Overexpression of ZNF169 promotes the growth and proliferation of colorectal cancer cells via the upregulation of ANKZF1.

Colorectal cancer (CRC) is one of the most common malignancies worldwide. The 5­year survival rate of patients diagnosed with the early stages of the disease is markedly higher than that of patients in the advanced stages. Therefore, identifying novel biomarkers and drug targets for CRC is critical for clinical practice. Zinc finger protein 169 (ZNF169) is a crucial transcription factor, and its role in CRC remains to be explored. The present study aimed to investigate the clinical relevance, function and underlying mechanisms of ZNF169 in CRC growth and proliferation. The Cancer Genome Atlas (TCGA) database was utilized to analyze the clinical relevance of ZNF169 in patients with CRC. Immunohistochemical staining was performed on tissue samples from patients with CRC to detect the expression of ZNF169. The HCT­116, HT­29 and RKO cell lines were employed for in vitro experiments. The overexpression and knockdown of ZNF169 were achieved by transfecting the cells with lentivirus and small interfering RNAs, respectively. Cell Counting Kit­8, colony formation and EdU staining assays were applied to investigate the function of ZNF169 in CRC cells. Dual luciferase activity and chromatin immunoprecipitation (ChIP)­quantitative PCR (qPCR) assays were performed to identify the regulatory effects of ZNF169 on the ankyrin repeat and zinc­finger domain­containing 1 (ANKZF1; also known as ZNF744) gene. Reverse transcription­quantitative PCR and western blot analysis were performed to measure mRNA and protein expression, respectively. The analysis of TCGA data revealed a positive correlation between ZNF169 and ANKZF1, with the overexpression of ANKZF1 being associated with a poor prognosis of patients with CRC. The experimental results demonstrated that ZNF169 was expression upregulated in CRC tissue compared with that in normal colon tissue. Gain­of­function and loss­of­function experiments revealed that ZNF169 enhanced the intensity of EdU staining, promoting the growth and proliferation of CRC cells. Furthermore, the overexpression of ZNF169 potentiated the transcriptional activity of the ANKZF1 gene, while the knockdown of ZNF169 produced the opposite results. ChIP­qPCR confirmed the interaction between ZNF169 and the promoter sequence of ANKZF1. Rescue experiments revealed that ZNF169 accelerated CRC cell growth and proliferation through the upregulation of ANKZF1. Furthermore, there was a positive correlation identified between ZNF169 and ANKZF1, and upregulation of ANKZF1 expression was associated with the poor prognosis of patients with CRC. On the whole, the present study demonstrates that ZNF169 contributes to CRC malignancy by potentiating the expression of ANKZF1. Thus, the regulation of ZNF169 and/or ANKZF1 expression may represent a viable strategy for the treatment patients with CRC with a high expression of ZNF169.

The occupational burnout among medical staff with high workloads after the COVID-19 and its association with anxiety and depression.

Objective: After the end of COVID-19, medical staff were immediately faced with a high workload, leading to widespread occupational burnout. This study aims to explore the level and influencing factors of burnout among medical staff during this period, as well as its relationship with anxiety and depression. Methods: The participants' levels of burnout were assessed using Maslach Burnout Inventory-Human Services Survey (MBI-HSS), and the reliability and validity of the questionnaire were evaluated through Cronbach's α and Confirmatory Factor Analysis (CFA). Independent sample t-test, chi-square test, and Pearson analysis were employed to determine the correlation between two sets of variables. Univariate and multivariate logistic regression analyses were conducted to identify significant factors influencing burnout. Finally, nomograms were used to predict the probability of burnout occurrence. Results: This study collected a total of 1,550 questionnaires, and after excluding 45 questionnaires that were duplicates or incomplete, a sample of 1,505 (97.1%) participants were included in the final statistical analysis. Both Cronbach's α and the fit indices of CFA demonstrated excellent adaptability of the Chinese version of MBI-HSS in this study. The overall prevalence rates for emotional exhaustion (EE), depersonalization (DP), and diminished personal accomplishment (PA) were 52.4, 55.3, and 30.6%, respectively. Obtaining psychological support, health condition, relationship with family members, and insufficient sleep were identified as common contributing factors to burnout among medical staff. Additionally, age and promotion pressure were also associated with burnout among doctors, and exceeding legal working hours was an important factor for nurse burnout. The C-index for the nomograms predicting burnout among doctors and nurses was 0.832 and 0.843, respectively. Furthermore, burnout exhibited a significant linear correlation with anxiety and depression. Conclusion: After the end of COVID-19, medical staff in high workload environments were facing severe burnout, which might lead to anxiety and depression. The occupational burnout of medical staff needed to be taken seriously and actively intervened.

Metabolomics analyses of cancer tissue from patients with colorectal cancer.

The alteration of metabolism is essential for the initiation and progression of numerous types of cancer, including colorectal cancer (CRC). Metabolomics has been used to study CRC. At present, the reprogramming of the metabolism in CRC remains to be fully elucidated. In the present study, comprehensive untargeted metabolomics analysis was performed on the paired CRC tissues and adjacent normal tissues from patients with CRC (n=35) using ultra­high­performance liquid chromatography­mass spectrometry. Subsequently, bioinformatic analysis was performed on the differentially expressed metabolites. The changes in these differential metabolites were compared among groups of patients based on sex, anatomical tumor location, grade of tumor differentiation and stage of disease. A total of 927 metabolites were detected in the tissue samples, and 24 metabolites in the CRC tissue were significantly different compared with the adjacent normal tissue. The present study revealed that the levels of three amino acid metabolites were increased in the CRC tissue, specifically, N­α­acetyl­Îµ­(2­propenal)­Lys, cyclo(Glu­Glu) and cyclo(Phe­Glu). The metabolites with decreased levels in the CRC tissue included quinaldic acid (also referred to as quinoline­2­carboxilic acid), 17α­ and 17ß­estradiol, which are associated with tumor suppression activities, as well as other metabolites such as, anhydro­ß­glucose, Asp­Arg, lysophosphatidylcholine, lysophosphatidylethanolamine (lysoPE), lysophosphatidylinositol, carnitine, 5'­deoxy­5'­(methylthio) adenosine, 2'­deoxyinosine­5'­monophosphate and thiamine monophosphate. There was no difference in the levels of the differential metabolites between male and female patients. The differentiation of CRC also showed no impact on the levels of the differential metabolites. The levels of lysoPE were increased in the right side of the colon compared with the left side of the colon and rectum. Analysis of the different tumor stages indicated that 2­aminobenzenesulfonic acid, P­sulfanilic acid and quinoline­4­carboxylic acid were decreased in stage I CRC tissue compared with stage II, III and IV CRC tissue. The levels of N­α­acetyl­Îµ­(2­propenal)­Lys, methylcysteine and 5'­deoxy­5'­(methylthio) adenosine varied at different stages of tumorigenesis. These differential metabolites were implicated in multiple metabolism pathways, including carbohydrate, amino acid, lipid, nucleotide and hormone. In conclusion, the present study demonstrated that CRC tumors had altered metabolites compared with normal tissue. The data from the metabolic profile of CRC tissues in the present study provided supportive evidence to understand tumorigenesis.

The Thermal Stress Problem of Bimodular Curved Beams under the Action of End-Side Concentrated Shear Force.

A bimodular material is a kind of material that presents two elastic moduli in tension and compression. In classical thermoelasticity, however, the bimodular material is rarely considered due to its complexity in analysis. In fact, almost all materials will present, more or less, bimodular characteristics, and in some cases, the mechanical properties of materials cannot be fully utilized simply by ignoring the bimodular characteristics. In this study, the thermal stress problem of bimodular curved beams under the action of end-side concentrated shear force is analytically and numerically investigated, in which the temperature rise modes in a thermal environment are considered arbitrary. Using the stress function method based on compatibility conditions, a two-dimensional solution of thermoelasticity of the bimodular curved beam subjected to end-side concentrated shear force was obtained. The results show that the solution for a bimodular curved beam with a thermal effect can be reduced to that of a bimodular curved beam without a thermal effect. At the same time, the numerical simulation for the problem verifies the correctness of the theoretical solution. The results may serve as a theoretical reference for the refined analysis and optimization of curved beams in a thermal environment.

Increased NOX1 and DUOX2 expression in the colonic mucosa of patients with chronic functional constipation.

To determine whether oxidative stress and inflammation are associated with constipation by examining the expression of the main producers of reactive oxygen species, nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, and pro-inflammatory cytokines in the colon of patients with chronic functional constipation. The colonic biopsies were collected from 32 patients with chronic functional constipation and 30 healthy subjects who underwent colonoscopy. Colonic mucosal histology was observed. Interleukin (IL)-1ß, IL-6, IL-8 messenger RNA (mRNA), and 4 members of NADPH oxidase (NOX1, NOX2, DUOX2, and NOX4) protein and mRNA were assessed by immunohistochemistry, western blotting, and reverse transcription polymerase chain reaction. The tissues from both patients and healthy subjects showed normal histological structure without increase of inflammatory cells. NOX1 protein and mRNA levels were significantly increased compared to controls (P < .05). DUOX2 protein, but not mRNA, was increased by 2-fold compared to controls (P < .05). The levels of NOX2 and NOX4 protein and mRNA demonstrated no significant difference between patients and control subjects. The levels of IL-1ß and IL-6 mRNA were significantly higher in constipation patients (P < .05), while IL-8 mRNA level was no different between the 2 groups. NADPH oxidase and pro-inflammatory cytokine might be involved in the pathogeneses of chronic functional constipation.

AHCYL1 Is a Novel Biomarker for Predicting Prognosis and Immunotherapy Response in Colorectal Cancer.

Background: Colorectal cancer (CRC) is the third most frequent cancer worldwide. The AHCYL1 gene is required for CNV and has a close association with the tumor immune microenvironment. However, the predictive value of the AHCYL1 gene in patients with CRC remains unknown. Methods: AHCYL1 gene with prognostic potential was comprehensively analyzed. Next, using LASSO Cox regression, we fully examined and integrated the AHCYL1 and AHCYL1-related genes from TCGA database. Meanwhile, TCGA database was used to study the connection between AHCYL1 and the tumor immune microenvironment and tumor mutation burden (TMB) in CRC. The influence of AHCYL1 in tumor growth and the recruiting ability of CD8+ T cells were verified, respectively, in vivo and in tissues. To ascertain the connection between AHCYL1 and AHCYL1-related genes and the prognosis of CRC, a prognostic model was created and validated. Result: We demonstrated that AHCYL1 has a differential expression and patients with AHCYL1 deletion get shorter survival in CRC. Additionally, the tissues without AHCYL1 have a weaker ability to recruit the natural killer (NK) cell, CD8+ T cells, and tumor-infiltrating lymphocytes (TILs) and response to immunotherapy. Additionally, knockdown of AHCYL1 promoted tumor growth in the CRC mouse model and recruited lower CD8+ T cells in CRC tissues. TCGA database was used to classify patients into low- and high-risk categories based on the expression of four genes. Meanwhile, we discovered an association between the low-risk group and a lower TMB and a higher response to immunotherapy. Finally, a predictive nomogram based on these genes was developed and verified, yielding a C-index of 0.74. Conclusion: For CRC patients, the prognostic model based on AHCYL1 and AHCYL1-related genes showed a high predictive performance in terms of prognosis and immunotherapy response.