Novel subtypes of metabolic associated steatotic liver disease linked to clinical outcomes: implications for precision medicine.

Background & Aims: Although metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with high multimorbidity and mortality, existing classification systems and risk prediction models largely ignore the heterogeneity of MASLD. Improved subtype definition could improve prediction of outcomes and inform new precision treatment strategies.

Methods: We analyzed individuals with MASLD from population-based electronic health record resource from UK Biobank (n = 125,197) and Health examinee dataset of Nanfang Hospital (n = 995).

Association between red blood cell indices and non-alcoholic fatty liver disease: Prospective study and two-sample Mendelian randomization analysis based on large cohorts.

Introduction And Objectives: Non-alcoholic fatty liver disease (NAFLD) is the primary contributor to persistent chronic liver disease which derives cardiovascular disease, malignancies, and related mortality. There is an association between red blood cell (RBC) indices and the incidence of NAFLD, but the causal relationship has not been determined. We aimed to investigate the association through prospective and Mendelian randomization (MR) analyses.

A high reticulocyte count is a risk factor for the onset of metabolic dysfunction-associated steatotic liver disease: Cross-sectional and prospective studies of data of 310,091 individuals from the UK Biobank.

Metabolic dysfunction-associated steatotic liver disease (MASLD) poses a considerable health risk. Nevertheless, its risk factors are not thoroughly comprehended, and the association between the reticulocyte count and MASLD remains uncertain. This study aimed to explore the relationship between reticulocyte count and MASLD.

Mechanistic Insights into the N-Hydroxylations Catalyzed by the Binuclear Iron Domain of SznF Enzyme: Key Piece in the Synthesis of Streptozotocin.

SznF, a member of the emerging family of heme-oxygenase-like (HO-like) di-iron oxidases and oxygenases, employs two distinct domains to catalyze the conversion of N-methyl-L-arginine (L-NMA) into N-nitroso-containing product, which can subsequently be transformed into streptozotocin. Using unrestricted density functional theory (UDFT) with the hybrid functional B3LYP, we have mechanistically investigated the two sequential hydroxylations of L-NMA catalyzed by SznF's binuclear iron central domain. Mechanism B primarily involves the O-O bond dissociation, forming Fe(IV)=O, induced by the H/e introduction to the Fe side of μ-1,2-peroxo-Fe(III/III), the substrate hydrogen abstraction by Fe(IV)=O, and the hydroxyl rebound to the substrate N radical.

Predictive Value of the Hepatic Immune Predictive Index for Patients with Primary Liver Cancer Treated with Immune Checkpoint Inhibitors.

Background: Immune checkpoint inhibitors (ICIs) have improved survival outcomes and resulted in long-term responses in primary liver cancer in some patients. Nevertheless, not all patients with PLC could benefit from immunotherapy. Therefore, it is necessary to identify patients suitable for such therapy.

Use of computed tomography-derived body composition to determine the prognosis of patients with primary liver cancer treated with immune checkpoint inhibitors: a retrospective cohort study.

Background: Immune checkpoint inhibitors (ICIs) have been used to successfully treat primary liver cancer (PLC); however, identifying modifiable patient factors associated with therapeutic benefits is challenging. Obesity is known to be associated with increased survival after ICI treatment; however, the relationship between body composition (muscle, fat) and outcomes is unclear. This study aimed to evaluate the association between sarcopenia and CT-derived fat content and the prognosis of ICIs for the treatment of PLC.

Mechanism for the Halogenation and Azidation of Lysine Catalyzed by Non-heme Iron BesD Enzyme.

Selective halogenation is important in synthetic chemistry. BesD, a new member of the non-heme Fe(II)/α-ketoglutarate (αKG)-dependent halogenase family, can activate the sp C-H bond and halogenate lysine, in particular without a carrier protein. Using the density functional calculations, a chlorination mechanism in BesD has been proposed, mainly including the formation of Cl-Fe(IV)=O through the αKG decarboxylation, the isomerization of Cl-Fe(IV)=O, the substrate hydrogen abstraction by Fe(IV)=O, and the rebound of chloro to the substrate carbon radical.

Impact of antibiotics on the efficacy of immune checkpoint inhibitors in the treatment of primary liver cancer.

Background And Aim: Immune checkpoint inhibitors (ICIs) are widely used in the treatment of liver cancer. However, the interaction with other drugs may change the efficacy of ICIs. Few studies investigated the effects of antibiotics (ATBs) on the efficacy of immunotherapy and the survival of patients with primary liver cancer receiving immunotherapy.

Splenomegaly in predicting the survival of patients with advanced primary liver cancer treated with immune checkpoint inhibitors.

Background & Aims: Immune checkpoint inhibitors (ICIs) play an increasingly important role in the treatment of primary liver cancer (PLC). Some patients with PLC experience symptoms of splenomegaly. Splenomegaly may affect the efficacy of ICIs due to an imbalance of the immune microenvironment.

Breakfast consumption frequency is associated with dyslipidemia: a retrospective cohort study of a working population.

Background: Dyslipidemia is a significant contributor to cardiovascular and cerebrovascular diseases. Research on the relationship between breakfast consumption frequency and dyslipidemia in the working population is lacking. Therefore, we aimed to investigate this relationship based on a retrospective cohort study of a large working population in China.

Identification of Potential Core Genes Between Primary and Metastatic Malignant Melanoma and Analysis of Their Immune Correlation.

Purpose: To identify the potential differential genes between primary and metastatic melanoma, screen out immune-related genes in core genes and analyze their immune correlation, thus searching for the early diagnostic biomarkers of cutaneous malignant melanoma (CMM) and the targets of curbing metastasis.

Materials And Methods: We analyzed two microarray datasets (GSE8401 and GSE46517) derived from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between primary and metastatic melanoma were screened out using the GEO2R tool.

Lung metastasis and lymph node metastasis are risk factors for hyperprogressive disease in primary liver cancer patients treated with immune checkpoint inhibitors.

Background: At present, some cancer patients experience hyperprogressive disease (HPD) after receiving immunotherapy. This study used the Response Evaluation Criteria in Solid Tumors 1.1 to evaluate the incidence of HPD in patients receiving immune checkpoint inhibitors (ICIs) for treating primary liver cancer (PLC) and to explore the risk factors for HPD.