Analysis of the susceptibility of refractory hepatitis C virus resistant to nonstructural 5A inhibitors.

Resistance-associated substitutions (RASs) of hepatitis C virus (HCV) affect the efficacy of direct-acting antivirals (DAAs). In this study, we aimed to clarify the susceptibility of the coexistence of nonstructural (NS) 5A Q24K/L28M/R30Q (or R30E)/A92K RASs, which were observed in patients with DAAs re-treatment failure and to consider new therapeutic agents. We used a subgenomic replicon system in which HCV genotype 1B strain 1B-4 was electroporated into OR6c cells derived from HuH-7 cells (Wild-type [WT]).

Development of Enzyme-Based Approaches for Recycling PET on an Industrial Scale.

Pollution by plastics such as polyethylene (PE), polypropylene (PP), polyvinyl chloride (PVC), polyurethane (PUR), polyamide (PA), polystyrene (PS), and poly(ethylene terephthalate) (PET) is now gaining worldwide attention as a critical environmental issue, closely linked to climate change. Among them, PET is particularly prone to hydrolysis, breaking down into its constituents, ethylene glycol (EG) and terephthalate (TPA). Biorecycling or bioupcycling stands out as one of the most promising methods for addressing PET pollution.

Usefulness of the aldehyde breath test for predicting metachronous recurrence in patients with esophageal squamous cell carcinoma and hypopharyngeal squamous cell carcinoma.

Background: The rate of metachronous recurrence after endoscopic submucosal dissection for early-stage esophageal squamous cell carcinoma and hypopharynx squamous cell carcinoma is as high (10-15%). The acetaldehyde breath test may detect acetaldehyde dehydrogenase 2 gene polymorphisms. Therefore, we evaluated its usefulness in assessing metachronous recurrence in patients with esophageal squamous cell carcinoma and hypopharynx squamous cell carcinoma.

Overview of the Properties of Glutamic Peptidases That Are Present in Plant and Bacterial Pathogens and Play a Role in Celiac Disease and Cancer.

Seven peptidase (proteinase) families─aspartic, cysteine, metallo, serine, glutamic, threonine, and asparagine─are in the peptidase database MEROPS, version 12.4 (https://www.ebi.

Clinical Effect of Lenvatinib Re-Administration after Transcatheter Arterial Chemoembolization in Patients with Intermediate Stage Hepatocellular Carcinoma.

The present study clarified the prognosis of intermediate-stage hepatocellular carcinoma (HCC) patients who received lenvatinib (LEN) followed by transcatheter arterial chemoembolization (TACE) on demand. We retrospectively evaluated 88 intermediate-stage HCC patients who received LEN. The median age was 74 (range: 47-92) years old, 67 patients were male, and 82 were classified as Child-Pugh A.

Early-phase prothrombin time-international normalized ratio in acute liver injury indicates the timing of therapeutic intervention and predicts prognostic improvement.

Aim: We investigated whether an early-phase prothrombin time-international normalized ratio (PT-INR) is an interventional prognostic indicator for patients with acute liver injury, including acute liver failure.

Methods: This was a multicenter retrospective observational study. We included 595 patients with alanine aminotransferase levels ≥300 U/L due to acute liver injury who were admitted to Kagoshima University Hospital or other collaborative investigation organizations between January 1, 2010, and December 31, 2015.

Dynamically Hidden Reaction Paths in the Reaction of CF + CO.

Reaction paths on a potential energy surface are widely used in quantum chemical studies of chemical reactions. The recently developed global reaction route mapping (GRRM) strategy automatically constructs a reaction route map, which provides a complete picture of the reaction. Here, we thoroughly investigate the correspondence between the reaction route map and the actual chemical reaction dynamics for the CF + CO reaction studied by guided ion beam tandem mass spectrometry (GIBMS).

Serine-Carboxyl Peptidases, Sedolisins: From Discovery to Evolution.

Sedolisin is a proteolytic enzyme, listed in the peptidase database MEROPS as a founding member of clan SB, family S53. This enzyme, although active at low pH, was originally shown not to be inhibited by an aspartic peptidase specific inhibitor, S-PI (pepstatin Ac). In this Perspective, the S53 family is described from the moment of original identification to evolution.

A case of autoimmune hepatitis with thymoma and myasthenia gravis.

A 44-year-old woman presented with cough, facial edema, and progressive fatigue. Computed tomography (CT) showed an anterior mediastinal mass, and laboratory findings showed liver injury. She was diagnosed with thymoma and scheduled for thymectomy after radiation and chemotherapy.

Metagenomic mining and structure-function studies of a hyper-thermostable cellobiohydrolase from hot spring sediment.

Enzymatic breakdown is an attractive cellulose utilisation method with a low environmental load. Its high temperature operation could promote saccharification and lower contamination risk. Here we report a hyper-thermostable cellobiohydrolase (CBH), named HmCel6A and its variant HmCel6A-3SNP that were isolated metagenomically from hot spring sediments and expressed in Escherichia coli.

Serine palmitoyltransferase long chain subunit 3 is associated with hepatocellular carcinoma in patients with NAFLD.

The prevalence of non-alcoholic fatty liver disease (NAFLD) is continuously increasing, with the proportion of patients with liver carcinogenesis due to non-alcoholic steatohepatitis (NASH) rising accordingly. Although it is important to identify individuals with hepatic carcinogenesis among patients with NAFLD, useful biomarkers have not yet been established. Previously, in a mouse model of diabetes mellitus without genetic modifications, we reported that a high-fat diet increases serine palmitoyltransferase long chain subunit 3 (SPTLC3) expression in liver tissue, accompanied by high frequency of liver carcinogenesis.

Features of patients who developed hepatocellular carcinoma after direct-acting antiviral treatment for hepatitis C Virus.

Background: The features of hepatitis C virus patients with a sustained virologic response (SVR) who developed hepatocellular carcinoma (HCC) after direct-acting antiviral (DAA) therapy are unclear.

Methods: The study population included 1494 DAA-SVR patients without a history of HCC. The cumulative carcinogenesis rate after the end of treatment (EOT) and factors related to HCC were analyzed.

Highly sensitive agglutinin-reactive fraction of α-fetoprotein is a predictive marker for hepatocarcinogenesis in long-term observation of patients with chronic liver disease.

Highly sensitive agglutinin-reactive fraction of α-fetoprotein (hs-AFP-L3) is a specific marker for hepatocellular carcinoma (HCC) and has been reliable in cases with a low serum α-fetoprotein (AFP) level. However, the biomarkers that contribute to hepatocarcinogenesis during the long-term observation are not yet clear. The present study reported the clinical utility of hs-AFP-L3 in the long-term observation of patients with chronic liver disease.

Acetaldehyde breath test as a cancer risk marker in patients with esophageal and hypopharyngeal squamous cell carcinoma.

Patients with inactive acetaldehyde dehydrogenase 2 (ALDH2) are at high risk for esophageal squamous cell carcinoma (ESCC) and hypopharyngeal squamous cell carcinoma (HPSCC). The acetaldehyde breath test (ABT) may demonstrate ALDH2 gene polymorphisms. We evaluated the usefulness of the ABT in patients with ESCC and HPSCC.

Changes in body composition and low blood urea nitrogen level related to an increase in the prevalence of fatty liver over 20 years: A cross-sectional study.

Aim: Qualitative body composition (BC) change, characterized by the combination of visceral fat gain and muscle loss, is drawing attention as a risk factor for fatty liver (FL). The present study aimed to describe trends in BC change and its association with FL in the Japanese population.

Methods: Data from medical checkups carried out on 56 639 Japanese participants every 5 years from 1997 to 2017 were analyzed.

Ideonella sakaiensis, PETase, and MHETase: From identification of microbial PET degradation to enzyme characterization.

Few reports have described the biological degradation or utilization of poly(ethylene terephthalate) (PET) to support microbial growth. We screened environmental samples from a PET bottle recycling site and identified the microbial consortium no. 46, which degraded amorphous PET at ambient temperature; thereafter, we isolated the resident Ideonella sakaiensis 201-F6 strain responsible for the degradation.

HGF-MET Signaling Shifts M1 Macrophages Toward an M2-Like Phenotype Through PI3K-Mediated Induction of Arginase-1 Expression.

Hepatocyte Growth Factor (HGF)-MET signaling is known to promote biological functions such as cell survival, cell motility, and cell proliferation. However, it is unknown if HGF-MET alters the macrophage phenotype. In this study, we aimed to study the effects of HGF-MET signaling on the M1 macrophage phenotype.

Viral and host factors are associated with retreatment failure in hepatitis C patients receiving all-oral direct antiviral therapy.

Aim: Direct-acting antiviral (DAA) therapy for hepatitis C virus is associated with high sustained virologic response rates. However, patients for whom DAA therapy fails acquire resistance-associated substitutions (RASs). We therefore evaluated the efficacy of DAA retreatment and factors associated with retreatment failure.

Synthesis and characterization of cyclobutenedione-bithiophene π-conjugated polymers: acetal-protecting strategy for Kumada-Tamao-Corriu coupling polymerization between aryl bromide and Grignard reagents.

Cyclobutenedione is an aromatic ring that exhibits strong electron-withdrawing properties but is susceptible to undesired reactions with nucleophiles. Herein, Kumada-Tamao-Corriu coupling polymerization of a cyclobutenedione monomer whose carbonyl groups are protected as acetals was achieved. Hydrolysis of the acetals afforded donor-acceptor type π-conjugated polymers consisting of cyclobutenedione as an acceptor unit and bithiophene as a donor unit.

Nonalcoholic fatty liver disease is associated with both subcutaneous and visceral adiposity: A cross-sectional study.

Nonalcoholic fatty liver disease (NAFLD) is recognized as a hepatic manifestation of metabolic syndrome because of the association with visceral obesity. However, the association between NAFLD and subcutaneous fat accumulation remains unclear.The study population included 3197 participants in regular health checkups, who were both hepatitis B virus surface antigen and hepatitis C virus antibody-negative, and consumed <20 g of alcohol per day.