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Triple-negative breast cancer (TNBC) is a subtype of breast cancer, and its mechanisms of occurrence and development remain unclear. In this study, we aim to investigate the role and molecular mechanisms of the demethylase FTO (fat mass and obesity-associated protein) in TNBC. Through analysis of public databases, we identify that FTO may regulate the maturation of miR-17-5p and subsequently influence the expression of zinc finger and BTB domain-containing protein 4 (ZBTB4), thereby affecting the occurrence and progression of TNBC. We screen for relevant miRNAs and mRNAs from the GEO and TCGA databases and find that the FTO gene may play a crucial role in TNBC. In vitro cell experiments demonstrate that overexpression of FTO can suppress the proliferation, migration, and invasion ability of TNBC cells and can regulate the maturation of miR-17-5p through an m6A-dependent mechanism. Furthermore, we establish a xenograft nude mouse model and collect clinical samples to further confirm the role and impact of the FTO/miR-17-5p/ZBTB4 regulatory axis in TNBC. Our findings unveil the potential role of FTO and its underlying molecular mechanisms in TNBC, providing new perspectives and strategies for the research and treatment of TNBC.

Objective To investigate the expression and clinical significance of silent information regulator 2 (SIRT2) form tissue of urothelial bladder cancer(UBC) and the effects of down-regulation of SIRT2 on the proliferation, invasion and migration of bladder cancer cells. Methods The expression of SIRT2 protein was detected in 95 samples of urothelial bladder cancer tissues and 39 paracancerous tissues using the immunohistochemical EnVision method. Its relationship with clinicopathological parameters was analyzed. The expression of SIRT2 mRNA in bladder cancer cell lines was detected by RT-qPCR, and the expression levels of SIRT2 protein in bladder cancer cell lines, 12 pairs of fresh bladder cancer tissues were detected by Western blot. Lentiviral infection was used to stably downregulate the SIRT2 gene in bladder cancer cell line T24. CCK8 and cell colony assays were performed to detect changes in cell proliferation ability and Transwell assay to detect changes in cell invasion and migration activity. Results The positive expression rate of SIRT2 in urothelial bladder cancer tissues was 84%(80/95), which was higher than that in normal uroepithelial tissues (5%, 2/39) (PConclusions SIRT2 is highly expressed in bladder uroepithelial carcinoma, and interfers with SIRT2 significantly and so inhibites bladder cancer cell proliferation, invasion and migration.

Inflammation plays an essential role in the phases of rheumatoid arthritis (RA) as the joints secrete a range of molecules that modulate the inflammatory process. While therapies based on physical properties have shown effectiveness in a range of animal experimental models, the understanding of their biological mechanisms remains unclear. The aim of this study was to investigate the immunomodulatory effects of a 0.1 terahertz (THz) wave in rheumatoid arthritis in an attempt to dissect the molecular pathways implicated. The collagen-induced rheumatoid arthritis (CIA) model joint mice were irradiated daily for 30 min over a period of 2 weeks with continuous 0.1 terahertz waves. High-throughput bulk RNA sequencing of the murine blood was performed to analyze and characterize the differences in gene expression changes between the control (Ctrl), CIA (RA), and CIA exposed to THz. Differentially expressed genes, canonical pathway analysis, gene set enrichment, and protein–protein interaction were further run on the selected DEGs. We found that terahertz exposure downregulated gene ontologies representing the "TGF-β signaling pathway", "apoptosis", "activation of T cell receptor signaling pathway", and "non-canonical NF-κB signal transduction". These observations were further confirmed by a decreased level in the expression of transcription factors Nfib and Nfatc3, and an increased level of Lsp1. In addition, the expression of Mmp8 was significantly restored. These results indicate that THz ultimately attenuates the inflammatory response of hemocytes through the T cell and NF-κB pathway, and these changes are reverberated in the blood transcriptome. In this first report of transcriptome sequencing in a model of rheumatoid arthritis exposed to terahertz waves, the downregulated DEGs were associated with anti-inflammatory effects. [ABSTRACT FROM AUTHOR]

Background: Gut microbiota dysbiosis induces intestinal barrier damage during parenteral nutrition (PN). However, the underlying mechanisms remain unclear. This study aimed to investigate gut microbiota dysbiosis, luminal short‐chain fatty acids, and autophagy in a mouse model and how these short‐chain fatty acids regulate autophagy. Methods: Eight‐week‐old male specific‐pathogen–free mice were randomly divided into a Chow group (standard diet and intravenous normal saline infusion) and a PN group (continuous infusion of PN nutrient solution) for 7 days. Caco‐2 cells were also treated with intestinal rinse solutions from Chow and PN mouse models. Results: Compared with the Chow group, the PN group exhibited increased Proteobacteria and decreased Firmicutes, correlating with decreased propyl acetate. In the PN group, intestinal tissue exhibited elevated adenosine monophosphate–activated protein kinase (AMPK) phosphorylation, LC3II protein levels, and Atg3 and Atg7 messenger RNA levels. P62 protein levels were decreased, indicating an increase of autophagy flux in the PN group. In the Caco‐2 cell model, cells treated with PN solution plus propyl acetate exhibited increased Claudin‐1 and occluding along with decreased interleukin‐6 and tumor necrosis factor α compared with those treated with PN solution alone. Propyl acetate addition inhibited the AMPK–mammalian target of rapamycin (mTOR) pathway, mitigating the excessive autophagy induced by the PN intestinal rinse solution in Caco‐2 cells. Conclusion: PN led to a significant reduction in propyl acetate levels in the intestine, excessive activation of autophagy, and barrier dysfunction. Propyl acetate inhibited excessive autophagy via the AMPK/mTOR signaling pathway and protected the intestinal barrier during PN. [ABSTRACT FROM AUTHOR]

To obtain knowledge is not the purpose of education, but to develop one's potential ability and to obtain wisdom is. We are living in a fast changing world and knowledge is growing explosively. Therefore, what facts or information students have known in your class is not the most important thing. What really matters is how efficiently students could learn and how those knowledge they have learned can help them to deal with their own tasks in the future. This article introduces our four-dimensional comprehensive course design and the teaching activities we used to optimize and improve students' learning and developing process.

BACKGROUND: Sucrose is an naturally abundant and easily fermentable feedstock for various biochemical production processes. By now, several sucrose utilization pathways have been identified and characterized. Among them, the pathway consists of sucrose permease and sucrose phosphorylase is an energy-conserving sucrose utilization pathway because it consumes less ATP when comparing to other known pathways. Bacillus amyloliquefaciens NK-1 strain can use sucrose as the feedstock to produce poly-γ-glutamic acid (γ-PGA), a highly valuable biopolymer. The native sucrose utilization pathway in NK-1 strain consists of phosphoenolpyruvate-dependent phosphotransferase system and sucrose-6-P hydrolase and consumes more ATP than the energy-conserving sucrose utilization pathway. RESULTS: In this study, the native sucrose utilization pathway in NK-1 was firstly deleted and generated the B. amyloliquefaciens 3Δ strain. Then four combination of heterologous energy-conserving sucrose utilization pathways were constructed and introduced into the 3Δ strain. Results demonstrated that the combination of cscB (encodes sucrose permease) from Escherichia coli and sucP (encodes sucrose phosphorylase) from Bifidobacterium adolescentis showed the highest sucrose metabolic efficiency. The corresponding mutant consumed 49.4% more sucrose and produced 38.5% more γ-PGA than the NK-1 strain under the same fermentation conditions. CONCLUSIONS: To our best knowledge, this is the first report concerning the enhancement of the target product production by introducing the heterologous energy-conserving sucrose utilization pathways. Such a strategy can be easily extended to other microorganism hosts for reinforced biochemical production using sucrose as substrate.

BACKGROUND: Poly-γ-glutamic acid (γ-PGA) is a valuable polymer with glutamate as its sole precursor. Enhancement of the intracellular glutamate synthesis is a very important strategy for the improvement of γ-PGA production, especially for those glutamate-independent γ-PGA producing strains. Corynebacterium glutamicum has long been used for industrial glutamate production and it exhibits some unique features for glutamate synthesis; therefore introduction of these metabolic characters into the γ-PGA producing strain might lead to increased intracellular glutamate availability, and thus ultimate γ-PGA production. RESULTS: In this study, the unique glutamate synthesis features from C. glutamicum was introduced into the glutamate-independent γ-PGA producing Bacillus amyloliquefaciens NK-1 strain. After introducing the energy-saving NADPH-dependent glutamate dehydrogenase (NADPH-GDH) pathway, the NK-1 (pHT315-gdh) strain showed slightly increase (by 9.1%) in γ-PGA production. Moreover, an optimized metabolic toggle switch for controlling the expression of ɑ-oxoglutarate dehydrogenase complex (ODHC) was introduced into the NK-1 strain, because it was previously shown that the ODHC in C. glutamicum was completely inhibited when glutamate was actively produced. The obtained NK-PO1 (pHT01-xylR) strain showed 66.2% higher γ-PGA production than the NK-1 strain. However, the further combination of these two strategies (introducing both NADPH-GDH pathway and the metabolic toggle switch) did not lead to further increase of γ-PGA production but rather the resultant γ-PGA production was even lower than that in the NK-1 strain. CONCLUSIONS: We proposed new metabolic engineering strategies to improve the γ-PGA production in B. amyloliquefaciens. The NK-1 (pHT315-gdh) strain with the introduction of NADPH-GDH pathway showed 9.1% improvement in γ-PGA production. The NK-PO1 (pHT01-xylR) strain with the introduction of a metabolic toggle switch for controlling the expression of ODHC showed 66.2% higher γ-PGA production than the NK-1 strain. This work proposed a new strategy for improving the target product in microbial cell factories.