Identification and interaction analysis of key genes and microRNAs in hepatocellular carcinoma by bioinformatics analysis

Complete list of differentially expressed genes (DEGs) in GSE22058. (DOCX 183 kb

Effect of low frequency magnetic fields on melanoma: tumor inhibition and immune modulation

BACKGROUND: We previously found that the low frequency magnetic fields (LF-MF) inhibited gastric and lung cancer cell growth. We suppose that exposure to LF-MF may modulate immune function so as to inhibit tumor. We here investigated whether LF-MF can inhibit the proliferation and metastasis of melanoma and influence immune function. METHODS: The effect of MF on the proliferation, cell cycle and ultrastracture of B16-F10 in vitro was detected by cell counting Kit-8 assay, flow cytometry, and transmission electron microscopy. Lung metastasis mice were prepared by injection of 2 × 10(5) B16-F10 melanoma cells into the tail vein in C57BL/6 mice. The mice were then exposed to an LF-MF (0.4 T, 7.5 Hz) for 43 days. Survival rate, tumor markers and the innate and adaptive immune parameters were measured. RESULTS: The growth of B16-F10 cells was inhibited after exposure to the LF-MF. The inhibition was related to induction of cell cycle arrest and decomposition of chromatins. Moreover, the LF-MF prolonged the mouse survival rate and inhibited the proliferation of B16-F10 in melanoma metastasis mice model. Furthermore, the LF-MF modulated the immune response via regulation of immune cells and cytokine production. In addition, the number of Treg cells was decreased in mice with the LF-MF exposure, while the numbers of T cells as well as dendritic cells were significantly increased. CONCLUSION: LF-MF inhibited the growth and metastasis of melanoma cancer cells and improved immune function of tumor-bearing mice. This suggests that the inhibition may be attributed to modulation of LF-MF on immune function and LF-MF may be a potential therapy for treatment of melanoma

Tumor-Activated T

Human γδ T cells display the principal characteristics of professional antigen-presenting cells (APCs), in addition to playing a vital role in immunity through cytokine secretion and their cytotoxic activity. However, it is not clear whether γδ T cells perform APC-like functions under pathological conditions. In this study, we showed that, in contrast to peripheral-derived γδ T cells directly isolated from PBMCs of gastric cancer patients, tumor-activated γδ T cells not only killed tumor cells efficiently but also strongly induced primary CD4(+) and CD8(+)   αβ T cells proliferation and differentiation. More importantly, they abrogated the immunosuppression induced by CD4(+)CD25(+) Treg cells and induced the cytotoxic function of CD8(+)   αβ T cells from patients with gastric cancer. In conclusion, tumor-activated γδ T cells can induce adaptive immune responses through their APC-like functions, and these cells may be a potentially useful tool in the development of tumor vaccines and immunotherapy

Depletion of TRRAP induces p53-independent senescence in liver cancer by downregulating mitotic genes

Hepatocellular carcinoma (HCC) is an aggressive subtype of liver cancer with few effective treatments and the underlying mechanisms that drive HCC pathogenesis remain poorly characterized. Identifying genes and pathways essential for HCC cell growth will aid the development of new targeted therapies for HCC. Using a kinome CRISPR screen in three human HCC cell lines, we identified transformation/transcription domain-associated protein (TRRAP) as an essential gene for HCC cell proliferation. TRRAP has been implicated in oncogenic transformation, but how it functions in cancer cell proliferation is not established. Here, we show that depletion of TRRAP or its co-factor, histone acetyltransferase KAT5, inhibits HCC cell growth via induction of p53- and p21-independent senescence. Integrated cancer genomics analyses using patient data and RNA-sequencing identified mitotic genes as key TRRAP/KAT5 targets in HCC, and subsequent cell cycle analyses revealed that TRRAP- and KAT5-depleted cells are arrested at G2/M phase. Depletion of TOP2A, a mitotic gene and TRRAP/KAT5 target, was sufficient to recapitulate the senescent phenotype of TRRAP/KAT5 knockdown. CONCLUSION: Our results uncover a role for TRRAP/KAT5 in promoting HCC cell proliferation via activation of mitotic genes. Targeting the TRRAP/KAT5 complex is a potential therapeutic strategy for HCC

Thymosin-β4 Mediates Hepatic Stellate Cell Activation by Interfering with CircRNA-0067835/miR-155/FoxO3 Signaling Pathway

Background/Aims: Hepatic stellate cells (HSCs) are the primary cell type responsible for liver fibrosis. Our study proved that thymosin beta 4 (Tβ4) has anti-fibrogenic effects in HSCs through PI3K/AKT pathway. However, the underlying mechanisms are not fully elucidated. Circular RNAs (circRNAs) play important roles in fine-tuning gene expression and are often deregulated in cancers. However, the expression profile and clinical significance of in liver fibrosis is still unknown. Therefore, we hypothesize that Tβ4 influences circRNAs in liver fibrosis. Methods: Circular RNA microarray was conducted to identify Tβ4-related circRNAs. Pathway analysis and miRNA response elements analysis was conducted to predict the potential roles of differentially expressed circRNAs in liver fibrosis. CCK8 assays and flow cytometric assays were conducted to clarify the role of circRNA in liver fibrosis. Bioinformatics analysis and in vitro experiments were conducted to clarify the mechanism of circRNA-mediated gene regulation in liver fibrosis. Results: A total of 644 differentially expressed circRNAs were identified between the Tβ4-depleted LX-2 cells and the control LX2 cells. The expression of circRNA-0067835 was significantly increased in the Tβ4-depleted LX-2 cells compared with control. Knockdown of circRNA-0067835 observably decreased LX-2 cell proliferation by causing G1 arrest and promoting apoptosis. Bioinformatics online programs predicted that circRNA-0067835 acted as miR-155 sponge to regulate FOXO3a expression, which was validated using luciferase reporter assay. Conclusion: Our experiments showed that circRNA-0067835 regulated liver fibrosis progression by acting as a sponge of miR-155 to promote FOXO3a expression, indicating that circRNA-0067835 may serve as a potential therapeutic target for patients with liver fibrosis

High Precision Visual Dimension Measurement Method with Large Range Based on Multi-Prism and M-Array Coding

The visual dimension measurement method based on non-splicing single lens has the contradiction between accuracy and range of measurement, which cannot be considered simultaneously. In this paper, a multi-camera cooperative measurement method without mechanical motion is proposed for the dimension measurement of thin slice workpiece. After the calibration of the multi-camera imaging system is achieved through a simple and efficient scheme, the high-precision dimension measurement with a large field of view can be completed through a single exposure. First, the images of the edges of the workpiece are compressed and combined by splitting and merging light through the multi-prism system, and the results are distributed to multiple cameras by changing the light path. Then, the mapping relationship between the global measurement coordinates and the image coordinates of each camera is established based on the globally unique M-array coding, and the image distortion is corrected by the coding unit composed of black and white blocks. Finally, the edge is located accurately by edge point detection at the sub-pixel level and curve fitting. The results of measuring a test workpiece with the dimension of 24 mm × 12 mm × 2 mm through a single exposure show that the repeated measurement accuracy can reach 0.2 µm and the absolute accuracy can reach 0.5 µm. Compared with other methods, our method can achieve the large-field measurement through only one exposure and without the mechanical movement of cameras. The measurement precision is higher and the speed is faster

YOLO-SASE: An Improved YOLO Algorithm for the Small Targets Detection in Complex Backgrounds

To improve the detection ability of infrared small targets in complex backgrounds, an improved detection algorithm YOLO-SASE is proposed in this paper. The algorithm is based on the YOLO detection framework and SRGAN network, taking super-resolution reconstructed images as input, combined with the SASE module, SPP module, and multi-level receptive field structure while adjusting the number of detection output layers through exploring feature weight to improve feature utilization efficiency. Compared with the original model, the accuracy and recall rate of the algorithm proposed in this paper were improved by 2% and 3%, respectively, in the experiment, and the stability of the results was significantly improved in the training process

Prediction of Pedestrian Crossing Behavior Based on Surveillance Video

Prediction of pedestrian crossing behavior is an important issue faced by the realization of autonomous driving. The current research on pedestrian crossing behavior prediction is mainly based on vehicle camera. However, the sight line of vehicle camera may be blocked by other vehicles or the road environment, making it difficult to obtain key information in the scene. Pedestrian crossing behavior prediction based on surveillance video can be used in key road sections or accident-prone areas to provide supplementary information for vehicle decision-making, thereby reducing the risk of accidents. To this end, we propose a pedestrian crossing behavior prediction network for surveillance video. The network integrates pedestrian posture, local context and global context features through a new cross-stacked gated recurrence unit (GRU) structure to achieve accurate prediction of pedestrian crossing behavior. Applied onto the surveillance video dataset from the University of California, Berkeley to predict the pedestrian crossing behavior, our model achieves the best results regarding accuracy, F1 parameter, etc. In addition, we conducted experiments to study the effects of time to prediction and pedestrian speed on the prediction accuracy. This paper proves the feasibility of pedestrian crossing behavior prediction based on surveillance video. It provides a reference for the application of edge computing in the safety guarantee of automatic driving

Modulating drug resistance by targeting BCRP/ABCG2 using retrovirus-mediated RNA interference.

The BCRP/ABCG2 transporter, which mediates drug resistance in many types of cells, depends on energy provided by ATP hydrolysis. Here, a retrovirus encoding a shRNA targeting the ATP-binding domain of this protein was used to screen for highly efficient agents that could reverse drug resistance and improve cell sensitivity to drugs, thus laying the foundation for further studies and applications.To target the ATP-binding domain of BCRP/ABCG2, pLenti6/BCRPsi shRNA recombinant retroviruses, with 20 bp target sequences starting from the 270th, 745th and 939th bps of the 6th exon, were constructed and packaged. The pLenti6/BCRPsi retroviruses (V-BCRPi) that conferred significant knockdown effects were screened using a drug-sensitivity experiment and flow cytometry. The human choriocarcinoma cell line JAR, which highly expresses endogenous BCRP/ABCG2, was injected under the dorsal skin of a hairless mouse to initiate a JAR cytoma. After injecting V-BCRPi-infected JAR tumor cells into the dorsal skin of hairless mice, BCRP/ABCG2 expression in the tumor tissue was determined using immunohistochemistry, fluorescent quantitative RT-PCR and Western blot analyses. After intraperitoneal injection of BCRP/ABCG2-tolerant 5-FU, the tumor volume, weight change, and apoptosis rate of the tumor tissue were determined using in situ hybridization. V-BCRPi increased the sensitivity of the tumor histiocytes to 5-FU and improved the cell apoptosis-promoting effects of 5-FU in the tumor.The goal of the in vivo and in vitro studies was to screen for an RNA interference recombinant retrovirus capable of stably targeting the ATP-binding domain of BCRP/ABCG2 (V-BCRPi) to inhibit its function. A new method to improve the chemo-sensitivity of breast cancer and other tumor cells was discovered, and this method could be used for gene therapy and functional studies of malignant tumors