Background Studies have indicated that monocyte-to-high-density lipoprotein cholesterol ratio (MHR) can be a reliable indicator of various diseases. However, the association between MHR and gallstone ...prevalence remains unclear. Therefore, this study aimed to explore any potential association between MHR and gallstone prevalence. Methods This study used data from the National Health and Nutrition Examination Survey (NHANES) 2017-March 2020. MHR was calculated as the monocyte count ratio to high-density lipoprotein cholesterol levels. Multiple logistic regression models, Cochran-Armitage trend test, and subgroup analyses were used to examine the association between MHR and gallstones. Results This study included 5907 participants, of whom 636 (10.77%) were gallstone formers. The study participants had a mean age of 50.78 + or - 17.33 years. After accounting for multiple covariables, the multiple logistic regression model showed a positive linear association between MHR and gallstone odds. The subgroup analyses and interaction testing results revealed that the association between MHR and gallstones was statistically different across strata, including sex, smoking, asthma, and hypertension. Conclusions Gallstone prevalence positively associated with elevated MHR, indicating that MHR can be employed as a clinical indicator to assess gallstone prevalence. Keywords: Monocyte-to-high-density lipoprotein-cholesterol ratio, Gallstone, NHANES, Cross-sectional study
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
During the Kobe earthquake in 1995, Daikai subway station suffered the severe collapse, which aroused people's more attention to the earthquake damage response of underground structures. In order to ...investigate the seismic failure mechanism of underground frame structures, a series of 1/50-scaled dynamic centrifuge tests were conducted. To make the underground structures produce a reasonable seismic failure mode in tests, an experimental scheme was designed in detail based on the author's previous numerical studies. With the purpose of simulating the vertical inertial effect of the overburden soil in the dynamic centrifuge tests, a certain proportion of steel grits were mixed into the overlying soil. A model structure finally occurred the overall collapse mode, which was similar to that of Daikai subway station. Based dynamic centrifuge tests, the seismic failure mechanism of shallow buried underground frame structure was analyzed and summarized in the paper. It could offer a reference for the cause of collapse of Daikai subway station. The series of tests provided valuable experimental data for further studies of the earthquake damage response of underground frame structures, and also enriched the testing technique for destructive model tests.
•Research on seismic failure mechanism of shallow buried underground frame structure.•Enrich the testing technique for destructive model tests of underground structure.•Provide a reasonable explanation for catastrophic causes of Daikai subway station.•Validated author's numerical works on seismic failure mechanism of underground structure.
Full text
Available for:
GEOZS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Obesity and metabolic disorders have gradually become public health-threatening problems. The metabolic disorder is a cluster of complex metabolic abnormalities which are featured by dysfunction in ...glucose and lipid metabolism, and results from the increasing prevalence of visceral obesity. With the core driving factor of insulin resistance, metabolic disorder mainly includes type 2 diabetes mellitus (T2DM), micro and macro-vascular diseases, non-alcoholic fatty liver disease (NAFLD), dyslipidemia, and the dysfunction of gut microbiota. Strategies and therapeutic attention are demanded to decrease the high risk of metabolic diseases, from lifestyle changes to drug treatment, especially herbal medicines. Indole is a parent substance of numerous bioactive compounds, and itself can be produced by tryptophan catabolism to stimulate glucagon-like peptide-1 (GLP-1) secretion and inhibit the development of obesity. In addition, in heterocycles drug discovery, the indole scaffold is primarily found in natural compounds with versatile biological activity and plays a prominent role in drug molecules synthesis. In recent decades, plenty of natural or synthesized indole deriviatives have been investigated and elucidated to exert effects on regulating glucose hemeostasis and lipd metabolism. The aim of this review is to trace and emphasize the compounds containing indole scaffold that possess immense potency on preventing metabolic disorders, particularly T2DM, obesity and NAFLD, along with the underlying molecular mechanisms, therefore facilitate a better comprehension of their druggability and application in metabolic diseases.
Display omitted
•Indole scaffold was introduced in this review as a privileged structure in drug design for alleviating diabetes.•Indole alkaloids have potential in preventing metabolic disorders, including diet-induced obesity and fatty liver disease.•Mechanism studies of antidiabetic synthesized indoles indicated that these molecules act via various targets.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
ALKBH5 and YTHDF1 are regarded as the eraser and reader, respectively, in N6-methyladenosine (m6A) modification. Recently, immune contexture has been drawing increasing attention in terms of the ...progression and treatment of cancers. This study aimed to determine the relationship between ALKBH5/YTHDF1 and immunological characteristics of colon adenocarcinoma (COAD).
Expression of ALKBH5 and YTHDF1 was investigated across TCGA and GEO validated in our study. Patients with COAD were divided into two clusters using consensus clustering based on the expression of ALKBH5 and YTHDF1. We then compared their clinical characteristics and performed gene set enrichment analysis (GSEA) to identify the functional differences. Immune infiltration analyses were conducted using ESTIMATE, CIBERSORT, and ssGSEA. In addition, we evaluated the expression of the targets of immune checkpoint inhibitors (ICIs) and calculated the tumor mutation burden (TMB) of the tumor samples. Weighted gene co-expression network analysis (WGCNA) was used to identify the genes related to both ALKBH5/YTHDF1 expression and immunity. GSE39582 was utilized for external validation of immunological features between the two clusters.
Cluster 2 had high expression of ALKBH5 and lesser so of YTHDF1, whereas Cluster 1 had just the reverse. Cluster 1 had a higher N stage and pathological stage than Cluster 2. The latter had stronger immune infiltration, higher expression of targets of ICIs, more TMB, and a larger proportion of deficiency in mismatch repair-microsatellite instability-high (dMMR-MSI-H) status than Cluster 1. Moreover, WGCNA revealed 14 genes, including PD1 and LAG3, related to both the expression of ALKBH5/YTHDF1 and immune scores.
ALKBH5 and YTHDF1 influence immune contexture and can potentially transform cold tumors into hot tumors in patients with COAD.
Electric load forecasting is a vital task for energy management and policy-making. However, it is also a challenging problem due to the complex and dynamic nature of electric load data. In this ...paper, a novel technique, called LSV/MOPA, has been proposed for electric load forecasting. The technique is a hybrid model that combines the advantages of Long Short-Term Memory (LSTM) and Support Vector Regression (SVR), two powerful artificial intelligence algorithms. The hybrid model is further optimized by a newly Modified Orca Predation Algorithm (MOPA), which enhances the forecasting accuracy and efficiency. The LSV/MOPA model has been applied to historical electric load data from South Korea, covering four regions and 20 years. The LSV/MOPA model has been compared with other state-of-the-art forecasting techniques, including SVR/FFA, LSTM/BO, LSTM-SVR, and CNN-LSTM. The results show that the LSV/MOPA model with minimum average mean absolute percentage deviation error, including 365 in northern region, 12.8 in southern region, 8.6 in central region, and 30.8 in eastern region, provides the best fitting and outperforms the other techniques in terms of the Mean Absolute Percentage Deviation (MAPD) index, achieving lower values for all regions and years. The LSV/MOPA model also exhibits faster convergence and better generalization than the other techniques. This study demonstrates the effectiveness and superiority of the LSV/MOPA model for electric load forecasting and suggests its potential applications in other sectors where accurate forecasting is crucial.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
Macrophage infiltration is crucial for colorectal cancer (CRC) immunotherapy. Detailed classification of macrophage subsets will facilitate the selection of patients suitable for ...immunotherapy. However, the classification of macrophages in CRC is not currently detailed.
Methods
In this study, we combined single-cell RNA sequencing (scRNA-seq) and bulk-seq to analyze patients with colorectal cancer. scRNA-seq data were used to study cell-cell communication and to differentiate immune-infiltrating cells and macrophage subsets. Bulk-seq data were used to further analyze immune infiltration, clinical features, tumor mutational burden, and expression of immune checkpoint molecules in patients with CRC having different macrophage subsets.
Results
Seven macrophage subpopulations were identified, among which indoleamine 2,3 dioxygenase 1 (IDO1) macrophages had the most significant difference in the degree of infiltration among normal, microsatellite-unstable, and microsatellite-stable populations. We then performed gene set variation analysis using 12 marker genes of IDO1 macrophages and divided the patients into two clusters: high-IDO1 macrophages (H-IDO1M) and low-IDO1 macrophages (L-IDO1M). H-IDO1M showed higher infiltration of immune cells, higher expression of immune checkpoints, and less advanced pathological stages than L-IDO1M (p < 0.05).
Conclusions
This study elucidated that IDO1-macrophage-based molecular subtypes can predict the response to immunotherapy in patients with CRC. The results provide new insights into tumor immunity and help in clinical decisions regarding designing effective immunotherapy for these patients.
•CBLC levels was elevated in tumor tissues of CRC patients.•CBLC promoted CRC cell proliferation, migration and invasion.•CBLC accelerated tumor growth and promoted tumor metastasis to the lung.•CBLC ...induced the activation of ERK signaling pathway.•CBLC decreased ABI1 protein levels through its ubiquitin ligase activity.•ABI1 overexpression abolished the effects of CBLC on the tumorigenesis of CRC.
CBLC (CBL proto-oncogene C) is an E3 ubiquitin protein ligase that plays a key role in cancers. However, the function and mechanism of CBLC in colorectal cancer (CRC) has not been fully elucidated. The aim of this study was to investigate the function of CBLC in CRC and its underlying molecular mechanism. High CBLC levels were certified in tumor tissues of CRC patients, and its expression was positively associated with TNM stage. Next, we explored the role of CBLC in CRC using gain or loss of function. For biological function analysis, CCK-8 cell proliferation, colony formation, flow cytometry, scratch, and transwell assays collectively suggested that CBLC overexpression promoted cell proliferation, cell cycle progression, migration and invasion. As observed, CBLC knockdown exhibited exactly opposite effects, resulting in impaired tumorigenicity in vitro. Xenograft studies displayed that CBLC overexpression accelerated tumor growth and promoted tumor metastasis to the lung, while the inhibitory effects of CBLC knockdown on tumorigenicity and metastasis ability of CRC cells was also confirmed. Furthermore, the molecular mechanism of CBLC in CRC was explored. CBLC induced the activation of ERK signaling pathway, further leading to its pro-tumor role. Notably, CBLC decreased ABI1 (Abelson interactor protein-1, a candidate tumor suppressor) protein levels through its ubiquitin ligase activity, while ABI1 upregulation abolished the effects of CBLC on the tumorigenesis of CRC. Taken together, these results demonstrate that CBLC acts as a tumor promoter in CRC through triggering the ubiquitination and degradation of ABI1 and activating the ERK signaling pathway. CBLC may be a potential novel target for CRC.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Natural products with good antioxidative properties have been paid increased attention globally. However, due to its chemical complexity, it is difficult to find out its antioxidative compounds. ...Herein, the chemical profiling and antioxidant capacity of CiNingJi (CNJ) were analyzed, as an example. By using UHPLC-Q-TOF/MS, a total of 82 compounds were tentatively deduced. Furthermore, its free radical scavenging capacity was assessed by different
in vitro
spectrophotometric-based assays. The result showed that one ingredient,
Rosa roxburghii
, plays a critical role in its antioxidant activity. In addition, 18 potential antioxidants were screened out in CNJ by comparing the difference of it with and without DPPH reaction. They were identified mainly as catechin, ellagic acid, kajiichigoside F1, and their derivatives or isomers. With the further quantification of major found antioxidants, our results may provide some knowledge on predicting the antioxidative compounds of natural products.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Colon cancer is a malignant tumor with high morbidity and mortality. Researchers have tried to interpret it from different perspectives and divided it into different subtypes to facilitate ...individualized treatment. With the rise in the use of immunotherapy, its value in the field of tumor has begun to emerge. From the perspective of immune infiltration, this study classified colon cancer according to the infiltration of M2 macrophages in patients with colon cancer and further explored the same.
Cibersort algorithm was used to analyze the level of immune cell infiltration in patients with colon cancer in The Cancer Genome Atlas (TCGA) database. Weighted gene co-expression network analysis (WGCNA), Consensus Clustering analysis, Lasso analysis, and univariate Kaplan-Meier analysis were used to screen and verify the hub genes associated with M2 macrophages. Principal component analysis (PCA) was used to establish the M2 macrophage-related score (M2I Score). The correlation between M2I Score and somatic cell variation and microsatellite instability (MSI) were analyzed. Furthermore, the correlation between M2 macrophage score and differences in immunotherapy sensitivity was also explored.
M2 macrophage infiltration was associated with poor prognosis. Four hub genes (ANKS4B, CTSD, TIMP1, and ZNF703) were identified as the progression-related genes associated with M2 macrophages. A stable and accurate M2I Score for M2 macrophages used in colon adenocarcinoma was determined based on four hub genes. The M2I Score was positively correlated with the tumor mutation load (TMB). The M2I Score of the group with high instability of microsatellites was higher than that of the group with low instability of microsatellites and microsatellite-stable group. Combined with the Cancer Immunome Atlas database, we concluded that patients with high M2I Scores were more sensitive to programmed cell death protein 1 (PD-1) inhibitors and PD-1 inhibitors combined with cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitors. The low-rating group may have better efficacy without immune checkpoint inhibitors or with CTLA4 inhibitors alone.
Four prognostic hub genes associated with M2 macrophages were screened to establish the M2I Score. Patients were divided into two subgroups: high M2I Score group and low M2I Score group. TMB, MSI, and sensitivity to immunotherapy were higher in the high-rated group. PD-1 inhibitors or PD-1 combined with CTLA-4 inhibitors are preferred for patients in the high-rated group who are more sensitive to immunotherapy.
The increasingly common usage of single-cell sequencing in cancer research enables analysis of tumor development mechanisms from a wider range of perspectives. Metabolic disorders are closely ...associated with liver cancer development. In recent years, liver cancer has been evaluated from different perspectives and classified into different subtypes to improve targeted treatment strategies. Here, we performed an analysis of liver cancer from the perspective of energy metabolism based on single-cell sequencing data. Single-cell and bulk sequencing data of liver cancer patients were obtained from GEO and TCGA/ICGC databases, respectively. Using the Seurat R package and protocols such as consensus clustering analysis, genes associated with energy metabolism in liver cancer were identified and validated. An energy metabolism-related score (EM score) was established based on five identified genes. Finally, the sensitivity of patients in different scoring groups to different chemotherapeutic agents and immune checkpoint inhibitors was analyzed. Tumor cells from liver cancer patients were found to divide into nine clusters, with cluster 4 having the highest energy metabolism score. Based on the marker genes of this cluster and TCGA database data, the five most stable key genes (ADH4, AKR1B10, CEBPZOS, ENO1, and FOXN2) were identified as energy metabolism-related genes in liver cancer. In addition, drug sensitivity analysis showed that patients in the low EM score group were more sensitive to immune checkpoint inhibitors and chemotherapeutic agents AICAR, metformin, and methotrexate.
PDF
