Chemotherapy has been the standard treatment for liver cancer. However, intrinsic or acquired drug resistance remains a major barrier to successful treatment. At present, the underlying molecular mechanisms of chemoresistance in liver cancer have not been elucidated. Dipeptidyl peptidase 9 (DPP9) is a member of the dipeptidyl peptidase IV family that has been found to be highly expressed in a variety of tumors, including liver cancer. It is unclear whether DPP9 affects chemoresistance in liver cancer. In this study, we find that DPP9 weakens the responses of liver cancer cells to chemotherapy drugs by up-regulating NQO1 and inhibiting intracellular ROS levels. In terms of mechanism, DPP9 inhibits ubiquitin-mediated degradation of NRF2 protein by binding to KEAP1, up-regulates NRF2 protein levels, promotes mRNA transcription of NQO1, and inhibits intracellular ROS levels. In addition, the NQO1 inhibitor dicoumarol can enhance the efficacy of chemotherapy drugs in liver cancer cells. Collectively, our findings suggest that inhibiting DPP9/NQO1 signaling can serve as a potential therapeutic strategy for liver cancer.

Raman spectroscopy has been efficiently used to recognize breast cancer tissue by detecting the characteristic changes in tissue composition in cancerization. In addition to chemical composition, the change in bio-structure may be easily obtained via polarized micro-Raman spectroscopy, aiding in identifying the cancerization process and diagnosis. In this study, a polarized Raman spectral technique is employed to obtain rich structural features and, combined with deep learning technology, to achieve discrimination of breast cancer tissue. The results reconfirm that the orientation of collagen fibers changes from parallel to vertical during breast cancerization, and there are significant structural differences between cancerous and normal tissues, which is consistent with previous reports. Optical anisotropy of collagen fibers weakens in cancer tissue, which is closely related with the tumor’s progression. To distinguish breast cancer tissue, a discrimination model is established based on a two-dimensional convolutional neural network (2D-CNN), where the input is a matrix containing the Raman spectra acquired at a set of linear polarization angles varying from 0° to 360°. As a result, an average discrimination accuracy of 96.01% for test samples is achieved, better than that of the KNN classifier and 1D-CNN that are based on non-polarized Raman spectra. This study implies that polarized Raman spectroscopy combined with 2D-CNN can effectively detect changes in the structure and components of tissues, innovatively improving the identification and automatic diagnosis of breast cancer with label-free probing and analysis.

Platelets play a critical role in tumor progression across various cancers. However, little is known about the molecular mechanisms and biological roles of exosomal long non-coding RNAs (lncRNAs) produced from platelets in colorectal cancer (CRC). Using RNA sequencing, we identified LINC00183 as the most upregulated lncRNA in platelet-derived exosomes (PLT-Exos) from CRC patients, compared to healthy individuals. Analysis of CRC tissue microarrays and TCGA-CRC patient data indicated that LINC00183 is often overexpressed in CRC, in association with advanced tumor stage and poor survival. Effective transfer of exosomal LINC00183 to human CRC cells was verified by FISH, western blotting, and RT-qPCR analyses. Co-incubation with PLT-Exos from CRC patients and overexpression of LINC00183 stimulated the proliferative and invasive capacities of CRC cells. RNA pull-down and RNA immunoprecipitation assays revealed that LINC00183 interacts with enolase 1 (ENO1). This interaction rescues ENO1 from ubiquitin-proteasome-mediated degradation by masking a critical K262 residue. Co-immunoprecipitation, western blotting, CUT&Tag, and gene knockdown and overexpression assays further revealed that the LINC00183-ENO1 interaction activates glycolysis in CRC cells, leading to lactate accumulation, H3K18 lactylation, and transcriptional upregulation of the oncogene GDF15. These results highlight LINC00183 as a possible therapeutic target for CRC.

Interventional brachytherapy, such as iodine-125(¹²⁵I), has improved the survival of obstructive late-stage esophageal cancer patients. However, most patients experience radioresistance after ¹²⁵I brachytherapy. It is key to decipher the underlying mechanism of ¹²⁵I radioresistance. In this study, we identified an endoplasmic reticulum-associated protein, P4HA2, which is upregulated and mediates resistance to ¹²⁵I treatment. Mechanistically, P4HA2 enhances mitochondrial autophagy (mitophagy) via the PINK1/parkin pathway by binding to ATAD3A. Clinically, high expression of P4HA2 correlates with shorter overall survival and predicts poor prognosis with ¹²⁵I brachytherapy. Moreover, the expression of P4HA2 is epigenetically increased by IGF2BP2 in an m⁶A-dependent manner. Notably, targeting P4HA2 with siRNA-based biocompatible nanomedicines significantly sensitizes ESCC to ¹²⁵I brachytherapy. Collectively, our results show the molecular mechanism of mitophagy-mediated ¹²⁵I radioresistance, which provides a potential therapeutic target and combinatorial strategy.

High contact stress between the vane tips and the cam ring is one of the main obstacles to improve the working pressure of a water hydraulic vane pump. A pressure-reducing valve for regulating the bottom pressure of the vanes at the pump suction zone is presented in this paper. Through optimization and simulation, it is found that the throttle structure has great influence on the dynamic performance of the pressure-reducing valve, and the triangular-rectangular groove is proved to be more suitable for the valve among all the investigated grooves. The theoretical analysis results show that the use of the pressure reducing valve can obviously reduce the contact forces between the cam ring and the vanes at the suction zone of the pump. The work in this research provides a feasible solution to improve the working pressure of a water hydraulic vane pump.

Background: To elucidate the mechanism by which icaritin—a novel agent for hepatocellular carcinoma (HCC)—remodels the tumor microenvironment (TME) by inhibiting HCC cell metabolism-mediated M2 polarization of tumor-associated macrophages (TAMs). Methods: Integrative approaches spanning in vitro Transwell cocultures, RNA-seq, LC3-based autophagy tracing, STX16 gene edition, and orthotopic xenografts mechanistically dissected the affective and mechanism of icaritin in remodeling TME. Results: Our results indicate that icaritin transcriptionally suppresses ALDOB in HCC cells to reduce lactate production. Consequently, the lactylation of histone H3 at lysine 9 and lysine 18 (H3K9/H3K18la) on the STX16 promoter is diminished, thereby ablating STX16 transcription. STX16 deficiency blocks autophagolysosome biogenesis, leading to the accumulation of autophagosomes in HCC cells. These autophagosomes are subsequently delivered to macrophages via extracellular vesicle (EVs) and then triggers autophagic cell death and p62-guided STAT3 destruction within the macrophages, thereby eliminating M2 TAMs and reprograming the tumor immune microenvironment. In vivo validation confirmed icaritin suppressed tumor growth and M2 macrophage infiltration via the ALDOB/STX16/autophagy/STAT3 axis. Conclusion: These results indicate that by orchestrating a novel "metabolism-epigenetics-autophagy-EVs" cascade to eliminate TAMs, icaritin targets ALDOB, STX16, and STAT3, revealing key nodes for therapeutic intervention.