Background
Colon adenocarcinoma (COAD) is a common digestive system malignancy with high mortality and poor prognosis. Accumulating evidence indicates that choline metabolism is closely related to ...tumorigenesis and development. However, the efficacy of choline metabolism-related signature in predicting patient prognosis, immune microenvironment and chemotherapy response has not been fully clarified.
Methods
Choline metabolism-related differentially expressed genes (DEGs) between normal and COAD tissues were screened using datasets from The Cancer Genome Atlas (TCGA), Kyoto Encyclopedia of Genes and Genomes (KEGG), AmiGO2 and Reactome Pathway databases. Two choline metabolism-related genes (CHKB and PEMT) were identified by univariate and multivariate Cox regression analyses. TCGA-COAD was the training cohort, and GSE17536 was the validation cohort. Patients in the high- and low-risk groups were distinguished according to the optimal cutoff value of the risk score. A nomogram was used to assess the prognostic accuracy of the choline metabolism-related signature. Calibration curves, decision curve analysis (DCA), and clinical impact curve (CIC) were used to improve the clinical applicability of the prognostic signature. Gene Ontology (GO) and KEGG pathway enrichment analyses of DEGs in the high- and low-risk groups were performed. KEGG cluster analysis was conducted by the KOBAS-i database. The distribution and expression of CHKB and PEMT in various types of immune cells were analyzed based on single-cell RNA sequencing (scRNA-seq). The CIBERSORT and ESTIMATE algorithms evaluated tumor immune cell infiltration in the high- and low-risk groups. Evaluation of the half maximal inhibitory concentration (IC
50
) of common chemotherapeutic drugs based on the choline metabolism-related signature was performed. Small molecule compounds were predicted using the Connectivity Map (CMap) database. Molecular docking is used to simulate the binding conformation of small molecule compounds and key targets. By immunohistochemistry (IHC), Western blot, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) experiments, the expression levels of CHKB and PEMT in human, mouse, and cell lines were detected.
Results
We constructed and validated a choline metabolism-related signature containing two genes (CHKB and PEMT). The overall survival (OS) of patients in the high-risk group was significantly worse than that of patients in the low-risk group. The nomogram could effectively and accurately predict the OS of COAD patients at 1, 3, and 5 years. The DCA curve and CIC demonstrate the clinical utility of the nomogram. scRNA-seq showed that CHKB was mainly distributed in endothelial cells, while PEMT was mainly distributed in CD4
+
T cells and CD8
+
T cells. In addition, multiple types of immune cells expressing CHKB and PEMT differed significantly. There were significant differences in the immune microenvironment, immune checkpoint expression and chemotherapy response between the two risk groups. In addition, we screened five potential small molecule drugs that targeted treatment for COAD. Finally, the results of IHC, Western blot, and qRT-PCR consistently showed that the expression of CHKB in human, mouse, and cell lines was elevated in normal samples, while PMET showed the opposite trend.
Conclusion
In conclusion, we constructed a choline metabolism-related signature in COAD and revealed its potential application value in predicting the prognosis, immune microenvironment, and chemotherapy response of patients, which may lay an important theoretical basis for future personalized precision therapy.
Abstract
To reduce food waste, many behavioural intervention experiments have been conducted worldwide, but their effectiveness remains unclear. To assess their impacts, we present a meta-analysis ...based on 58 studies, selected after screening 1143 papers, which were conducted between 2011 and 2021 covering 26 533 participants. We confirm that behavioural interventions have a moderate effect (
z
= 0.22) on food waste reduction, with education programs having the most significant impact and informational feedback having the least. We also show that interventions in elementary and middle school settings marginally improve the overall effect size (
P
< 0.1), and controlled experiments exhibit a higher effect size compared to pre-post experiments in education interventions (
P
< 0.05). Finally, we present a roadmap to guide future research in the next decade to further improve our understanding on the effects of behavioural interventions to reduce food waste.
Patients with inflammatory bowel disease (IBD) often require immunosuppressive therapy and are hence susceptible to various opportunistic viral and bacterial infections. In this regard, many studies ...on IBD and COVID-19 have been conducted. However, no bibliometric analysis has been performed. This study provides a general overview of IBD and COVID-19.
Publications about IBD and COVID-19 from 2020 to 2022 were retrieved from the Web of Science Core Collection (WoSCC) database. Bibliometric analysis was performed using VOSviewer, CiteSpace, and HistCite.
A total of 396 publications were retrieved and considered in this study. The maximum number of publications were from the United States, Italy, and England, and the contributions of these countries were significant. Kappelman ranked first in article citations. The Icahn School of Medicine at Mount Sinai and
were the most prolific affiliation and journal, respectively. The most influential research topics were "management", "impact", "vaccination", and "receptor". The following keywords represented research frontiers: "depression", "the quality of life of IBD patients", "infliximab", "COVID-19 vaccine", and "second vaccination".
Over the past 3 years, most studies on IBD and COVID-19 have focused on clinical research. In particular, topics such as "depression", "the quality of life of IBD patients", "infliximab", "COVID-19 vaccine", and "second vaccination" were noted to have received much attention recently. Future research should focus on our understanding of the immune response to COVID-19 vaccination in biologically treated patients, the psychological impact of COVID-19, IBD management guidelines, and the long-term impact of COVID-19 in IBD patients. This study will provide researchers with a better understanding of research trends on IBD during COVID-19.
Helicobacter pylori (H. pylori) infection is the most common etiology of chronic gastric. H. pylori gastritis would gradually evolve into gastric atrophy, intestinal metaplasia, dysplasia and ...malignant lesions. Herein, this study aimed to investigate the potential impact of H. pylori colonization density and depth on the severity of histological parameters of gastritis.
A prospective monocentric study was conducted from December 2019 to July 2022, enrolling patients with confirmed chronic H. pylori infection via histopathological evaluation. H. pylori colonization status was detected by immunohistochemical staining, pathological changes of gastric specimens were detected by hematoxylin eosin staining. Epidemiological, endoscopic and histopathological data were collected.
A total of 1120 patients with a mean age of 45.8 years were included. Regardless of the previous history of H. pylori eradication treatment, significant correlations were observed between the density and depth of H. pylori colonization and the intensity of gastritis activity (all P < 0.05). Patients with the lowest level of H. pylori colonization density and depth exhibited the highest level of mild activity. In whole participants and anti-H. pylori treatment-naive participants, H. pylori colonization density and depth were markedly correlated with the severity of chronic gastritis and gastric atrophy (all P < 0.05). H. pylori colonization density (P = 0.001) and depth (P = 0.047) were significantly associated with ulcer formation in patients naive to any anti-H. pylori treatment. No significant associations were observed between the density and depth of H. pylori colonization and other histopathological findings including lymphadenia, lymphoid follicle formation and dysplasia.
As the density and depth of H. pylori colonization increased, so did the activity and severity of gastritis, along with an elevated risk of ulcer formation.
Previous studies have shown that tumor size has an impact on the prognosis of hepatocellular carcinoma (HCC). Whether tumor size is related to the prognosis of distant metastatic HCC is unclear. The ...purpose of this study was to investigate the effect of tumor size on the prognosis of distant metastatic HCC.
Data on patients with HCC were collected from the (SEER) database of surveillance, epidemiology and final results. Propensity score matching (PSM) was used to reduce confounding factors and comprehensively evaluate the clinicopathological features and prognosis of distant metastatic HCC.
There were 189 patients with distant metastatic HCC whose tumor size was ≤ 50 mm and 615 patients with a tumor size > 50 mm. The tumor sizes of distant metastatic HCC patients were associated with race, grade, surgical treatment, N and AFP. The Kaplan-Meier analysis showed that the mortality rate of patients with a tumor size > 50 mm was higher than that of patients with a tumor size ≤ 50 mm (p = 0.00062). However, there were no significant differences in mortality rates after adjusting for confounding variables by using propensity score matching (p = 0.23).
This propensity score matching study provides the best data in support of the following assertions: tumor size is not an independent prognostic factor for distant metastatic HCC.
Horizontal well technology is a promising method for oil and gas development. During cementing operations in horizontal wells, it was found that conventional casing centralizers could not meet the ...requirements for casing cementing in expanded wellbores. Therefore, a new type of casing centralizer needs to be designed for horizontal well sections that have undergone enlargement. By analyzing the most common materials currently used, 45 steel was selected for the spring leaf of the novel casing centralizer. To evaluate the centralization effect of the horizontal well casing centralizer, a casing centralization degree evaluation function was established, and a wellbore-centralizer mechanical model was proposed using the finite element method to simulate the working conditions of the centralizer spring leaf in ϕ215.9 and ϕ311.2 mm well sections. On this basis, a wellbore-centralizer-casing coupling model that does not consider the effect of wellbore fluid on the casing was established to simulate the centralization characteristics of the new casing centralizer and traditional centralizer under different wellbore sizes. Simulation results show that the average casing centralization degree of the new centralizer is 85.53%, while that of the traditional centralizer is 55.58%. That is, the horizontal well casing centralizer can maintain a good centralization effect on the casing string.
T-cell immunoglobulin domain and mucin domain-3 (Tim-3) is a versatile immunomodulator that protects against intestinal inflammation. Necroptosis is a type of cell death that regulates intestinal ...homeostasis and inflammation. The mechanism(s) underlying the protective role of macrophage Tim-3 in intestinal inflammation is unclear; thus, we investigated whether specific Tim-3 knockdown in macrophages drives intestinal inflammation via necroptosis. Tim-3 protein and mRNA expression were assessed via double immunofluorescence staining and single-cell RNA sequencing (sc-RNA seq), respectively, in the colonic tissues of patients with inflammatory bowel disease (IBD) and healthy controls. Macrophage-specific Tim3-knockout (Tim-3M−KO) mice were generated to explore the function and mechanism of Tim-3 in dextran sodium sulfate (DSS)-induced colitis. Necroptosis was blocked by pharmacological inhibitors of receptor-interacting protein kinase (RIP)1, RIP3, and reactive oxygen species (ROS). Additionally, in vitro experiments were performed to assess the mechanisms of neutrophil necroptosis induced by Tim-3 knockdown macrophages. Although Tim-3 is relatively inactive in macrophages during colon homeostasis, it is highly active during colitis. Compared to those in controls, Tim-3M−KO mice showed increased susceptibility to colitis, higher colitis scores, and increased pro-inflammatory mediator expression. Following the administration of RIP1/RIP3 or ROS inhibitors, a significant reduction in intestinal inflammation symptoms was observed in DSS-treated Tim-3M−KO mice. Further analysis indicated the TLR4/NF-κB pathway in Tim-3 knockdown macrophages mediates the TNF-α-induced necroptosis pathway in neutrophils. Macrophage Tim-3 regulates neutrophil necroptosis via intracellular ROS signaling. Tim-3 knockdown macrophages can recruit neutrophils and induce neutrophil necroptosis, thereby damaging the intestinal mucosal barrier and triggering a vicious cycle in the development of colitis. Our results demonstrate a protective role of macrophage Tim-3 in maintaining gut homeostasis by inhibiting neutrophil necroptosis and provide novel insights into the pathogenesis of IBD.
Display omitted
•Tim-3 expression is significantly increased in macrophages from patients with IBD.•Macrophage Tim-3 deficiency increases DSS-induced colitis susceptibility by inducing neutrophil necroptosis..•Tim-3 knockdown macrophages induce neutrophil chemotaxis and necroptosis via the release of IL-8 and TNF-α.•Macrophage Tim-3 inhibits neutrophil necroptosis via downregulating TLR4/NF-κB signaling pathway.•ROS plays a critical role in macrophage Tim-3 deficiency-mediated necroptosis.
Colon adenocarcinoma (COAD) is one of the most common clinically malignant tumours of the digestive system, with high incidence and mortality and poor prognosis. Interferon-gamma (IFN-γ) and long ...noncoding RNAs (lncRNAs) have prognostic values and were closely associated with immune microenvironment in COAD. Thus, identifying IFN-γ-related lncRNAs may be valuable in predicting the survival of patients with COAD. In this study, we identified IFN-γ-related lncRNAs and divided COAD patients from the Cancer Genome Atlas (TCGA) database into training and validation sets. Pearson’s correlation analysis and least absolute shrinkage and selection operator (LASSO) Cox regression were performed to select IFN-γ-related lncRNA-associated prognoses. Thirteen lncRNAs (AC025165.8, AC091633.3, FENDRR, LINC00882, LINC01828, LINC01829, MYOSLID, RP11-154H23.4, RP11-20J15.3, RP11-324L17.1, RP11-342A23.2, RP11-805I24.3, SERTAD4-AS1) were identified to construct an IFN-γ-related lncRNA prognostic signature in TCGA training (n =213) and validation (n =213) cohorts. COAD patient risk scores were calculated and classified into high- and low-risk groups based on the median value of the risk scores in each dataset. We compared the overall survival (OS) of patients stratified by age, gender, and stage. The OS in the high-risk group was significantly shorter than that in the low-risk group. In addition, the clinical nomogram incorporating the prognostic signature and clinical features showed a high concordance index of 0.78 and accurately predicted 1-, 3-, and 5-year survival times among COAD patients in the high- and low-risk groups. Based on the risk model, the high- and low-risk groups exhibited distinct differences in the immune system by gene set enrichment analysis (GSEA) functional annotation, and differentially expressed genes (DEGs) between the high- and low-risk groups were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. We investigated the expression of multiple immune checkpoint genes in the high- and low-risk groups and plotted Kaplan-Meier survival curves, indicating that immune checkpoint genes, such as LAG3 and PD. L1, STING and TIM 3, were also expressed differently between the two risk groups. Subsequently, there were dramatic differences in mutated genes, SNV (single nucleotide variants) classes, variant types and variant allele frequencies between low- and high-risk patients with COAD. Patients stratified by risk scores had different sensitivities to common chemotherapeutic agents. Finally, we used quantitative real-time polymerase chain reaction (qRT-PCR) assays to demonstrate that three lncRNAs were significantly differentially expressed in COAD tissues and adjacent normal tissues. Considered together, a thirteen-lncRNA prognostic signature has great potential to be a prognostic biomarker and could play an essential role in the immune microenvironment of COAD.
Innovation products from historical cultural architectural have widely adopted 3D printing technology in recent years. To study the applicability of existing 3D printing materials, it is necessary to ...analyze the performance indicators of 3D printing materials and carry out material science experiments. Step 1: the material performance index composition of cultural innovation products was derived by integrating the literature of cultural heritage, product design, quality system, and material science. Step 2: The columns of Chengs’ Miyake in Huizhou were taken as the creative source. Its geometric shape model was obtained through 3D scanning, and the design of the cultural innovation products was completed. Step 3: Photosensitive resin, nylon, and stainless steel, three commonly used 3D printing materials, were used to make samples, with one sample of each material. Finally, we carried out material science tests according to the material performance index. The experimental data of three materials were obtained and compared. The properties of the three 3D printing materials, photosensitive resin, nylon, and stainless steel, have advantages and disadvantages. Still, they all struggle to meet the needs of cultural and creative products in historical buildings. It is necessary to integrate the three materials’ properties to develop new 3D printing materials.
