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Gastric cancer (GC) is one of the most common malignancies worldwide and has high morbidity and mortality rates. It is essential to elucidate the molecular events of GC proliferation and invasion, which will provide new therapeutic targets for GC. The inactivation of transforming growth factor‐β receptor 2 (TGFβR2) correlates with cancer cell growth and metastasis, but the mechanisms underlying the downregulation of TGFβR2 expression remain unknown. MicroRNAs (miRNAs) act as post‐transcriptional regulators and play a key role in the development of cancers. Bioinformatics analysis and luciferase reporter assays have shown that miR‐155 directly binds to the 3′‐UTR of TGFβR2 mRNA. In this study, we found that the TGFβR2 protein levels, but not mRNA levels, were downregulated in GC tissues, and the levels of miR‐155 were significantly increased in GC tissues. We deduced that miR‐155 was inversely correlated with TGFβR2 in GC cells. In vitro studies showed that overexpression of miR‐155 in SGC7901 inhibited the expression of TGFβR2 and then promoted GC cell proliferation and migration, whereas miR‐155 inhibitor showed opposite effects. In addition, the tumor‐suppressing function of TGFβR2 was verified by using siRNA and TGFβR2 overexpressing plasmids. The results showed that miR‐155 promotes cell growth and migration by negatively regulating TGFβR2. Thus, miR‐155‐regulated TGFβR2 as a potential therapeutic target in GC. This study demonstrated for the first time that miR‐155 can target TGFβR2 to promote GC growth and invasion, and we identified the miR‐155 — TGF?R2 axis in GC.

Aflatoxin is a potent mycotoxin and a common source of grain contamination that leads to great economic losses and health problems. Although distilled baijiu cannot be contaminated by aflatoxin, its presence in the brewing process affects the physiological activities of micro-organisms and reduces product quality. Bacillus cereus XSWW9 capable of degrading aflatoxin B1 (AFB1) was isolated from daqu using coumarin as the sole carbon source. XSWW9 degraded 86.7% of 1 mg/L AFB1 after incubation at 37 °C for 72 h and tolerated up to 1 mg/L AFB1 with no inhibitory effects. Enzymes in the cell-free supernatant of XSSW9 played a significant role in AFB1 degradation. The AFB1-degradation activity was sensitive to protease K and SDS treatment, which indicated that extracellular proteins were responsible for the degradation of AFB1. In order to investigate the AFB1-degradation ability of XSSW9 during the baijiu brewing process, AFB1 and XSWW9 were added to grain fermentation (FG-T) and normal grain fermentation without AFB1, while normal grain fermentation without AFB1 and XSWW9 was used as a control (FG-C). At the end of the fermentation, 99% AFB1 was degraded in the residue of fermented grains. The differences of microbial communities in the fermented grains showed that there were no significant differences between FG-T and FG-C in the relative abundance of dominant genera. The analysis of volatile compounds of their distillation showed that the contents of skeleton flavor components was similar between FG-T and FG-C. These results offer a basis for the development of effective strategies to reduce the effect of AFB1 on the brewing process and ensure that the production of baijiu is stable.

Background. Endometriosis is an inflammatory gynecological disease leading to deep pelvic pain, dyspareunia, and infertility. The pathophysiology of endometriosis is complex and depends on a variety of biological processes and pathways. Therefore, there is an urgent need to identify reliable biomarkers for early detection and accurate diagnosis to predict clinical outcomes and aid in the early intervention of endometriosis. We screened transcription factor- (TF-) immune-related gene (IRG) regulatory networks as potential biomarkers to reveal new molecular subgroups for the early diagnosis of endometriosis. Methods. To explore potential therapeutic targets for endometriosis, the Gene Expression Omnibus (GEO), Immunology Database and Analysis Portal (ImmPort), and TF databases were used to obtain data related to the recognition of differentially expressed genes (DEGs), differentially expressed IRGs (DEIRGs), and differentially expressed TFs (DETFs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the DETFs and DEIRGs. Then, DETFs and DEIRGs were further validated in the external datasets of GSE51981 and GSE1230103. Then, we used quantitative real-time polymerase chain reaction (qRT-PCR) to verify the hub genes. Simultaneously, the Pearson correlation analysis and protein-protein interaction (PPI) analyses were used to indicate the potential mechanisms of TF-IRGs at the molecular level and obtain hub IRGs. Finally, the receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic value of the hub IRGs. Results. We screened a total of 94 DETFs and 121 DEIRGs in endometriosis. Most downregulated DETFs showed decreased expression in the endometria of moderate/severe endometriosis patients. The top-ranked upregulated DEIRGs were upregulated in the endometra of infertile women. Functional analysis showed that DETFs and DEIRGs may be involved in the biological behaviors and pathways of endometriosis. The TF-IRG PPI network was successfully constructed. Compared with the control group, high C3, VCAM1, ITGB2, and C3AR1 expression had statistical significance in endometriosis among the hub DEIRGs. They also showed higher sensitivity and specificity by ROC analysis for the diagnosis of endometriosis. Finally, compared with controls, C3 and VCAM1 were highly expressed in endometriosis tissue samples. In addition, they also showed high specificity and sensitivity for diagnosing endometriosis. Conclusion. Overall, we discovered the TF-IRG regulatory network and analyzed 4 hub IRGs that were closely related to endometriosis, which contributes to the diagnosis of endometriosis. Additionally, we verified that DETFs or DEIRGs were associated with the clinicopathological features of endometriosis, and external datasets also confirmed the hub IRGs. Finally, C3 and VCAM1 were highly expressed in endometriosis tissue samples compared with controls and may be potential biomarkers of endometriosis, which are helpful for the early diagnosis of endometriosis.

[This corrects the article DOI: 10.3389/fimmu.2023.1115504.].

Colorectal cancer is one of the most common cancers around the world, which is a severe threat to people’s health. SMAD4 belongs to the dwarfin/SMAD family, which plays a crucial role in TGF-β and BMP signal pathways. As the molecular characterization of colon cancer patients following SMAD4 mutations remains unclear, we integrated multi-omics data of SMAD4 mutant patients to reveal the profile of molecular characterization of SMAD4 mutation. A missense mutation is the most common mutant type of SMAD4. Patients with SMAD4 mutation had worse survival. Tumor tissues from patients carrying the SMAD4 mutation showed a reduction in various immune cells, such as CD4 + memory T cells and memory B cells. Many differential genes were identified compared to the SMAD4 mutation-free group and could be significantly enriched for tumor- and immune-related signaling pathways. In addition, the mutant group had different drug sensitivities than the non-mutant group.

Endometriosis (EM) is a benign, multifactorial, immune-mediated inflammatory disease that is characterized by persistent activation of the NF-κB signaling pathway and some features of malignancies, such as proliferation and lymphangiogenesis. To date, the pathogenesis of EM is still unclear. In this study, we investigated whether BST2 plays a role in the development of EM. Bioinformatic analysis was performed with data from public databases to identify potential candidate targets for drug treatment. Experiments were conducted at the cell, tissue, and mouse EM model levels to characterize the aberrant expression patterns, molecular mechanisms, biological behaviors of endometriosis as well as treatment outcomes. BST2 was significantly upregulated in ectopic endometrial tissues and cells compared with control samples. Functional studies indicated that BST2 promoted proliferation, migration, and lymphangiogenesis and inhibited apoptosis and . The transcription factor (TF) IRF6 induced high BST2 expression by directly binding the BST2 promoter. The underlying mechanism by which BST2 functions in EM was closely related to the canonical NF-κB signaling pathway. New lymphatic vessels may serve as a channel for the infiltration of immune cells into the endometriotic microenvironment; these immune cells further produce the proinflammatory cytokine IL-1β, which in turn further activates the NF-κB pathway to promote lymphangiogenesis in endometriosis. Taken together, our findings provide novel insight into the mechanism by which BST2 participates in a feedback loop with the NF-κB signaling pathway and reveal a novel biomarker and potential therapeutic target for endometriosis.

Background Ovarian cancer is a common gynecological disease and seriously endangers women's health. Currently, there is still a lack of effective molecular markers for the diagnosis and treatment of ovarian cancer. The present study aimed to investigate the molecular markers associated with ovarian cancer. Methods The molecular and gene related to ovarian cancer were extracted from GEO database and TCGA database by bioinformatics, and the related genes and functions were further analyzed. The results were verified by qPCR, WB, CCK-8 and Transwell experiments. Results Data analysis showed that PTH2R gene was highly expressed in tumors, and 51 HUB genes were obtained. Finally, experimental verification showed that PTH2R gene was highly expressed in ovarian cancer, and PTH2R gene was involved in the proliferation, invasion and metastasis of ovarian cancer cells. Conclusions After experimental verification, we found that knocking down the expression of PTH2R can inhibit the proliferation, invasion and migration of tumor cells.PTH2R is expected to become a new molecular marker for ovarian cancer.

Background High-grade serious ovarian carcinoma (HGSOC) is a subtype of ovarian cancer with a different prognosis attributable to genetic heterogeneity. The prognosis of patients with advanced HGSOC requires prediction by genetic markers. This study systematically analyzed gene expression profile data to establish a genetic marker for predicting HGSOC prognosis. Methods The RNA-seq data set and information on clinical follow-up of HGSOC were retrieved from Gene Expression Omnibus (GEO) database, and the data were standardized by DESeq2 as a training set. On the other hand, HGSOC RNA sequence data and information on clinical follow-up were retrieved from The Cancer Genome Atlas (TCGA) as a test set. Additionally, ovarian cancer microarray data set was obtained from GEO as the external validation set. Prognostic genes were screened from the training set, and characteristic selection was performed using the least absolute shrinkage and selection operator (LASSO) with 80% re-sampling for 5000 times. Genes with a frequency of more than 2000 were selected as robust biomarkers. Finally, a gene-related prognostic model was validated in both the test and GEO validation sets. Results A total of 148 genes were found to be significantly correlated with HGSOC prognosis. The expression profile of these genes could stratify HGSOC prognosis and they were enriched to multiple tumor-related regulatory pathways such as tyrosine metabolism and AMPK signaling pathway. AKR1B10 and ANGPT4 were obtained after 5000-time re-sampling by LASSO regression. AKR1B10 was associated with the metastasis and progression of several tumors. In this study, Cox regression analysis was performed to create a 2-gene signature as an independent prognostic factor for HGSOC, which has the ability to stratify risk samples in all three data sets ( p  < 0.05). The Gene Set Enrichment Analysis (GSEA) discovered abnormally active REGULATION_OF_AUTOPHAGY and OLFACTORY_TRANSDUCTION pathways in the high-risk group samples. Conclusion This study resulted in the creation of a 2-gene molecular prognostic classifier that distinguished clinical features and was a promising novel prognostic tool for assessing the prognosis of HGSOC. RiskScore was a novel prognostic model which might be effective in guiding accurate prognosis of HGSOC.

Gastric cancer is one of the most common malignancies worldwide; however, the molecular mechanism in tumorigenesis still needs exploration. BCL2L11 belongs to the BCL-2 family, and acts as a central regulator of the intrinsic apoptotic cascade and mediates cell apoptosis. Although miRNAs have been reported to be involved in each stage of cancer development, the role of miR-24 in GC has not been reported yet. In the present study, miR- 24 was found to be up-regulated while the expression of BCL2L11 was inhibited in tumor tissues of GC. Studies from both in vitro and in vivo shown that miR-24 regulates BCL2L11 expression by directly binding with 3＇UTR of mRNA, thus promoting cell growth, migration while inhibiting cell apoptosis. Therefore, miR-24 is a novel onco-miRNA that can be potential drug targets for future clinical use.

For a large-aperture space telescope, one of the key techniques is the method for designing the lightweight primary mirror assembly (PMA). In order to minimize the mirror surface error under axial gravity, lateral gravity, and polishing pressure at the same time, a method for topology optimization with multi-objective function combined with parametric optimization is introduced in this paper. The weighted compliance minimum is selected as the objective function to maximum the mirror structural stiffness. Then sensitivity analysis method and size optimization are used to determine the mirror structure parameters. Compared with two types of commonly used lightweight configurations, the new configuration design shows obvious superiority. In addition, the surface figure root mean square (RMS) of the mirror mounted by given bipod flexure (BF) under 1 g lateral gravity is minimized only with a value of 3.58 nm, which proves the effectiveness of the design method proposed in this paper.