Sucrose-preferring gut microbes prevent host obesity by producing exopolysaccharides.

Commensal bacteria affect host health by producing various metabolites from dietary carbohydrates via bacterial glycometabolism; however, the underlying mechanism of action remains unclear. Here, we identified Streptococcus salivarius as a unique anti-obesity commensal bacterium. We found that S.

[Detection of brain MRI abnormalities before symptom onset in case of Creutzfeldt-Jakob disease with compound heterozygous PRNP mutation (V180I/M232R)].

In an 81-year-old man, brain diffusion-weighted MRI revealed punctate high-intensity lesions in the bilateral frontal cortex. Three months later, these lesions had extended into the cerebral cortices. Six months after the original MRI, the patient developed cognitive decline.

Efficacy of asfotase alfa in a patient with adult-onset hypophosphatasia without obvious bone lesions: a case report with review of literature.

The use of asfotase alfa, a bone-targeted recombinant alkaline phosphatase (ALP) enzyme, for the treatment of adult-onset hypophosphatasia (HPP) remains controversial, particularly in patients without evident bone abnormalities. We report the case of a 41-year-old woman with a history of Graves' disease, who presented with progressive joint pain and severe fatigue. Despite the absence of bone lesions, the patient was diagnosed with HPP based on persistently low alkaline phosphatase levels, family history, and a novel heterozygous ALPL variant (p.

Screening for social anxiety disorder in students of Jordan universities after COVID-19 pandemic: a cross-sectional survey study.

Objective: To examine the prevalence rate of social anxiety disorder (SAD) among university students in Jordan after the COVID-19 pandemic and its associated predictors.

Design: A cross-sectional online survey study that was conducted in Jordan between January and December 2023.

Setting: Universities in Jordan.

Widening access to isotretinoin in primary care: an evaluation of New Zealand national dispensing data for isotretinoin for acne, 2008-2023.

Objectives: To identify what changes in the prescribing of isotretinoin have occurred since funded prescriber access was widened in 2009 from 'dermatologist only' prescribing to include 'general practitioners (GPs) and nurse practitioners working within their scope of practice'.

Design: Evaluation of isotretinoin dispensing data from 2008 to 2023 using the national annual prescribing data obtained from the New Zealand Pharmaceutical National Collection database.

Setting: All New Zealand citizens prescribed and dispensed funded isotretinoin for acne from 2008 to 2023 were included.

CRAmed: a conditional randomization test for high-dimensional mediation analysis in sparse microbiome data.

Motivation: Numerous microbiome studies have revealed significant associations between the microbiome and human health and disease. These findings have motivated researchers to explore the causal role of the microbiome in human complex traits and diseases. However, the complexities of microbiome data pose challenges for statistical analysis and interpretation of causal effects.

Carbon monoxide alleviates endotoxin-induced acute lung injury via NADPH oxidase inhibition in macrophages and neutrophils.

Sepsis is a life-threatening condition caused by severe infection and often complicates acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) due to the collapse of the oxidative and inflammatory balance induced by microbial pathogens, including lipopolysaccharides (LPS). In sepsis-related ARDS/ALI, NADPH oxidase (NOX) and toll-like receptors (TLR) in neutrophils and macrophages are key players in initiating oxidative and inflammatory imbalances. Although NOX and TLR activation has been linked to carbon monoxide (CO), the mechanism by which CO affects sepsis-related ARDS/ALI through NOX and TLR remains unknown.

Alkalinity exposure induced growth inhibition, intestinal histopathological changes, and down-regulated nutrient transporter expression in Nile Tilapia: The ameliorative role of dietary camel whey protein hydrolysates.

Alkaline stress impairs fish productivity and performance and, therefore, is considered one of the major challenges facing aquaculture. In this work, the effects of supplementing diets with camel whey protein hydrolysates (WPH) on growth, digestion, antioxidant capacity, and gene expression were investigated in Nile tilapia (Oreochromis niloticus) under alkaline stress. A total of 160 fish (16.

Chalcogen dihydrobenzofuran compounds as potential neuroprotective agents: an in vitro and in silico biological investigation.

Oxidative stress arises from an imbalance between reactive species (RS) production and the antioxidant defense, increasing the brain susceptibility to neurodegenerative and psychiatric diseases. Besides, changes in the expression or activity of neurotransmitter metabolism enzymes, such as monoamine oxidases (MAO), are also associated with mental disorders, including depression. Considering this, antioxidant and MAO-A activity inhibitory potential of six 2,3-chalcogenodihydrobenzofurans (2,3-DHBF) was investigated through in vitro and in silico tests.

Optimized pure cellulose from rice straw using low alkali concentration for sustainable nanocellulose and nanohydrogel production with enhanced dye reduction.

Conversion of rice straw into nanocellulose offers a sustainable approach to agricultural waste management, yielding an industrially important product with potential applications. This work focuses on effectively extracting pure cellulose from both widely used Basmati and Parmal rice straw (BRS and PRS) using less alkali concentrations (3-5 % NaOH). The process was optimized via Box Behnken design at 90-150 °C temperatures for 90-150 min, which resulted in 88.

Key epigenetic enzymes modulated by natural compounds contributes to tumorigenicity.

Dysregulation of epigenetic regulation is observed in numerous tumor cells. The therapeutic effects of natural products on tumors were investigated through a comprehensive analysis of active ingredients derived from various structured natural products. The analysis focuses on regulating key enzymes involved in epigenetic control.

A benzoxazolyl urea inhibits VraS and enhances antimicrobials against vancomycin intermediate-resistant Staphylococcus aureus.

Vancomycin intermediate-resistant Staphylococcus aureus (VISA) is a pathogen of concern. VraS, a histidine kinase, facilitates the VISA phenotype. Here, we reveal a benzoxazolyl urea (chemical 1) that directly inhibits VraS and enhances vancomycin to below the clinical breakpoint against an archetypal VISA strain, Mu50.

Assessing the Impacts of Drug Loading and Polymer Type on Dissolution Behavior and Diffusive Flux of GDC-6893 Amorphous Solid Dispersions.

It is desirable but remains challenging to develop high drug load amorphous solid dispersions (ASDs) without compromising their quality attributes and bio-performance. In this work, we investigated the impacts of formulation variables, such as drug loading (DL) and polymer type, on dissolution behavior, diffusive flux, and in vitro drug absorption of ASDs of a high T compound, GDC-6893. ASDs with two polymers (HPMCAS and PVPVA) and various DLs (20 - 80%) were produced by spray drying and their drug-polymer miscibility was evaluated using solid-state nuclear magnetic resonance (ssNMR).

The impact of glidant addition on the loss-in-weight feeding of active pharmaceutical ingredients.

In recent years, continuous manufacturing (CM) has become increasingly popular in the pharmaceutical industry for the production of oral solid dosage (OSD) forms. Most of the newly developed active pharmaceutical ingredients (APIs) nowadays are extremely cohesive and sticky with a mean particle size particle of <100μm, a wide particle size distribution (PSD) and a high tendency to agglomerate, making them difficult to accurately dose using loss-in-weight equipment during CM. In this research paper, the effect of various glidants on the volumetric and gravimetric feeding of several APIs was assessed.

Development of Chimeric Nanobody-Granzyme B Functionalized Ferritin Nanoparticles for Precise Tumor Therapy.

T-cell lymphomas (TCLs) are heterogeneous malignancies with limited treatment options and poor outcomes. The efficacy of traditional T-cell therapies, including chimeric antigen receptor (CAR) T cells, is often constrained by immunosuppressive factors and the tumor microenvironment. On the other hand, although direct Granzyme B (GrB) administration can effectively induce tumor cell apoptosis, it lacks universal tumor targeting and efficient cellular entry mechanisms.

The Mechanism of Bovis Culus Sativus Protecting BBB Damage in Stroke: Insights from Network Pharmacology, Bioinformatics, and Experiments.

Ethnopharmacological Relevance: Bovis calculus (BC) has a medicinal history of over 2,000 years in treating stroke in China. Bovis Culus Sativus (BCS) has similar pharmacological effects to BC. Due to the scarcity of BC, BCS is often used as a substitute for BC in clinical practice for treating stroke in traditional Chinese medicine.

The role of carbon and nitrogen ratio on sewage sludge microbiota for producing polyhydroxyalkanoates.

The products of an advanced sewage sludge fermentation process can be used to generate polyhydroxyalkanoates (PHAs), precursors of bioplastics considered excellent candidates for replacing petroleum-derived plastics. The aerobic feast-anoxic famine cycling strategy has proven to be an efficient method for enriching sewage sludge microbiota with PHA-producing microorganisms. This work evaluated the effect of different carbon to nitrogen ratios (C/N) of 3.

Assessing the impact of non-pharmaceutical interventions against COVID-19 on 64 notifiable infectious diseases in Australia: A Bayesian Structural Time Series model.

Background: Several studies have examined the effect of non-pharmaceutical interventions (NPIs) on COVID-19 and other infectious diseases in Australia and globally. However, to our knowledge none have sufficiently explored their impact on other infectious diseases with robust time series model. In this study, we aimed to use Bayesian Structural Time Series model (BSTS) to systematically assess the impact of NPIs on 64 National Notifiable Infectious Diseases (NNIDs) by conducting a comprehensive and comparative analysis across eight disease categories within each Australian state and territory, as well as nationally.

On the formation and stability mechanisms of diverse lipid-based nanostructures for drug delivery.

In the evolving landscape of nanotechnology and pharmaceuticals, lipid nanostructures have emerged as pivotal areas of research due to their unique ability to mimic biological membranes and encapsulate active molecules. These nanostructures offer promising avenues for drug delivery, vaccine development, and diagnostic applications. This comprehensive review explores the complex mechanisms underlying the formation and stability of various lipid nanostructures, including lipid liquid crystalline nanoparticles and solid lipid nanoparticles.

Synthesis and biological evaluation of new dual APN/NEP inhibitors as potent analgesics.

An alternative approach for the management of acute and chronic pains involves prolonging the half-life of endogenous opiates, such as enkephalins that are released in response to nociceptive stimuli. This can be achieved through the inhibition of enzymatic pathways responsible for the hydrolysis of these peptides, particularly targeting Aminopeptidase N (APN) and Neutral Endopeptidase (NEP). In this study, we designed and synthesized a series of dual enkephalinase inhibitors (DENKIs) targeting both APN and NEP as novel analgesic treatments.

Fragment-Based Drug Discovery: Small Fragments, Big Impact - Success Stories of Approved Oncology Therapeutics.

Fragment-Based Drug Discovery (FBDD) has revolutionized drug discovery by overcoming the challenges of traditional methods like combinatorial chemistry and high-throughput screening (HTS). Leveraging small, low-molecular-weight fragments, FBDD achieves higher hit rates, reduced screening costs, and faster development timelines for clinically relevant drug candidates. This review explores FBDD's core principles, innovative methodologies, and its success in targeting diverse protein classes, including previously "undruggable" targets.

Design, Synthesis, Biocompatibility, molecular docking and molecular dynamics studies of novel Benzo[b]thiophene-2-carbaldehyde derivatives targeting human IgM Fc Domains.

In this study, three novel derivatives of benzo[b]thiophene-2-carbaldehyde (BTAP1, BTAP2, and BTAP3) were successfully synthesized and comprehensively characterized using spectroscopic techniques including FTIR, UV-VIS, HNMR, and CNMR. Thermal analysis through TGA and DTA demonstrated remarkable thermal stability with a maximum threshold at 270 °C. Spectroscopic investigations revealed π → π* transitions in all compounds, attributed to the conjugated system comprising benzothiophene rings connected to bromophenyl/ aminophenyl/phenol rings via α, β-unsaturated ketone bridges.

Safety and efficacy of tamoxifen in non-ambulant patients with Duchenne muscular dystrophy: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial (TAMDMD Group B).

Most patients with Duchenne muscular dystrophy (DMD) are non-ambulant. Preserving proximal motor function is crucial, rarely studied. Tamoxifen, a selective oestrogen receptor modulator, reduced signs of muscular pathology in a DMD mouse model.