Metal-Phenolic Network-Coated Nanoparticles as Stabilizers for the Engineering of Pickering Emulsions with Bioactivity.

Pickering emulsions stabilized by functional nanoparticles (NPs) have received considerable attention for improving the physical stability and biological function of NPs. Herein, hydrophobic polyphenols were chosen as phenolic ligands to form metal-phenolic network (MPN) coatings on NPs (e.g., silica, polystyrene) mediated by the sono-Fenton reaction. The MPN coatings modulated the surface wettability and charges of NPs and achieved emulsification behavior for preparing Pickering emulsions with pH responsiveness and oxidation resistance. A series of polyphenols, including resveratrol, rutin, naringin, and curcumin, were used to form MPN coatings on NPs, which served as stabilizers for the engineering of functionalized oil-in-water (O/W) Pickering emulsions. This work provides a new avenue for the use of hydrophobic polyphenols to modulate NP emulsifiers, which broadens the application of polyphenols for constructing Pickering emulsions with antioxidant properties.

Interferon-γ+ Th1 activates intrahepatic resident memory T cells to promote HBsAg loss by inducing M1 macrophage polarization.

The immune mechanism underlying hepatitis B surface antigen (HBsAg) loss, particularly type I inflammatory response, during pegylated interferon-α (PEG-IFN) therapy remains unclear. In this study, we aimed to elucidate such immune mechanisms. Overall, 82 patients with chronic hepatitis B (CHB), including 41 with HBsAg loss (cured group) and 41 uncured patients, received nucleos(t)ide analogue and PEG-IFN treatments. Blood samples from all patients, liver tissues from 14 patients with CHB, and hepatic perfusate from 8 liver donors were collected for immune analysis. Jurkat, THP-1 and HepG2.2.15 cell lines were used in cell experiments. The proportion of IFN-γ+ Th1 cells was higher in the cured group than in the uncured group, which was linearly correlated with HBsAg decline and alanine aminotransferase (ALT) levels during treatment. However, CD8+ T cells were weakly associated with HBsAg loss. Serum and intrahepatic levels of Th1 cell-associated chemokines (C-X-C motif chemokine ligand [CXCL] 9, CXCL10, CXCL11, IFN-γ) were significantly lower in the cured patients than in patients with a higher HBsAg quantification during therapy. Serum from cured patients induced more M1 (CD68+CD86+ macrophage) cells than that from uncured patients. Patients with chronic HBV infection had significantly lower proportions of CD86+ M1 and CD206+ M2 macrophages in their livers than healthy controls. M1 polarization of intrahepatic Kupffer cells promoted HBsAg loss by upregulating the effector function of tissue-resident memory T cells with increased ALT levels. IFN-γ+ Th1 activates intrahepatic resident memory T cells to promote HBsAg loss by inducing M1 macrophage polarization.

Vpr driving DNA methylation variation of CD4 + T cells in HIV-1 infection.

BACKGROUND: Despite the existence of available therapeutic interventions for HIV-1, this virus remains a significant global threat, leading to substantial morbidity and mortality. Within HIV-1-infected cells, the accessory viral protein r (Vpr) exerts control over diverse biological processes, including cell cycle progression, DNA repair, and apoptosis. The regulation of gene expression through DNA methylation plays a crucial role in physiological processes, exerting its influence without altering the underlying DNA sequence. However, a thorough examination of the impact of Vpr on DNA methylation in human CD4 + T cells has not been conducted. METHODS: In this study, we employed base-resolution whole-genome bisulfite sequencing (WGBS), real-time quantitative RCR and western blot to explore the effect of Vpr on DNA methylation of host cells under HIV-1 infection. RESULTS: We observed that HIV-1 infection leads to elevated levels of global DNA methylation in primary CD4 + T cells. Specifically, Vpr induces significant modifications in DNA methylation patterns, particularly affecting regions within promoters and gene bodies. These alterations notably influence genes related to immune-related pathways and olfactory receptor activity. Moreover, Vpr demonstrates a distinct ability to diminish the levels of methylation in histone genes. CONCLUSIONS: These findings emphasize the significant involvement of Vpr in regulating transcription through the modulation of DNA methylation patterns. Together, the results of this investigation will considerably enhance our understanding of the influence of HIV-1 Vpr on the DNA methylation of host cells, offer potential avenues for the development of more effective treatments.

Higher TP53BP2 expression is associated with HBsAg loss in peginterferon-α-treated patients with chronic hepatitis B.

BACKGROUND & AIMS: HBsAg loss is only observed in a small proportion of patients with chronic hepatitis B (CHB) who undergo interferon treatment. Investigating the host factors crucial for functional cure of CHB can aid in identifying individuals who would benefit from peginterferon-α (Peg-IFNα) therapy. METHODS: We conducted a genome-wide association study (GWAS) by enrolling 48 patients with CHB who achieved HBsAg loss after Peg-IFNα treatment and 47 patients who didn't. In the validation stage, we included 224 patients, of whom 90 had achieved HBsAg loss, to validate the identified significant single nucleotide polymorphisms. To verify the functional involvement of the candidate genes identified, we performed a series of in vitro and in vivo experiments. RESULTS: GWAS results indicated a significant association between the rs7519753 C allele and serum HBsAg loss in patients with CHB after Peg-IFNα treatment (p = 4.85 × 10-8, odds ratio = 14.47). This association was also observed in two independent validation cohorts. Expression quantitative trait locus analysis revealed higher hepatic TP53BP2 expression in individuals carrying the rs7519753 C allele (p = 2.90 × 10-6). RNA-sequencing of liver biopsies from patients with CHB after Peg-IFNα treatment revealed that hepatic TP53BP2 levels were significantly higher in the HBsAg loss group compared to the HBsAg persistence group (p = 0.035). In vitro and in vivo experiments demonstrated that loss of TP53BP2 decreased interferon-stimulated gene levels and the anti-HBV effect of IFN-α. Mechanistically, TP53BP2 was found to downregulate SOCS2, thereby facilitating JAK/STAT signaling. CONCLUSION: The rs7519753 C allele is associated with elevated hepatic TP53BP2 expression and an increased probability of serum HBsAg loss post-Peg-IFNα treatment in patients with CHB. TP53BP2 enhances the response of the hepatocyte to IFN-α by suppressing SOCS2 expression. IMPACT AND IMPLICATIONS: Chronic hepatitis B (CHB) remains a global public health issue. Although current antiviral therapies are more effective in halting disease progression, only a few patients achieve functional cure for hepatitis B with HBsAg loss, highlighting the urgent need for a cure for CHB. This study revealed that the rs7519753 C allele, which is associated with high expression of hepatic TP53BP2, significantly increases the likelihood of serum HBsAg loss in patients with CHB undergoing Peg-IFNα treatment. This finding not only provides a promising predictor for HBsAg loss but identifies a potential therapeutic target for Peg-IFNα treatment. We believe our results are of great interest to a wide range of stakeholders based on their potential clinical implications.

Restoring neuronal iron homeostasis revitalizes neurogenesis after spinal cord injury.

Spinal cord injury (SCI) can lead to iron overloading and subsequent neuronal ferroptosis, which hinders the recovery of locomotor function. However, it is still unclear whether the maintenance of neuronal iron homeostasis enables to revitalize intrinsic neurogenesis. Herein, we report the regulation of cellular iron homeostasis after SCI via the chelation of excess iron ions and modulation of the iron transportation pathway using polyphenol-based hydrogels for the revitalization of intrinsic neurogenesis. The reversed iron overloading can promote neural stem/progenitor cell differentiation into neurons and elicit the regenerative potential of newborn neurons, which is accompanied by improved axon reinnervation and remyelination. Notably, polyphenol-based hydrogels significantly increase the neurological motor scores from ~8 to 18 (out of 21) and restore the transmission of sensory and motor electrophysiological signals after SCI. Maintenance of iron homeostasis at the site of SCI using polyphenol-based hydrogels provides a promising paradigm to revitalize neurogenesis for the treatment of iron accumulation-related nervous system diseases.

Mesenchymal Stem Cells Promote Polarization of M2 Macrophages in Mice with Acute-On-Chronic Liver Failure via Mertk/JAK1/STAT6 Signaling.

Acute-on-chronic liver failure (ACLF) is a severe disease with a high mortality. Macrophage-related inflammation plays a crucial role in ACLF development. Mesenchymal stem cells (MSCs) treatment was demonstrated to be beneficial in ACLF in our previous study; however, the underlying mechanisms remain unknown. Therefore, mouse bone marrow-derived MSCs were used to treat an ACLF mouse model or cocultured with RAW264.7/J774A.1 macrophages that were stimulated with LPS. Histological and serological parameters and survival were analyzed to evaluate efficacy. We detected changes of Mer tyrosine kinase (Mertk), JAK1/STAT6, inflammatory cytokines, and markers of macrophage polarization in vitro and in vivo. In ACLF mice, MSCs improved liver function and 48-h survival of ACLF mice and alleviated inflammatory injury by promoting M2 macrophage polarization and elevated Mertk expression levels in macrophages. This is significant, as Mertk regulates M2 macrophage polarization via the JAK1/STAT6 signaling pathway.

Lactobacillus co-fermentation of Cerasus humilis juice alters chemical properties, enhances antioxidant activity, and improves gut microbiota.

Fermentation with Lactobacillus has been shown to improve the nutritional value of juice. In this study, Cerasus humilis juice was fermented using two commercial probiotics, namely, Lactobacillus acidophilus and Lactobacillus plantarum. The total antioxidant capacity (TAOC), viable count, chemical properties, antioxidant activity after in vitro digestion, and alterations in the gut microbiota composition of the fermented juice were investigated. After fermentation, the TAOC increased from 107.66 U mL-1 to 126.72 U mL-1; viable count increased from 5.85 lg (CFU mL-1) to 8.17 lg (CFU mL-1); and the contents of total phenols, total flavonoids, proanthocyanins, four organic acids, and 29 amino acids had changed. Overall, 47 compounds were identified in the juice, 20 of which were enriched after fermentation. Furthermore, Lactobacillus co-fermentation improved the antioxidant properties of the juice after in vitro digestion and increased the abundance of probiotics to regulate the gut microbiota. These findings illustrate the potential use of Lactobacillus acidophilus and Lactobacillus plantarum in the co-fermentation of C. humilis juice to enhance its nutritional and functional properties.

Integrated HBV DNA and cccDNA maintain transcriptional activity in intrahepatic HBsAg-positive patients with functional cure following PEG-IFN-based therapy.

BACKGROUND: Hepatitis B surface antigen (HBsAg) seroclearance marks regression of hepatitis B virus (HBV) infection. However, more than one-fifth of patients with functional cure following pegylated interferon-based therapy may experience HBsAg seroreversion. The mechanisms causing the HBV relapse remain unclear. AIM: To investigate the level and origin of HBV transcripts in patients with functional cure and their role in predicting relapse. METHODS: Liver tissue obtained from patients with functional cure, as well as uncured and treatment-naïve HBeAg-negative patients with chronic hepatitis B (CHB) were analysed for intrahepatic HBV markers. HBV capture and RNA sequencing were used to detect HBV integration and chimeric transcripts. RESULTS: Covalently closed circular DNA (cccDNA) levels and the proportion of HBsAg-positive hepatocytes in functionally cured patients were significantly lower than those in uncured and treatment-naïve HBeAg-negative patients. Integrated HBV DNA and chimeric transcripts declined in functionally cured patients compared to uncured patients. HBsAg-positive hepatocytes present in 25.5% of functionally cured patients, while intrahepatic HBV RNA remained in 72.2%. The levels of intrahepatic HBV RNA, integrated HBV DNA, and chimeric transcripts were higher in functionally cured patients with intrahepatic HBsAg than in those without. The residual intrahepatic HBsAg in functionally cured patients was mainly derived from transcriptionally active integrated HBV DNA; meanwhile, trace transcriptional activity of cccDNA could also remain. Two out of four functionally cured patients with intrahepatic HBsAg and trace active cccDNA experienced HBV relapse. CONCLUSION: Integrated HBV DNA and cccDNA maintain transcriptional activity and maybe involved in HBsAg seroreversion in intrahepatic HBsAg-positive patients with functional cure and linked to virological relapse.

Double Plasma Molecular Adsorption System with Sequential Low-dose Plasma Exchange in Patients with Hepatitis B Virus-related Acute-on-chronic Liver Failure: A Prospective Study.

Background and Aims: To investigate the safety and efficacy of double plasma molecular adsorption system (DPMAS) with sequential low-dose plasma exchange (LPE) in treating early hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). Methods: Clinical data of patients with HBV-ACLF were prospectively collected, including patients in a DPMAS with sequential LPE (DPMAS+LPE) group and those in a standard medical treatment (SMT) group. The primary endpoint was death or liver transplantation (LT) at 12 weeks of follow-up. Propensity-score matching was performed to control the effects of confounding factors on prognosis between the two groups. Results: After 2 weeks, total bilirubin, alanine aminotransferase, blood urea nitrogen levels, and Chinese Group on the Study of Severe Hepatitis B score, were significantly lower in the DPMAS+LPE group than those in the SMT group (p<0.05). After 4 weeks, laboratory parameters of the two groups were similar. The cumulative survival rate of the DPMAS+LPE group was significantly higher than that of the SMT group at 4 weeks (97.9% vs. 85.4%, p=0.027), but not at 12 weeks (85.4% vs. 83.3%, p=0.687). Cytokine levels were significantly lower in 12-week survival group than in the death-or-LT group (p<0.05). Functional enrichment analysis showed that downregulated cytokines were mainly involved in positive regulation of proliferation and activation of lymphocytes and monocytes, regulation of immune effect response, regulation of endotoxin response, and glial cell proliferation. Conclusion: DPMAS+LPE significantly improved the 4-week cumulative survival rate, and ameliorated the inflammatory response in patients. DPMAS+LPE may be a promising modality for patients with early HBV-ACLF.

Anticonvulsive Effect of Glucosyl Xanthone Mangiferin on Pentylenetetrazol (PTZ)-Induced Seizure-Provoked Mice.

Anxiety and depression are major side effects induced by currently available antiepileptic drugs; apart from this, they also diminish intelligence and language skills which cause hepatic failure, anemia, etc. Hence, in this study, we assessed antiepileptic effect of a phytochemical mangiferin. Epilepsy, a prevalent non communicable neurological disorder, affects infants and older population throughout the world. Epilepsy-induced comorbidities are more severe and if not treated cautiously lead to disability and even worse cases, mortality. The onset and duration of convulsion were observed. Seizure severity score was assessed by provoking kindling with 35 mg/kg PTZ. Prooxidants and antioxidants were measured to assess the antioxidant effect of mangiferin. Inflammatory markers were measured to determine the anti-inflammatory effect of mangiferin. The levels of neurotransmitters and ATPases were quantified to evaluate the neuroprotective effect of mangiferin. Mangiferin significantly decreased the onset and duration convulsion. It also decreased the seizure severity score, locomotor activity, and immobilization effectively. The excitatory neurotransmitter was reduced, and inhibitory neurotransmitter was increased in mice treated with mangiferin. Overall, our results confirm that mangiferin efficiently protects mice from PTZ-induced seizures. It can be subjected to further research to be prescribed as a potent antiepileptic drug.

Bone marrow mesenchymal stem cell-derived small extracellular vesicles promote liver regeneration via miR-20a-5p/PTEN.

Balancing hepatocyte death and proliferation is key to non-transplantation treatments for acute liver failure (ALF), which has a high short-term mortality rate. Small extracellular vesicles (sEVs) may act as mediators in the repair of damaged liver tissue by mesenchymal stem cells (MSCs). We aimed to investigate the efficacy of human bone marrow MSC-derived sEVs (BMSC-sEVs) in treating mice with ALF and the molecular mechanisms involved in regulating hepatocyte proliferation and apoptosis. Small EVs and sEV-free BMSC concentrated medium were injected into mice with LPS/D-GalN-induced ALF to assess survival, changes in serology, liver pathology, and apoptosis and proliferation in different phases. The results were further verified in vitro in L-02 cells with hydrogen peroxide injury. BMSC-sEV-treated mice with ALF had higher 24 h survival rates and more significant reductions in liver injury than mice treated with sEV-free concentrated medium. BMSC-sEVs reduced hepatocyte apoptosis and promoted cell proliferation by upregulating miR-20a-5p, which targeted the PTEN/AKT signaling pathway. Additionally, BMSC-sEVs upregulated the mir-20a precursor in hepatocytes. The application of BMSC-sEVs showed a positive impact by preventing the development of ALF, and may serve as a promising strategy for promoting ALF liver regeneration. miR-20a-5p plays an important role in liver protection from ALF by BMSC-sEVs.

Landslide Monitoring along the Dadu River in Sichuan Based on Sentinel-1 Multi-Temporal InSAR.

The Dadu River travels in the mountainous areas of southwestern China, one of regions with the most hazards that has long suffered from frequent geohazards. The early identification of landslides in this region is urgently needed, especially after the recent Luding earthquake (MS 6.8). While conventional ground-based monitoring techniques are limited by the complex terrain conditions in these alpine valley regions, space interferometric synthetic aperture radar (InSAR) provides an incomparable advantage in obtaining surface deformation with high precision and over a wide area, which is very useful for long-term and slow geohazard monitoring. In this study, more than 500 Sentinel-1 SAR images with four frames acquired during 2017~2022 were collected to detect the hidden landslide regions from the Jinchuan to Ebian Section along the Dadu River, based on joint-scatterer InSAR (JS-InSAR) and small baseline subset (SBAS) techniques. The results showed that our method could be successfully applied for landslide monitoring in complex mountainous regions. Furthermore, 143 potential landslide regions spreading over an 800 km area along the Dadu River were extracted by integrating the deformation measurements and optical images. Our study can provide a reference for large-scale geological hazard surveys in mountainous areas, and the InSAR technique will be encouraged for the local government in future long-term monitoring applications in the Dadu River Basin.

LAG3+ erythroid progenitor cells inhibit HBsAg seroclearance during finite pegylated interferon treatment through LAG3 and TGF-ß.

HBsAg seroclearance, the ideal aim of anti-hepatitis B virus (HBV) treatment, cannot be achieved easily. Anemia is another common issue for chronic hepatitis B (CHB) patients, which leads to elevation of erythroid progenitor cells (EPCs) and immune suppression in cancer. This study investigated the role of EPCs in HBsAg seroclearance following pegylated interferon-α (PEG-IFN) treatment. CD45+EPC accumulation in CHB patients and an AAV/HBV mice model was found in the circulation and liver by flow cytometry and immunofluorescence tests. Wright-Giemsa staining showed that these pathological CD45+EPCs presented elevated erythroid cells with relative immature morphologies and atypical cells compared with the control cells. CD45+EPCs were associated with immune tolerance and decreased HBsAg seroclearance during finite PEG-IFN treatment. CD45+EPCs suppressed antigen non-specific T cell activation and HBV-specific CD8+T cells, partially through transforming growth factor ß (TGF-ß). RNA-seq revealed that CD45+EPCs in patients with CHB presented a distinct gene expression profile compared with CD45-EPCs and CD45+EPCs from cord blood. Notably, CD45+EPCs from patients with CHB expressed high level of Lymphocyte-activation gene 3 (LAG3), an immune checkpoint molecule, and were then defined as LAG3+EPCs. LAG3+EPCs diminished the function of antigen presenting cells through LAG3, which was another mechanism by which LAG3+EPCs' suppressed HBV-specific CD8+T cells. Anti-LAG3 and anti-TGF-ß combination treatment decreased serum HBeAg, HBV DNA levels and HBsAg level, as well as HBsAg-expression in hepatocytes during PEG-IFN treatment in the AAV/HBV mice model. Conclusions: LAG3+EPCs inhibited the efficacy of PEG-IFN treatment on HBsAg seroclearance induced by LAG3 and TGF-ß. Anti-LAG3, anti-TGF-ß and PEG-IFN combination treatment might facilitate HBV clearance.

96-Week Treatment of Tenofovir Amibufenamide and Tenofovir Disoproxil Fumarate in Chronic Hepatitis B Patients.

Background and Aims: Tenofovir amibufenamide (TMF) is a novel phosphoramidated prodrug of tenofovir with noninferior efficacy and better bone and renal safety to tenofovir disoproxil fumarate (TDF) in 48 weeks of treatment. Here, we update 96-week comparison results. Methods: Patients with chronic hepatitis B were assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks. The virological suppression was defined as HBV DNA levels <20 IU/mL at week 96. Safety was evaluated thoroughly with focusing on bone, renal, and metabolic parameters. Results: Virological suppression rates at week 96 were similar between TMF and TDF group in both HBeAg-positive and HBeAg-negative populations. Noninferior efficacy was maintained in the pooled population, while it was first achieved in patients with HBV DNA ≥7 or 8 log10 IU/mL at baseline. Non-indexed estimated glomerular filtration rate for renal safety assessment was adopted, while a smaller decline of which was seen in the TMF group than in the TDF group (p=0.01). For bone mineral density, patients receiving TMF displayed significantly lower reduction levels in the densities of spine, hip, and femur neck at week 96 than those receiving TDF. In addition, the lipid parameters were stable after week 48 in all groups while weight change still showed the opposite trend. Conclusions: TMF maintained similar efficacy at week 96 compared with TDF with continued superior bone and renal safety profiles (NCT03903796).

Impact of nonalcoholic fatty liver disease status change on antiviral efficacy of nucleos(t)ide analogues in HBeAg-positive chronic hepatitis B.

Data on the dynamic changes in chronic hepatitis B (CHB) patients with nonalcoholic fatty liver disease (NAFLD) during antiviral therapy are scarce. We aimed to investigate the evolution of NAFLD status change in CHB patients treated with nucleos(t)ide analogues (NAs) and its influence on therapeutic outcomes. This retrospective study included 164 HBeAg-positive CHB patients from a randomized controlled trial who were treated with NAs for 104 weeks and underwent paired liver biopsies. Histological evaluation was performed at baseline and Week 104. The patients were divided into four groups according to NAFLD status changes. From baseline to Week 104, the overall percentage of CHB patients with concurrent NAFLD increased from 17.1% to 26.2% (p = 0.044). Among them, 7 of 28 patients (25.0%) with NAFLD at baseline showed NAFLD remission at week 104, while 22 of 136 patients (16.2%) without NAFLD at baseline developed new-onset NAFLD. In subgroup analyses, the new-onset and sustained NAFLD groups showed significantly lower rates of biochemical response at week 104 as compared to the sustained non-NAFLD group (77.3% and 57.1% vs. 93.9%, respectively; all p < 0.05), as well as fibrosis improvement (31.8% and 42.9% vs. 69.3%, respectively; all p < 0.05). NAFLD status changes did not influence the virological response, HBeAg seroconversion, and necroinflammation improvement (all p > 0.05). In HBeAg-positive CHB patients receiving NAs therapy, new-onset and sustained NAFLD may counteract the benefits of antiviral therapy, reducing the rate of biochemical response and fibrosis improvement.

Reduction in Intrahepatic cccDNA and Integration of HBV in Chronic Hepatitis B Patients with a Functional Cure.

Background and Aims: Functional cure (FC) is characterized by the clearance of the hepatitis B surface antigen from the serum of patients with chronic hepatitis B (CHB). However, the level of intrahepatic covalently closed circular DNA (cccDNA) and hepatitis B virus (HBV) integration remains unclear. We conducted this study to determine them and reveal their value in the treatment of CHB. Methods: There were two sessions to elucidate the changes in intrahepatic cccDNA and HBV integration after antiviral therapy. In the first session, 116 patients were enrolled and divided into FC, non-functional cure (NFC), and CHB groups, including 48 patients with functionally cured CHB, 27 with CHB without functional cure after antiviral treatment, and 41 with treatment-naïve CHB. Patients were tested for both intrahepatic cccDNA and other viral markers. All patients in the FC group were followed up for at least 24 weeks to observe relapse. In the second session, another ten patients were included for in-depth whole-genome sequencing to analyze HBV integration. Results: Thirteen patients in the FC group were negative for intrahepatic cccDNA. Intrahepatic cccDNA was much higher in the CHB group compared with the FC group. Seven patients had HBsAg seroreversion, including two with virological relapse. Integration of HBV was detected in one (33.3%) functionally cured patients and in seven (100%) with CHB. 28.0% of the HBV breakpoints were assigned in the 1,500 nt to 1,900 nt range of the HBV genome. Conclusions: After achieving an FC, the rate of intrahepatic cccDNA and HBV integration was significantly reduced in patients with CHB. For those patients who cleared intrahepatic cccDNA, the chances of developing virological relapse were even lower.

Colonization with Carbapenem-Resistant Enterobacteriaceae Contributes to Unfavorable Outcomes in End-Stage Liver Disease Patients.

Carbapenem-resistant Enterobacteriaceae (CRE) are the highest priority pathogens of the World Health Organization, and their prevalence in end-stage liver disease (ESLD) patients is increasing. CRE colonization is an independent risk factor for CRE infections. We aimed to assess risk factors and explore the relationship between CRE colonization, infection, and prognosis in patients with ESLD. A total of 311 patients with ESLD were screened for CRE colonization by fecal swabs from October 2020 to January 2022. Antimicrobial susceptibility was tested using the broth microdilution method. Carbapenem resistance genes, multilocus sequence type, and capsular serotype were analyzed by polymerase chain reaction (PCR). Seventeen CRE strains were detected, among which the most common was Klebsiella pneumoniae. The CRE colonization rate was 5.5%. Artificial liver support was an independent risk factor for CRE colonization. Compared to the non-CRE colonization group, the colonization group had a higher incidence of CRE infection and a worse prognosis. Furthermore, these strains were not closely related, and all were sensitive to polymyxin and tigecycline. There was a high colonization rate in ESLD patients, and colonization strains were highly diverse. CRE colonization deserves attention in these patients, especially when treated with artificial liver support.

High Expression of POGK Predicts Poor Prognosis in Patients with Hepatocellular Carcinoma.

OBJECTIVE: Kruppel-associated box (KRAB) proteins reportedly play a dual role in neoplastic transformation. At present, little is known about the function of the proteins encoded by the human pogo transposable element derived with KRAB domain (POGK) gene. Herein, we evaluated the prognostic significance of POGK expression in patients with hepatocellular carcinoma (HCC). METHODS: The data of HCC patients was downloaded from The Cancer Genome Atlas (TCGA) database. To determine the relationship between POGK and clinical features, logistic regression was applied. Cox regression and Kaplan-Meier analyses were used to evaluate the correlation between POGK and survival rates. Gene ontology (GO) analysis and Gene set enrichment analysis (GSEA) were conducted to identify the enriched pathways and functions associated with POGK. RESULTS: A total of 374 HCC patients were identified in TCGA. POGK was significantly upregulated in HCC and correlated with tumor status (p = 0.036), race (p = 0.025), weight (p = 0.002), body mass index (p = 0.033), histologic grade (p < 0.001), and alpha-fetoprotein (p < 0.001). High POGK expression in HCC patients correlated with a poor outcome in terms of overall survival (p = 0.0018), progression-free survival (p = 0.0087), relapse-free survival (p = 0.045), and disease-specific survival (p = 0.014), according to Kaplan-Meier analysis. Receiver operating characteristic curve analysis showed that the area under the curve of POGK expression for HCC diagnosis was 0.891. GSEA showed that high POGK expression might activate mitotic prometaphase, kinesins, homologous DNA pairing and strand exchange, MET activates PTK2 signaling pathway, G1 to S cell cycle control, Aurora B pathway, ncRNAs involved in WNT signaling pathway, hepatitis C, and ncRNAs involved in the STAT3 signaling pathway. POGK expression correlated with the abundance of adaptive and innate immunocytes in HCC. CONCLUSION: High expression of POGK has high diagnostic and prognostic values in patients with HCC. Moreover, POGK expression is correlated with immune infiltration in HCC.