IFIT1 + neutrophil is a causative factor of immunosuppressive features of poorly cohesive carcinoma (PCC).

The importance of the immune microenvironment in poorly cohesive carcinoma (PCC) has been highlighted due to its limited response rate to conventional therapy and emerging treatment resistance. A combination of clinical cohorts, bioinformatics analyses, and functional/molecular experiments revealed that high infiltration of Interferon Induced Protein with Tetratricopeptide Repeats 1 (IFIT1) + tumor-associated neutrophils (TANs) is a distinguishing feature of PCC patients. Upregulation of IFIT1 + TANs promote migration and invasion of gastric cancer (GC) cell lines (MKN45 and MKN74) and stimulates the growth of cell-derived xenograft models. Besides, by promoting macrophage secreted phosphoprotein 1 (SPP1) expression and facilitating cancer-associated fibroblast and endothelial cell recruitment and activation through TANs, IFIT1 promotes a mesenchymal phenotype, which is associated with a poor prognosis. Importantly, compared to non-PCC (NPCC), PCC tumors is more immunosuppressive. Mechanistically, IFIT1 can be stimulated by IFN-γ and contributes to the expression of Programmed Cell Death 1 Ligand (PDL1) in TANs. We demonstrated in mouse models that IFIT1 + PDL1 + TANs can induce acquired resistance to anti-PD-1 immunotherapy, which may be responsible for the difficulty of PCC patients to benefit from immunotherapy. This work highlights the role of IFIT1 + TANs in mediating the remodeling of the tumor immune microenvironment and immunotherapeutic resistance and introduces IFIT1 + TANs as a promising target for precision therapy of PCC.

Correlation between hemoglobin and the risk of common malignant tumors: a 1999-2020 retrospective analysis and causal association analysis.

BACKGROUND: The role of hemoglobin (HGB) in common malignant tumors remains unclear. METHODS: A retrospective analysis was conducted to identify the correlation between HGB levels and risk of 15 malignant tumors using 50,085 samples from the National Health and Nutrition Examination Survey. Mendelian Randomization analyses (MRAs) were performed based on genome-wide association study data to assess the causal relationship between HGB levels and these malignant tumors using more than 700,000 samples. The robustness of the MRA results was confirmed through various analytical methods. Fifty-six in-house samples were used to investigate the correlation between HGB levels and the prognosis in prostate cancer (PRCA) using the Kaplan-Meier curve. RESULTS: High HGB levels were associated with a higher risk for patients with cervix cancer, melanoma, and non-melanoma skin cancer (OR > 1.000, p < 0.05). It served as a protective factor for colon cancer, esophagus cancer, stomach cancer, bone cancer, lung cancer, renal cancer, and PRCA (OR < 1.000, p < 0.05). Furthermore, MRAs suggested that elevated HGB levels were correlated with a reduced risk of PRCA (OR = 0.869, p < 0.05), with no significant association observed between this marker and the remaining 14 malignant tumors. No pleiotropy or heterogeneity was found in the ultimate results for MRAs (p-values > 0.05), suggesting the robustness of the results. The results derived from the in-house data revealed a relationship between higher HGB values and a more favorable prognosis in PRCA (p < 0.05). CONCLUSION: High circulating HGB levels may play a protective prognostic role for PRCA and serve as a protective factor against the occurrence of PRCA.

Risk factors for one-year mortality following discharge in patients with acute aortic dissection: development and validation of a predictive model in a cross-sectional study.

PURPOSE: This study was aimed to identify the risk factors that influence the mortality risk in patients with acute aortic dissection (AAD) within one year after discharge, and aimed to construct a predictive model for assessing mortality risk. METHODS: The study involved 320 adult patients obtained from the Medical Information Mart for Intensive Care (MIMIC) database. Logistic regression analysis was conducted to identify potential risk factors associated with mortality in AAD patients within one year after discharge and to develop a predictive model. The performance of the predictive model was assessed using the receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA). To further validate the findings, patient data from the First Affiliated Hospital of Guangxi Medical University (157 patients) were analyzed. RESULTS: Univariate and multivariate logistic regression analyses revealed that gender, length of hospital stay, highest blood urea nitrogen (BUN_max), use of adrenaline, and use of amiodarone were significant risk factors for mortality within one year after discharge (p < 0.05). The constructed model exhibited a consistency index (C-index) and an area under the ROC curve of 0.738. The calibration curve and DCA demonstrated that these indicators had a good degree of agreement and utility. The external validation results of the model also indicated good predictability (AUC = 0.700, p < 0.05). CONCLUSION: The personalized scoring prediction model constructed by gender, length of hospital stays, BUN_max levels, as well as the use of adrenaline and amiodarone, can effectively identify AAD patients with high mortality risk within one year after discharge.

CDK6 is a novel predictive and prognosis biomarker correlated with immune infiltrates in multiple human neoplasms, including small cell lung carcinoma.

The roles of cyclin-dependent kinase 6 (CDK6) in various cancers, including small cell lung carcinoma (SCLC), remain unclear. Here, 111,54 multi-center samples were investigated to determine the expression, clinical significance, and underlying mechanisms of CDK6 in 34 cancers. The area under the curve (AUC), Cox regression analysis, and the Kaplan-Meier curves were used to explore the clinical value of CDK6 in cancers. Gene set enrichment analysis and correlation analysis were performed to detect potential CDK6 mechanisms. CDK6 expression was essential in 24 cancer cell types. Abnormal CDK6 expression was observed in 14 cancer types (e.g., downregulated in breast invasive carcinoma; p < 0.05). CDK6 allowed six cancers to be distinguished from their controls (AUC > 0.750). CDK6 expression was a prognosis marker for 13 cancers (e.g., adrenocortical carcinoma; p < 0.05). CDK6 was correlated with several immune-related signaling pathways and the infiltration levels of certain immune cells (e.g., CD8+ T cells; p < 0.05). Downregulated CDK6 mRNA and protein levels were observed in SCLC (p < 0.05, SMD = - 0.90). CDK6 allowed the identification of SCLC status (AUC = 0.91) and predicted a favorable prognosis for SCLC patients (p < 0.05). CDK6 may be a novel biomarker for the prediction and prognosis of several cancers, including SCLC.

Clinical Significance and Underlying Mechanisms of CELSR3 in Metastatic Prostate Cancer Based on Immunohistochemistry, Data Mining, and In Silico Analysis.

Background: The treatment and survival rate of patients with metastatic prostate cancer (MPCa) remain unsatisfactory. Herein, the authors investigated the clinical value and potential mechanisms of cadherin EGF LAG seven-pass G-type receptor 3 (CELSR3) in MPCa to identify novel targets for clinical diagnosis and treatment. Materials and Methods: mRNA microarray and RNA-Seq (n = 1246 samples) data were utilized to estimate CELSR3 expression and to assess its differentiation ability in MPCa. Similar analyses were performed with miRNA-221-3p. Immunohistochemistry performed on clinical samples were used to evaluate the protein expression level of CELSR3 in MPCa. Based on CELSR3 differentially coexpressed genes (DCEGs), enrichment analysis was performed to investigate potential mechanisms of CELSR3 in MPCa. Results: The pooled standard mean difference (SMD) for CELSR3 was 0.80, demonstrating that CELSR3 expression was higher in MPCa than in localized prostate cancer (LPCa). CELSR3 showed moderate potential to distinguish MPCa from LPCa. CELSR3 protein expression was found to be markedly upregulated in MPCa than in LPCa tissues. The authors screened 894 CELSR3 DCEGs, which were notably enriched in the focal adhesion pathway. miRNA-221-3p showed a significantly negative correlation with CELSR3 in MPCa. Besides, miRNA-221-3p expression was downregulated in MPCa than in LPCa (SMD = -1.04), and miRNA-221-3p was moderately capable of distinguishing MPCa from LPCa. Conclusions: CELSR3 seems to play a pivotal role in MPCa by affecting the focal adhesion pathway and/or being targeted by miRNA-221-3p.

Down-Regulation of Activating Transcription Factor 3 (ATF3) in Hepatoblastoma and Its Relationship with Ferroptosis.

PURPOSE: The molecular mechanisms and signal pathways of ferroptosis in hepatoblastoma (HB) have not yet been clarified. In previous studies, activating transcription factor 3 (ATF3) was reported to be correlated with several tumors, but the clinical significance of ATF3 has never been determined. Herein, we investigated the clinicopathological value and mechanisms of ATF3 in regulating ferroptosis in HB. METHODS: The mRNA microarray and RNA-sequencing data of 402 samples from our hospital and public databases were used to estimate ATF3 expression and assess its clinical role in HB. The standard mean difference (SMD) and summary receiver operating characteristic curves were utilized to judge the discrimination ability of ATF3 between HB and non-HB liver tissues. We examined the expression variation of ATF3 in HB cells after the treatment with erastin. We also predicted the target genes of ATF3 as a transcriptional factor from public Chromatin Immunoprecipitation-sequencing data and selected the ferroptosis-related genes for a signaling pathway analysis. RESULTS: In ten series, the pooled SMD for ATF3 was -0.91, demonstrating that ATF3 expression was predominantly lower in HB than in non-HB liver tissues. ATF3 down-regulation showed moderate potential to distinguish HB from non-HB liver tissues (area under curves = 0.83, 95% confidence interval = 0.79-0.86). Altogether, 4855 putative targets of ATF3 as a transcriptional factor were collected, among which, 60 genes were ferroptosis-related. CONCLUSION: The down-regulated ATF3 expression may play a vital role in the occurrence of HB possible partially by regulating ferroptosis.

[Expression regulation of plant ascorbate peroxidase and its tolerance to abiotic stresses].

Ascorbate peroxidase (APX), a type I heme peroxidase, catalyzes oxidation of ascorbic acid. It possesses a high degree of specificity to ascorbic acid. APX gene cluster consists of four sub-clusters: the gene clusters of cytosol, chloroplast, mitochondria, and peroxidase. As a key component of hydrogen peroxide detoxification system, the ascorbate-glutathione cycle, APX plays a vital role in the metabolism of H2O2 of plant cells. Studies showed that APX is one of the most important enzymes, which modulate the cellular H2O2 level in redox signaling system. The expression mechanisms of APX isoenzymes are quite complex. Briefly, cytosolic APX is regulated by a variety of signals; two chloroplastic APX isoenzymes are tissue-dependently regulated by alternative splicing. Generated APXs could regulate redox signaling in cells, which further boosts plants tolerance to abiotic stresses. This review focuses on recent advances concerning catalytic prop-erties, physiological function, and gene expressing regulation and abio-stress responding mechanism of APX.

[Preliminary investigation of viruses to the wild tree shrews (Tupaia belangeri Chinese)].

Virological testing and monitoring is a fundamental part of quality control of experimental animals. However, there are few papers regarding the spectrum and status of natural infection in wild tree shrews with human and animal pathogenic viruses. Using enzyme-linked immunosorbent adsorption assay (ELISA), we tested sixty wild tree shrews captured from Qinglong, an outskirt region of Kunming, Yunnan Province, China for eleven viruses, including herpes simplex virus, coxsackie virus, influenza virus, HAV, HBV, HCV, HDV, dengue virus, hemorrhagic fever virus and measles virus. Our results showed that, in the serum samples, 22/60 (36.7%) and 1/60 (1.67%) were antibody positive for herpes simplex virus and coxsackie virus, respectively, and 4/60 (6.7%) were antigen positive for rotavirus in the feces. The remaining species of viruses were negative in these tree shrews. Based on these results, we propose that herpes simplex virus, coxsackie virus and cotavirus should be listed as top priority for routine virological monitoring of tree shrews.