Semi-Supervised Building Extraction with Optical Flow Correction Based on Satellite Video Data in a Tsunami-Induced Disaster Scene.

Data and reports indicate an increasing frequency and intensity of natural disasters worldwide. Buildings play a crucial role in disaster responses and damage assessments, aiding in planning rescue efforts and evaluating losses. Despite advances in applying deep learning to building extraction, challenges remain in handling complex natural disaster scenes and reducing reliance on labeled datasets. Recent advances in satellite video are opening a new avenue for efficient and accurate building extraction research. By thoroughly mining the characteristics of disaster video data, this work provides a new semantic segmentation model for accurate and efficient building extraction based on a limited number of training data, which consists of two parts: the prediction module and the automatic correction module. The prediction module, based on a base encoder-decoder structure, initially extracts buildings using a limited amount of training data that are obtained instantly. Then, the automatic correction module takes the output of the prediction module as input, constructs a criterion for identifying pixels with erroneous semantic information, and uses optical flow values to extract the accurate corresponding semantic information on the corrected frame. The experimental results demonstrate that the proposed method outperforms other methods in accuracy and computational complexity in complicated natural disaster scenes.

Transcriptomic analysis reveals a novel regulatory factor of ECHDC1 involved in lipid metabolism of non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is the highest incidence of chronic liver disease worldwide characterized by lipid accumulation in the liver. The full understanding of the lipogenesis of NAFLD is extreme importance. Here, whole-genome transcriptome analysis was performed on liver tissues of NAFLD patients and healthy controls to identify the differentially expressed genes and find new pathways and target genes related to the lipogenesis of NAFLD. Combined with the Gene Expression Omnibus (GEO) database, we found 86 overlapping genes, many of which are related to lipid metabolism of NAFLD. ECHDC1 is one of 86 overlapping genes, and its role in NAFLD has not been reported. The expression of ECHDC1 was significantly increased in liver tissue of patients with NAFLD than that of healthy controls, and oil Red O intensity was positively correlated with the expression levels of ECHDC1. Inhibition of ECHDC1 expression in HepG2 cells by RNAi significantly reduced intracellular lipid droplet number in vitro. In summary, this study analyzed pathogenic factors related to NAFLD at the whole-genome level and demonstrated that ECHDC1 may be involved in the occurrence and development of NAFLD by regulating hepatic lipid metabolism.

Identification of MAP3K4 as a novel regulation factor of hepatic lipid metabolism in non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a metabolic disorder with abnormal lipid metabolism. The present study was to identify regulatory genes related to lipid droplets (LDs) abnormal accumulation in NAFLD. METHODS: transcriptomic analysis and bioinformatics analysis (GEO database) were used to identify potential genes in abnormal lipid metabolism of NAFLD. A candidate gene MAP3K4 expression were detected by immunohistochemistry staining in NAFLD and controls. RNA interference and immunoblotting were used to verify the roles of MAP3K4 in the formation of hepatic LDs. RESULTS: A total of 134 candidate genes were screened, including 44 up-regulated genes and 90 down-regulated genes. 29 genes in the protein-protein interaction (PPI) were selected as hub genes, including MAP3K4. The expression levels of MAP3K4 were positively correlated with NAFLD activity score (r = 0.702, p = 0.002). Furthermore, we found a positive correlation of MAP3K4 expression with serum total cholesterol (r = 0.564, p = 0.023), uric acid levels (r = 0.520, p = 0.039), and body mass index (r = 0.574, p = 0.020). Downregulation of MAP3K4 decreased LDs accumulation in HepG2 cells and reduced the expression of CGI-58 and Plin-2 by imbibition of JNK and group IVA cytosolic phospholipase A2 (cPLA2) activation. CONCLUSION: The study revealed a number of regulatory genes related to hepatic lipid metabolism of NAFLD, and demonstrated that MAP3K4 played a pivotal role in the hepatic lipogenesis of NAFLD.

Identification of CYP46A1 as a new regulator of lipid metabolism through CRISPR-based whole-genome screening.

Abnormal lipid droplet (LD) metabolism causes a variety of disorders, especially to nonalcoholic fatty liver disease (NAFLD). But the mechanism of abnormal aggregation of LD is still not fully elucidated. Here, Genome-wide CRISPR-Cas9 knockout (GeCKO) screening was employed to identify candidate genes regulating LD metabolism in L02 cell. We analyzed simultaneously the transcriptomics of liver tissues of NAFLD to find potential genes involved in pathogenesis of NAFLD. After integration these data, we found that the expression of 43 candidate genes from the GeCKO screening was also decreased in tissues of NAFLD patients. Many of these 43 overlapping genes have been reported to play an important role in the formation of LD. Subsequently, we focused on CYP46A1, one of 43 candidate genes and mitochondria-related genes. We confirmed that the protein expression of CYP46A1 is deceased in tissues of NAFLD patients. Downregulation or overexpression of CYP46A1 affected LD accumulation in vitro. Deficiency of CYP46A1 impaired mitochondrial morphology and function, which may be responsible for the accumulation of LD. In summary, this study explored regulatory factors of LD accumulation at the whole-genome level, and demonstrated that CYP46A1 regulated LD formation involving in NAFLD pathogenesis. It provides new clues for studying the molecular mechanisms of diseases related to abnormal lipid metabolism.

Prognostic factors influencing outcome in adult liver transplantation using hypernatremic organ donation after brain death.

BACKGROUND: Hypernatremic donors was regarded as the expanded criteria donors in liver transplantation. The study was to investigate the effects of donor hypernatremia on the outcomes of liver transplantation and identify the prognostic factors possibly contributing to the poor outcomes. METHODS: Donor serum sodium levels before procurement were categorized as normal sodium (< 155 mmol/L), moderate high sodium (155-170 mmol/L), and severe high sodium (≥ 170 mmol/L). Furthermore, we subdivided the 142 hypernatremic donors (≥ 155 mmol/L) into two subgroups: subgroup A, the exposure time of liver grafts from hypernatremia to reperfusion was < 36 h; and subgroup B, the exposure time was ≥ 36 h. The outcomes included initial graft function, survival rates of grafts and recipients, graft loss and early events within the first year following liver transplantation. RESULTS: There were no significant differences in the 1-year survival rates of grafts and recipients, 1-year graft loss rates and early events among the normal, moderate high and severe high sodium groups. However, the overall survival rates of grafts and recipients in subgroup A were significantly higher than those in subgroup B. Cox model showed that the exposure time (HR = 1.117; 95% CI: 1.053-1.186; P < 0.001), cold ischemia time (HR = 1.015; 95% CI: 1.006-1.024; P = 0.001) and MELD (HR = 1.061; 95% CI: 1.003-1.121; P = 0.037) were the important prognostic factors contributing to the poor outcomes of recipients with hypernatremic donors. CONCLUSIONS: The level of donor sodium immediately before organ procurement does not have negative effects on the early outcomes following adult liver transplantation. For hypernatremia liver donors, minimization of the exposure time from hypernatremia to reperfusion is critical to prevent graft loss.

MicroRNA-146a-5p enhances radiosensitivity in hepatocellular carcinoma through replication protein A3-induced activation of the DNA repair pathway.

Hepatocellular carcinoma (HCC) is known for its high mortality rate worldwide. Based on intensive studies, microRNA (miRNA) expression functions in tumor suppression. Therefore, we aimed to evaluate the contribution of miR-146a-5p to radiosensitivity in HCC through the activation of the DNA damage repair pathway by binding to replication protein A3 (RPA3). First, the limma package of R was performed to differentially analyze HCC expression chip, and regulative miRNA of RPA3 was predicted. Expression of miR-146a-5p, RPA3, and DNA damage repair pathway-related factors in tissues and cells was determined. The effects of radiotherapy on the expression of miR-146a-5p and RPA3 as well as on cell radiosensitivity, proliferation, cell cycle, and apoptosis were also assessed. The results showed that there exists a close correlation between miR-146a and the radiotherapy effect on HCC progression through regulation of RPA3 and the DNA repair pathway. The positive rate of ATM, pCHK2, and Rad51 in HCC tissues was higher when compared with that of the paracancerous tissues. SMMC-7721 and HepG2 cell proliferation were significantly inhibited following 8 Gy 6Mv dose. MiR-146a-5p restrained the expression of RPA3 and promoted the expression of relative genes associated with the DNA repair pathway. In addition, miR-146a-5p overexpression suppresses cell proliferation and enhances radiosensitivity and cell apoptosis in HCC cells. In conclusion, the present study revealed that miR-146a-5p could lead to the restriction of proliferation and the promotion of radiosensitivity and apoptosis in HCC cells through activation of DNA repair pathway and inhibition of RPA3.

Foxp3-modified bone marrow mesenchymal stem cells promotes liver allograft tolerance through the generation of regulatory T cells in rats.

BACKGROUND: The transcription factor forkhead box P3 (Foxp3) is a master regulatory gene necessary for the development and function of CD4(+)CD25(+) regulatory T cells (Tregs). Mesenchymal stem cells (MSC) have recently emerged as promising candidates for cell-based immunosuppression/tolerance induction protocols. Thus, we hypothesized that MSC-based Foxp3 gene therapy would improve immunosuppressive capacity of MSC and induce donor-specific allograft tolerance in rat's liver allograft model. METHODS: The present study utilized a lentivirus vector to overexpress the therapeutic gene Foxp3 on MSC. In vivo, Injections of 2 × 10(6) MSC, FUGW-MSC or Foxp3-MSC into the portal vein were carried out immediately after liver transplantation. RESULTS: Successful gene transfer of Foxp3 in MSC was achieved by lentivirus carrying Foxp3 and Foxp3-MSC engraftment in liver allograft was confirmed by fluorescence microscopy. Foxp3-MSC treatment significantly inhibited the proliferation of allogeneic ACI CD4(+) T cells to splenocytes (SC) from the same donor strain or third-party BN rat compared with MSC. Foxp3-MSC suppressive effect on the proliferation of CD4(+) T cells is contact dependent and associated with Programmed death ligand 1(PD-L1) upregulation in MSC. Co-culture of CD4(+) T cells with Foxp3-MSC results in a shift towards a Tregs phenotype. More importantly, Foxp3-MSC monotherapy achieved donor-specific liver allograft tolerance and generated a state of CD4(+)CD25(+)Foxp3(+) Tregs-dependent tolerance. CONCLUSION: Foxp3-engineered MSC therapy seems to be a promising and attractive cell therapy approach for inducing immunosuppression or transplant tolerance.

Splenic artery trunk embolization reduces the surgical risk of liver transplantation.

BACKGROUND: Portal hypertension is one of the most important clinical conditions that cause intraoperative intensive hemorrhage in cirrhotic patients undergoing liver transplantation. Pre-transplant portal decompression may reduce the intraoperative bleeding during liver transplantation. METHODS: Splenic artery trunk embolization (SATE) was performed one month prior to liver transplantation. Platelet count, prealbumin, international normalized ratio, and blood flow in the portal vein and hepatic artery were monitored before and one month after SATE. The measurements above were collected on admission and before surgery in the non-SATE patients, who served as controls. We also recorded the intraoperative blood loss, operating time, required transfusion, post-transplant ascites, and complications within three months after operation in all patients. RESULTS: SATE significantly reduced portal venous blood flow, increased hepatic arterial blood flow, normalized platelet count, and improved prealbumin and international normalized ratio in the patients before liver transplantation. Compared to the non-SATE patients, the pre-transplant SATE significantly decreased the operating time, intraoperative bleeding, post-transplant ascites and severe surgical complications. CONCLUSION: Pre-transplant SATE decreases portal pressure, improves liver function reserve, and reduces the surgical risk of liver transplantation effectively in patients with severe portal hypertension.

Unveiling the role of disulfidptosis-related genes in the pathogenesis of non-alcoholic fatty liver disease.

Backgrounds: Non-alcoholic fatty liver disease (NAFLD) presents as a common liver disease characterized by an indistinct pathogenesis. Disulfidptosis is a recently identified mode of cell death. This study aimed to investigate the potential role of disulfidptosis-related genes (DRGs) in the pathogenesis of NAFLD. Methods: Gene expression profiles were obtained from the bulk RNA dataset GSE126848 and the single-cell RNA dataset GSE136103, both associated with NAFLD. Our study assessed the expression of DRGs in NAFLD and normal tissues. Weighted gene co-expression network analysis (WGCNA) and differential expression analysis were employed to identify the key NAFLD-specific differentially expressed DRGs (DE-DRGs). To explore the biological functions and immune regulatory roles of these key DE-DRGs, we conducted immune infiltration analysis, functional enrichment analysis, consensus clustering analysis, and single-cell differential state analysis. Finally, we validated the expression and biological functions of DRGs in NAFLD patients using histology and RNA-sequencing transcriptomic assays with human liver tissue samples. Results: Through the intersection of WGCNA, differentially expressed genes, and DRGs, two key DE-DRGs (DSTN and MYL6) were identified. Immune infiltration analysis indicated a higher proportion of macrophages, T cells, and resting dendritic cells in NAFLD compared to control liver samples. Based on the key DE-DRGs, Two disulfidptosis clusters were defined in GSE126848. Cluster 1, with higher expression of the key DE-DRGs, exhibited increased immune infiltration abundance and was closely associated with oxidative stress and immune regulation compared to cluster 2. High-resolution analysis of mononuclear phagocytes highlighted the potential role of MYL6 in intrahepatic M1 phenotype Kupffer cells in NAFLD patients. Our transcriptome data revealed that the expression levels of the majority of DRGs were significantly increased in NAFLD patients. NAFLD patients exhibit elevated MYL6 correlating with inflammation, oxidative stress, and disease severity, offering promising diagnostic specificity. Conclusion: This comprehensive study provides evidence for the association between NAFLD and disulfidptosis, identifying potential target genes and pathways in NAFLD. The identification of MYL6 as a possible treatment target for NAFLD provided a novel understanding of the disease's development.

Mitochondrial dysfunction affects hepatic immune and metabolic remodeling in patients with hepatitis B virus-related acute-on-chronic liver failure.

BACKGROUND: Immune dysregulation and metabolic derangement have been recognized as key factors that contribute to the progression of hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF). However, the mechanisms underlying immune and metabolic derangement in patients with advanced HBV-ACLF are unclear. AIM: To identify the bioenergetic alterations in the liver of patients with HBV-ACLF causing hepatic immune dysregulation and metabolic disorders. METHODS: Liver samples were collected from 16 healthy donors (HDs) and 17 advanced HBV-ACLF patients who were eligible for liver transplantation. The mitochondrial ultrastructure, metabolic characteristics, and immune microenvironment of the liver were assessed. More focus was given to organic acid metabolism as well as the function and subpopulations of macrophages in patients with HBV-ACLF. RESULTS: Compared with HDs, there was extensive hepatocyte necrosis, immune cell infiltration, and ductular reaction in patients with ACLF. In patients, the liver suffered severe hypoxia, as evidenced by increased expression of hypoxia-inducible factor-1α. Swollen mitochondria and cristae were observed in the liver of patients. The number, length, width, and area of mitochondria were adaptively increased in hepatocytes. Targeted metabolomics analysis revealed that mitochondrial oxidative phosphorylation decreased, while anaerobic glycolysis was enhanced in patients with HBV-ACLF. These findings suggested that, to a greater extent, hepa-tocytes used the extra-mitochondrial glycolytic pathway as an energy source. Patients with HBV-ACLF had elevated levels of chemokine C-C motif ligand 2 in the liver homogenate, which stimulates peripheral monocyte infiltration into the liver. Characterization and functional analysis of macrophage subsets revealed that patients with ACLF had a high abundance of CD68+ HLA-DR+ macrophages and elevated levels of both interleukin-1ß and transforming growth factor-ß1 in their livers. The abundance of CD206+ CD163+ macrophages and expression of interleukin-10 decreased. The correlation analysis revealed that hepatic organic acid metabolites were closely associated with macrophage-derived cytokines/chemokines. CONCLUSION: The results indicated that bioenergetic alteration driven by hypoxia and mitochondrial dysfunction affects hepatic immune and metabolic remodeling, leading to advanced HBV-ACLF. These findings highlight a new therapeutic target for improving the treatment of HBV-ACLF.

Alterations of axis inhibition protein 1 (AXIN1) in hepatitis B virus-related hepatocellular carcinoma and overexpression of AXIN1 induces apoptosis in hepatocellular cancer cells.

Axis inhibition protein 1 (AXIN1) is a negative regulator of Wnt/beta-catenin signaling via regulating the level of beta-catenin. However, the role of AXIN1 in the tumorigenesis and progression of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) is less clear. PCR sequence analysis, immunohistochemistry, and Western blot were performed on 22 HBV-related HCC samples and corresponding nontumor liver tissues to detect variants in AXIN1 gene and the expression level of AXIN1. Human hepatoma cell lines SNU475 and SNU423 were transfected with pCDNA3.1-AXIN1-myc or AXIN1 G425S-myc mutant. The growth curve and apoptosis rate of cell lines, phosphorylation of beta-catenin, and cell cycle regulatory proteins depending on beta-catenin transcriptional activity were detected. We identified four mutations of AXIN1 in 22 primary HBV-related HCCs and demonstrated a lower expression of AXIN1 in HBV-related HCC tissues than that in paired adjacent nontumor tissues. Overexpression of AXIN1 wild-type but not AXIN1 mutant inhibited the growth of HCC cell lines, accelerated their apoptosis, and negatively regulated beta-catenin-dependent transcriptional activity. Our study revealed that alterations of AXIN1 were involved in HBV-related HCC. Overexpression of AXIN1 but not AXIN1 mutant negatively regulated beta-catenin-dependent transcriptional activity and downregulated the level of cell cycle regulatory proteins, suggesting that AXIN1 may be a potential target for gene therapy of primary HCC.

Angiotensin II induces endothelin-1 expression in human hepatic stellate cells.

BACKGROUND: Both angiotensin (Ang)-II and endothelin-1 (ET-1) are involved in the pathogenesis of liver fibrosis. Activated hepatic stellate cells (HSCs) are considered a key effector of liver fibrosis. AIMS: To explore the effect of Ang-II on ET-1 expression in cultured human HSCs and the underlying mechanisms. METHODS: Human HSCs were treated with Ang-II in different concentrations (0.1, 0.5, 1, 5, or 10 nM) for different lengths of time (0.5, 1, 2, 4, or 6 h) with or without transcription inhibitor actinomycin D, Ang-II type 1 (AT1) receptor blocker losartan, AT2 receptor blocker PD123177, or different kinase inhibitors. RESULTS: Ang-II increased the ET-1 mRNA level in a statistically significant dose- and time-dependent manner within 4 h, which led to dose-dependent up-regulation of the ET-1 protein level. Actinomycin D (1 mg/ml), losartan (50 µM), and phosphatidylinositol-3 kinase inhibitor LY294002 (50 µM) abolished the promoting effect of Ang-II on ET-1 expression. Ang-II (10 nM) significantly increased the expression of α-smooth muscle actin and type I collagen in HSCs, which was abolished by losartan, LY294002, ET A receptor blocker BQ123, and ET-1 siRNA, but not PD123177 and ET B receptor blocker BQ788. CONCLUSIONS: Ang-II induces ET-1 expression in human HSCs via the AT1 receptor by the PI3 K/Akt signaling pathway. The ET-1/ET A receptor axis could mediate the promoting effects of Ang-II on HSCs' transdifferentiation into myofibroblast-like cells. This is the first evidence of crosstalk between the Ang-II/AT1 axis and the ET-1 system in regard to the pathogenesis of liver fibrosis.

PIAS1 Alleviates Hepatic Ischemia-Reperfusion Injury in Mice through a Mechanism Involving NFATc1 SUMOylation.

Recently, attentions have come to the alleviatory effect of protein inhibitor of activated STAT1 (PIAS1) in hepatic ischemia-reperfusion injury (HIRI), but the underlying molecular mechanistic actions remain largely unknown, which were illustrated in the present study. Microarray-based analysis predicted a possible regulatory mechanism involving the PIAS1/NFATc1/HDAC1/IRF-1/p38 MAPK signaling axis in HIRI. Then, growth dynamics of hypoxia/reoxygenation- (H/R-) exposed hepatocytes and liver injury of HIRI-like mice were delineated after the alteration of the PIAS1 expression. We validated that PIAS1 downregulation occurred in H/R-exposed hepatocytes and HIRI-like mice, while the expression of NFATc1, HDAC1, and IRF-1 and phosphorylation levels of p38 were increased. PIAS1 inactivated p38 MAPK signaling by inhibiting HDAC1-mediated IRF-1 through NFATc1 SUMOylation, thereby repressing the inflammatory response and apoptosis of hepatocytes in vitro, and alleviated liver injury in vivo. Collectively, the NFATc1/HDAC1/IRF-1/p38 MAPK signaling axis is highlighted as a promising therapeutic target for potentiating hepatoprotective effects of PIAS1 against HIRI.

Genome-Wide Knockout Screen Identifies EGLN3 Involving in Ammonia Neurotoxicity.

Hepatic encephalopathy (HE) is a brain dysfunction associated with poor quality of life, increased morbidity and mortality. The pathogenesis of HE is still not fully clarified and effective therapeutic strategies are imperative. Among multiple factors that contribute to the pathophysiological process of HE, ammonia neurotoxicity is thought to be central in the pathogenesis of HE. Therefore, in this study, we subjected SH-SY5Y cells to ammonia insult and performed a pooled genome-wide CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein 9) knockout screen to unveil the underlying molecular mechanisms of ammonia neurotoxicity and discover new potential therapeutic targets for HE. We found that EGLN3 (egl-9 family hypoxia-inducible factor 3) UCP3,GTPBP5, OR4D11 and SDR9C7 with 6 unique sgRNAs may contribute to protection against ammonia injury, while EGLN3 may be most related to ammonia resistance. We knocked down EGLN3 by transfecting neurons with specific shRNA lentivirus and confirmed that EGLN3 knockdown decreased ammonia-induced caspase-3 activation and apoptosis. We also demonstrated that EGLN3 knockdown ameliorated ammonia induced decreased expression of Bcl-2, increased expression of Bax and inhibited release of cytochrome c into the cytosol in neurons, suggesting that EGLN3 inhibition protected against ammonia induced apoptosis through mitochondrial dependent apoptosis pathway. Future therapeutic strategies regulating EGLN3 may be applied to the management of HE.

Factors Prognostic of Survival in Liver Transplant Recipients with Hepatitis B Virus Related Acute-on-Chronic Liver Failure.

Objectives: Factors prognostic of survival in liver transplant (LT) recipients with hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF) remain unclear. This study evaluated risk factors for survival in LT recipients with HBV-ACLF and determined the scoring system optimal for assessing patient prognosis. Methods: This retrospective study included 323 HBV-ACLF related patients undergoing LT, including 112, 146, and 65 patients with HBV-ACLF grades 1, 2, and 3, respectively. Overall survival (OS) was estimated by the Kaplan-Meier method, and factors associated with survival were analysed by multivariate Cox proportional hazards models. Pretransplant prognostic scoring systems were compared by receiver operating characteristic (ROC) curve analysis. Results: The one-year survival rate was significantly lower in HBV-ACLF grade 3 (80.0%) than in grades 1 (93.8%) and 2 (91.8%) recipients (p=0.0063). Cox multivariate analysis showed that age >53 years (hazard ratio (HR) 3.731; 95% confidence interval (CI) 1.640-8.407), WBC count >8.6 × 109/L (HR 4.544; 95% CI 1.140-18.107), HBV-ACLF 3 (HR 2.729; 95% CI 1.050-7.096), and cold ischaemia time >8.5 hours (HR 2.867; 95% CI, 1.38-5.921) were independently prognostic of 1-year survival. Comparisons of pretransplant scoring systems showed that chronic liver failure-consortium ACLF score (CLIF-C ACLFs) was superior to COSSH-ACLF, MELD-Na, and MELD scores in predicting 1-year OS in these patients. Conclusions: Age >53 years, WBC counts >8.6 × 109/L, HBV-ACLF grade 3, and cold ischaemia time >8.5 hours are independently prognostic of OS in LT recipients with HBV-ACLF. CLIF-C ACLFs is superior to other scoring methods in predicting 1-year OS in these patients.

Hemodynamic alterations with large spontaneous splenorenal shunt ligation during adult deceased donor liver transplantation.

Background: A large spontaneous splenorenal shunt (SRS) will greatly impact portal inflow to the graft during liver transplantation (LT). Direct ligation of a large SRS is an uncommon surgical procedure and the hemodynamic consequences of this procedure are unknown. Methods: In this retrospective study, we described our technique for direct ligation of a large SRS and the consequent hemodynamic changes during LT. 3-Dimensional computed tomography and Doppler ultrasonography were used to evaluate SRS and portal vein blood flow volume (PFV). Results: A total of 22 recipients had large SRS including 13 with PFV <85 ml/min/100 g (ligation group) and 9 with PFV ≥85 ml/min/100 g (no ligation group). The diameter of SRS was significantly larger in the ligation group than in the non-ligation group (22.92 ± 4.18 vs. 16.24 ± 3.60 mm; p = 0.0009). In all ligation patients, the SRS was easily identified and isolated, it was located just below the distal pancreas and beside the inferior mesenteric vein. PV flow increased significantly from 68.74 ± 8.77 to 116.80 ± 16.50 ml/min/100 g (p < 0.0001) after ligation; this was followed by a reduction in peak systolic velocity of the hepatic artery from 58.17 ± 14.87 to 46.67 ± 13.28 cm/s (p = 0.0013). Conclusions: Direct ligation of large SRS was an effective and safe surgical procedure to overcome the problem of portal hypoperfusion during LT.

Risk Factors of Early Allograft Dysfunction in Patients With Hepatitis B Virus-Related Acute-on-Chronic Liver Failure After Deceased Donor Liver Transplant.

OBJECTIVES: Hepatitis B virus-related acute-on-chronic liver failure remains a life-threatening syndrome, and transplant is the definitive treatment. Early allograft dysfunction is a postoperative complication and affects morbidity and mortality. We studied the risk factors associated with early allograft dysfunction in livertransplantrecipients with hepatitis B virus-related acute-on-chronic liver failure. MATERIALS AND METHODS: This single-center retrospective study of early allograft dysfunction is based on data from January 2015 to June 2020 for 323 recipients with hepatitis B virus-related acute-on-chronic liver failure and 445 with only hepatitis B virus infection (control group). Data that correlated with early allograft dysfunction and outcome were analyzed. RESULTS: Incidence of early allograft dysfunction in patients with hepatitis B virus-related acute-on-chronic liver failure was significantly higher versus the control group (39.3% vs 21.1%; P < .001). Transplant recipients with hepatitis B virus-related acute-onchronic liver failure who developed early allograft dysfunction had lower 90-day, 180-day, and 360-day patient survival rates versus patients with no early allograft dysfunction (89.0% vs 98.0%, 82.7% vs 97.5%, and 80.3% vs 96.4%, respectively; P < .001). Pretransplant kidney failure (odds ratio, 2.644; 95% CI, 1.019-6.864; P = .046), pretransplant coagulation failure (odds ratio, 2.162; 95% CI, 1.291-3.621; P = .003), and operative time (odds ratio, 1.005; 95% CI, 1.002-1.008; P = .003) were independent risk factors for early allograft dysfunction in liver transplant recipients with hepatitis B virus-related acute-onchronic liver failure. There was a synergistic effect of early allograft dysfunction and preoperative kidney/coagulation failure on survival rates of liver transplant recipients with hepatitis B virus-related acute-on-chronic liver failure. CONCLUSIONS: Preoperative kidney/coagulation failure and operative time were independent risk factors of early allograft dysfunction in deceased donor liver transplant recipients with hepatitis B virus-related acute-on-chronic liver failure. The combination of early allograft dysfunction and preoperative kidney/coagulation failure was significantly associated with lower survival of these recipients.

IRX3 plays an important role in the pathogenesis of metabolic-associated fatty liver disease by regulating hepatic lipid metabolism.

Metabolic-associated fatty liver disease (MAFLD) affects approximately a quarter of the global population. Identification of the key genes and pathways involved in hepatic lipid metabolism is of the utmost importance for the diagnosis, treatment, and prevention of MAFLD. In this study, differentially expressed genes were identified through whole-genome transcriptional analysis of liver tissue from MAFLD patients and healthy controls, and a series of lipid metabolism-related molecules and pathways were obtained through pathway analysis. Subsequently, we focused on Iroquois homeobox protein 3 (IRX3), one of 13 transcription factors that were screened from the 331 differentially expressed genes. The transcription factor IRX3 was significantly decreased in the liver tissue of patients with MAFLD when compared with healthy controls. Pearson's correlation analysis showed that the expression levels of IRX3 in liver tissue were negatively correlated with serum total cholesterol, triglycerides, low-density lipoprotein cholesterol, and uric acid levels. The overexpression and interference of IRX3 induced the increased and decreased lipid droplet accumulation in vitro, respectively. Moreover, interference of IRX3 expression increased mitochondrial fragmentation and reduced the activity of the mitochondrial respiratory chain complex IV. In summary, the study demonstrated that IRX3 regulated hepatic lipid metabolism of MAFLD, and also revealed the effect of IRX3 on mitochondria might be an important mechanism by which IRX3 regulated hepatic lipid metabolism of MAFLD.

Farnesoid X Receptor Deficiency Induces Hepatic Lipid and Glucose Metabolism Disorder via Regulation of Pyruvate Dehydrogenase Kinase 4.

Farnesoid X receptors (FXR) are bile acid receptors that play roles in lipid, glucose, and energy homeostasis. Synthetic FXR-specific agonists have been developed for treating nonalcoholic fatty liver disease (NAFLD) patients. However, the detailed mechanism remains unclear. To investigate the effects of FXR on NAFLD and the possible mechanism, FXR-null mice were fed either a normal or a high-fat diet. The FXR-null mice developed hepatomegaly, steatosis, accumulation of lipid droplets in liver cells, glucose metabolism disorder, and elevated serum lipid levels. Transcriptomic results showed increased expression of key lipid synthesis and glucose metabolism-related proteins. We focused on pyruvate dehydrogenase kinase 4 (PDK4), a key enzyme involved in the regulation of glucose and fatty acid (FA) metabolism and homeostasis. Subsequently, we confirmed an increase in PDK4 expression in FXR knockout cells. Moreover, inhibition of PDK4 expression alleviated lipid accumulation in hepatocytes caused by FXR deficiency in vivo and in vitro. Our results identify FXR as a nuclear transcription factor that regulates glucose and lipid metabolism balance through PDK4, providing further insights into the mechanism of FXR agonists in the treatment of metabolic diseases.

Long Non-coding RNA TMEM220-AS1 Suppressed Hepatocellular Carcinoma by Regulating the miR-484/MAGI1 Axis as a Competing Endogenous RNA.

Long non-coding RNAs (lncRNAs) have a considerable regulatory influence on multiple biological processes. Nevertheless, the role of TMEM220-AS1 in hepatocellular carcinoma (HCC) remains unclear. We used The Cancer Genome Atlas (TCGA) database to analyze the differentially expressed lncRNAs. qRT-PCR was used to verify the results for a large population. The in vitro effects of TMEM220-AS1 on HCC cells were determined using Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, and Transwell assays in HCC cells. We used qRT-PCR and western blotting to identify the epithelial-mesenchymal transition (EMT). Moreover, we performed bioinformatics analysis, western blotting, dual luciferase reporter gene assay, RNA pull-down, and RNA binding protein immunoprecipitation (RIP) to investigate the underlying molecular mechanisms of TMEM220-AS1 function. Finally, the function of TMEM220-AS1 was verified in vivo. The results showed that TMEM220-AS1 was expressed at considerably low levels in HCC. It was demonstrated that malignant phenotypes and EMT of HCC cells were promoted by the knock down of TMEM220-AS1 both in vivo and in vitro. TMEM220-AS1, which was detected primarily in the cytoplasm, functioned as an miRNA sponge to bind miR-484 and promote the level of membrane-associated guanylate kinase, WW, and PDZ domain containing 1 (MAGI1), thereby curbing the malignant phenotypes of HCC cells. In conclusion, low levels of TMEM220-AS1 promote proliferation and metastasis through the miR-484/MAGI1 axis in HCC.