Search Results (4,690)

Inflammation plays a crucial role in atherosclerosis and nonalcoholic fatty liver disease (NAFLD). We previously engineered a recombinant Lactococcus lactis strain expressing the Ling-Zhi immunomodulatory protein (L. lactis-LZ8). This study investigated the anti-atherosclerotic effects of L. lactis-LZ8 in rabbits fed a high-fat diet (HFD). Changes in body weight, serum lipid profiles, and liver function were monitored. The aorta and liver tissues were analyzed for gross pathology and histopathology. Eight-week administration of L. lactis-LZ8 with HFD ameliorated atherosclerosis by downregulating protein and gene expression associated with lipid metabolism and inflammation in the aortas. The rabbits receiving L. lactis-LZ8 exhibited a significant dose-dependent reduction in hepatic fat accumulation. RNA sequencing of the livers revealed that inflammatory genes in the L. lactis-LZ8 groups were downregulated compared to the HFD group. Disease ontology enrichment analysis indicated that these genes were involved in atherosclerosis. Gene set enrichment analysis plots revealed significant enrichment in the gene sets related to cholesterol homeostasis. CIBERSORT immune cell fraction analysis indicated significant infiltration by regulatory T cells, CD8+ T cells, activated dendritic cells, and natural killer cells in the L. lactis-LZ8 group. Our studies underscore LZ8’s role in precision nutrition, providing a potential solution to the current challenges in modifying atherosclerosis and NAFLD. Full article

The development of fetal organs can be impacted by systemic changes in maternal circulation, with the placenta playing a pivotal role in maintaining pregnancy homeostasis and nutrient exchange. In clinical obstetrics, oxytocin (OXT) is commonly used to induce labor. To explore the potential role of OXT in the placental homeostasis of OXT, we compared OXT levels in neonatal cord blood among neonates (23–42 weeks gestation) whose mothers either received prenatal OXT or experienced spontaneous labor. Our previous research revealed that the oxytocin receptor (OXTR), essential in forming the blood–retina barrier, is expressed in the retinal pigment epithelium (RPE). We hypothesized that perinatal OXT administration might influence the development of the neural retina and its vasculature, offering therapeutic potential for retinal diseases such as retinopathy of prematurity (ROP). Plasma OXT levels were measured using a commercial OXT ELISA kit. Human fetal RPE (hfRPE) cells treated with OXT (10 µM) were assessed for gene expression via RNA sequencing, revealing 14 downregulated and 32 upregulated genes. To validate these differentially expressed genes (DEGs), hfRPE cells were exposed to OXT (0.01, 0.1, 1, or 10 µM) for 12 h, followed by RNA analysis via real-time PCR. Functional, enrichment, and network analyses (Gene Ontology term, FunRich, Cytoscape) were performed to predict the affected pathways. This translational study suggests that OXT likely crosses the placenta, altering fetal OXT concentrations. RNA sequencing identified 46 DEGs involved in vital metabolic and signaling pathways and critical cellular components. Our results indicate that the perinatal administration of OXT may affect neural retina and retinal vessel development, making OXT a potential therapeutic option for developmental eye diseases, including ROP. Full article

This paper offers an in-depth review of the latest advancements in the automatic generation of medical case-based multiple-choice questions (MCQs). The automatic creation of educational materials, particularly MCQs, is pivotal in enhancing teaching effectiveness and student engagement in medical education. In this review, we explore various algorithms and techniques that have been developed for generating MCQs from medical case studies. Recent innovations in natural language processing (NLP) and machine learning (ML) for automatic language generation have garnered considerable attention. Our analysis evaluates and categorizes the leading approaches, highlighting their generation capabilities and practical applications. Additionally, this paper synthesizes the existing evidence, detailing the strengths, limitations, and gaps in current practices. By contributing to the broader conversation on how technology can support medical education, this review not only assesses the present state but also suggests future directions for improvement. We advocate for the development of more advanced and adaptable mechanisms to enhance the automatic generation of MCQs, thereby supporting more effective learning experiences in medical education. Full article

Obesity confers risk for cardiovascular disease and vascular dementia. However, genomic alterations modulated by obesity in endothelial cells in the brain and their relationship to other neurovascular unit (NVU) cells are unknown. We performed single nuclei RNA sequencing (snRNAseq) of the NVU (endothelial cells, astrocytes, microglia, and neurons) from the hippocampus of obese (ob/ob) and wild-type (WT) male mice to characterize obesity-induced transcriptomic changes in a key brain memory center and assessed blood–brain barrier permeability (BBB) by gadolinium-enhanced magnetic resonance imaging (MRI). Ob/ob mice displayed obesity, hyperinsulinemia, and impaired glucose tolerance. snRNAseq profiled 14 distinct cell types and 32 clusters within the hippocampus of ob/ob and WT mice and uncovered differentially expressed genes (DEGs) in all NVU cell types, namely, 4462 in neurons, 1386 in astrocytes, 125 in endothelial cells, and 154 in microglia. Gene ontology analysis identified important biological processes such as angiogenesis in endothelial cells and synaptic trafficking in neurons. Cellular pathway analysis included focal adhesion and insulin signaling, which were common to all NVU cell types. Correlation analysis revealed significant positive correlations between endothelial cells and other NVU cell types. Differentially expressed long non-coding RNAs (lncRNAs) were observed in cells of the NVU-affecting pathways such as TNF and mTOR. BBB permeability showed a trend toward increased signal intensity in ob/ob mice. Taken together, our study provides in-depth insight into the molecular mechanisms underlying cognitive dysfunction in obesity and may have implications for therapeutic gene targeting. Full article

Temperature is one of the critical factors affecting the physiological functions of fish. With ongoing global warming, changes in water temperature have a profound impact on fish species. Alternative splicing, being a significant mechanism for gene expression regulation, facilitates fish to adapt and thrive in dynamic and varied aquatic environments. Our study used transcriptome sequencing to analyze alternative splicing in largemouth bass gills at 34 °C for 24 h. The findings indicated an increase in both alternative splicing events and alternative splicing genes after high temperature treatment. Specifically, the comparative analysis revealed a total of 674 differential alternative splicing events and 517 differential alternative splicing genes. Enrichment analysis of differential alternative splicing genes revealed significant associations with various gene ontology (GO) terms and KEGG pathways, particularly in immune-related pathways like necroptosis, apoptosis, and the C-type lectin receptor signaling pathway. These results emphasize that some RNA splicing-related genes are involved in the response of largemouth bass to high temperatures. Full article

Mpox, caused by the Mpox virus (MPXV), emerged globally in 2022 with the Clade IIb strain, presenting a critical public health challenge. While MPXV is primarily characterized by fever and rash, gastrointestinal (GI) complications, such as diarrhea and proctitis, have also been observed. This study is a reanalysis of GSE219036 without own data and focuses on the impact of MPXV infection on the colon, using human-induced pluripotent stem cell-derived colon organoids as a model. We applied a tailored statistical framework for RNA-seq data, Generalized Linear Models with Quasi-Likelihood F-tests and Relaxed Magnitude–Altitude Scoring (GLMQL-RMAS), to identify differentially expressed genes (DEGs) across MPXV clades: MPXV I (Zr-599 Congo Basin), MPXV IIa (Liberia), and MPXV IIb (2022 MPXV). Through a novel methodology called Cross-RMAS, we ranked genes by integrating statistical significance and biological relevance across all clades. Machine learning analysis using the genes identified by Cross-RMAS, demonstrated 100% accuracy in differentiating between the different MPXV strains and mock samples. Furthermore, our findings reveal that MPXV Clade I induces the most extensive alterations in gene expression, with significant upregulation of stress response genes, such as HSPA6 and FOS, and downregulation of genes involved in cytoskeletal organization and vesicular trafficking, such as PSAP and CFL1. In contrast, Clade IIb shows the least impact on gene expression. Through Gene Ontology (GO) analysis, we identified pathways involved in protein folding, immune response, and epithelial integrity that are disrupted in infected cells, suggesting mechanisms by which MPXV may contribute to GI symptoms. Full article

This paper explores the idea, occasionally discernible in Leibniz’s writings, that civil bodies can achieve a real or substantial union through the ’mystical body’ of the Church. The starting question is: can the ‘person’ of the state attain real internal union even if it is not a natural person? This theme is examined in light of Leibniz’s interest in the ontology of complex aggregates (including civil ‘bodies’ or ‘persons’), the miracle of the Eucharist, the mystery of transubstantiation, and the unity of the Church. Since his very early Demonstrationes Catholicae, he had strived to demonstrate that the body of the Church, despite being—so to speak—‘scattered’, can be regarded as a Respublica with a strong internal degree of unity, primarily due to the communion that the faithful share through the Eucharist. This article thus analyses both early and mature texts in which Leibniz discusses the bond established among the faithful by the presence of Christ in the Eucharist, arguing that he experimented with the idea that the spiritual union possible within the Church’s ‘mystical body’ and its aggregative capacity could transform European Christian states not only politically but also substantially. Full article

Gastric cancer (GC) is a complex and highly variable disease, ranking among the top five cancers diagnosed globally, and a leading cause of cancer-related deaths. Emerging from stomach lining cells amid chronic inflammation, it often advances to preneoplastic stages. Late-stage diagnoses and treatment challenges highlight the critical need for early detection and innovative biomarkers, motivating this study’s focus on identifying theranostic markers through gene ontology analysis. By exploring deregulated biological processes, this study aims to uncover insights into cancer progression and associated markers, potentially identifying novel theranostic candidates in GC. Using public data from The Human Protein Atlas, this study pinpointed 299 prognostic genes, delineating 171 with unfavorable prognosis and 128 with favorable prognosis. Functional enrichment and protein–protein interaction analyses, supported by RNAseq results and conducted via Metascape and Cytoscape, highlighted five genes (vWF, FN1, THBS1, PCDH7, and F5) with promising theranostic potential. Notably, FN1 and THBS1 exhibited significant promise, with FN1 showing a 370% expression increase in cancerous tissue, and it is possible that FN1 can also indicate the stratification status in GC. While further validation is essential, these findings provide new insights into molecular alterations in GC and potential avenues for clinical application of theranostic markers. Full article

Since the discovery of quantum mechanics, the fact that the wavefunction is defined on the $3\mathbf{n}$-dimensional configuration space rather than on the 3-dimensional space has seemed uncanny to many, including Schrödinger, Lorentz, and Einstein. Even today, this continues to be seen as a significant issue in the foundations of quantum mechanics. In this article, it will be shown that the wavefunction is, in fact, a genuine object on space. While this may seem surprising, the wavefunction does not possess qualitatively new features that were not previously encountered in objects known from Euclidean geometry and classical physics. The methodology used involves finding equivalent reinterpretations of the wavefunction exclusively in terms of objects from the geometry of space. The result is that we will find the wavefunction to be equivalent to geometric objects on space in the same way as was always the case in geometry and physics. This will be demonstrated to hold true from the perspective of Euclidean geometry, but also within Felix Klein’s Erlangen Program, which naturally fits into the classification of quantum particles by the representations of spacetime isometries, as realized by Wigner and Bargmann, adding another layer of confirmation. These results lead to clarifications in the debates about the ontology of the wavefunction. From an empirical perspective, we already take for granted that all quantum experiments take place in space. I suggest that the reason why this works is that they can be interpreted naturally and consistently with the results presented here, showing that the wavefunction is an object on space. Full article

Plant grafting using dwarfing rootstocks is one of the important cultivation measures in the sweet cherry (Prunus avium) industry. In this work, we aimed to explore the effects of the dwarfing rootstock “Pd1” (Prunus tomentosa) on sweet cherry ‘Shuguang2’ scions by performing morphological observations using the paraffin slice technique, detecting GA (gibberellin) and IAA (auxin) contents using UPLC-QTRAP-MS (ultra-performance liquid chromatography coupled with a hybrid triple quadrupole-linear ion trap mass spectrometer), and implementing integration analyses of the epigenome and transcriptome using whole-genome bisulfite sequencing and transcriptome sequencing. Anatomical analysis indicated that the cell division ability of the SAM (shoot apical meristem) in dwarfing plants was reduced. Pd1 rootstock significantly decreased the levels of GAs and IAA in sweet cherry scions. Methylome analysis showed that the sweet cherry genome presented 15.2~18.6%, 59.88~61.55%, 28.09~33.78%, and 2.99~5.28% methylation at total C, CG, CHG, and CHH sites, respectively. Shoot tips from dwarfing plants exhibited a hypermethylated pattern mostly due to increased CHH methylation, while leaves exhibited a hypomethylated pattern. According to GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis, DMGs (differentially methylated genes) and DEGs (differentially expressed genes) were enriched in hormone-related GO terms and KEGG pathways. Global correlation analysis between methylation and transcription revealed that mCpG in the gene body region enhanced gene expression and mCHH in the region near the TSS (transcription start site) was positively correlated with gene expression. Next, we found some hormone-related genes and TFs with significant changes in methylation and transcription, including SAURs, ARF, GA2ox, ABS1, bZIP, MYB, and NAC. This study presents a methylome map of the sweet cherry genome, revealed widespread DNA methylation alterations in scions caused by dwarfing rootstock, and obtained abundant genes with methylation and transcription alterations that are potentially involved in rootstock-induced growth changes in sweet cherry scions. Our findings can lay a good basis for further epigenetic studies on sweet cherry dwarfing and provide valuable new insight into understanding rootstock–scion interactions. Full article

Sacha Inchi (Plukenetia volubilis) oil press-cake (SIPC) represents a new source of proteins of high biological value, with promissory food applications. However, knowledge of these proteins remains limited. In this study, a Sacha Inchi protein concentrate (SPC) was extracted from the SIPC, and proteomic analysis was performed to identify the major alkaline-soluble proteins. The electrophoretic profile highlighted the efficacy of alkaline pH and moderate temperature to extract the major proteins, from which a group of proteins, not previously reported, were registered. LC-MS/MS analyses produced abundant high-quality fragmentation spectra. Utilizing the Euphorbiaceae database (DB), 226 proteins were identified, with numerous well-assigned spectra remaining unidentified. PEAKS Studio v11.5 software generated 1819 high-quality de novo peptides. Data are available via ProteomeXchange with identifier PXD052665. Gene ontology (GO) classification allowed the identification of sequenced proteins associated with biological processes, molecular functions, and cellular components in the seed. Consequently, the principal alkali-soluble proteins from SPC were characterized through derived functional analysis, covering 24 seed-storage-, 27 defense-, and 12 carbohydrate- and lipid-metabolism-related proteins, crucial for human nutrition due to their sulfur-containing amino acids, antioxidant properties, and oil yields, respectively. This research makes a significant contribution to the current understanding of the Sacha Inchi proteome and offers valuable insights for its potential applications in the food industry. Full article

Coronary microvascular dysfunction (CMD) represents a principal etiological factor in ischemic heart disease. Nonetheless, a considerable subset of CMD patients experiences diagnostic delays attributable to the inadequacy of current diagnostic methodologies; which in turn results in deferred therapeutic interventions and elevated mortality rates. This study seeks to elucidate the distinct metabolic profile associated with CMD in rat models and to identify specific diagnostic markers that could enhance the diagnostic accuracy for CMD. In this study, 18 Wistar rats were randomly allocated into two groups: the sham group and the CMD group. The CMD group received injections of embolic microspheres into the left ventricle to establish a CMD model. Subsequently, non-targeted metabolomics and acetylated proteomics analyses were conducted. Machine-learning techniques were employed to identify the co-diagnostic markers of the disease. This study identified 53 key proteins through differential expression proteins (DEPs) and modular proteins analysis. Subsequently, four core proteins (Emc1; Ank1; Fbln2; and Hp) were determined as diagnostic markers for CMD using lasso regression, support vector machine, and random forest methodologies. Receiver operating characteristic curve analysis further demonstrated robust diagnostic performance. Gene ontology and kyoto encyclopedia of genes and genome enrichment analyses indicated that the DEPs were predominantly associated with metabolic pathways. Ultimately, the integrative analysis of proteomics and metabolomics suggested that the central metabolic mechanism underlying CMD pathogenesis may be linked to the tricarboxylic acid cycle. This study revealed specific changes in the proteomic and metabolic profiles of CMD rats and identified four diagnostic markers, which are proteins and metabolites that could be potential diagnostic biomarkers for CMD. Full article

A combination of network pharmacology, molecular docking and ADME/drug-likeness predictions was employed to explore the potential of Salvia officinalis compounds to interact with key targets involved in the pathogenesis of T2DM. These were predicted using the SwissTargetPrediction, Similarity Ensemble Approach and BindingDB databases. Networks were constructed using the STRING online tool and Cytoscape (v.3.9.1) software. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis and molecular docking were performed using DAVID, SHINEGO 0.77 and MOE suite, respectively. ADME/drug-likeness parameters were computed using SwissADME and Molsoft L.L.C. The top-ranking targets were CTNNB1, JUN, ESR1, RELA, NR3C1, CREB1, PPARG, PTGS2, CYP3A4, MMP9, UGT2B7, CYP2C19, SLCO1B1, AR, CYP19A1, PARP1, CYP1A2, CYP1B1, HSD17B1, and GSK3B. Apigenin, caffeic acid, oleanolic acid, rosmarinic acid, hispidulin, and salvianolic acid B showed the highest degree of connections in the compound-target network. Gene enrichment analysis identified pathways involved in insulin resistance, adherens junctions, metabolic processes, IL-17, TNF-α, cAMP, relaxin, and AGE-RAGE in diabetic complications. Rosmarinic acid, caffeic acid, and salvianolic acid B showed the most promising interactions with PTGS2, DPP4, AMY1A, PTB1B, PPARG, GSK3B and RELA. Overall, this study enhances understanding of the antidiabetic activity of S. officinalis and provides further insights for future drug discovery purposes. Full article

Mechanized construction is being fully implemented in the electric power infrastructure domain to ensure construction safety, enhance project quality, and improve efficiency. Traditional methods of designing mechanized construction plans are often inefficient due to their labor-intensive processes and heavy reliance on human expertise. This study introduces and evaluates an ontology-guided system designed to automate mechanized construction planning for power grid projects. The developed ontology effectively models domain-specific knowledge, enabling the semantic integration of data from various sources. By leveraging SPARQL queries, the ontology-guided system incorporates knowledge reasoning capabilities that facilitate the automated selection of construction equipment and the generation of comprehensive construction plans. A prototype system incorporating an ontology-guided mechanism has been developed, showcasing marked enhancements in efficiency and accuracy over traditional manual methods, as evidenced by case studies and expert evaluations. The research results emphasize the potential of ontology-guided systems in innovating architectural planning, providing an extensible and standardized approach. Expert evaluation indicates that the system achieves 71.38% effectiveness in generating mechanized construction plans. Full article

Differences between orbital and subcutaneous abdominal fat in the same patient have been noted but not formally investigated, previously. The objective of this research was to compare the differential expression of protein profiles in subcutaneous abdominal and orbital adipose tissues. In this cross-sectional, observational study, orbital fat tissue was sampled from 10 patients who underwent blepharoplasty and agreed to provide a small sample of subcutaneous abdominal fat. Shotgun mass spectrometry was performed on the extracted proteome. Data were analyzed using protein appearance patterns, differential expression and statistical enrichment. Protein analysis revealed significant differences in proteomics and differential expression between the orbital and subcutaneous abdominal adipose tissues, which presented five proteins that were uniquely expressed in the orbital fat and 18 in the subcutaneous abdominal fat. Gene Ontology analysis identified significantly different cellular processes and components related to the extracellular matrix or basement membrane components. This analysis shows the differences between orbital and subcutaneous abdominal fat found in proteomics differential expression, uniquely expressed proteins, and cellular processes. Further research is needed to correlate specific proteins and cellular processes to the mechanism of fat accumulation and obesity. Full article