(1) Background: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide with limited treatment satisfaction. Finding new therapeutic targets has remained a major challenge. Ferroptosis is an iron-dependent cell death program that plays a regulatory role in HBV infection and HCC development. It is necessary to classify the roles of ferroptosis or ferroptosis-related genes (FRGs) in HBV-related HCC progression. (2) Methods: We conducted a matched case–control study from the TCGA database, retrospectively collecting demographic data and common clinical indicators from all subjects. The Kaplan–Meier curve, univariate and multivariate cox regression analysis of the FRGs were used to explore the risk factors for HBV-related HCC. The CIBERSORT algorithm and TIDE algorithm were executed to evaluate the functions of FRGs in the tumor-immune environment. (3) Results: A total of 145 HBV-positive HCC patients and 266 HBV-negative HCC patients were enrolled in our study. Four ferroptosis related genes (FANCD2, CS, CISD1 and SLC1A5) were positively correlated with the progression of HBV-related HCC. Among them, SLC1A5 was an independent risk factor for HBV-related HCC, and correlated with poor prognosis, advanced progression and an immunosuppression microenvironment. (4) Conclusions: Here, we revealed that a ferroptosis-related gene, SLC1A5, may be an excellent predictor of HBV-related HCC and may provide insight into the development of innovative possible therapeutic techniques.

Background: Exosomes are essential for hepatocellular carcinoma (HCC) progression and have garnered significant interest as novel targets for diagnostic, prognostic, and therapeutic approaches. This study aims to identify potential exosome-related biomarkers for the development of useful strategies for HCC diagnosis and therapy. Methods: Three datasets obtained from the Gene Expression Omnibus (GEO) were utilized to identify differentially expressed genes (DEGs) in HCC. Through Gene Ontology (GO) analysis and protein–protein interaction (PPI) network, overall survival (OS) analysis, Cox analyses, and diethylnitrosamine (DEN)-induced HCC mouse model detection, exosome-related hub gene was screened out, followed by a prognostic value assessment and immune-correlates analysis based on the Cancer Genome Atlas (TCGA) dataset. The hub gene-containing exosomes derived from Hepa1-6 cells were isolated and characterized using differential ultracentrifugation, transmission electron microscopy scanning, and Western blot. Ultrasound-guided intrahepatic injection, cell co-culture, CCK-8, and flow cytometry were performed to investigate the effects of the hub gene on macrophage infiltration and polarization in HCC. Results: A total of 83 DEGs enriched in the extracellular exosome term, among which, FTCD, HRA, and C8B showed the strongest association with the progression of HCC. FTCD was independently associated with a protective effect in HCC and selected as the hub gene. The presence of FTCD in exosomes was confirmed. FTCD-stimulated macrophages were polarized towards the M1 type and suppressed HCC cells proliferation. Conclusions: FTCD is a potential exosome-related biomarker for HCC diagnosis, prognosis, and treatment. The crosstalk between FTCD-containing exosomes and macrophages in HCC progression deserves further investigation.

To reduce the inhibition sensitivity of a thermoresistant xylanase AusM to xylanase inhibitor protein (XIP)-type in wheat flour, the site-directed mutagenesis was conducted based on the computer-aided redesign. First, fourteen single-site variants and one three-amino acid replacement variant in the thumb region of an AusM-encoding gene (AusM) were constructed and expressed in E. coli BL21(DE3), respectively, as predicted theoretically. At a molar ratio of 100:1 between SyXIP-I/xylanase, the majority of mutants were nearly completely inactivated by the inhibitor SyXIP-I, whereas AusM^N127A retained 62.7% of its initial activity and AusM^PKK retained 100% of its initial activity. The optimal temperature of the best mutant AusM^PKK was 60 °C, as opposed to 60–65 °C for AusM, while it exhibited improved thermostability, retaining approximately 60% of its residual activity after heating at 80 °C for 60 min. Furthermore, AusM^PKK at a dosage of 1000 U/kg was more effective than AusM at 4000 U/kg in increasing specific bread loaf volume and reducing hardness during bread production and storage. Directed evolution of AusM significantly reduces inhibition sensitivity, and the mutant enzyme AusM^PKK is conducive to improving bread quality and extending its shelf life.

Natural products have been used extensively around the world for many years as therapeutic, prophylactic, and health-promotive agents. Ribes himalense Royle ex Decne, a plant used in traditional Tibetan medicine, has been demonstrated to have significant antioxidant and anti-inflammatory properties. However, the material basis of its medicinal effects has not been sufficiently explored. In this study, we established an integrated strategy by online HPLC-1,1-diphenyl-2-picrylhydrazyl, medium-pressure liquid chromatography, and HPLC to achieve online detection and separation of antioxidants in Ribes himalense extracts. Finally, four antioxidants with quercetin as the parent nucleus were obtained, namely, Quercetin-3-O-β-D-glucopyranoside-7-O-α-L-rhamnopyranoside, Quercetin-3-O-β-D-xylopyranosyl(1-2)-β-D-glucopyranoside, Quercetin-3-O-β-D-glucopyranoside, and Quercetin-3-O-β-D-galactoside. Until now, the four antioxidants in Ribes himalense have not been reported in other literatures. Meanwhile, the free-radical-scavenging ability of them was evaluated by DPPH assay, and potential antioxidant target proteins were explored using molecular docking. In conclusion, this research provides insights into the active compounds in Ribes himalense which will facilitate the advancement of deeper studies on it. Moreover, such an integrated chromatographic strategy could be a strong driver for more efficient and scientific use of other natural products in the food and pharmaceutical industries.

The effects of single- (Lactobacillus fermentum) or mixed-strain (Lactobacillus fermentum, Kluyveromyces marxianus) fermentation of red bean with or without wheat bran on sourdough bread quality and nutritional aspects were investigated. The results showed that, compared to unfermented controls, the tannins, phytic acid, and trypsin inhibitor levels were significantly reduced, whereas the phytochemical (TPC, TFC, and gallic acid) and soluble dietary fiber were increased in sourdough. Meanwhile, more outstanding changes were obtained in sourdough following a mixed-strain than single-strain fermentation, which might be associated with its corresponding β-glucosidase, feruloyl esterase, and phytase activities. An increased specific volume, reduced crumb firmness, and greater sensory evaluation of bread was achieved after mixed-strain fermentation. Moreover, diets containing sourdough, especially those prepared with mixed-strain-fermented red bean with wheat bran, significantly decreased serum pro-inflammatory cytokines levels, and improved the lipid profile, HDL/LDL ratio, glucose tolerance, and insulin sensitivity of mice. Moreover, gut microbiota diversity increased towards beneficial genera (e.g., Bifidobacterium), accompanied with a greater increase in short-chain fatty acid production in mice fed on sourdough-based bread diets compared to their controls and white bread. In conclusion, mixed-strain fermentation’s synergistic effect on high fiber-legume substrate improved the baking, sensory quality, and prebiotic effect of bread, leading to potential health benefits in mice.

The acidic tumor microenvironment plays a critical role in promoting liver cancer cell survival by enhancing glycolysis and adaptive mechanisms. Acid-sensing ion channel 1 (ASIC1) is a key regulator of pH sensing, but its role in liver cancer progression and underlying mechanisms remain unclear. In this study, we examined ASIC1 expression in clinical liver tumor tissues using immunohistochemistry and immunofluorescence, correlating it with tumor stages. HepG2 and Li-7 cells were cultured in tumor supernatant and acidic conditions to mimic the tumor microenvironment. Western blotting assessed the expression of ASIC1 and glycolysis-related enzymes, with siRNA transfections used to investigate ASIC1 and phosphofructokinase muscle-type (PFKM) in liver cancer cell survival. Our results showed that ASIC1 expression was significantly elevated in liver tumor tissues and correlated with tumor progression. Acidic conditions increased ASIC1 expression in both cell lines, enhancing cell survival, while knockdown of ASIC1 reduced viability and increased apoptosis, particularly under acidic conditions. Moreover, PFKM silencing reversed the survival advantage conferred by ASIC1, confirming PFKM as a critical downstream effector. Additionally, lactate dehydrogenase (LDH) and phosphofructokinase (PFK) activity assays showed no significant changes, suggesting other regulatory mechanisms may also be involved. These findings suggest that the ASIC1/PFKM pathway promotes liver cancer cell survival in acidic environments, representing a potential therapeutic target for disrupting tumor adaptation in liver malignancies.