: A Pilot Study
by Fabiola Raffone, Danilo Atripaldi, Eugenia Barone, Luigi Marone, Marco Carfagno, Francesco Mancini, Angelo Maria Saliani and Vassilis Martiadis
Clin. Pract. 2025, 15(3), 56; https://doi.org/10.3390/clinpract15030056 - 10 Mar 2025
Abstract
Background/Objectives: Eating disorders (EDs) are complex psychopathological conditions involving dysfunctional eating behaviors, excessive body image concerns, and impaired emotional regulation. Among moral emotions, guilt plays a significant role in ED dynamics, influencing both symptomatology and interpersonal relationships. This study examines specific guilt subtypes [...] Read more.
Background/Objectives: Eating disorders (EDs) are complex psychopathological conditions involving dysfunctional eating behaviors, excessive body image concerns, and impaired emotional regulation. Among moral emotions, guilt plays a significant role in ED dynamics, influencing both symptomatology and interpersonal relationships. This study examines specific guilt subtypes (normative and altruistic guilt) using a specific psychometric tool. Methods: Forty-three adults with anorexia nervosa (AN), bulimia nervosa (BN), or binge eating disorder (BED) were recruited from the Eating Disorder Center of the University of Campania “Luigi Vanvitelli” or referred by psychotherapists. Diagnoses followed DSM-5 criteria. Participants completed the Moral Orientation Guilt Scale (MOGS), assessing guilt subtypes, and the Eating Disorder Inventory-2 (EDI-2), measuring ED symptomatology. Spearman’s rank correlation and stepwise multiple regression analyses were used to identify relationships between guilt dimensions and ED-related symptoms. Results: MOGS subscales were positively correlated with ED symptomatology. Normative guilt was significantly associated with binging and purging (ρ = 0.26, p < 0.05), while altruistic guilt predicted higher interpersonal distrust (t = 3.4, p < 0.01). Regression analysis revealed that age negatively influenced interpersonal distrust (t = −2.9, p < 0.01). Conclusions: In the population examined, guilt significantly influences ED symptomatology and interpersonal functioning, with specific dimensions linked to distinct behaviors and traits. Therapeutic interventions targeting guilt may enhance treatment outcomes by addressing ED emotional underpinnings. However, the results should be interpreted with caution due to the small sample size and lack of longitudinal data to establish causality. Further research with larger samples and longitudinal designs is necessary to validate these findings. Full article
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<p>Correlation matrix (Spearman’s ρ—heatmap) between MOGS subscales and diagnosis. MNV, Moral Norm Violation factor; MODI, Moral Orientation Dirtiness factor; EMPATHY, Empathy factor; HARM, Harm factor; * <span class="html-italic">p</span> = 0.05; ** <span class="html-italic">p</span> = 0.01; *** <span class="html-italic">p</span> = 0.001; darker represent stronger correlation.</p>
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<p>Correlation matrix (Spearman’s ρ—heatmap) between MOGS subscales and EDI-2 symptoms scales. MNV, Moral Norm Violation factor; MODI, Moral Orientation Dirtiness factor; EMPATHY, Empathy factor; HARM, Harm factor; EDI_DFT, Drive for Thinness subscale; EDI_B, Bulimia subscale; EDI_BD, Body Dissatisfaction subscale; * <span class="html-italic">p</span> = 0.05; ** <span class="html-italic">p</span> = 0.01; *** <span class="html-italic">p</span> = 0.001; darker represent stronger correlation.</p>
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<p>Correlational matrix (Spearman’s ρ—heatmap) between MOGS subscales and EDI-2 psychological features subscales. MNV, Moral Norm Violation factor; MODI, Moral Orientation Dirtiness factor; EMPATHY, Empathy factor; HARM, Harm factor; EDI_IN, Ineffectiveness subscale; EDI_MF, Maturity Fears subscale; EDI_SI, Social Insecurity subscale; EDI_ID, Interpersonal Distrust subscale; EDI_IR, Impulse Regulation subscale; EDI_IA, Interoceptive Awareness subscale; EDI_P, Perfectionism subscale; EDI_A, Ascetism subscale; * <span class="html-italic">p</span> = 0.05; ** <span class="html-italic">p</span> = 0.01; *** <span class="html-italic">p</span> = 0.001; darker represent stronger correlation.</p>
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<p>Marginal effect of HARM on EDI_ID (<b>left</b>); marginal effect of age on EDI_ID (<b>right</b>). EDI_ID, Interpersonal Distrust subscale.</p>
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18 pages, 2959 KiB  
Article
Risk Analysis of Service Slope Hazards for Highways in the Mountains Based on ISM-BN
by Haojun Liu, Xudong Zha and Yang Yin
Appl. Sci. 2025, 15(6), 2975; https://doi.org/10.3390/app15062975 - 10 Mar 2025
Viewed by 36
Abstract
To effectively mitigate service slope disaster risks in mountainous areas and enhance the overall safety of highway operations, based on the geological and structural characteristics of slopes, considering slope technical conditions, overall stability, and potential disaster consequences, 25 important influencing factors are systematically [...] Read more.
To effectively mitigate service slope disaster risks in mountainous areas and enhance the overall safety of highway operations, based on the geological and structural characteristics of slopes, considering slope technical conditions, overall stability, and potential disaster consequences, 25 important influencing factors are systematically identified. The identification process integrates insights from the relevant literature, expert opinions, and historical disaster maintenance records of such slopes. An integrated approach combining Interpretive Structural Modeling (ISM) and Bayesian Networks (BNs) is utilized to conduct a quantitative analysis of the interrelationships and impact strength of factors influencing the disaster risk of mountainous service highway slopes. The aim is to reveal the causal mechanism of slope disaster risk and provide a scientific basis for risk assessment and prevention strategies. Firstly, the relationship matrix is constructed based on the relevant prior knowledge. Then, the reachability matrix is computed and partitioned into different levels to form a directed graph from which the Bayesian network structure is constructed. Subsequently, the expert’s subjective judgment is further transformed into a set of prior and conditional probabilities embedded in the BN to perform causal inference to predict the probability of risk occurrence. Real-time diagnosis of disaster risk triggers operating slopes using backward reasoning, sensitivity analysis, and strength of influence analysis capabilities. As an example, the earth excavation slope in the mountainous area of Anhui Province is analyzed using the established model. The results showed that the constructed slope failure risk model for mountainous operating highways has good applicability, and the possibility of medium slope failure risk is high with a probability of 34%, where engineering geological conditions, micro-topographic landforms, and the lowest monthly average temperature are the main influencing factors of slope hazard risk for them. The study not only helps deepen the understanding of the evolutionary mechanisms of slope disaster risk but also provides theoretical support and practical guidance for the safe operation and disaster prevention of mountainous highways. The model offers clear risk information, serving as a scientific basis for managing service slope disaster risks. Consequently, it effectively reduces the likelihood of slope disasters and enhances the safety of highway operation. Full article
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<p>The proposed methodology flowchart.</p>
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<p>Fishbone diagram for disaster risk analysis of service soil cut slopes.</p>
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<p>The directed graph based on ISM.</p>
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<p>Bayesian network (BN) for service slope disaster risk.</p>
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<p>Results of BN backward inference, sensitivity analysis, and optimal causal chain analysis.</p>
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<p>BN reasoning for disaster risk on service soil cut slope K466 + 000.</p>
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19 pages, 3261 KiB  
Article
Risk Assessment of Hydrogen Fuel System Leakage in Ships Based on Noisy-OR Gate Model Bayesian Network
by Gen Li, Haidong Zhang, Shibo Li and Chunchang Zhang
J. Mar. Sci. Eng. 2025, 13(3), 523; https://doi.org/10.3390/jmse13030523 - 9 Mar 2025
Viewed by 234
Abstract
To mitigate the risk of hydrogen leakage in ship fuel systems powered by internal combustion engines, a Bayesian network model was developed to evaluate the risk of hydrogen fuel leakage. In conjunction with the Bow-tie model, fuzzy set theory, and the Noisy-OR Gate [...] Read more.
To mitigate the risk of hydrogen leakage in ship fuel systems powered by internal combustion engines, a Bayesian network model was developed to evaluate the risk of hydrogen fuel leakage. In conjunction with the Bow-tie model, fuzzy set theory, and the Noisy-OR Gate model, an in-depth analysis was also conducted to examine both the causal factors and potential consequences of such incidents. The Bayesian network model estimates the likelihood of hydrogen leakage at approximately 4.73 × 10−4 and identifies key risk factors contributing to such events, including improper maintenance procedures, inadequate operational protocols, and insufficient operator training. The Bow-tie model is employed to visualize the causal relationships between risk factors and their potential consequences, providing a clear structure for understanding the events leading to hydrogen leakage. Fuzzy set theory is used to address the uncertainties in expert judgments regarding system parameters, enhancing the robustness of the risk analysis. To mitigate the subjectivity inherent in root node probabilities and conditional probability tables, the Noisy-OR Gate model is introduced, simplifying the determination of conditional probabilities and improving the accuracy of the evaluation. The probabilities of flash or pool fires, jet fires, and vapor cloud explosions following a leakage are calculated as 4.84 × 10−5, 5.15 × 10−5, and 4.89 × 10−7, respectively. These findings highlight the importance of strengthening operator training and enforcing stringent maintenance protocols to mitigate the risks of hydrogen leakage. The model provides a valuable framework for safety evaluation and leakage risk management in hydrogen-powered ship fuel systems. Full article
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<p>The risk assessment framework for hydrogen leakage.</p>
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<p>Diagram of a simple BN.</p>
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<p>Diagram of a simple BN schematic of diesel–hydrogen dual-fuel engine setup.</p>
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<p>Bow-tie model of hydrogen leak accident.</p>
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<p>The “AND” and “OR” gate in fault tree and Bayesian network representation.</p>
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<p>BN model for evaluating leakage risk in hydrogen-powered ship fuel systems using GeNle.</p>
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<p>Posterior probability update of the model.</p>
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<p>Comparison of prior and posterior probabilities of basic events.</p>
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19 pages, 6309 KiB  
Article
Coupled Resonance Fiber-Optic SPR Sensor Based on TRIZ
by Cuilan Zhu, Haodi Zhai, Yonghao Wang, Xiangru Suo, Tianyu Zhu and Shuowei Jin
Photonics 2025, 12(3), 244; https://doi.org/10.3390/photonics12030244 - 9 Mar 2025
Viewed by 81
Abstract
This paper aims to enhance the sensitivity of fiber-optic surface plasmon resonance (SPR) sensors by innovatively applying TRIZ (Theory of Inventive Problem Solving). To identify the key challenges faced by current SPR sensors, methods such as functional analysis, causal analysis, and the Nine-Window [...] Read more.
This paper aims to enhance the sensitivity of fiber-optic surface plasmon resonance (SPR) sensors by innovatively applying TRIZ (Theory of Inventive Problem Solving). To identify the key challenges faced by current SPR sensors, methods such as functional analysis, causal analysis, and the Nine-Window method are employed. Utilizing TRIZ tools, including Technical Contradiction, Physical Contradiction, the Smart Little Man method, and object–field analysis, innovative solutions are proposed, involving transparent indium tin oxide (ITO) thin films, an asymmetric photonic crystal fiber structure with elliptical pores, and titanium dioxide (TiO2) thin films. Experimental results reveal a significant improvement in sensitivity, with an average of 9961.90 nm/RIU and a peak of 12,503.56 nm/RIU within the refractive index range of 1.33061 to 1.40008, representing a 456% increase compared to the original gold-film fiber-optic SPR sensor. These findings have potential applications in biosensing, environmental monitoring, and food safety. Full article
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<p>Schematic diagram of fiber-optic sensing system.</p>
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<p>A graphical representation of the functional analysis of the engineering system.</p>
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<p>Causal analysis diagram, blue represents the problem found, and red represents the root cause of the problem.</p>
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<p>Nine-Window analysis diagram.</p>
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<p>Photonic crystal fiber with eight air holes.</p>
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<p>In the initial state, the blue little man (mode field) is confined within the red little man’s air holes.</p>
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<p>An increase in the effective mode field area after changing the shape of the air holes.</p>
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<p>(<b>a</b>) A model of the photonic crystal fiber SPR sensor with an elliptical air hole structure. (<b>b</b>) Mode field variation in the photonic crystal fiber SPR sensor with an elliptical air hole structure.</p>
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<p>Object–field analysis.</p>
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<p>(<b>a</b>) Schematic diagram of titanium dioxide network structure. (<b>b</b>) Fiber-optic sensor model after addition of titanium dioxide. (<b>c</b>) Electric field distribution of sensor after addition of titanium dioxide.</p>
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<p>(<b>a</b>) Optical fiber sensor model diagram. (<b>b</b>) Optical fiber sensor structural parameters. (<b>c</b>) Optical fiber sensor mesh diagram.</p>
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<p>Sensor preparation process.</p>
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<p>Schematic diagram of refractive index testing experiment.</p>
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<p>(<b>a</b>) Fiber core loss curve for different test liquid concentrations obtained through simulation. (<b>b</b>) Polynomial fitting curve between different test liquid concentrations and wavelength obtained through simulation. (<b>c</b>) Refractive index curve for different test liquid concentrations obtained through experiments. (<b>d</b>) Linear fitting curve between different test liquid concentrations and simulated wavelength obtained through experiments.</p>
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<p>The wavelength shift in the SPR sensor induced by different solvents at the same concentration.</p>
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25 pages, 1558 KiB  
Article
Configurational Pathways for Fintech-Empowered Sustainable Innovation in SRDIEs Under Financing Constraints
by Fang Ji, Junlin Wu and Yiran Li
Sustainability 2025, 17(6), 2397; https://doi.org/10.3390/su17062397 - 9 Mar 2025
Viewed by 181
Abstract
The high-quality development of specialized, refined, distinctive, and innovative enterprises (SRDIEs) is essential for advancing an innovation-driven strategy. This paper investigates the impact of financial technology (Fintech) on sustainable innovation within SRDIEs that face financing challenges, analyzing it from supply-side, demand-side, and environmental [...] Read more.
The high-quality development of specialized, refined, distinctive, and innovative enterprises (SRDIEs) is essential for advancing an innovation-driven strategy. This paper investigates the impact of financial technology (Fintech) on sustainable innovation within SRDIEs that face financing challenges, analyzing it from supply-side, demand-side, and environmental perspectives. We utilize fuzzy-set Qualitative Comparative Analysis (fSQCA) and Necessary Condition Analysis (NCA) to explore the configurational paths and complex causal effects of Fintech in facilitating the innovation of SRDIEs amid financing challenges. By employing a combination of NCA and fsQCA, this study identifies several effective pathways through which Fintech enhances the innovation efficiency of SRDIEs. We develop an integrative model to enhance innovation inputs, outputs, and sustainability. The key findings include the following: (1) Fintech significantly enhances innovation output, supported by business efficiency and digital intelligence; (2) two distinct pathways for achieving high-innovation inputs are identified, driven by Fintech intensity and effective credit allocation, with specialization and financial mismatches serving as auxiliary factors; (3) the core conditions of Fintech intensity and the financing environment, along with competitive banking, promote innovation motivation and sustainability in highly specialized enterprises. The conclusions of this study provide both theoretical and practical insights for SRDIEs to tackle innovation challenges characterized by an “inability to innovate”, a “lack of willingness to innovate”, and “ineffectiveness in innovation”, enabling their transition from merely being “able to innovate” and “daring to innovate” to becoming “proficient in sustainable innovation”. These findings offer differentiated sustainable innovation solutions for enterprises through three avenues: capacity building on the demand side, channel optimization on the supply side, and ecological cultivation on the environmental side. Full article
(This article belongs to the Special Issue Advances in Economic Development and Business Management)
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<p>Research framework.</p>
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<p>Knowledge map of co-occurring keywords in Fintech research.</p>
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<p>Theoretical framework of Fintech-driven innovation pathways for SRDIEs.</p>
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38 pages, 3722 KiB  
Article
Multi-Ancestry Transcriptome-Wide Association Studies of Cognitive Function, White Matter Hyperintensity, and Alzheimer’s Disease
by Dima L. Chaar, Zheng Li, Lulu Shang, Scott M. Ratliff, Thomas H. Mosley, Sharon L. R. Kardia, Wei Zhao, Xiang Zhou and Jennifer A. Smith
Int. J. Mol. Sci. 2025, 26(6), 2443; https://doi.org/10.3390/ijms26062443 - 9 Mar 2025
Viewed by 124
Abstract
Genetic variants increase the risk of neurocognitive disorders in later life, including vascular dementia (VaD) and Alzheimer’s disease (AD), but the precise relationships between genetic risk factors and underlying disease etiologies are not well understood. Transcriptome-wide association studies (TWASs) can be leveraged to [...] Read more.
Genetic variants increase the risk of neurocognitive disorders in later life, including vascular dementia (VaD) and Alzheimer’s disease (AD), but the precise relationships between genetic risk factors and underlying disease etiologies are not well understood. Transcriptome-wide association studies (TWASs) can be leveraged to better characterize the genes and biological pathways underlying genetic influences on disease. To date, almost all existing TWASs on VaD and AD have been conducted using expression studies from individuals of a single genetic ancestry, primarily European. Using the joint likelihood-based inference framework in Multi-ancEstry TRanscriptOme-wide analysis (METRO), we leveraged gene expression data from European ancestry (EA) and African ancestry (AA) samples to identify genes associated with general cognitive function, white matter hyperintensity (WMH), and AD. Regions were fine-mapped using Fine-mapping Of CaUsal gene Sets (FOCUS). We identified 266, 23, 69, and 2 genes associated with general cognitive function, WMH, AD (using EA GWAS summary statistics), and AD (using AA GWAS), respectively (Bonferroni-corrected alpha = p < 2.9 × 10−6), some of which had been previously identified. Enrichment analysis showed that many of the identified genes were in pathways related to innate immunity, vascular dysfunction, and neuroinflammation. Further, the downregulation of ICA1L was associated with a higher WMH and with AD, indicating its potential contribution to overlapping AD and VaD neuropathology. To our knowledge, our study is the first TWAS on cognitive function and neurocognitive disorders that used expression mapping studies for multiple ancestries. This work may expand the benefits of TWASs beyond a single ancestry group and help to identify gene targets for pharmaceuticals or preventative treatments for dementia. Full article
(This article belongs to the Special Issue The Role of Genetics in Dementia)
22 pages, 4778 KiB  
Article
Multi-Omics Analysis of the Anoikis Gene CASP8 in Prostate Cancer and Biochemical Recurrence (BCR)
by Shan Huang and Hang Yin
Biomedicines 2025, 13(3), 661; https://doi.org/10.3390/biomedicines13030661 - 7 Mar 2025
Viewed by 162
Abstract
Background: Prostate cancer, as an androgen-dependent malignant tumor in older men, has attracted the attention of a wide range of clinicians. BCR remains a significant challenge following early prostate cancer treatment. Methods: The specific expression pattern of the Anoikis gene set in prostate [...] Read more.
Background: Prostate cancer, as an androgen-dependent malignant tumor in older men, has attracted the attention of a wide range of clinicians. BCR remains a significant challenge following early prostate cancer treatment. Methods: The specific expression pattern of the Anoikis gene set in prostate cancer cells was first explored by single-cell and spatial transcriptomics analysis. Genes causally associated with prostate cancer were screened using Summary-data-based Mendelian Randomization (SMR). Subsequently, we explored the role and mechanism of CASP8 in prostate cancer cells and defined a new cell type: the CASP8 T cell. We constructed a prediction model that can better predict the BCR of prostate cancer, and explored the differences in various aspects of clinical subgroups, tumor microenvironments, immune checkpoints, drug sensitivities, and tumor-immune circulations between high- and low-risk groups. The results of SMR analysis indicated that CASP8 could increase the risk of prostate cancer. Based on the differential genes of CASP8-positive and -negative T cells, we constructed a four-gene prognostic model with a 5-year AUC of 0.713. Results: The results revealed that high-risk prostate cancer BCR patients had various characteristics such as higher tumor purity, higher BCR rate, downregulated SIRPA immune checkpoints, and unique drug sensitivity. Conclusions: In summary, CASP8 may be a potential biomarker for prostate cancer. Full article
(This article belongs to the Section Cancer Biology and Oncology)
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<p>Single-cell and spatial transcriptome analyses of the Anoikis gene set in prostate cancer. (<b>A</b>) demonstrates the strength of cellular communication between the seven cell types. Colors from blue to red indicate a gradual increase in intensity. (<b>B</b>) demonstrates ligand–receptor interactions between AnoikishighT and monocytes. Darker to lighter colors and smaller to larger circles indicate a gradual increase in the strength of the interaction; circles with a border indicate a significant interaction and vice versa. (<b>C</b>) shows the UMAP downscaled images of the eight cell clusters. (<b>D</b>) shows the downscaled density map of the Anoikis gene set in T cells. The color from blue to yellow indicates a gradual increase in density. (<b>E</b>) illustrates the reverse chronological analysis of the Anoikis gene set in T cells. The position of the box represents the developmental starting point, and the arrow points to the developmental end point. In (<b>F</b>), (a)–(g) are the spatial expression characteristics of AnoikishighT, AnoikislowT, monocytes, endothelial cells, epithelial cells, NK cells, and smooth muscle cells, respectively. The homotypic cell network of AnoikishighT is shown in (<b>G</b>) (a). The degree from 0 to 6 indicates that the central cell is surrounded by a gradually increasing number of cells of the same type. (<b>G</b>) (b) shows the interactions region of the heterotypic cell network. (<b>G</b>) (c) is an enrichment scoring image of the interaction between AnoikishighT and monocytes. Darker colors represent stronger interactions. (<b>H</b>) demonstrates the degree of influence of spatial environment on different cell types (R2 benefit). (<b>I</b>) represents the proportion of predicted contribution of different spatial scales to cell types. Green indicates a spatial scale with radius 0; yellow indicates a spatial scale with radius 5; and blue indicates a spatial scale with radius 15. (<b>J</b>) demonstrates the co-expression analysis between cell subpopulations at different spatial scales. (a)–(c) show the analysis of different cell subpopulations at spatial scales of 0, 5, and 15, respectively. The figures shown in the left column are interaction heatmaps of cells at different spatial scales. The color gradient represents the strength of these interactions, with darker colors indicating stronger inter-actions. The images in the right column are community plots at different spatial scales. Each community represents a group of cells that are tightly distributed in space, and these cells may share functional similarities or collaborate in biological processes.</p>
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<p>SMR analysis and single-cell analysis of <span class="html-italic">CASP8</span> in the prostate. (<b>A</b>) is a gene–trait association loci map from SMR analysis: images of association loci with prostate cancer for all genes within the same locus as <span class="html-italic">CASP8</span>. (<b>B</b>) shows the difference in expression levels of <span class="html-italic">CASP8</span> in tumor and normal tissues. Blue indicates tumor tissue and yellow indicates normal tissue. **** <span class="html-italic">p</span> &lt; 0.0001. (<b>C</b>) demonstrates the expression difference of <span class="html-italic">CASP8</span> in different cells of tumor and normal tissues. Green represents epithelial cells; yellow represents T cells; orange represents endothelial cells. (<b>D</b>) shows the ratio of high and low <span class="html-italic">CASP8</span> expression in T cells within tumors and normal tissues. White indicates high <span class="html-italic">CASP8</span> expression, and pink indicates low <span class="html-italic">CASP8</span> expression. (<b>E</b>) demonstrates the HALLMARK pathway enrichment differences between high- and low-<span class="html-italic">CASP8</span>-expression groups in T cells. Blue in Cluster indicates the high expression of <span class="html-italic">CASP8</span>; red indicates the low expression of <span class="html-italic">CASP8</span>. Blue in Direction indicates downregulation and red indicates upregulation. * <span class="html-italic">p</span> &lt; 0.05; ** <span class="html-italic">p</span> &lt; 0.01; *** <span class="html-italic">p</span> &lt; 0.001; **** <span class="html-italic">p</span> &lt; 0.0001. No color in RRA indicates nonsignificant results; red indicates significant results.</p>
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<p>Single-cell and spatial transcriptome analysis of <span class="html-italic">CASP8</span> in prostate cancer. (<b>A</b>) shows the expression levels of <span class="html-italic">CASP8</span> in different cell types. The size of the circle represents the size of the expression ratio; the darker the blue color, the higher the expression level. (<b>B</b>) shows the intensity of cellular communication between the seven cell types. The blue to red color indicates a gradual increase in intensity. (<b>C</b>) shows the ligand–receptor interaction between <span class="html-italic">CASP8</span>+T and monocytes. Darker to lighter colors and smaller to larger circles indicate a gradual increase in the strength of the interaction; a bordered circle indicates a significant interaction and vice versa. (<b>D</b>) shows a downscaled density plot of <span class="html-italic">CASP8</span> in T cells. The blue to yellow color indicates a gradual increase in density. (<b>E</b>) shows the reverse chronological analysis of <span class="html-italic">CASP8</span> in T cells. The position of the box represents the developmental starting point and the arrow points to the developmental end point. The spatial expression characteristics of <span class="html-italic">CASP8</span>-T, <span class="html-italic">CASP8</span>+T, monocytes, endothelial cells, epithelial cells, NK cells, and smooth muscle cells are shown in (<b>F</b>) (a)–(g), respectively. The transition from blue to red indicates a gradual increase in the expression of the cell type in that spatial region. (<b>G</b>) shows the correlation analysis between different cell types. Blue color indicates low correlation and orange color indicates high correlation. (<b>H</b>) shows the degree of influence of spatial environment on different cell types (R2 benefit). (<b>I</b>) indicates the proportion of predicted contribution of different spatial scales to cell types. Green indicates a spatial scale of radius 0; yellow indicates a spatial scale of radius 5; and blue indicates a spatial scale of radius 15. (<b>J</b>) shows the co-expression analysis between cell subpopulations at different spatial scales. (a)–(c) show the analysis of different cell subpopulations at spatial scales of 0, 5, and 15, respectively. The figures shown in the left column are interaction heatmaps of cells at different spatial scales. The color gradient represents the strength of these interactions, with darker colors indicating stronger inter-actions. The images in the right column are community plots at different spatial scales. Each community represents a group of cells that are tightly distributed in space, and these cells may share functional similarities or collaborate in biological processes. (<b>K</b>) (a) shows the homotypic cell network of <span class="html-italic">CASP8</span>+T cells. From 0 to 6 indicates that the central cell is surrounded by progressively more homotypic cells. (<b>K</b>) (b) shows the interaction region of the heterotypic cell network between <span class="html-italic">CASP8</span>+T cells and monocytes. (<b>K</b>) (c) is an image of the enrichment score of <span class="html-italic">CASP8</span>+T cells interacting with monocytes. Darker colors represent stronger interactions.</p>
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<p>Construction of a BCR prognostic model for prostate cancer. (<b>A</b>) shows a schematic of the results of the one-way Cox regression analysis. (<b>B</b>,<b>C</b>) are lasso regressions for feature selection. (<b>D</b>) shows the survival analysis of the training set, test set, and full sample; risk score curve and scatter plot; and time-based ROC curve. (<b>E</b>) is the nomogram of 3-, 4-, and 5-year BCR probabilities used for prediction. (<b>F</b>) is the calibration curve for the nomogram. The diagonal line represents the perfect prediction of the ideal model. The colored solid line represents the agreement between the nomogram-predicted BCR probability and the actual probability for a given follow-up period. (<b>G</b>) shows the decision curve analysis of nomogram, risk score, and each clinical indicator. (<b>H</b>) shows the immunohistochemical results of <span class="html-italic">CASP8</span> and core genes in tumor and normal tissues (scale bars: 200 μm).</p>
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<p>Clinical subgroup analysis of prognostic models. (<b>A</b>) shows a comparison of survival analyses between age ≤ 70 and age &gt; 70. (<b>B</b>) shows a comparison of survival analysis between Gleason ≤ 7 and Gleason &gt; 7. (<b>C</b>) shows the comparison of survival analysis between PSA ≤ 10 and PSA &gt; 10. (<b>D</b>) shows the comparison of survival analysis between stages T1–2 and T3–4.</p>
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<p>Tumor microenvironment, GSEA, tumor–immune circulation, immune checkpoints, and drug sensitivity analysis between high- and low-risk groups. (<b>A</b>) shows the tumor microenvironment analysis between high- and low-risk groups. (a) is the analysis of the difference in stromal score, immune score, ESTIMATE score, and tumor purity between the high- and low-risk groups. (b)–(e) are peak plots of stromal score, immune score, ESTIMATE score, and tumor purity between high- and low-risk groups, respectively. (<b>B</b>) shows the GSEA analysis of the high- and low-risk groups. A convex upward curve indicates upregulation of the pathway and a convex downward curve indicates downregulation of the pathway. (<b>C</b>) is the tumor–immune circulation analysis of the high- and low-risk groups. * indicates that key steps in the cycle differ in the high- and low-risk groups. Blue color indicates high-risk group and yellow color indicates low risk. (<b>D</b>) is an immune checkpoint analysis of the high- and low-risk groups. * indicates that checkpoints are significantly different between high- and low-risk groups. Blue color indicates high-risk group and yellow color indicates low-risk group. (<b>E</b>) shows the drug sensitivity analysis between the high- and low-risk groups. Blue color indicates low-risk group and red color indicates high-risk group.</p>
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14 pages, 1520 KiB  
Article
Exploring the Causal Effects of Micronutrient Supplementation on Susceptibility to Viral Pneumonia: A Mendelian Randomization Study
by Shunran Li, Mingting Cui, Ziwen Song, Jianhui Yuan and Caijun Sun
Pathogens 2025, 14(3), 263; https://doi.org/10.3390/pathogens14030263 - 7 Mar 2025
Viewed by 206
Abstract
Viral infections have been a severe challenge for global public health, and viral pneumonia is becoming increasingly critical in the post-pandemic era. Observational and basic studies have demonstrated a strong link between host nutrient status and anti-viral immune responses, and nutritional supplements were [...] Read more.
Viral infections have been a severe challenge for global public health, and viral pneumonia is becoming increasingly critical in the post-pandemic era. Observational and basic studies have demonstrated a strong link between host nutrient status and anti-viral immune responses, and nutritional supplements were shown to improve the prognosis of viral infectious diseases. However, there is limited research on the relationship between essential micronutrients and the susceptibility to viral pneumonia. In addition, current studies are often confounded by biases and reverse causality, undermining their reliability. In this study, to fill the gap, we employed Mendelian randomization to investigate the causal relationship between supplementation of vitamins and minerals and the susceptibility to viral pneumonia. Our analysis found that vitamin B6 is a protective factor against viral pneumonia, while selenium supplementation is a risk factor. These findings provide insights for the use of dietary supplements and the prevention and control of viral pneumonia, especially when micronutrient supplementation is used as an adjunctive therapy for viral infections. Full article
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<p>Flow chart of the study design. LD: Linkage Disequilibrium; SNP: Single Nucleotide Polymorphism; MR: Mendelian Randomization; IVW: Inverse Variance-Weighted.</p>
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<p>Forest plot of the MR analysis results. The purple arrow indicates the extension of the confidence interval; due to space constraints in the plot, the endpoints of the confidence interval cannot be displayed.</p>
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<p>Scatter plots of MR analysis. (<b>A</b>) Scatter plot of effect of Vitamin B6 on viral pneumonia. (<b>B</b>) Scatter plot of effect of Selenium on viral pneumonia.</p>
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<p>Leave-one-out analysis of the effects of Vitamin B6 and Selenium on viral pneumonia. (<b>A</b>) Leave-one-out analysis of the effects of Vitamin B6 on viral pneumonia. (<b>B</b>) Leave-one-out analysis for the effect of Selenium on viral pneumonia. The red lines represent the cumulative effect of all SNPs.</p>
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13 pages, 1624 KiB  
Proceeding Paper
Granger Causality Analysis of Air Pollutants and Meteorological Parameters
by Wong Yee Ping, Zulkifli Abd Rais, Norazrin Ramli, Norazian Mohamed Noor, Ahmad Zia Ul-Saufie, Hazrul Abdul Hamid and Mohd Khairul Nizam Mahmad
Environ. Earth Sci. Proc. 2025, 33(1), 6; https://doi.org/10.3390/eesp2025033006 - 6 Mar 2025
Viewed by 56
Abstract
This study investigated the relationships between air pollutants (PM10, SO2, NO2, O3, CO) and meteorological parameters (wind speed, relative humidity, ambient temperature) across urban, suburban, and industrial areas in Malaysia from 2017 to 2021. Using [...] Read more.
This study investigated the relationships between air pollutants (PM10, SO2, NO2, O3, CO) and meteorological parameters (wind speed, relative humidity, ambient temperature) across urban, suburban, and industrial areas in Malaysia from 2017 to 2021. Using data from six monitoring stations, this research employed descriptive analysis, trend analysis, and Granger causality testing to uncover complex interactions. The results revealed distinct patterns: suburban areas showed strong ambient temperature-ozone (p-value = 0.0063) and relative humidity–nitrogen dioxide relationships (p-value = 0.0411); industrial zones exhibited bidirectional causality between SO2 and PM10 and had a strong nitrogen dioxide–PM10 relationship (p-value = 0.0292); urban areas exhibited complex multi-pollutant interactions. Notably, the 2020 Movement Control Order significantly improved air quality. This research provides crucial insights for targeted air quality management strategies, contributing to public health improvements and aligning with global sustainability goals. Full article
18 pages, 7554 KiB  
Article
OsRNE Encodes an RNase E/G-Type Endoribonuclease Required for Chloroplast Development and Seedling Growth in Rice
by Huimin Fang, Lili Song, Kangwei Liu, Yishu Gu, Yao Guo, Chao Zhang and Long Zhang
Int. J. Mol. Sci. 2025, 26(5), 2375; https://doi.org/10.3390/ijms26052375 - 6 Mar 2025
Viewed by 157
Abstract
Chloroplast biogenesis is a crucial biological process in plants. Endoribonuclease E (RNase E) functions in the RNA metabolism of chloroplast and plays a vital role for chloroplast development in Arabidopsis. However, despite sharing 44.7% of its amino acid sequence identity with Arabidopsis [...] Read more.
Chloroplast biogenesis is a crucial biological process in plants. Endoribonuclease E (RNase E) functions in the RNA metabolism of chloroplast and plays a vital role for chloroplast development in Arabidopsis. However, despite sharing 44.7% of its amino acid sequence identity with Arabidopsis RNase E, the biological function of rice OsRNE (Oryza sativa RNase E) remains unknown. Here, we identified a white leaf and lethal 1 (wll1) mutant that displayed white leaves and died at the seedling stage. The causal gene OsRNE was isolated by MutMap+ method. CRISPR/Cas9-mediated knockout of OsRNE resulted in white leaves and seedling lethality, confirming OsRNE as the causal gene for the wll1 phenotype. The albino phenotype of osrne mutant was associated with decreased chlorophyll content and abnormal thylakoid morphology in the chloroplast. The absence of OsRNE led to a significant reduction in the Rubisco large subunit (RbcL), and the 23S and 16S chloroplast rRNAs were nearly undetectable in the osrne mutant. OsRNE transcripts were highly expressed in green tissues, and the protein was localized to chloroplasts, indicating its essential role in photosynthetic organs. Furthermore, transcriptome analysis showed that most of the genes associated with photosynthesis and carbohydrate metabolism pathways in the osrne mutant were significantly down-regulated compared with those in WT. Chlorophyll- and other pigment-related genes were also differentially expressed in the osrne mutant. Our findings demonstrated that OsRNE plays an important role in chloroplast development and chlorophyll biosynthesis in rice. Full article
(This article belongs to the Special Issue Genetic Regulation of Plant Growth and Protection)
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<p>Isolation of causal mutation in white leaf phenotype through MutMap+ method. (<b>A</b>,<b>B</b>) Comparison of the four-day-old (<b>A</b>) and ten-day-old (<b>B</b>) seedlings of YD8 and <span class="html-italic">wll1</span>. Scale bars = 2 cm (<b>A</b>) and 5 cm (<b>B</b>). (<b>C</b>) Gene structure of <span class="html-italic">LOC_Os08g23430</span>. The candidate Indel (a single base C deletion) locates at the 12th exon of <span class="html-italic">LOC_Os08g23430</span> gene. (<b>D</b>) Sequence chromatograms of <span class="html-italic">wll1</span> mutation. The transcript of the mutant would encode a protein with 967 amino acids. Red box represents the missing single base C.</p>
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<p>Knockout of <span class="html-italic">OsRNE</span> leads to albino phenotype. (<b>A</b>) Two independent lines were generated by CRISPR/Cas9 in the first exon of the <span class="html-italic">OsRNE</span> gene. (<b>B</b>) Mutation events were confirmed by Sanger sequencing. Red box represents the insertion of single base. (<b>C</b>) The transcript of <span class="html-italic">osrne</span> mutants would encode a protein with 68 amino acids. Red fonts show the amino acids formed by the frameshift mutation. The full-length CDS of <span class="html-italic">OsRNE</span> encodes a protein of 1085 amino acids, and <a href="#ijms-26-02375-f002" class="html-fig">Figure 2</a>C shows the first 100 amino acids in ZH11. (<b>D</b>–<b>G</b>) Phenotypic analyses of WT and <span class="html-italic">osrne-1</span> seedlings. (<b>D</b>,<b>E</b>) Seedlings of WT (<b>D</b>) and heterozygous mutant (<b>E</b>) at the two-leaf stage in the field. The red arrows represent white seedlings separated from the heterozygous mutant. (<b>F</b>,<b>G</b>) The leaves of normal green (<b>F</b>) and white seedlings (<b>G</b>) at the two-leaf stage. Scale bars = 10 mm (<b>F</b>,<b>G</b>).</p>
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<p>Analyses of pigment contents and rRNA from WT and <span class="html-italic">osrne-1</span> mutant. (<b>A</b>) Pigment contents in leaves at the two-leaf stage. Chl a, chlorophyll a; Chl b, chlorophyll b; Car, carotenoid. Error bars represent SD (standard deviation) of three biological replicates. Asterisks indicate a significant difference between the WT and <span class="html-italic">osrne-1</span> by Student’s <span class="html-italic">t</span>-test; ** <span class="html-italic">p</span> &lt; 0.01. (<b>B</b>) SDS-PAGE analysis of total proteins in leaves WT and <span class="html-italic">osrne-1</span> mutant. (<b>C</b>,<b>D</b>) rRNA analysis using Agilent 2100 in WT (<b>C</b>) and <span class="html-italic">osrne-1</span> (<b>D</b>) leaves at the two-leaf stage.</p>
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<p>Chloroplasts ultrastructure in WT and <span class="html-italic">osrne-1</span> mesophyll cells at the two-leaf stage. (<b>B</b>,<b>E</b>,<b>H</b>) represent the magnified regions indicated by red outline in (<b>A</b>,<b>C</b>,<b>E</b>), respectively. (<b>C</b>,<b>F</b>,<b>I</b>) represent the magnified regions indicated by blue outline in (<b>B</b>,<b>E</b>,<b>H</b>), respectively. GT, grana thylakoid; ST, stroma thylakoid. Scale bars = 5 μm (<b>A</b>,<b>D</b>,<b>G</b>), 1 μm (<b>B</b>,<b>E</b>,<b>H</b>) and 0.5 μm (<b>C</b>,<b>F</b>,<b>I</b>).</p>
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<p>Expression pattern of <span class="html-italic">OsRNE</span> and subcellular localization of OsRNE. (<b>A</b>) Expression patterns of <span class="html-italic">OsRNE</span> based on the rice eFP browser. (<b>B</b>) qRT-PCR analysis of <span class="html-italic">OsRNE</span> relative expression level in different tissues at the heading stage. R, roots; C, culms; L, flag leaves; LS, leaf sheaths; P, panicles before heading. Error bars represent ± SD (<span class="html-italic">n</span> = 3). Confocal microscope images showing the subcellular localization of OsRNE-GFP in tobacco leaf (<b>C</b>) and rice protoplast (<b>D</b>). Signals from GFP fluorescence, chlorophyll autofluorescence, bright field, and merged images are shown. Scale bars = 10 µm (<b>C</b>) and 5 µm (<b>D</b>).</p>
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<p>Transcriptome analysis of WT and <span class="html-italic">osrne-1</span> seedlings. (<b>A</b>) Number of DEGs from comparison of <span class="html-italic">osrne-1</span> and WT seedling transcriptomes. (<b>B</b>) Volcano plot of significantly up- or down-regulated DEGs. (<b>C</b>) GO enrichment analysis of the up-regulated DEGs. (<b>D</b>) GO enrichment analysis of the down-regulated DEGs. (<b>E</b>) KEGG pathway enrichment analysis of the up-regulated DEGs. (<b>F</b>) KEGG pathway enrichment analysis of the down-regulated DEGs.</p>
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<p>Differential map of genes in photosynthesis and carbohydrate metabolism pathways between WT and <span class="html-italic">osrne-1</span>. (<b>A</b>) Differential genes in photosynthesis pathway. (<b>B</b>) Differential genes of photosynthesis-antenna proteins. (<b>C</b>) Differential genes of carbon fixation in photosynthetic organisms. (<b>D</b>) Differential genes of carotenoid biosynthesis. (<b>E</b>) Differential genes of flavonoid biosynthesis. (<b>F</b>) Differential genes of flavone and flavonol biosynthesis. Blue boxes represent down-regulated genes, red boxes represent up-regulated genes, green boxes represent plant-specific genes, and dark green boxes represent both up-regulated genes and down-regulated genes.</p>
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<p>Differential expression of chlorophyll metabolism and chloroplast development genes in WT and <span class="html-italic">osrne-1</span>. The graphs show the log<sub>2</sub> ratio of transcript levels involved in chlorophyll biosynthesis (<b>A</b>) and chlorophyll degradation pathway (<b>B</b>) in <span class="html-italic">osrne-1</span> compared with WT. Raw data are shown in <a href="#app1-ijms-26-02375" class="html-app">Supplementary Tables S8 and S9</a>. (<b>C</b>) Expression level of genes related to chloroplast biogenesis using qRT-PCR. (<b>D</b>) Expression level of genes related to photosynthesis using qRT-PCR. (<b>E</b>) Expression level of genes related to chlorophyll synthesis using qRT-PCR. The relative expression level of each gene was normalized using <span class="html-italic">Actin</span> as the internal control. Error bars are based on three independent biological replicates. Asterisks indicate statistically significant differences compared to the WT (** <span class="html-italic">p</span> &lt; 0.01).</p>
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31 pages, 6359 KiB  
Article
Time-Varying Market Efficiency: A Focus on Crude Oil and Commodity Dynamics
by Young-Sung Kim, Do-Hyeon Kim, Dong-Jun Kim and Sun-Yong Choi
Fractal Fract. 2025, 9(3), 162; https://doi.org/10.3390/fractalfract9030162 - 6 Mar 2025
Viewed by 229
Abstract
This study investigated market efficiency across 20 major commodity assets, including crude oil, utilizing fractal analysis. Additionally, a rolling window approach was employed to capture the time-varying nature of efficiency in these markets. A Granger causality test was applied to assess the influence [...] Read more.
This study investigated market efficiency across 20 major commodity assets, including crude oil, utilizing fractal analysis. Additionally, a rolling window approach was employed to capture the time-varying nature of efficiency in these markets. A Granger causality test was applied to assess the influence of crude oil on other commodities. Key findings revealed significant inefficiencies in RBOB(Reformulated Blendstock for Oxygenated Blending) Gasoline, Palladium, and Brent Crude Oil, largely driven by geopolitical risks that exacerbated supply–demand imbalances. By contrast, Copper, Kansas Wheat, and Soybeans exhibited greater efficiency because of their stable market dynamics. The COVID-19 pandemic underscored the time-varying nature of efficiency, with short-term volatility causing price fluctuations. Geopolitical events such as the Russia–Ukraine War exposed some commodities to shocks, while others remained resilient. Brent Crude Oil was a key driver of market inefficiency. Our findings align with Fractal Fractional (FF) concepts. The MF-DFA method revealed self-similarity in market prices, while inefficient markets exhibited long-memory effects, challenging the Efficient Market Hypothesis. Additionally, rolling window analysis captured evolving market efficiency, influenced by external shocks, reinforcing the relevance of fractal fractional models in financial analysis. Furthermore, these findings can help traders, policymakers, and researchers, by highlighting Brent Crude Oil as a key market indicator and emphasizing the need for risk management and regulatory measures. Full article
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<p>Return time series for all selected commodity assets.</p>
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<p>The curve of the multifractal fluctuation function <math display="inline"><semantics> <mrow> <mi>F</mi> <mi>q</mi> <mo>(</mo> <mi>s</mi> <mo>)</mo> </mrow> </semantics></math> compared to <span class="html-italic">s</span> in a log−log plot of the average return for all the indices in developed countries.</p>
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<p>Generalized Hurst exponents <math display="inline"><semantics> <mrow> <mi>h</mi> <mo>(</mo> <mi>q</mi> <mo>)</mo> </mrow> </semantics></math> of the index return in developed countries.</p>
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<p>The multifractal spectra of each index return in frontier countries.</p>
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<p>Descending order <math display="inline"><semantics> <mrow> <mo>Δ</mo> <mi>α</mi> </mrow> </semantics></math> and the commodity assets.</p>
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<p>The dynamics of <math display="inline"><semantics> <mrow> <mo>Δ</mo> <mi>α</mi> </mrow> </semantics></math> using a rolling window for developed countries. The window length was 400 days.</p>
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<p>Scatter plot of the GPR index and <math display="inline"><semantics> <mrow> <mo>Δ</mo> <mi>α</mi> </mrow> </semantics></math> series.</p>
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19 pages, 323 KiB  
Article
The Effects of Financial Knowledge, Skill, and Self-Assessed Knowledge on Financial Well-Being, Behavior, and Objective Situation
by Nathan Phelps and Adam Metzler
Int. J. Financial Stud. 2025, 13(1), 44; https://doi.org/10.3390/ijfs13010044 - 6 Mar 2025
Viewed by 225
Abstract
The effects of certain abilities on financial outcomes have been debated for several years. Some argue that financial knowledge is key to financial success, while others have found financial skill and self-assessed knowledge are more important. This study contributes to this debate by [...] Read more.
The effects of certain abilities on financial outcomes have been debated for several years. Some argue that financial knowledge is key to financial success, while others have found financial skill and self-assessed knowledge are more important. This study contributes to this debate by providing a descriptive analysis, whereby regression is used to study the simultaneous effects of financial knowledge, financial skill, and self-assessed knowledge on financial well-being, financial behavior, and objective financial situation. Although our methodology does not allow us to determine if relationships are causal, we show that self-assessed knowledge has little to no relationship with financial well-being, may have contrasting relationships with components of objective financial situation, and is weakly associated with good financial behaviors. Financial skill has the strongest relationship with financial well-being and financial behaviors, as well as some components of objective financial situation. Despite having a relatively weak (compared to financial skill) association with financial well-being and financial behaviors, financial knowledge has the strongest relationship with many components of objective financial situation. Full article
(This article belongs to the Special Issue Advance in the Theory and Applications of Financial Literacy)
16 pages, 3592 KiB  
Article
Multi-Omics Analysis Revealed the Molecular Mechanisms Affecting Average Daily Gain in Cattle
by Mingjuan Gu, Hongyu Jiang, Fengying Ma, Shuai Li, Yaqiang Guo, Lin Zhu, Caixia Shi, Risu Na, Yu Wang and Wenguang Zhang
Int. J. Mol. Sci. 2025, 26(5), 2343; https://doi.org/10.3390/ijms26052343 - 6 Mar 2025
Viewed by 69
Abstract
The average daily gain (ADG) is a critical index for evaluating growth rates in cattle and is closely linked to the economic benefits of the cattle industry. Heredity is one of the factors affecting the daily gain of cattle. However, the molecular mechanisms [...] Read more.
The average daily gain (ADG) is a critical index for evaluating growth rates in cattle and is closely linked to the economic benefits of the cattle industry. Heredity is one of the factors affecting the daily gain of cattle. However, the molecular mechanisms regulating ADG remain incompletely understood. This study aimed to systematically unravel the molecular mechanisms underlying the divergence in ADG between high average daily gain (HADG) and low average daily gain (LADG) Angus cattle through integrated multi-omics analyses (microbiome, metabolome, and transcriptome), hypothesizing that the gut microbiota–host gene–metabolism axis is a key regulatory network driving ADG divergence. Thirty Angus cattle were classified according to their HADG and LADG. Fecal and serum samples were collected for 16S, fecal metabolome, and blood transcriptome analysis. The results showed that compared with the LADG group, the abundance of Firmicutes increased in the HADG group, while the abundance of Bacteroidetes and Proteobacteria decreased. Metabolomics and transcriptomic analysis revealed that KEGG pathways associated with differentially expressed genes (DEGs) and differentially abundant metabolites (DAMs) were enriched in bile acid metabolism. Spearman correlation analysis showed that Oscillospira was positively correlated with ZBTB20 and negatively correlated with RADIL. ZBTB20 was negatively correlated with dgA-11_gut_group. This study analyzed the regulatory mechanism of average daily gain of beef cattle from genetic, metabolic, and microbial levels, providing a theoretical basis for analyzing the mechanism of differential daily gain of beef cattle, and has important significance for improving the production performance of beef cattle. The multi-omics network provides biomarker foundations for machine learning-based ADG prediction models, offering potential applications in precision breeding. While these biomarkers show promise for precision breeding, their causal roles require further validation. The conclusions are derived from a single breed (Angus) and gender (castrated males). Future studies should include females and diverse breeds to assess generalizability. Full article
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<p>The 16S sequencing of fecal samples from HADG and LADG cattle. The α-diversity (alpha diversity) plots with chao1 index (<b>A</b>) and Shannon index (<b>B</b>). (<b>C</b>) Principal coordinate analysis (PCoA) of fecal microbial communities based on the Bray–Curtis distance. (<b>D</b>) The distribution of microbiota at the phylum level. (<b>E</b>) The distribution of microbiota at the genus level. (<b>F</b>) Venn diagram. (<b>G</b>) Histogram of LDA value distribution of LEfSe analysis. (<b>H</b>) PICRUSt2 analysis.</p>
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<p>Metabolome analysis of fecal samples from HADG and LADG cattle. (<b>A</b>) PCA score plot of the metabolome. (<b>B</b>) OPLS-DA score plot of all the metabolite features. (<b>C</b>) Number of up- and down-regulated differentially abundant metabolites. (<b>D</b>) Volcano diagram of differentially abundant metabolites. (<b>E</b>) KEGG enrichment analysis of differentially abundant metabolites from HADG and LADG cattle.</p>
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<p>Transcriptome analysis of blood samples from HADG and LADG cattle. (<b>A</b>) The number of up- and down-regulated differentially expressed genes (DEGs). (<b>B</b>) Volcano diagram of the differentially expressed genes. (<b>C</b>) Differentially expressed gene KEGG enrichment. (<b>D</b>) PPI network of differentially expressed genes.</p>
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<p>Multi-omics correlation analysis. (<b>A</b>) Spearman correlation chord plot of differential microbial and differentially expressed genes. (<b>B</b>) A heat map of the correlation analysis between differential microbial and differentially expressed genes. (<b>C</b>) Spearman correlation chord plot of differentially abundant metabolites and differentially expressed genes. (<b>D</b>) A heat map of the correlation analysis between differentially abundant metabolites and differentially expressed genes. metabolite 1 represents 6h-dibenzo[b,d]pyran, 3-(1,1-dimethylheptyl)-6a,7,10,10a-tetrahydro-1-methoxy-6,6,9-trimethyl-, (6ar,10ar)-; metabolite 2 represents 1h-pyrrole-3-propanoic acid, 5-[(1,2-dihydro-2-oxo-3h-indol-3-ylidene)methyl]-2,4-dimethyl-; * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001.</p>
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<p>Integration of microbiome, transcriptome, and metabolome. (<b>A</b>) Mantel test correlation plot. The thickness of the line represents the size of the Mantel test correlation coefficient; the color of the line indicates the <span class="html-italic">p</span>-value of the Mantel test. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01. (<b>B</b>) A network diagram of microbiome, transcriptome, and metabolome. Different nodes in the diagram mark different microbiota, metabolites, or genes. The shape of the microbiota is circular, the shape of the metabolites is triangular, and the shape of the genes is square. (<b>C</b>) A Sankey diagram showing the correlation of genes–microorganisms–metabolites.</p>
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16 pages, 13435 KiB  
Article
Evidence for Genetic Causal Association Between the Gut Microbiome, Derived Metabolites, and Age-Related Macular Degeneration: A Mediation Mendelian Randomization Analysis
by Pinghui Wei, Shan Gao and Guoge Han
Biomedicines 2025, 13(3), 639; https://doi.org/10.3390/biomedicines13030639 - 5 Mar 2025
Viewed by 290
Abstract
Background/Objectives: Despite substantial research, the causal relationships between gut microbiota (GM) and age-related macular degeneration (AMD) remain unclear. We aimed to explore these causal associations using Mendelian randomization (MR) and elucidate the potential mechanisms mediated by blood metabolites. Methods: We utilized [...] Read more.
Background/Objectives: Despite substantial research, the causal relationships between gut microbiota (GM) and age-related macular degeneration (AMD) remain unclear. We aimed to explore these causal associations using Mendelian randomization (MR) and elucidate the potential mechanisms mediated by blood metabolites. Methods: We utilized the 211 GM dataset (n = 18,340) provided by the MiBioGen consortium. AMD outcome data were sourced from the MRC Integrated Epidemiology Unit (IEU) OpenGWAS Project. We performed bidirectional MR, two mediation analyses, and two-step MR to assess the causal links between GM and different stages of AMD (early, dry, and wet). Results: Our findings indicate that the Bacteroidales S24.7 group and genus Dorea are associated with an increased risk of early AMD, while Ruminococcaceae UCG011 and Parasutterella are linked to a higher risk of dry AMD. Conversely, Lachnospiraceae UCG004 and Anaerotruncus are protective against dry AMD. In the case of wet AMD, Intestinimonas and Sellimonas increase risk, whereas Anaerotruncus and Rikenellaceae RC9 reduce it. Additionally, various blood metabolites were implicated: valine, arabinose, creatine, lysine, alanine, and apolipoprotein A1 were associated with early AMD; glutamine and hyodeoxycholate—with a reduced risk of dry AMD; and androsterone sulfate, epiandrosterone sulfate, and lipopolysaccharide—with a reduced risk of wet AMD. Notably, the association between family Oxalobacteraceae and early AMD was mediated by valine, accounting for 19.1% of the association. Conclusions: This study establishes causal links between specific gut microbiota and AMD, mediated by blood metabolites, thereby enhancing our understanding of the gut–retina axis in AMD pathophysiology. Full article
(This article belongs to the Collection Feature Papers in Microbiology in Human Health and Disease)
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<p>Overview of the Mendelian randomization (MR) framework used to investigate the causal effect of the gut microbiota, blood metabolites derived from the gut microbiota, and age-related macular degeneration (AMD).</p>
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<p>Causal relationship between the gut microbiota (GM) and age-related macular degeneration (AMD). (<b>A</b>) Causal and sensitivity analyses were conducted for each gut microbiome taxon across five levels in relation to AMD. The outer circle represents the <span class="html-italic">p</span>-value of the heterogeneity test (Cochran’s Q), followed by the GM taxon name, the <span class="html-italic">p</span>-value of the pleiotropy test (MR-Egger regression), and the <span class="html-italic">p</span>-value based on the IVW results (significant results highlighted in red). Color coding for the <span class="html-italic">p</span>-values is based on an RGB color scale (<span class="html-italic">p</span> = 0, #ACD6EC; <span class="html-italic">p</span> = 0.5, #90ee90; <span class="html-italic">p</span> = 1, #F5A899). (<b>B</b>) The Mendelian randomization (MR) results reveal the causal relationship between the GM and AMD. With OR = 1 as the reference line, the left side indicates that this GM is a protective factor for AMD, while the right side indicates that this GM is a risk factor for AMD. (<b>C</b>) The Sankey diagram illustrates the relationship between the GM and AMD phenotypes. The leftmost side represents the phylum where the gut microbiota comes from, the middle represents the GM, and the rightmost side represents AMD phenotypes.</p>
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<p>Causal analysis of gut microbiome (GM)-derived metabolites and AMD based on Mendelian randomization (MR) analyses. (<b>A</b>–<b>C</b>) Results of early, dry, and wet AMD, respectively. From outside to inside, the <span class="html-italic">p</span>-values of inverse-variance weighted (IVW), MR-Egger, weighted median, simple mode, and weighted mode are represented, respectively. The odds ratio (OR) value of the IVW method is represented in the innermost side. Groups A, L, C, N, E, X, and F represent amino acids, lipids, carbohydrates, nucleotides, energy, xenobiotics, and fatty acids, respectively. (<b>D</b>) The mediation effect of “gut microbiota–blood metabolites–AMD” in two-step Mendelian randomization. (<b>E</b>) The Mendelian randomization (MR) results reveal the causal relationship between the GM and AMD. With OR = 1 as the reference line, the left side indicates that this metabolite is a protective factor for AMD, while the right side indicates that this metabolite is a risk factor for AMD. CI indicates confidence intervals.</p>
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13 pages, 1178 KiB  
Article
Molecular Characterization of an EMS-Induced Ab-γg-Rich Saponin Mutant in Soybean (Glycine max (L.) Merr.)
by Junbeom Park, Haereon Son, Hyun Jo, Chigen Tsukamoto, Jinwon Lee, Jeong-Dong Lee, Hak Soo Seo and Jong Tae Song
Agronomy 2025, 15(3), 648; https://doi.org/10.3390/agronomy15030648 - 5 Mar 2025
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Abstract
Soybean is particularly known for accumulating saponins in its seeds. This study aimed to identify a causal gene to control an increase in Ab-γg saponin in PE1607 from an EMS-treated population of the soybean cultivar Pungsannamul. Segregation analysis in F2 seeds verified [...] Read more.
Soybean is particularly known for accumulating saponins in its seeds. This study aimed to identify a causal gene to control an increase in Ab-γg saponin in PE1607 from an EMS-treated population of the soybean cultivar Pungsannamul. Segregation analysis in F2 seeds verified that a single recessive allele controlled the increased Ab-γg saponin in PE1607. Bulk segregant analysis and mutant individuals identified the candidate region, containing the previously reported Sg-3 (Glyma.10G104700) gene, encoding a glucosyltransferase responsible for conjugating glucose as the third sugar at the C-3 position of the aglycone. NGS identified SNPs in the upstream of the Sg-3 gene, designated as the sg-3b allele. Expression analysis revealed that PE1607 exhibited a threefold decrease in Sg-3 expression in the hypocotyls compared to the Pungsannamul. Moreover, Sg-3 expressions significantly differed between the hypocotyls and cotyledons in developing seeds, with relatively low expression observed in the cotyledons. The results conclude that sg-3b allele may contribute to the reduced Sg-3 expression, resulting in an increase in Ab-γg saponin in PE1607. In addition, in the cotyledons, DDMP-βg and DDMP-βa saponins are present, containing rhamnose instead of glucose as the third sugar at the C-3 position of aglycone. This suggests that Sg-3, known as glucosyltransferase, does not significantly contribute to saponin biosynthesis in cotyledons. Full article
(This article belongs to the Special Issue Advances in Crop Molecular Breeding and Genetics—2nd Edition)
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Figure 1

Figure 1
<p>Saponin phenotypes of wild-type and mutant soybean lines in seed hypocotyls. (<b>a</b>) Thin-layer chromatography (TLC) analysis of seed hypocotyls from wild-type cultivars (Pungsannamul and Uram) and the mutant line (PE1607). (<b>b</b>) Liquid chromatography with photodiode array and tandem mass spectrometry (LC-PDA-MS/MS) profiles of saponin extracts from seed hypocotyls of Pungsannamul (upper panel) and PE1607 (lower panel). Saponins are indicated by an upside-down black triangle. (<b>c</b>) Quantification of saponins in seed hypocotyls using LC-PDA-MS/MS. Asterisks indicate significant differences regarding each saponin compound between Pungsannamul and PE1607 using Student’s <span class="html-italic">t</span>-test (* <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01). Error bars represent ± standard deviation of three biological replicates.</p>
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<p>Mapping analysis of PE1607 crossing populations and gene structure of <span class="html-italic">Sg-3</span> (<span class="html-italic">Glyma.10G104700</span>). (<b>a</b>) Bulk segregant analysis (BSA) mapping and narrowing-down of the candidate region in the Uram × PE1607 F<sub>2</sub> population. The BSA mapping results are shown with white bars, which correspond to the PE1607 genotype. The results are presented in four individual mutant lines from two F<sub>2</sub> populations, and the white bar corresponds to the PE1607 genotype. The overlapping candidate region, 18 Mb, is highlighted in a box with diagonal lines, and the location of the <span class="html-italic">Sg-3</span> gene is indicated by an arrow. Physical positions are based on Wm82.a4.v1. Details of the lines used in the cross are provided in <a href="#app1-agronomy-15-00648" class="html-app">Table S1</a>. (<b>b</b>) Gene structure of <span class="html-italic">Sg-3</span> (<span class="html-italic">Glyma.10G104700</span>) including the upstream, 5′–UTR and 3′–UTR. The coding region of the <span class="html-italic">Sg-3</span> gene is represented by a black box, the 5′–UTR and 3′–UTR of the <span class="html-italic">Sg-3</span> gene are indicated by white boxes, and the upstream region of the <span class="html-italic">Sg-3</span> gene is marked by a gray box. The SNPs in PE1607, compared to the wild-type varieties (Pungsannamul, Uram, Jinpung, and Williams 82), are indicated by a black line, with the SNP variation marked by an arrow to show the change in PE1607 on the right side. The SNP used in this study for the SimpleProbe assay is indicated by a red line (<a href="#app1-agronomy-15-00648" class="html-app">Figure S3</a>).</p>
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<p>Expression profiles of the <span class="html-italic">Sg-3</span> gene in hypocotyls and cotyledons of developing seeds. Expression levels were calculated relative to the constitutively expressed gene (<span class="html-italic">Cons7</span>) used as the reference. Error bars represent ± standard deviation of three biological replicates. Asterisks indicate significant differences between Pungsannamul and PE1607 using Student’s <span class="html-italic">t</span>-test (* <span class="html-italic">p</span> &lt; 0.05, ns; not significant).</p>
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