Structure-based discovery of novel diarylpyrimidines as potent and selective Non-Nucleoside reverse transcriptase inhibitors: From CH(CN)-Biphenyl-Diarylpyrimidines to CNNH-Biphenyl-Diarylpyrimidines.

In order to enhance the anti-HIV-1 potency and selectivity of the previously reported compound 3 (EC = 27 nM, SI = 1361), a series of novel biphenyl-diarylpyrimidine derivatives were developed by employing structure-based drug design strategy. Among these derivatives, compound M44 demonstrated the most potent inhibitory activity against wild-type (WT) HIV-1 as well as five drug-resistant mutants (EC = 5-148 nM), which were 5-173 times more potent than that of 3 (EC = 27-9810 nM). Furthermore, this analogue exhibited approximately 11-fold lower cytotoxicity (CC = 54 μM) than that of etravirine and rilpivirine.

Duodenal-jejunal bypass ameliorates MASLD in rats by regulating gut microbiota and bile acid metabolism through FXR pathways.

Background: Although bariatric and metabolic surgical methods, including duodenal-jejunal bypass (DJB), were shown to improve metabolic dysfunction-associated steatotic liver disease (MASLD) in clinical trials and experimental rodent models, their underlying mechanisms remain unclear. The present study therefore evaluated the therapeutic effects and mechanisms of action of DJB in rats with MASLD.

Methods: Rats with MASLD were randomly assigned to undergo DJB or sham surgery.

Comparison of clinical outcomes in patients with refractory ascites treated with either TIPS, tunneled peritoneal catheter, or ascites pump.

Background: Refractory ascites (RA) remains a serious complication in patients with cirrhosis. Currently, the insertion of a TIPS is considered the standard of care in these patients. To achieve symptom control in those with TIPS contraindications, tunneled peritoneal catheters (PeCa) or ascites pumps were introduced.

CHOLANGIOCARCINOMA: EPIDEMIOLOGY, HISTOPATHOLOGY, AND POTENTIAL PROGNOSTIC AND THERAPEUTIC IMPLICATIONS IN A COHORT FROM A REFERENCE CENTER IN SOUTHERN BRAZIL.

Background: Cholangiocarcinoma (CCA) is a rare neoplasm, with high mortality, originating in the bile ducts. Its incidence is higher in Eastern countries due to the endemic prevalence of liver parasites. Factors such as metabolic syndrome, smoking, and pro-inflammatory conditions are also linked to the disease.

Engineered extracellular vesicles with DR5 agonistic scFvs simultaneously target tumor and immunosuppressive stromal cells.

Small extracellular vesicles (sEVs) are nanosized vesicles. Death receptor 5 (DR5) mediates extrinsic apoptosis. We engineer DR5 agonistic single-chain variable fragment (scFv) expression on the surface of sEVs derived from natural killer cells.

Dental caries and related factors in the elderly of the Azar cohort population: A cross-sectional study.

Objective: Oral health is often overlooked among the elderly due to the numerous comorbidities prevalent in this population. However, oral health significantly influences quality of life by affecting both general health and psychological well-being. The present study aimed to assess dental caries in elderly individuals using the DMFT index (decayed, missing, and filled teeth) and to explore its relationship with various factors based on data from the Azar cohort study in Iran.

Hypochlorous Acid-Activatable NIR Fluorescence/Photoacoustic Dual-Modal Probe with High Signal-to-Background Ratios for Imaging of Liver Injury and Plasma Diagnosis of Sepsis.

Hypochlorous acid can be employed as a biomarker for blood infection (such as sepsis) and tissue damage (such as drug-induced liver injury, DILI), and the diagnosis of tissue damage or blood infection can be achieved through the detection of hypochlorous acid in relevant biological samples. Considering the complex environment and the diverse interferences in living organisms and blood plasma, developing new detection methods for HClO with high signal-to-background ratios is particularly important, and it can improve the accuracy of detection and quality of imaging based on a higher contrast, which makes the detection of HClO clearer and more accurate. Here, based on the advantages of the NIR fluorescence/photoacoustic dual-modal probe, we reported a hypochlorous acid-activatable NIR fluorescence/photoacoustic dual-modal probe (NIRF-PA-HClO) based on the spirolactam ring-opening strategy in this paper.

Effectiveness and Safety of Adalimumab in Patients With Very Early-Onset Inflammatory Bowel Disease: A Retrospective Study on Behalf of the Porto Inflammatory Bowel Disease Working Group of European Society for Pediatric Gastroenterology Hepatology and Nutrition.

Background And Aims: Patients with very early-onset inflammatory bowel disease (VEO-IBD), with an age of onset < 6 years, can present with severe manifestations and may require biologic therapy. Infliximab and adalimumab are approved for induction and maintenance in pediatric IBD patients but are licensed only above the age of 6 years. Effectiveness and safety data on adalimumab in this patient population are lacking.

Bacterial components-driven intrahepatic CXCR5 B cells are important population for MASH progression through inducing inflammation.

Metabolic dysfunction-associated steatohepatitis (MASH) is characterized by severe liver inflammation and fibrosis due to an imbalanced immune response caused by enhanced bacterial components. The progression of MASH is closely linked to increased permeability of intestinal mucosal barrier facilitating enter of bacterial components into hepatic portal venous system. B cells are important immune cells for adaptive responses and enhance hepatic inflammation through cytokine production and T cell activation.

Fecal Microbiota Transplantation from Young-Trained Donors Improves Cognitive Function in Old Mice Through Modulation of the Gut-Brain Axis.

The gut-brain axis is a bidirectional communication pathway that modulates cognitive function. A dysfunctional gut-brain axis has been associated with cognitive impairments during aging. Therefore, we propose evaluating whether modulation of the gut microbiota through fecal microbiota transplantation (FMT) from young-trained donors (YT) to middle-aged or aged mice could enhance brain function and cognition in old age.

Genetically Predicted Gene Expression Effects on Changes in Red Blood Cell and Plasma Polyunsaturated Fatty Acids.

Polyunsaturated fatty acids (PUFAs) including omega-3 and omega-6 are obtained from diet and can be measured objectively in plasma or red blood cells (RBCs) membrane biomarkers, representing different dietary exposure windows. In vivo conversion of omega-3 and omega-6 PUFAs from short- to long-chain counterparts occurs via a shared metabolic pathway involving fatty acid desaturases and elongase. This analysis leveraged genome-wide association study (GWAS) summary statistics for RBC and plasma PUFAs, along with expression quantitative trait loci (eQTL) to estimate tissue-specific genetically predicted gene expression effects for delta-5 desaturase (FADS1), delta-6 desaturase (FADS2), and elongase (ELOVL2) on changes in RBC and plasma biomarkers.

Comparison of Referral Rates and Costs Using Fibrosis-4 and Enhanced Liver Fibrosis (ELF) Testing Strategies for Initial Evaluation of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) in a Veteran Population.

Background: Global metabolic dysfunction-associated steatotic liver disease (MASLD) prevalence is estimated at 30% and projected to reach 55.7% by 2040. In the Veterans Affairs (VA) healthcare system, an estimated 1.

[Not Available].

Introduction-Aim: Spontaneous bacterial peritonitis (SBP) is a common complication in cirrhotic patients and is associated with a high mortality rate. The aim of this study is to determine the epidemiological and bacteriological profile of spontaneous bacterial peritonitis, as well as antibiotic resistance among hospitalized patients at CHU Mohammed VI, in order to guide empirical antibiotic choices for better management. Methods: This is a prospective study conducted over a period of 12 months, from January to December 2023, focusing on all requests for bacteriological examination of ascitic fluid samples.

Porous Silicon Particle-Assisted Mass Spectrometry Technology Unlocks Serum Metabolic Fingerprints in the Progression From Chronic Hepatitis B to Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a common malignancy and generally develops from liver cirrhosis (LC), which is primarily caused by the chronic hepatitis B (CHB) virus. Reliable liquid biopsy methods for HCC screening in high-risk populations are urgently needed. Here, we establish a porous silicon-assisted laser desorption ionization mass spectrometry (PSALDI-MS) technology to profile metabolite information hidden in human serum in a high throughput manner.

A Menu for Microbes: Unraveling Appetite Regulation and Weight Dynamics Through the Microbiota-Brain Connection Across the Lifespan.

Appetite, as the internal drive for food intake, is often dysregulated in a broad spectrum of conditions associated with over- and under-nutrition across the lifespan. Appetite regulation is a complex, integrative process comprising psychological and behavioral events, peripheral and metabolic inputs, and central neurotransmitter and metabolic interactions. The microbiota-gut-brain axis has emerged as a critical mediator of multiple physiological processes, including energy metabolism, brain function, and behavior.

Molecular docking to investigate HLA-associated idiosyncratic drug reactions.

Idiosyncratic drug reactions (IDRs) pose severe threats to patient health. Unlike conventionally dose-dependent side effects, they are unpredictable and frequently manifest as life-threatening conditions, such as severe cutaneous adverse reactions (SCARs) and drug-induced liver injury (DILI). Some HLA alleles, such as , , and , are known risk factors for adverse reactions induced by multiple drugs.

Current status of drug therapy for chronic hepatitis B.

In this editorial, we comment on the article by Meng . Chronic hepatitis B (CHB) is a significant global health problem, particularly in developing countries. Hepatitis B virus (HBV) infection is one of the most important risk factors for cirrhosis and hepatocellular carcinoma.

Prognostic model for esophagogastric variceal rebleeding after endoscopic treatment in liver cirrhosis: A Chinese multicenter study.

Background: Rebleeding after recovery from esophagogastric variceal bleeding (EGVB) is a severe complication that is associated with high rates of both incidence and mortality. Despite its clinical importance, recognized prognostic models that can effectively predict esophagogastric variceal rebleeding in patients with liver cirrhosis are lacking.

Aim: To construct and externally validate a reliable prognostic model for predicting the occurrence of esophagogastric variceal rebleeding.

Human leukocyte antigen and donor-specific antibodies in liver transplantation.

In this article, we comment on an article published in a recent issue of the . We specifically focus on the roles of human leukocyte antigen (HLA) and donor-specific antibodies (DSAs) in pediatric liver transplantation (LT), as well as the relationship between immune rejection after LT and DSA. Currently, LT remains the standard of care for pediatric patients with end-stage liver disease or severe acute liver failure.

Vedolizumab serum trough concentrations with and without thiopurines in ulcerative colitis: The prospective VIEWS pharmacokinetics study.

Background: Ulcerative colitis (UC) is a chronic inflammatory condition requiring continuous treatment and monitoring. There is limited pharmacokinetic data on vedolizumab during maintenance therapy and the effect of thiopurines on vedolizumab trough concentrations is unknown.

Aim: To investigate the exposure-response relationship of vedolizumab and the impact of thiopurine withdrawal in UC patients who have achieved sustained clinical and endoscopic remission during maintenance therapy.

Predicting colorectal adenomatous polyps in patients with chronic liver disease: A novel nomogram.

Background: Colorectal polyps are commonly observed in patients with chronic liver disease (CLD) and pose a significant clinical concern because of their potential for malignancy.

Aim: To explore the clinical characteristics of colorectal polyps in patients with CLD, a nomogram was established to predict the presence of adenomatous polyps (AP).

Methods: Patients with CLD who underwent colonoscopy at Tianjin Second People's Hospital from January 2020 to May 2023 were evaluated.

Imaging characteristics of hypervascular focal nodular hyperplasia-like lesions in patients with chronic alcoholic liver disease.

Background: Focal nodular hyperplasia (FNH)-like lesions are hyperplastic formations in patients with micronodular cirrhosis and a history of alcohol abuse. Although pathologically similar to hepatocellular carcinoma (HCC) lesions, they are benign. As such, it is important to develop methods to distinguish between FNH-like lesions and HCC.

Trends of alkaline phosphatase to prealbumin ratio in patients with hepatitis B linked to hepatocellular carcinoma development.

Background: Chronic hepatitis B often progresses silently toward hepatocellular carcinoma (HCC), a leading cause of mortality worldwide. Early detection of HCC is crucial, yet challenging.

Aim: To investigate the role of dynamic changes in alkaline phosphatase to prealbumin ratio (APR) in hepatitis B progression to HCC.

Genetic structure of populations in wildlife of north and northeast Iran.

is a parasite prevalent in the temperate regions of the vast Palearctic realm, including Iran. In this study, we investigated infection in road-killed animals and carcasses in northern and northeastern Iran by artificial digestion. We assessed species identification and intraspecific genetic diversity using the markers 5S ribosomal DNA intergenic spacer (5S rDNA), internal transcribed spacer I (ITS1), and cytochrome oxidase subunit I ().