Glycyrrhizin (GA) is the most essential active ingredient in licorice root, and has a wide range of biological and pharmacological activities. The present study aimed to conduct a detailed analysis of the effects of GA on liver cancer (LC) cell proliferation and the Warburg effect. Hexokinase-2 (HK2) is a glycolytic enzyme that catalyzes the Warburg effect. To this end, the LC HepG2 cell line was transfected with small interfering RNA-HK2 or pCDNA3.1-HK2, followed by GA treatment. A Cell Counting Kit-8 assay and EdU staining were employed to evaluate the proliferation rate of LC cells. The expression levels of HK2 and the phosphorylation level of AKT were measured by reverse transcription-quantitative PCR and western blotting, respectively. Furthermore, the glucose uptake capacity and lactic acid content were assessed by kits, and the glycolysis level was evaluated by assessing the extracellular acidification rate (ECAR) and the oxygen consumption rate (OCR). A pronounced increase in the OCR, and decreases in the cell proliferation, glucose uptake capacity, lactic acid content, ECAR and HK2 expression were detected in LC cells subjected to GA treatment or HK2-knockdown. Conversely, overexpression of HK2 reversed these trends, indicating that glycyrrhizin may inhibit LC cell proliferation and the Warburg effect through suppression of HK2. In addition, it was revealed that the PI3K/AKT signaling pathway was associated with LC cell proliferation and the Warburg effect; notably, treatment of LC cells with the AKT agonist SC79 induced elevation of the ECAR, cell proliferation, glucose uptake capacity, lactic acid content, phosphorylated-AKT and HK2 expression, and suppressed the OCR. In conclusion, GA may inhibit the Warburg effect and cell proliferation in LC by suppressing HK2 through blockade of the PI3K/AKT signaling pathway.
To investigate the effect of long noncoding RNA (LINC01419)/miR‐485‐5p/LSM4 on the malignant behavior of hepatocellular carcinoma (HCC) cells. The expressions of LINC01419, miR‐485‐5p, and LSM4 were determined in HCC at the cellular and clinical levels, and cell biological behavior was evaluated. The relationships between LINC01419, miR‐485‐5p, and LSM4 were predicted and verified. Additionally, the subcellular localization of LINC01419 in HCC cells was analyzed. Finally, an animal experiment was conducted to confirm the effect of LINC01419 silencing on tumor growth. in HCC tissues and cells, LINC01419 and LSM4 were increasingly expressed, but miR‐485‐5p was decreasingly expressed. LINC01419 negatively regulated miR‐485‐5p‐ and miR‐485‐5p‐targeted LSM4. LINC01419 was localized in the cytoplasm of HCC cells. Downregulation of miR‐485‐5p or upregulation of LSM4 reversed the inhibition of HCC cell malignant behavior by LINC01419 interference. LINC01419 sponges miR‐485‐5p to upregulate LSM4 expression, thereby facilitating the biological behavior of HCC cells.
The metasurface hybridized with vanadium dioxide (VO2) can be dynamically tuned, which has attracted enormous attention in recent years and orbital angular momentum (OAM) multiplexing based on metasurfaces has shown promising prospects in terahertz communications. However, existing research on VO2 metasurface focuses on the metallic metasurface. The dielectric VO2 metasurface used for OAM multiplexing is rarely reported to the present. This paper proposed a terahertz reconfigurable dielectric metasurface hybridized with VO2 for two-dimensional multichannel multiplexing combing with spatial and frequency domains. The metasurface works in both reflection and transmission modes and simultaneously the polarization control and operating frequency band regulation can be realized by switching the VO2 from the metallic state to the insulator state. For the reflective or transmissive metasurface, when 4×M-channel (M is a positive integer) off-axis plane waves are incident on the metasurface, the co-polarization reflected or cross-polarization transmitted waves are transformed into 4×M-channel orthogonal on-axis beams with topological or frequency orthogonality. A metasurface composed of 14 × 14 unit cells is designed for verification. The simulated result shows that two-dimensional 12-channel multiplexing combing with OAM and frequency by the designed metasurface can be realized on the reflection and transmission modes in two different frequency bands. The proposed metasurface has great potential in terahertz communications.
50 Background: Extrahepatic cholangiocarcinoma (ECC) and intrahepatic cholangiocarcinoma (ICC) are two types of malignant tumors that arise from the bile duct epithelium at different locations. Currently, effective treatment options for these tumors are limited, and their microenvironmental differences remain poorly understood. Methods: We collected retrospective clinicopathological data of ECC (N=64) and ICC (N=153) patients from our hospital and integrated public database information to analyze the clinical characteristics, survival, and prognosis of ECC and ICC. We performed single-cell sequencing (scRNA-seq) and spatial transcriptomic techniques on three ECC and three ICC tumor tissues. Verification of scRNA-seq results was done using immunohistochemistry, flow cytometry, and polychromatic immunofluorescence. Additionally, we analyzed RNA and ATAC sequencing data for exhausted CD8+ T cells TEX obtained from ICC and ECC tissue samples. We used InferCNV to infer copy number variations (CNVs) of epithelial cells from ICC and ECC. Results: Our results showed that ECC and ICC differ in their clinical characteristics such as age, gender, bilirubin, CEA, and outcome. ECC had higher copy number amplification variation and exhibited inflammatory signaling and ongoing immunoediting, reflected in higher immune checkpoint expression such as PDCD1, CTLA4, and LAG3, and tumor infiltration with highly differentiated dysfunctional PDCD1+ LAG3+ CXCL13+ exhausted CD8+ T cells (TEX) and precursors of exhausted T (TPEX). RNA velocity analysis revealed different developmental trajectories of T cells in ECC and ICC, predominantly in naive/stem-like and memory T cells. We also identified a trefoil factor 3 (TFF3)-positive epithelial subpopulation in ECC. TFF3+ epithelial cells had closer interaction with CTHRC1+ fibroblasts, which induced more CD8+ T cells to TEX and TPEX. TFF3+ cells exhibited higher CNV scores and higher PD-L1 and PD-L2 expression, and co-localized with TEX and TPEX, providing one explanation for the immunosuppressive environment in ECC and suggesting a potential response to immune checkpoint therapy (ICT). Conclusions: Our study provides a comprehensive characterization of the cellular heterogeneity landscape of ECC and ICC, which can guide the optimization of personalized cancer immunotherapy. We identified potential biomarkers and targets for immunotherapies, and our findings shed light on the underlying mechanisms of tumor immune evasion and provide a foundation for further research in this area.
The rotational Doppler effect (RDE) occurs when a vortex beam carrying orbital angular momentum (OAM) is normally incident on the center of a rotating target, which is widely applied for the angular velocity measurement of the rotating target and OAM detection. The combined vortex beam based on coherent beam combining technology has many unique advantages, such as high power and excellent quality. In this paper, the combined vortex beam is used as the detection source to measure the rotating target at a distance of 1 kilometer, we prove the feasibility of the combined vortex beam can be used to measure the rotational speed. However, there are some misaligned incidence conditions such as lateral displacement and oblique angle between the optical axis and the rotation axis. We analyze the change of the OAM spectrum and characteristic peak's intensity with the increase of misalignment. The results show the OAM mode of the probing beam will expand to the adjacent modes, resulting in a series of discrete frequency-shifted signals including the characteristic peaks, when the optical axis does not coincide with the rotation axis. When deviation exceeds a certain value, the dispersion is too large to cause the frequency characteristic peaks are gradually submerged in the scattering signals. These analyses provide a reference for the practical detection of rotational speed in remote sensing.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.