Predicting Immune Flares in Untreated Chronic Hepatitis B Patients Using Novel Risk Factors and the FLARE-B Score.

Background And Aims: Risk factors of chronic hepatitis B (CHB) immune flares are poorly understood. The primary aim of this study was to discover predictors of the CHB flare in non-cirrhotic, untreated CHB patients and develop a simple risk-stratifying score to predict the CHB flare. The secondary aim was to compare different machine learning methods for prediction.

Poly-Dha Sequences as -polypeptides: An Original Mechanistic Postulate Leads to the Discovery of a Long-Acting Vasodilator KU04212.

The construction of polypeptides was revolutionized by Merrifield's solid-phase synthesis more than half a century ago. Herein, we explore a completely different approach to making peptides. We test an original mechanistic postulate wherein a single peptide made entirely of dehydroalanine (Dha) residues can give rise to regio- and stereodefined peptides by iterative conjugate addition of one- or two-electron nucleophiles.

Carbocyclic setmelanotide analogs maintain biochemical potency at melanocortin 4 receptors.

The melanocortin 4 receptor (MC4R) plays a critical role in satiety and energy homeostasis, and its dysregulation is implicated in numerous hyperphagic and obese disease states. Setmelanotide, a disulfide-based cyclic peptide, can rescue MC4R activity and treat obesities caused by genetic defects in MC4R signaling. But this peptide has moderate blood-brain barrier penetrance and metabolic stability, which can limit its efficacy in practice.

Dietary protein defends lean mass and maintains the metabolic benefits of glucagon receptor agonism in mice.

Objective: Glucagon has long been proposed as a component of multi-agonist obesity therapeutics due to its ability to induce energy expenditure and cause weight loss. However, chronic glucagon-receptor agonism has been associated with a reduction in circulating amino acids and loss of lean mass. Importantly, it is currently not known whether the metabolic benefits of glucagon can be maintained under contexts that allow the defence of lean mass.

Unlocking flavin photoacid catalysis through electrophotochemistry.

Molecular flavins are one of the most versatile photocatalysts. They can coordinate single and multiple electron transfer processes, gift hydrogen atoms, form reversible covalent linkages that support group transfer mechanisms, and impart photonic energy to ground state molecules, priming them for downstream reactions. But one mechanism that has not featured extensively is the ability of flavins to act as photoacids.

Chronic treatment with glucagon-like peptide-1 and glucagon receptor co-agonist causes weight loss-independent improvements in hepatic steatosis in mice with diet-induced obesity.

Objectives: Co-agonists at the glucagon-like peptide-1 and glucagon receptors (GLP1R/GCGR) show promise as treatments for metabolic dysfunction-associated steatotic liver disease (MASLD). Although most co-agonists to date have been heavily GLP1R-biased, glucagon directly acts on the liver to reduce fat content. The aims of this study were to investigate a GCGR-biased co-agonist as treatment for hepatic steatosis in mice.

Fasting pancreatic polypeptide predicts incident microvascular and macrovascular complications of type 2 diabetes: An observational study.

Aims: Pancreatic polypeptide (PP) is elevated in people with vascular risk factors such as type 2 diabetes or increased visceral fat. We investigated potential relationships between PP and microvascular and macrovascular complications of diabetes.

Materials And Methods: Animal study: Subcutaneous PP infusion for 4 weeks in high fat diet mouse model.

Centering Digital Health Equity During Technology Innovation: Protocol for a Comprehensive Scoping Review of Evidence-Based Tools and Approaches.

Background: In the rush to develop health technologies for the COVID-19 pandemic, the unintended consequence of digital health inequity or the inability of priority communities to access, use, and receive equal benefits from digital health technologies was not well examined.

Objective: This scoping review will examine tools and approaches that can be used during digital technology innovation to improve equitable inclusion of priority communities in the development of digital health technologies. The results from this study will provide actionable insights for professionals in health care, health informatics, digital health, and technology development to proactively center equity during innovation.

Intracellular delivery of oncolytic viruses with engineered Salmonella causes viral replication and cell death.

As therapies, oncolytic viruses regress tumors and have the potential to induce antitumor immune responses that clear hard-to-treat and late-stage cancers. Despite this promise, clearance from the blood prevents treatment of internal solid tumors. To address this issue, we developed virus-delivering Salmonella (VDS) to carry oncolytic viruses into cancer cells.

Spectral and Electrochemical Properties of Common Photocatalysts in Water: A Compendium for Aqueous Photoredox Catalysis.

Electrochemical potentials of photocatalysts are solvent dependent. One of the largest discrepancies is observed when water is used in place of organic solvents as the reaction media. Unfortunately, the redox potentials for many photocatalysts in water have not been determined, at least under one unifying set of conditions, and this greatly hinders the rational design of sustainable and biocompatible photoredox reactions.

Intra-islet glucagon signalling regulates beta-cell connectivity, first-phase insulin secretion and glucose homoeostasis.

Objective: Type 2 diabetes (T2D) is characterised by the loss of first-phase insulin secretion. We studied mice with β-cell selective loss of the glucagon receptor (Gcgr X Ins-1), to investigate the role of intra-islet glucagon receptor (GCGR) signalling on pan-islet [Ca] activity and insulin secretion.

Methods: Metabolic profiling was conducted on Gcgr and littermate controls.

Endothelial-Specific Reduction in Arf6 Impairs Insulin-Stimulated Vasodilation and Skeletal Muscle Blood Flow Resulting in Systemic Insulin Resistance in Mice.

Background: Much of what we know about insulin resistance is based on studies from metabolically active tissues such as the liver, adipose tissue, and skeletal muscle. Emerging evidence suggests that the vascular endothelium plays a crucial role in systemic insulin resistance; however, the underlying mechanisms remain incompletely understood. Arf6 (ADP ribosylation factor 6) is a small GTPase that plays a critical role in endothelial cell function.

Pharmacologic Characterization of Substituted Nitazenes at , , and Opioid Receptors Suggests High Potential for Toxicity.

The benzimidazole opioids (substituted nitazenes) are highly potent opiod receptor (MOR) agonists with heroin- or fentanyl-like effects. These compounds have caused hospitalizations and fatal overdoses. We characterized the in vitro pharmacology and structure-activity relationships of 19 nitazenes with substitutions at three positions of the benzimidazole core.

Effect of Concurrent Metabolic Dysfunction-Associated Steatotic Liver Disease on Serial Non-invasive Fibrosis Markers in Chronic Hepatitis B.

Background & Aims: Concurrent hepatic steatosis has diverse effects on chronic hepatitis B (CHB), however the combined effects of metabolic dysfunction-associated steatotic liver disease (MASLD) and CHB on liver fibrosis progression remains unclear. The primary aim of this study was to utilize serial fibrosis measurements to compare the dynamic change in fibrosis in CHB patients with/without concurrent MASLD. The secondary aim was to investigate factors associated with steatosis development and regression in CHB patients.

Metabolic-associated fatty liver disease and hepatocellular carcinoma: a prospective study of characteristics and response to therapy.

Background And Aim: The rising incidence of hepatocellular carcinoma (HCC) in Australia is related to increasing rates of metabolic-associated fatty liver disease (MAFLD). This study aimed to prospectively characterize the metabolic profile, lifestyle, biometric features, and response to treatment of HCC patients in an Australian population.

Method: Multicenter prospective cohort analysis of newly diagnosed HCC patients at six multidisciplinary team meetings over a 2-year period.