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Abstract Background Hepatocellular carcinoma (HCC) is a common type of malignant tumor where the prognosis is dismal. Circular RNA (CircRNA) is a novel RNA that regulates downstream gene transcription and translation to influence the progression of HCC. However, the regulatory relationship that exists between E3 ligases, which is a class of post-translational modifying proteins, and circRNA remains unclear. Methods Based on the E3 ubiquitin ligase in the competitive endogenous RNA (ceRNA) network, a circRNA-regulated E3 ubiquitin ligase signature (CRE3UL) was developed. A CRE3UL signature was created using the least absolute shrinkage and selection operator (Lasso) and Cox regression analysis and merged it with clinicopathologic characteristics to generate a nomogram for prognosis prediction. The pRRophetic algorithm was utilized and immunological checkpoints were analyzed to compare the responses of patients in the high-risk group (HRG) and low-risk group (LRG) to targeted therapy and immunotherapy. Finally, experimental research will further elucidate the relationship between E3 ubiquitin ligase signature and HCC. Results HRG patients were found to have a worse prognosis than LRG patients. Furthermore, significant variations in prognosis were observed among different subgroups based on various clinical characteristics. The CRE3UL signature was identified as being an independent prognostic indicator. The nomogram that combined clinical characteristics and the CRE3UL signature was found to accurately predict the prognosis of HCC patients and demonstrated greater clinical utility than the current TNM staging approach. According to anticancer medication sensitivity predictions, the tumors of HRG patients were more responsive to gefitinib and nilotinib. From immune-checkpoint markers analysis, immunotherapy was identified as being more probable to assist those in the HRG. Conclusions We found a significant correlation between the CRE3UL signature and the tumor microenvironment, enabling precise prognosis prediction for HCC patients. Additionally, a nomogram was developed that performs well in predicting the overall survival (OS) of HCC patients. This provides valuable guidance for clinicians in devising specific personalized treatment strategies. Graphical Abstract

Abstract 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.

Abstract Background The role of the membrane-associated RING-CH (MARCH) family in carcinogenesis has been widely studied, but the member of this family, RNF173, has not yet been thoroughly explored in the context of hepatocellular carcinoma (HCC). Methods With the use of an HCC tissue microarray and IHC staining, we aim to determine the differential expression of RNF173 in HCC patients and its clinical significance. The biological role of RNF173 is investigated through in vitro and in vivo experiments. RNA sequencing, mass spectrometry, and immunoprecipitation are performed to uncover the underlying mechanism of RNF173's impact on the development of HCC. Results The mRNA and protein levels of RNF173 were significantly lower in HCC tissues than in normal tissues. HCC patients with low RNF173 expression had shorter overall survival and recurrence-free survival, and RNF173 was significantly correlated with tumor number, tumor capsule, tumor differentiation, and BCLC stage. In addition, in vitro and in vivo experiments showed that RNF173 downregulation exacerbated tumor progression, including migration, invasion, and proliferation. GRB2 is a key molecule in the RAF/MEK/ERK pathway. RNF173 inhibits the RAF/MEK/ERK signaling by ubiquitinating and degrading GRB2, thereby suppressing HCC cell proliferation, invasion and migration. Combining clinical samples, we found that HCC patients with high RNF173 and low GRB2 expression had the best prognosis. Conclusion RNF173 inhibits the invasion and metastasis of HCC by ubiquitinating and degrading GRB2, thereby suppressing the RAF/MEK/ERK signaling pathway. RNF173 is an independent risk factor for the survival and recurrence of HCC patients. RNF173 may serve as a novel prognostic molecule and potential therapeutic target for HCC. Video Abstract Graphical Abstract Graphical abstract Model of RNF173 on RAF/MEK/ERK signaling. RNF173 knockdown resulted in impaired ubiquitination and degradation of GRB2, leading to the activation of the RAF/MEK/ERK signaling pathway and promotion of invasion and metastasis in HCC cells.

Three-dimensional reconstruction from point clouds is an important research topic in computer vision and computer graphics. However, the discrete nature, sparsity, and noise of the original point cloud contribute to the results of 3D surface generation based on global features often appearing jagged and lacking details, making it difficult to describe shape details accurately. We address the challenge of generating smooth and detailed 3D surfaces from point clouds. We propose an adaptive octree partitioning method to divide the global shape into local regions of different scales. An iterative loop method based on GRU is then used to extract features from local voxels and learn local smoothness and global shape priors. Finally, a moving least-squares approach is employed to generate the 3D surface. Experiments demonstrate that our method outperforms existing methods on benchmark datasets (ShapeNet dataset, ABC dataset, and Famous dataset). Ablation studies confirm the effectiveness of the adaptive octree partitioning and GRU modules.

Aberrant expression of deubiquitinases (DUBs) is significantly associated with tumorigenesis. However, the precise impact of deubiquitination on the tumour microenvironment (TME) and immunotherapy in hepatocellular carcinoma (HCC) remains unclear. In this study, we comprehensively characterized the transcriptional and genetic alterations of 26 overall survival (OS)-related DUBs in HCC. The consensus clustering algorithm was used to identify patients with distinct deubiquitination patterns. We then established a DUBscore model using the principal component analysis (PCA) algorithm to quantify the deubiquitination patterns of individual HCC patients. Finally, we performed weighted gene coexpression network analysis (WGCNA) to identify the key DUBs. Consequently, three distinct deubiquitination patterns were identified, each showing significant differences in the characteristics of the TME, immune response, and clinical prognosis. Further analysis revealed that the DUBscore was an independent prognostic factor and could predict the response to immunotherapy for patients with HCC. Ultimately, BRCC3 was identified as a key DUB based on the DUBscore, which was significantly overexpressed in tumour tissues, as confirmed by qRT‒PCR and immunohistochemistry (IHC). We analysed the distribution and expression of BRCC3 in various types of immune cells using single-cell RNA sequencing (scRNA-seq). In conclusion, our study revealed the crucial role of deubiquitination patterns in shaping TME complexity and diversity. A more personalized and effective antitumour immunotherapy strategy can be developed by utilizing the DUBscore model to identify deubiquitination patterns in individual HCC patients. Our findings also highlight that BRCC3 may serve as a potential therapeutic target in HCC and a predictive marker for immunotherapeutic response.

BackgroundPrevious studies have suggested an association between gut microbiota and primary biliary cholangitis (PBC). Nonetheless, the causal relationship between gut microbiota and PBC risk remains unclear.MethodsA bidirectional two-sample Mendelian Randomization (MR) study was employed using summary statistical data for gut microbiota and PBC from the MiBioGen consortium and Genome-Wide Association Studies (GWAS) database to investigate causal relationships between 211 gut microbiota and PBC risk. Inverse variance weighted (IVW) method was the primary analytical approach to assess causality, and the pleiotropy and heterogeneity tests were employed to verify the robustness of the findings. Additionally, we performed reverse MR analyses to investigate the possibility of the reverse causal association.ResultsThe IVW method identified five gut microbiota that demonstrated associations with the risk of PBC. Order Selenomonadales [odds ratio (OR) 2.13, 95% confidence interval (CI) 1.10–4.14, p = 0.03], Order Bifidobacteriales (OR 1.58, 95% CI 1.07–2.33, p = 0.02), and Genus Lachnospiraceae_UCG_004 (OR 1.64, 95%CI 1.06–2.55, p = 0.03) were correlated with a higher risk of PBC, while Family Peptostreptococcaceae (OR 0.65, 95%CI 0.43–0.98, p = 0.04) and Family Ruminococcaceae (OR 0.33, 95%CI 0.15–0.72, p = 0.01) had a protective effect on PBC. The reverse MR analysis demonstrated no statistically significant relationship between PBC and these five specific gut microbial taxa.ConclusionThis study revealed that there was a causal relationship between specific gut microbiota taxa and PBC, which may provide novel perspectives and a theoretical basis for the clinical prevention, diagnosis, and treatment of PBC.

To provide a theoretical basis for the effects of functional oligosaccharides on the oral microorganisms, the efficacy of several oligosaccharides on the growth, acid production, adherence and biofilm formation of three cariogenic bacteria including Streptococcus mutans, Porphyromonas gingivalis, Fusobacterium nucleatum were investigated. The three cariogenic bacteria were cultured in TSB medium with xylooligosaccharides, galactooligosaccharides, fructooligosaccharide and isomaltooligosaccharide at the different concentrations, and the absorbance, pH, adhesiveness as well as biofilm formation inhibitory activity were measured for 48 h. The effects of different oligosaccharides on bacterial growth, acid production and adhesion were compared and analyzed. The results showed that four oligosaccharides had inhibitory effects on three kinds of cariogenic bacteria, and xylooligosaccharide had the highest inhibitory effect. Xylo-oligosaccharides and galactooligosaccharides at 0.5% concentration could significantly inhibit the acid production of the three cariogenic bacteria. Compared with xylitol and other oligosaccharides, the inhibition rate of xylo-oligosaccharide on the three pathogens was 60% higher when the xylo-oligosaccharide concentration was more than 5%. The adhesion rates of the four oligosaccharides at 7% concentration to the three cariogenic bacteria were all less than 50%. When the concentration of galactooligosaccharides and xylo-oligosaccharide was greater than 5%, the biofilm formation of the three cariogenic bacteria was inhibited well. By comparison with sorbitol, the combination use of xylo-oligosaccharide, xylitol, galactooligosaccharides had more obvious inhibition on the growth of the three pathogenic bacteria.

The demand for high-performance dielectrics has increased due to the rapid development of modern electric power and electronic technology. Composite dielectrics, which can overcome the limitations of traditional single polymers in thermal conductivity, dielectric properties and mechanical performance, have received considerable attention. In this study, we report a multifunctional nanocomposite material fabricated by blending fluorinated graphene (F-graphene) with epoxy resin. The F-graphene/epoxy composite exhibited a high thermal conductivity of 0.3304 W·m−1·K−1 at a low filler loading of 1.0 wt.%, which was 67.63% higher than that of pure epoxy. The composite dielectric also showed high breakdown strength (78.60 kV/mm), high dielectric constant (8.23), low dielectric loss (−11 S·m−1). Moreover, the composite demonstrated high thermal stability and strong mechanical strength. It is believed that the F-graphene/epoxy composite has outstanding performance in various aspects and can enable the development and manufacturing of advanced electric power and electronic equipment devices.

Spirulina (Arthrospira) is the largest microalgal product by tonnage and value. There are roughly 90% of Spirulina powder and tablets is sold as human nutritional supplements. Spirulina is recognized as a superfood growingly among people, and the mechanism beyond the functional phenomena is also ongoing researching. The relationship between recommended daily intake (RDI, 3 g/d) of Spirulina and recommended nutrition intake (RNI) or adequate intake (AI) is analyzed, and the Spirulina is a good supplement for premier protein, iron, vitamin A, vitamin B12, vitamin K1 and K2. Spirulina is also an effective supplement for manganese and iodine elements. This paper also briefly reviews the progress in the medical and pharmaceutical functions to human beings of Spirulina powder. The clinical trials show that Spirulina is a proficient nutraceuticals in controlling hypertension, diabetes, obese, etc. Finally, the progress of the application of Spirulina in food industry is also discussed. For the heat and light sensitivity of phycocyanin and chlorophyll, there is an urgent demand for the solution of stable Spirulina and new derivatives.

In underwater radiated noise measurement using a vertical linear array, a diagonalization-decorrelation-based diagonal denoising method is proposed to improve the denoising effect for spatially correlated noise. Firstly, the ambient noise cross-spectral matrix is measured without the radiated noise source. Subsequently, the eigenvector matrix of the ambient noise cross-spectral matrix is utilized to implement a unitary transformation for the received data, which eliminates the correlation of the received noise and transforms the received noise cross-spectral matrix into a diagonal matrix, then the noise components are removed by diagonal denoising. Finally, the denoised cross-spectral matrix is used to estimate the power of the radiated noise by beamforming. Consequently, the influence of spatially correlated noise on radiated noise measurement is reduced. The effectiveness of the proposed method is validated and compared with the diagonal denoising method and the whitening-decorrelation-based diagonal denoising method via numerical simulations and experimental data. Under the ideal condition, the noise reduction performances of the proposed method and the whitening-decorrelation-based diagonal denoising method are equal and better than that of the diagonal denoising method. In practice, the number of snapshots is limited, so there is an inevitable mismatch between the ambient noise cross-spectral matrix and the received noise cross-spectral matrix due to the randomness of noise. The mismatch results in imperfect whitening and diagonalization, which reduces the denoising effect. However, the simulation results indicate that the proposed method still reduces more correlated noise and has a better performance on underwater radiated noise measurement compared with the diagonal denoising method and the whitening-decorrelation-based diagonal denoising method even if the number of snapshots is finite.

As bistable composite laminated plate and shell structures are often exposed to dynamic environments in practical applications, the global and local dynamics of a bistable asymmetric composite laminated shell subjected to the base excitation is presented in this paper. Temperature difference, base excitation amplitude, and detuning parameters are discussed. With the change of temperature difference, the super-critical pitchfork bifurcation occurs. Three equilibrium solutions corresponding to three equilibrium configurations (two stable configurations and one unstable configuration) can be obtained. With the increase of excitation amplitude, local and global dynamics play a leading role successively. The global dynamics between the two stable configurations behave as the periodic vibration, the quasi-periodic vibration, the chaotic vibration and dynamic snap-through when the excitation amplitude is large enough. The local dynamics that are confined to a single stable configuration behave as 1:2 internal resonance, saturation and permeation when the excitation amplitude is small. Dynamic snap-through and large-amplitude vibrations with two potential wells for the global dynamics will lead to a broad application prospect of the bistable asymmetric composite laminated shell in energy harvesting devices.

The nonlinear behaviors and energy harvesting of an unsymmetric cross-ply square composite laminated plate with a piezoelectric patch is presented. The unsymmetric cross-ply square composite laminated plate has two stable equilibrium positions by applying thermal stress, thus having snap-through with larger amplitude between the two stable equilibrium positions relative to the general laminated plate. Based on the von-Karman large deformation theory, the nonlinear electromechanical coupling equations of motion of the unsymmetric composite laminated plate with a piezoelectric patch are derived by using Hamilton’s principle. The influence of the base excitation amplitude on nonlinear behaviors and energy harvesting are investigated. For different base excitation amplitudes, the motions of the system demonstrate periodic motion, quasi-periodic motion, chaotic motion and snap-through, and two single-well chaotic attractors and a two-well chaos attractor coexist. Moreover, the power generation efficiency is optimal when the excitation amplitude is in a certain range due to its own unique nonlinear characteristics. The unsymmetric cross-ply square composite laminated plate subjected to thermal stress can actually be called a kind of bistable composite shell structure that has a broad application prospect in combination with morphing aircraft, large deployable antenna and solar panel, which are very likely to have nonlinear vibration.