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The communication between tumor-derived elements and stroma in the metastatic niche has a critical role in facilitating cancer metastasis. Yet, the mechanisms tumor cells use to control metastatic niche formation are not fully understood. Here we report that in the lung metastatic niche, high-metastatic hepatocellular carcinoma (HCC) cells exhibit a greater capacity to convert normal fibroblasts to cancer-associated fibroblasts (CAFs) than low-metastatic HCC cells. We show high-metastatic HCC cells secrete exosomal miR-1247-3p that directly targets B4GALT3, leading to activation of β1-integrin–NF-κB signaling in fibroblasts. Activated CAFs further promote cancer progression by secreting pro-inflammatory cytokines, including IL-6 and IL-8. Clinical data show high serum exosomal miR-1247-3p levels correlate with lung metastasis in HCC patients. These results demonstrate intercellular crosstalk between tumor cells and fibroblasts is mediated by tumor-derived exosomes that control lung metastasis of HCC, providing potential targets for prevention and treatment of cancer metastasis. How tumor cells control metastatic niche formation is not fully understood. Here, the authors show in a lung metastatic niche, high-metastatic hepatocellular carcinoma cells secrete exosomal miR-1247-3p that leads to activation of β1-integrin-NF-κBsignalling, converting fibroblasts to cancer-associated fibroblasts.

Low-quality power grid image data can greatly affect the effect of deep learning in the power industry. Therefore, adopting accurate image quality assessment techniques is essential for screening high-quality power grid images. Although current blind image quality assessment (BIQA) methods have made some progress, they usually use only one type of feature and ignore other factors that affect the quality of images, such as noise and brightness, which are highly relevant to low-quality power grid images with noise, underexposure, and overexposure. Therefore, we propose a multi-dimension distortion feature network (MDFN) based on CNN and Transformer, which considers high-frequency (edges and details) and low-frequency (semantic and structural) features of images, along with noise and brightness features, to achieve more accurate quality assessment. Specifically, the network employs a dual-branch feature extractor, where the CNN branch captures local distortion features and the Transformer branch integrates both local and global features. We argue that separating low-frequency and high-frequency components enables richer distortion features. Thus, we propose a frequency selection module (FSM) which extracts high-frequency and low-frequency features and updates these features to achieve global spatial information fusion. Additionally, previous methods only use the CLS token for predicting the quality score of the image. Considering the issues of severe noise and exposure in power grid images, we design an effective way to extract noise and brightness features and combine them with the CLS token for the prediction. The results of the experiments indicate that our method surpasses existing approaches across three public datasets and a power grid image dataset, which shows the superiority of our proposed method.

Induction of tumor vascular normalization is a crucial measure to enhance immunotherapy efficacy. cGAS-STING pathway is vital for anti-tumor immunity, but its role in tumor vasculature is unclear. Herein, using preclinical liver cancer models in Cgas / Sting -deficient male mice, we report that the interdependence between tumor cGAS and host STING mediates vascular normalization and anti-tumor immune response. Mechanistically, TET2 mediated IL-2/STAT5A signaling epigenetically upregulates tumor cGAS expression and produces cGAMP. Subsequently, cGAMP is transported via LRRC8C channels to activate STING in endothelial cells, enhancing recruitment and transendothelial migration of lymphocytes. In vivo studies in male mice also reveal that administration of vitamin C, a promising anti-cancer agent, stimulates TET2 activity, induces tumor vascular normalization and enhances the efficacy of anti-PD-L1 therapy alone or in combination with IL-2. Our findings elucidate a crosstalk between tumor and vascular endothelial cells in the tumor immune microenvironment, providing strategies to enhance the efficacy of combinational immunotherapy for liver cancer. Activation of the cGAS-STING pathway has been associated with the promotion of anti-tumor immunity. Here the authors show that TET2 upregulates tumor cGAS to activate STING in endothelial cells, inducing tumor vascular normalization and enhancing efficacy of anti-PD-L1 alone or combined with IL-2 in liver cancer preclinical models.

Stem cell behaviors are regulated by multiple microenvironmental cues. As an external signal, mechanical stiffness of the extracellular matrix is capable of governing stem cell fate determination, but how this biophysical cue is translated into intracellular signaling remains elusive. Here, we elucidate mechanisms by which stem cells respond to microenvironmental stiffness through the dynamics of the cytoskeletal network, leading to changes in gene expression via biophysical transduction signaling pathways in two-dimensional culture. Furthermore, a putative rapid shift from original mechanosensing to de novo cell-derived matrix sensing in more physiologically relevant three-dimensional culture is pointed out. A comprehensive understanding of stem cell responses to this stimulus is essential for designing biomaterials that mimic the physiological environment and advancing stem cell-based clinical applications for tissue engineering.

Vitamin C (L-ascorbic acid, ascorbate, VC) is a potential chemotherapeutic agent for cancer patients. However, the anti-tumor effects of pharmacologic VC on hepatocellular carcinoma (HCC) and liver cancer stem cells (CSCs) remain to be fully elucidated. Panels of human HCC cell lines as well as HCC patient-derived xenograft (PDX) models were employed to investigate the anti-tumor effects of pharmacologic VC. The use of VC and the risk of HCC recurrence were examined retrospectively in 613 HCC patients who received curative liver resection as their initial treatment. In vitro and in vivo experiments further demonstrated that clinically achievable concentrations of VC induced cell death in liver cancer cells and the response to VC was correlated with sodium-dependent vitamin C transporter 2 (SVCT-2) expressions. Mechanistically, VC uptake via SVCT-2 increased intracellular ROS, and subsequently caused DNA damage and ATP depletion, leading to cell cycle arrest and apoptosis. Most importantly, SVCT-2 was highly expressed in liver CSCs, which promoted their self-renewal and rendered them more sensitive to VC. In HCC cell lines xenograft models, as well as in PDX models, VC dramatically impaired tumor growth and eradicated liver CSCs. Finally, retrospective cohort study showed that intravenous VC use was linked to improved disease-free survival (DFS) in HCC patients (adjusted HR = 0.622, 95% CI 0.487 to 0.795, p  < 0.001). Our data highlight that pharmacologic VC can effectively kill liver cancer cells and preferentially eradicate liver CSCs, which provide further evidence supporting VC as a novel therapeutic strategy for HCC treatment. Liver cancer: vitamin C preferentially kills cancer stem cells and improves patient outcomes Pharmacologic doses of vitamin C preferentially eradicate liver cancer stem cells and are associated with improved outcomes in patients. A team led by Hong-Yang Wang and Wen Yang from the Second Military Medical University in Shanghai, China, showed that clinically achievable concentrations of vitamin C effectively killed liver cancer cells and preferentially eradicated cancer stem cells in culture and in mouse transplant models. Cells with higher expression levels of a vitamin C transporter protein were more susceptible to the treatment, which explains why cancer stem cells, which highly express this transportor and use it for their own self-renewal, were especially sensitive to take in vitamin C, which led to a cascade that resulted in DNA damage, energy depletion, and ultimately cell death. A retrospective analysis of 613 patients with liver cancer showed that those who received intravenous vitamin C lived longer without disease relapse.

Background Previous studies have demonstrated the important role of fatty acid desaturase 2 (FADS2) in governing tumorigenesis and tumor metastasis. Although FADS2 is an essential regulator of fatty acid metabolism, its prognostic and immunotherapeutic value remains uncertain. Methods The role of FADS2 was investigated across different types of tumors. Besides, the relationship between FADS2 and survival prognosis, clinicopathologic features, tumor-infiltrating immune cells, immunoregulatory genes, chemokines, chemokines receptor, tumor mutational burden (TMB), and microsatellite instability (MSI) was also explored. FADS2-related genes enrichment analysis was performed to further explore the molecular function of FADS2. Finally, the relationship between FADS2 expression and altered functional states in single-cell levels across different tumor cells was explored. Results FADS2 was increased in most tumor tissues. Elevated FADS2 expression was associated with a poor overall survival (OS) and disease-free survival (DFS). FADS2 amplification was germane to worse progress-free survival (PFS). In addition, FADS2 correlated with the majority of tumor-infiltrating immune cells, immunoregulatory genes, and chemokines. Especially, FADS2 expression positively correlated with cancer-associated fibroblast (CAFs) infiltration. Gene Ontology and KEGG analysis demonstrated that FADS2 was involved in the fatty acid metabolic process, arachidonic acid metabolism, RAS, PPAR, and VEGF pathway. FADS2 had a positive relationship with tumor biological behaviors such as inflammation, cell cycle, proliferation, DNA damage, and DNA repair response in single-cell levels. Conclusions FADS2 can serve as a potential prognostic and immunotherapeutic biomarker for multiple tumors, revealing new insights and evidence for cancer treatment.

CD146 plays a key role in cancer progression and metastasis. Cancer stem cells (CSCs) are responsible for tumor initiation, drug resistance, metastasis, and recurrence. In this study, we explored the role of CD146 in the regulation of liver CSCs. Here, we demonstrated that CD146 was highly expressed in liver CSCs. CD146 overexpression promoted the self-renewal ability and chemoresistance of Hepatocellular Carcinoma (HCC) cells in vitro and tumorigenicity in vivo. Inversely, knockdown of CD146 restrained these abilities. Mechanistically, CD146 activated the NF-κB signaling to up-regulate JAG2 expression and activated the Notch signaling, which resulted in increased stemness of HCC. Furthermore, JAG2 overexpression restored the Notch signaling activity, the stemness, and chemotherapeutic resistance caused by CD146 knockdown. These results demonstrated that CD146 positively regulates HCC stemness by activating the JAG2-NOTCH signaling. Combined targeting of CD146 and JAG2 may represent a novel therapeutic strategy for HCC treatment.

Crosstalk between cancer cells and the immune microenvironment is determinant for liver cancer progression. A tumor subpopulation called liver cancer stem cells (CSCs) significantly accounts for the initiation, metastasis, therapeutic resistance, and recurrence of liver cancer. Emerging evidence demonstrates that the interaction between liver CSCs and immune cells plays a crucial role in shaping an immunosuppressive microenvironment and determining immunotherapy responses. This review sheds light on the bidirectional crosstalk between liver CSCs and immune cells for liver cancer progression, as well as the underlying molecular mechanisms after presenting an overview of liver CSCs characteristic and their microenvironment. Finally, we discuss the potential application of liver CSCs-targeted immunotherapy for liver cancer treatment.

Introduction A potential link between venous thromboembolism and the risk of ovarian cancer has been identified in clinical practice. However, it is unclear whether there is a causal relationship between the two. In this study, we applied a univariate two-sample Mendelian randomization method to explain the possible link between venous thromboembolism and ovarian cancer pathogenesis at the genetic level, and pointed out that lipid metabolism and ovarian cancer pathogenesis have innovative basic experimental directions. Objective This study explored the causal effect between a history of venous thromboembolism and the risk of ovarian cancer. Methods Genome-Wide Association Study (GWAS) data of venous thromboembolism patients (n = 9176) of the same ethnicity were selected as study exposures, and GWAS data of ovarian cancer patients (n = 1218) of the same ethnicity were selected as study exposures. In this study, univariate two-sample Mendelian randomization analysis (UVMR) was performed separately using inverse variance weighted (IVW), MR-Egger regression, and weighted median (WM) to assess causal effects. In this study, Cochran’s Q test, MR-Egger regression intercept term, MR-PRESSO, and leave-one-out method were used for sensitivity analysis to assess the stability and reliability of the results. Results The GWAS data screened in this study were all European ethnicity data. In this study, we found that genetically predicted history of venous thromboembolism was associated with an upward trend in ovarian cancer incidence, and the results of Weighted median, Simple mode, Weighted mode, and MR Egger showed a similar trend (OR = 1.0006, 95% CI: 1.00007–1.0013, p < 0.05). There was no heterogeneity of results (p = 0.18) and no horizontal pleiotropy (p = 0.77). The instrumental variables selected for venous thromboembolism in this study were all strong instrumental variables (F = 669.7). The results of the sensitivity analysis remained consistent. Conclusion The results of this study indicate that patients with a history of venous thromboembolism are at increased risk of developing ovarian cancer and point to possible associations between lipid metabolism genes, such as CYP4V2, and the development of ovarian cancer, which provide interesting directions for further basic research.

As a function of a circular polarization beam splitter (CPBS), combining a linear polarization beam splitter with a quarter-wave plate results in a polarization error in a circular polarization fiber-optic circuit. To relieve the error, chiral dual-core photonic crystal fiber (DC-PCF) is investigated as a kind of an efficient circular polarization beam splitter by using the chiral plane-wave expansion (PWE) method. On the basis of the competitive effect in polarization and coupling length between the circular asymmetry of the structure and the chirality of the medium, the effects of the structure and the chirality are analyzed. The numerical results demonstrate that a CPBS needs the weak circular asymmetry in its structure and a relatively stronger chirality of the medium. Then, a kind of CPBS based on chiral DC-PCF is designed with weaker chirality, with a central wavelength of 1.55 μm. The simulation shows the superior performance of having a shorter coupling length and a higher extinction ratio. Furthermore, the dual-wavelength of 1.55 μm and 1.30 μm with left-circular polarization can further be separated by the corresponding chiral DC-PCF. The results show promising applications for the circular polarized multiplexer/demultiplexer in fiber laser communication systems.