Hepatocellular carcinoma (HCC) is one of the most common aggressive tumors in the world. Despite the availability of various treatments, its prognosis remains poor due to the lack of specific diagnostic indicators and the high heterogeneity of HCC cases. CircRNAs are noncoding RNAs with stable and highly specific expression. Extensive research evidence suggests that circRNAs mediate the pathogenesis and progression of HCC through acting as miRNA sponges, protein modulators, and translation templates. Tumor microenvironment (TME) has become a hotspot of immune-related research in recent years due to its effects on metabolism, secretion and immunity of HCC. Accordingly, understanding the role played by circRNAs in TME is important for the study of HCC. This review will discuss the crosstalk between circRNAs and TME in HCC. In addition, we will discuss the current deficiencies and controversies in research on circRNAs and predict future research directions.
Breast cancer is one of the leading causes of death in cancer categories, followed by lung, colorectal, and ovarian among the female gender across the world. 10H-3,6-diazaphenothiazine (PTZ) is a thiazine derivative compound that exhibits many pharmacological activities. Herein, we proceed to investigate the pharmacological activities of PTZ toward breast cancer MCF-7 cells as a representative in vitro breast cancer cell model. The PTZ exhibited a proliferation inhibition (IC50 = 0.895 µM) toward MCF-7 cells. Further, cell cycle analysis illustrated that the S-phase checkpoint was activated to achieve proliferation inhibition. In vitro cytotoxicity test on three normal cell lines (HEK293 normal kidney cells, MCF-10A normal breast cells, and H9C2 normal heart cells) demonstrated that PTZ was more potent toward cancer cells. Increase in the levels of reactive oxygen species results in polarization of mitochondrial membrane potential (ΔΨm), together with suppression of mitochondrial thioredoxin reductase enzymatic activity suggested that PTZ induced oxidative damages toward mitochondria and contributed to improved drug efficacy toward treatment. The RT2 PCR Profiler Array (human apoptosis pathways) proved that PTZ induced cell death via mitochondria-dependent and cell death receptor-dependent pathways, through a series of modulation of caspases, and the respective morphology of apoptosis was observed. Mechanistic studies of apoptosis suggested that PTZ inhibited AKT1 pathways resulting in enhanced drug efficacy despite it preventing invasion of cancer cells. These results showed the effectiveness of PTZ in initiation of apoptosis, programmed cell death, toward highly chemoresistant MCF-7 cells, thus suggesting its potential as a chemotherapeutic drug.
The application of artificial neural networks (ANNs) can be found in numerous fields, including image and speech recognition, natural language processing, and autonomous vehicles. As well, intrusion detection, the subject of this paper, relies heavily on it. Different intrusion detection models have been constructed using ANNs. While ANNs are relatively mature to construct intrusion detection models, some challenges remain. Among the most notorious of these are the bloated models caused by the large number of parameters, and the non-interpretability of the models. Our paper presents Convolutional Kolmogorov-Arnold Networks (CKANs), which are designed to overcome these difficulties and provide an interpretable and accurate intrusion detection model. Kolmogorov-Arnold Networks (KANs) are developed from the Kolmogorov-Arnold representation theorem. Meanwhile, CKAN incorporates a convolutional computational mechanism based on KAN. The model proposed in this paper is constructed by incorporating attention mechanisms into CKAN's computational logic. The datasets CICIoT2023 and CICIoMT2024 were used for model training and validation. From the results of evaluating the performance indicators of the experiments, the intrusion detection model constructed based on CKANs has an attractive application prospect. As compared with other methods, the model can predict a much higher level of accuracy with significantly fewer parameters. However, it is not superior in terms of memory usage, execution speed and energy consumption.
Gills are the main respiratory organs of fish and bear important physiological and immunological functions, but the functional heterogeneity of interlamellar cell mass (ILCM) at the single-cell level has rarely been reported. Here, we identified 19 cell types from the gills of crucian carp (Carassius auratus) by single-cell RNA sequencing (scRNA-seq) in combination with histological analysis. We annotated ILCM and analyzed its functional heterogeneity at the single-cell level for the first time. Functional enrichment analysis and cell cycle analysis identified ILCM as a type of metabolically active cells in a state of constant proliferation, and identified the major pathways responsible for ILCM immunoregulation. Histological analysis revealed the morphology and positional relationships of 6 cell types. Meanwhile, the gene regulatory network of ILCM was established through weighted gene co-expression network analysis (WGCNA), and one transcription factor and five hub genes related to immunoregulation were identified. We found that pyroptosis might be an important pathway responsible for the immune response of ILCM. Our findings provide an insight into the physiological and immune functions of gills and ILCM at the single-cell level and lay a solid foundation for further exploration of the molecular mechanism of ILCM immunity functions.