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To investigate the mechanism of oral sodium taurocholate on liver regeneration after portal vein ligation. A rat model of 70% portal vein ligation (PVL) was established. The rats were randomly divided into a sodium taurocholate intervention group (PVL treatment, PVLT) and a normal diet control group (PVL control, PVLC). Histological damage and bile duct hyperplasia were assessed by H&E and CK19 staining. Liver regeneration capacity was evaluated by measuring the ratio of non-ligated liver lobe weight to total liver weight and the expression of Ki67 protein. Liver function was assessed by measuring serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), total bile acids (TBA), and hepatic TBA levels. Transcriptome analysis was performed using bulk RNA sequencing, combined with qPCR validation of gene expression related to bile acid metabolism. In the non-ligated lobes of both PVLT and PVLC groups, we found mild bile duct hyperplasia confined to the portal areas (p > 0.05), with no evident histological damage. Ki67 expression peaked on the second day after surgery in both groups, with more significant liver regeneration observed in the PVLT group. Sodium taurocholate administration led to bile acid accumulation and concomitant liver function injury. Transcriptome analysis revealed that differentially expressed genes were significantly enriched in the bile acid secretion pathway, and Gene Set Enrichment Analysis (GSEA) suggested activation of the Hippo signaling pathway. Sodium taurocholate promotes liver regeneration after portal vein ligation by regulating bile acid metabolism and the Hippo signaling pathway.

Adaptive Optics (AO) technology is an effective means to compensate for wavefront distortion, but its inherent delay error will cause the compensation wavefront on the deformable mirror (DM) to lag behind the changes in the distorted wavefront. Especially when the change in the wavefront is higher than the Shack–Hartmann wavefront sensor (SHWS) sampling frequency, the multi-frame delay will seriously limit its correction performance. In this paper, a highly stable AO prediction network based on deep learning is proposed, which only uses 10 frames of prior wavefront information to obtain high-stability and high-precision open-loop predicted slopes for the next six frames. The simulation results under various distortion intensities show that the prediction accuracy of six frames decreases by no more than 15%, and the experimental results also verify that the open-loop correction accuracy of our proposed method under the sampling frequency of 500 Hz is better than that of the traditional non-predicted method under 1000 Hz.

Background: Integrating immune checkpoint inhibitors with multi-target tyrosine kinase inhibitors presents an innovative and hopeful strategy in liver cancer treatment. Nonetheless, a degree of resistance to this treatment is noticeable in certain patients. Alternative splicing (AS) represents a common biological process that controls the variety of life functions via isoforms. Purpose: Investigating how gene AS affects the effectiveness of combined immunotherapy in treating hepatocellular carcinoma (HCC). Methods: Our retrospective examination focused on AS's effect on immune therapy effectiveness, utilizing accessible tissue sequencing and clinical records for HCC. For corroborating our results, we gathered samples of drug-resistant HCC tissue, nearby tissues, HCC tissue with high drug responsiveness, and healthy liver tissue from clinical studies. Results: The study revealed a link between the frequency of AS occurrences, the expression levels of programmed cell death 1 ligand 1, and the resistance to tumor medications. Our study detailed the AS occurrences in HCC, leading to the creation of a risk-assessment function and a predictive model using AS data. The results of our study revealed that the risk score effectively distinguished between various immune subtypes and the effectiveness of immune therapy. Additional examination of the chosen AS occurrences uncovered their effects on both the immune microenvironment and cellular immunity. Our investigation also delved into the regulatory framework of AS, uncovering the role of stringently controlled splicing factors in the emergence of tumors and the modulation of the body's immune response. Conclusions: Increased AS in HCC diminishes the efficacy of immunotherapy; conversely, more AS in peritumoral tissue elevates the likelihood of tumor immune evasion.

Combination therapy of anti‐programmed cell death protein‐1 (PD‐1) antibodies and tyrosine kinase inhibitors (TKIs) has significantly improved the prognosis for hepatocellular carcinoma (HCC), but many patients still have unsatisfactory outcomes. CD8 T cells are known to exert a pivotal function in the immune response against tumors. Nevertheless, most CD8 T cells in HCC tissues are in a state of exhaustion, losing the cytotoxic activity against malignant cells. Cytokines, mainly secreted by immune cells, play an important role in the occurrence and development of tumors. Here, we demonstrated the changes in exhausted CD8T cells during combination therapy by single‐cell RNA sequencing (scRNA‐seq) analysis on tumor samples before and after treatment. Combination therapy exerted a substantial impact on the exhausted CD8T cells, particularly in terms of cytokine expression. CCL5 was the most abundantly expressed cytokine in CD8T cells and exhausted CD8T cells, and its expression increased further after treatment. Subsequently, we discovered the CCL5/CCR5/CYP1A1 pathway through RNA sequencing (RNA‐seq) on CCL5‐stimulated Huh7 cells and verified through a series of experiments that this pathway can mediate the resistance of liver cancer cells to lenvatinib. Tissue experiments showed that after combination therapy, the CCL5/CCR5/CYP1A1 pathway was activated, which can benefit the residual tumor cells to survive treatment. Tumor‐bearing mouse experiments demonstrated that bergamottin (BGM), a competitive inhibitor of CYP1A1, can enhance the efficacy of both lenvatinib and combination therapy. Our research revealed one mechanism by which hepatoma cells can survive the combination therapy, providing a theoretical basis for the refined treatment of HCC. Hepatocellular carcinoma (HCC) tissue possessed a stronger metabolic reprogramming capacity for lenvatinib compared with liver tissue during the combination theapy based on anti‐PD1 antibody plus lenvatinib, as reflected by the activation of the CCL5/CCR5/CYP1A1 pathway. CYP1A1 inhibitor could improve the efficacy of lenvatinib or combination therapy for HCC.

The exhausted CD8+T (Tex) cells are a unique cell population of activated T cells that emerges in response to persistent viral infection or tumor antigens. Tex cells showed the characteristics of aging cells, including weakened self-renewal ability, effector function inhibition, sustained high expression of inhibitory receptors including PD-1, TIGIT, TIM-3, and LAG-3, and always accompanied by metabolic and epigenetic reprogramming. Tex cells are getting more and more attention in researching immune-related diseases and tumor immunotherapy. However, studies on Tex-related models for tumor prognosis are still lacking. We hope to establish a risk model based on Tex-related genes for HCC prognosis. Tex-related GEO datasets from different pathologic factors (chronic HBV, chronic HCV, and telomere shortening) were analyzed respectively to acquire differentially expressed genes (DEGs) by the 'limma' package of R. Genes with at least one intersection were incorporated into Tex-related gene set. GO, KEGG, and GSEA enrichment analyses were produced. Hub genes and the PPI network were established and visualized by the STRING website and Cytoscape software. Transcription factors and targeting small molecules were predicted by the TRUST and CLUE websites. The Tex-related HCC prognostic model was built by Cox regression and verified based on different datasets. Tumor immune dysfunction and exclusion (TIDE) and SubMap algorithms tested immunotherapy sensitivity. Finally, qRT-PCR and Flow Cytometry was used to confirm the bioinformatic results. Hub genes such as AKT1, CDC6, TNF and their upstream transcription factor ILF3, Regulatory factor X-associated protein, STAT3, JUN, and RELA/NFKB1 were identified as potential motivators for Tex. Tex-related genes SLC16A11, CACYBP, HSF2, and ATG10 built the HCC prognostic model and helped with Immunotherapy sensitivity prediction. Our study demonstrated that Tex-related genes might provide accurate prediction for HCC patients in clinical decision-making, prognostic assessment, and immunotherapy. In addition, targeting the hub genes or transcription factors may help to reverse T cell function and enhance the effect of tumor immunotherapy.

Hepatic tuberculosis (HTB) is rare extrapulmonary tuberculosis that is clinically similar to liver malignancy, making it difficult for correct diagnoses. Pathology is the gold standard for tuberculosis diagnosis. However, there are few reports on the pathological features of HTB. A total of 32 HTB cases were considered and the differences in pathological features and drug resistance were analyzed and compared with those for pulmonary tuberculosis (PTB). Enhanced CT scans showed ring-shaped delayed enhancement during the arterial, venous, and delayed phases. Most HTB cases were single lesions, with the highest incidence in the right lobe, and the average lesion volume was smaller than that of PTB. The frequency of granuloma in pathological changes, the overall share of the lesion area in the HTB group, and the number of foxp3 + cells were significantly higher than in the PTB group. However, no statistically significant differences were observed between the two groups’ other pathological features and immune cell numbers. The immune microenvironment of the normal tissues surrounding the lesion was further analyzed. The findings showed that the number of macrophages and foxp3 + cells in the HTB group was significantly higher than in the PTB group. No significant difference in drug resistance was detected between the HTB and PTB groups. In conclusion, there are substantial differences in the characterization of pathological feature and immune microenvironment between HTB and PTB. The frequency of granuloma and subsequent overall share of the lesion area was significantly higher in HTB compared to PTB.

As a regulatory subunit of cyclin kinase, CKS1B promotes cancer development and is associated with poor prognosis in multiple cancer patients. However, the intrinsic role of CKS1B in pancreatic cancer remains elusive. In our research, CKS1B expression in pancreatic tumor tissue was higher than that in normal tissue by TCGA, Oncomine and CPTAC databases analysis. Similar result was verified in our center tissues by qRT-PCR. CKS1B expression was closely relevant to histologic grading, prognosis, and TMB. GSEA showed that CKS1B mainly participated in the regulation of autophagy and T cell receptor signaling pathway. Furthermore, CIBERSORT analysis showed that there was a strong correlation between CKS1B expression and tumor immune cells infiltration. Drug sensitivity analysis showed that patients with high CKS1B expression appeared to be more sensitive to gemcitabine, 5-fluorouracil, and paclitaxel. We then investigated cell viability and migratory ability by CCK8 and transwell assay, respectively. Results indicated that CKS1B knockdown by short hairpin RNA significantly reduced pancreatic cancer cell viability and invasion via regulating PD-L1 expression. In conclusion, our research further demonstrates the role of CKS1B in pancreatic cancer and the signaling pathways involved. The association of CKS1B with immune infiltration and immune checkpoint may provide a new direction for immunotherapy of pancreatic cancer.

Recently, immunotherapy combined with targeted therapy has significantly prolonged the survival time and improved the quality of life of patients with hepatocellular carcinoma (HCC). However, HCC treatment remains challenging due to the high heterogeneity of this malignancy. Sorafenib, the first-line drug for the treatment of HCC, can inhibit the progression of HCC by inducing ferroptosis. Ferroptosis is associated with the formation of an immunosuppressive microenvironment in tumours. Moreover, long non-coding RNAs (lncRNAs) are strongly associated with ferroptosis and the progression of HCC. Discovery of ferroptosis-related lncRNAs (FR-lncRNAs) is critical for predicting prognosis and the effectiveness of immunotherapy and targeted therapies to improve the quality and duration of survival of HCC patients. Herein, all cases from The Cancer Genome Atlas (TCGA) database were divided into training and testing groups at a 6:4 ratio to construct and validate the lncRNA signatures. Least Absolute Shrinkage and Selection Operator (LASSO) regression and Cox regression analyses were used to screen the six FR-lncRNAs (including MKLN1-AS, LINC01224, LNCSRLR, LINC01063, PRRT3-AS1, and POLH-AS1). Kaplan–Meier (K–M) and receiver operating characteristic (ROC) curve analyses demonstrated the optimal predictive prognostic ability of the signature. Furthermore, a nomogram indicated favourable discrimination and consistency. For further validation, we used real-time quantitative polymerase chain reaction (qRT-PCR) to analyse the expression of LNCSRLR, LINC01063, PRRT3-AS1, and POLH-AS1 in HCC tissues. Moreover, we determined the ability of the signature to predict the effects of immunotherapy and targeted therapy in patients with HCC. Gene set enrichment analysis (GSEA) and somatic mutation analysis showed that ferroptosis-related pathways, immune-related pathways, and TP53 mutations may be strongly associated with the overall survival (OS) outcomes of HCC patients. Overall, our study suggests that a new risk model of six FR-lncRNAs has a significant prognostic value for HCC and that it could contribute to precise and individualised HCC treatment.

Portal vein ligation (PVL) combined with in situ splitting (ISS) has been shown to induce remarkable liver regeneration in patients. The purpose of this study was to establish a model of PVL+ISS in rats for exploring the possible mechanisms of liver regeneration using these techniques. Rats were randomly assigned to three experimental groups: selective PVL, selective PVL+ISS and sham operation. The hepatic regeneration rate (HRR), Ki-67, liver biochemical determinations and histopathology were assessed at 24, 48, and 72 h and 7 days after the operation. The microcirculation of the median lobes before and after ISS was examined by laser speckle contrast imaging. Meanwhile, cytokines such as TNF-α, IL-6, HGF and HSP70 in regenerating liver lobes at 24 h was investigated by RT-PCR and ELISA. The HRR of PVL+ISS was much higher than that of the PVL at 72 h and 7 days after surgery (p<0.01). The expression of Ki-67 in hepatocytes in the regenerating liver lobe was stronger in the PVL+ISS group than in the PVL group at 48 and 72 h (p<0.01). There was a significant reduction in microcirculation blood perfusion of the left median lobe before and after ISS. Liver biochemical determinations and histopathology demonstrated more severe hepatocyte injury in the PVL+ISS group. Both the mRNA levels of TNF-α and IL-6 and the protein levels of TNF-α, IL-6 and HGF in regenerating liver lobes were higher in the PVL+ISS than the PVL alone. The higher HRR in the PVL+ISS compared with the PVL confirmed that we had successfully established a PVL+ISS model in rats. The possible mechanisms included the reduced microcirculation blood perfusion of the left median lobe and up-regulation of cytokines in the regenerating lobes after ISS.

Background Intrahepatic cholangiocarcinoma (ICC) is a fatal primary liver cancer, and its long-term survival rate remains poor. RNA-binding proteins (RBPs) play an important role in critical cellular processes, failure of any one or more processes can lead to the development of multiple cancers. This study aimed to explore pivotal biomarkers and corresponding mechanisms to predict the prognosis of patients with ICC. Methods The transcriptomic and clinical information of patients were collected from The Cancer Genome Atlas and Gene Expression Omnibus databases. Bioinformatic methods were used to identify survival-related and differentially-expressed biomarkers. Quantitative real-time PCR (qRT-PCR) and immunohistochemistry were used to detect the expression levels of key biomarkers in independent real-world cohorts. Subsequently, a prognostic signature was constructed that effectively distinguished patients in the high- and low-risk groups. Independent prognosis analysis was used to verify the signature’s independent predictive capabilities, and two nomograms were developed to predict survival. Results PIWIL4 and SUPT5H were identified and considered as pivotal biomarkers, and the same expression trends of upregulation in ICC were also validated via qRT-PCR and immunohistochemistry in the separate real-world sample cohorts. The prognostic signature showed good predictive capabilities according to the area under the curve. The correlation of the biomarkers with the tumour microenvironment suggested that the high riskScore was positively related to the enrichment of resting natural killer cells and activated memory CD4 + T cells. Conclusion In the present study, we demonstrated that PIWIL4 and SUPT5H could be used as novel prognostic biomarkers to develop a prognostic signature. This study provides potential biomarkers of prognostic value for patients with intrahepatic cholangiocarcinoma.