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Biomechanical assessments are essential for the understanding of physiological states and the characterization of certain tissue pathologies such as liver cirrhosis. In this work, we showed by the photoacoustic viscoelasticity (PAVE) imaging that obvious mechanical change was also observed in the development of the acute hepatitis owing to the hepatocyte enlargement and intracellular fluid increment, indicating that the PAVE technique can be developed as a supplementary method for detecting acute hepatitis in future. The feasibility of the PAVE imaging is validated by a group of agar phantoms. Furthermore, acute hepatitis pathological animal models were established and imaged ex vivo and in situ by the PAVE technique to demonstrate its capability for the mechanical characterization of acute hepatitis, and the imaging results were consistent with pathological results. The feasibility study of detecting acute hepatitis by the PAVE technique proved that this method has potential to be developed as a clinical biomechanical imaging method to supplement current clinical strategy for liver disease detection.
Atomic force microscopy (AFM) has been widely used to acquire surface topography upon different scanning modes and to quantify mechanical properties of a cell using single-point ramp force mode. However, these traditional measurements need massive force curves originating from multiple points of a cell to exclude the potential errors resulted from limited and factitious selections of testing points, making the measurements time-consuming and highly localized. PeakForce Quantitative NanoMechanics (PF QNM) is a high-speed (faster by 3-4 order of magnitude) and global surface mechanical property mapping method with high spatial resolution, overcoming the drawbacks of traditional ramp mode especially used for a live cell with high heterogeneity. In this protocol, we elaborated how to run PF QNM measurements for live cells and relevant modification may be needed when extending this method to other cell-like soft materials.
Immunotherapy, especially immune checkpoint inhibitors, is becoming a promising treatment for hepatocellular carcinoma (HCC). However, the response rate remains limited due to the heterogeneity of HCC samples. Molecular subtypes of HCC vary in genomic background, clinical features, and prognosis. This study aims to compare the immune profiles between HCC subtypes and find subtype-specific immune characteristics that might contribute to the prognosis and potential of immunotherapy. The immune profiles consist of immune-related genes, cytolytic activity, immune pathways, and tumorinfiltrating lymphocytes. HCC-c1 samples showed an overall higher activation level of immune genes and pathways, and this pattern was consistent in validation sets. We associated the difference in immune profiles with the activation level of cancer hallmarks and genomic mutations. There was a negative correlation between most of the metabolism pathway and immune-related pathways in HCC samples. CTNNB1/WNT signaling pathway mutation, one of the common mutations in HCC, appears to be associated with the expression of immune genes as well. These results reveal the difference of immune profiles between HCC subtypes and possible reasons and influence, which may also deepen our understanding of the carcinogenesis process.