FIT-graph: A multi-grained evolutionary graph based framework for disease diagnosis.

Early assessment, with the help of machine learning methods, can aid clinicians in optimizing the diagnosis and treatment process, allowing patients to receive critical treatment time. Due to the advantages of effective information organization and interpretable reasoning, knowledge graph-based methods have become one of the most widely used machine learning algorithms for this task. However, due to a lack of effective organization and use of multi-granularity and temporal information, current knowledge graph-based approaches are hard to fully and comprehensively exploit the information contained in medical records, restricting their capacity to make superior quality diagnoses. To address these challenges, we examine and study disease diagnosis applications in-depth, and propose a novel disease diagnosis framework named FIT-Graph. With novel medical multi-grained evolutionary graphs, FIT-Graph efficiently organizes the extracted information from various granularities and time stages, maximizing the retention of valuable information for disease inference and ensuring the comprehensiveness and validity of the final disease inference. We compare FIT-Graph with two real-world clinical datasets from cardiology and respiratory departments with the baseline. The experimental results show that its effect is better than the baseline model, and the baseline performance of the task is improved by about 5% in multiple indices.

A metabolomic signature of FIGO stage I and II endometrial cancer.

Endometrial cancer (EC) is a malignant tumor of the female reproductive tract. Due to its rapid growth and invasiveness, EC is currently the only gynecological neoplasm with rising incidence and mortality rates. It is of great significance to explore the metabolomics signature of stage I and II EC for the diagnosis and treatment. A mass spectrometry-based untargeted metabolomics approach was used to explore preoperative serum metabolites in the normal and stage I and II EC patients. The metabolites were mapped to the Ingenuity pathway analysis (IPA) database to determine the potential biomarkers and metabolic pathways that differ between EC patients and healthy controls. The top analysis-ready molecules of upregulated D-glucose thiamine and downregulated cholesterol, arachidonic acid, palmitic acid, oleic acid, stearic acid, linoleic acid may be the most related metabolites. These potential biomarkers have essential functions in regulating vital metabolic pathways associated with stage I and II EC. Additionally, our pathway analysis revealed five significantly related pathways according to the metabolite differentials. Finally, the disease and function prediction of the initial pathway analysis suggested that small molecule biochemistry, lipid metabolism, and organismal injury and abnormalities were associated with EC cases. Over 25 metabolites were differentially expressed in stage I and II EC. In addition, the six most significant metabolites were related to stage I and stage II EC cases. Ingenuity pathway analysis revealed potential biomarkers and metabolic pathways revolved to EC. In this paper, candidate endogenous biomarkers were defined as the basis for disease diagnosis and individualized treatment monitoring and revealed the mechanism of EC occurrence and development.

Metabolomics study on revealing the inhibition and metabolic dysregulation in Pseudomonas fluorescens induced by 3-carene.

3-Carene is a monoterpenoid that has an effective inhibitory ability against Pseudomonas fluorescens (P. fluorescens) which can induce a range of food contamination problems. In this study, ultra-performance liquid chromatography-mass spectrometry (UPLC-MS)-based metabolomics was used to elucidate the antimicrobial mechanism of 3-carene in P. fluorescens. Multivariate analysis of the metabolite data revealed significant differences in the potential metabolite profiles between groups. The results of univariate analysis showed that significant changes in 42 metabolites were observed after treatment with 3-carene for 12 h when compared to the control group. Moreover, 3-carene treatment resulted in disturbances in many metabolic processes, including amino acid metabolism, pantothenate and coenzyme A (CoA) biosynthesis and the tricarboxylic acid (TCA) cycle. These results provide a new insight into the antimicrobial mechanisms of 3-carene in P. fluorescens and enhance our understanding of the antimicrobial mechanism from a metabolic perspective.

MiR-646 suppresses proliferation and metastasis of non-small cell lung cancer by repressing FGF2 and CCND2.

MicroRNA-646 (miR-646) has been implicated in several other cancers; however, its functional mechanism in non-small cell lung cancer (NSCLC) remains unclear. In this study, we observed the downregulation of miR-646 expression in NSCLC tissues and cell lines. Low-level expression of miR-646 was associated with metastasis and stage of NSCLCs. Functional assays showed that overexpression of miR-646 could suppress NSCLC cell proliferation, clonogenicity, invasion, and inhibit epithelial-mesenchymal transition (EMT), whereas decreased miR-646 expression showed the opposite effects. Importantly, miR-646 overexpression attenuated in vivo tumor growth and metastasis in nude mice models. Mechanically, miR-646 directly targeted and suppressed fibroblast growth factor 2 (FGF2) and cyclin D2 (CCND2) expression. Reintroduction of FGF2 and CCND2 attenuated miR-646-mediated suppression of proliferation and invasion in NSCLC. Collectively, these results demonstrate that miR-646 acts as a tumor suppressor in NSCLC by targeting FGF2 and CCND2, and may serve as a therapeutic target for patients with NSCLC.

Antimicrobial Activity and Proposed Action Mechanism of 3-Carene against Brochothrix thermosphacta and Pseudomonas fluorescens.

3-Carene is an antimicrobial monoterpene that occurs naturally in a variety of plants and has an ambiguous antibacterial mechanism against food-borne germs. The antibacterial effects and action mechanism of 3-carene against Gram-positive Brochothrix thermosphacta ACCC 03870 and Gram-negative Pseudomonas fluorescens ATCC 13525 were studied. Scanning electron microscopy (SEM) examination and leakage of alkaline phosphatase (AKP) verified that 3-carene caused more obvious damage to the morphology and wall structure of B. thermosphacta than P. fluorescens. The release of potassium ions and proteins, the reduction in membrane potential (MP), and fluorescein diacetate (FDA) staining further confirmed that the loss of the barrier function of the cell membrane and the leakage of cytoplasmic contents were due to the 3-carene treatment. Furthermore, the disorder of succinate dehydrogenase (SDH), malate dehydrogenase (MDH), pyruvate kinase (PK), and ATP content indicated that 3-carene could lead to metabolic dysfunction and inhibit energy synthesis. In addition, the results from the fluorescence analysis revealed that 3-carene could probably bind to bacterial DNA and affect the conformation and structure of genomic DNA. These results revealed that 3-carene had strong antibacterial activity against B. thermosphacta and P. fluorescens via membrane damage, bacterial metabolic perturbations, and genomic DNA structure disruption, interfering in cellular functions and even causing cell death.