Single-cell multi-omics deciphers hepatocyte dedifferentiation and illuminates maintenance strategies.

Due to the similarity to human hepatocytes, porcine hepatocytes play an important role in hepatic research and drug evaluation. However, once hepatocytes were cultured in vitro, it was often prone to dedifferentiate, resulting in the loss of their characteristic features and normal functions, which impede their application in liver transplantation and hepatotoxic drugs evaluation. Up to now, this process has yet to be thoroughly investigated from the single-cell resolution and multi-omics perspective.

Synaptic Targets and Cellular Sources of CB1 Cannabinoid Receptor and Vesicular Glutamate Transporter-3 Expressing Nerve Terminals in Relation to GABAergic Neurons in the Human Cerebral Cortex.

Cannabinoid receptor 1 (CB1) regulates synaptic transmission through presynaptic receptors in nerve terminals, and its physiological roles are of clinical relevance. The cellular sources and synaptic targets of CB1-expressing terminals in the human cerebral cortex are undefined. We demonstrate a variable laminar pattern of CB1-immunoreactive axons and electron microscopically show that CB1-positive GABAergic terminals make type-2 synapses innervating dendritic shafts (69%), dendritic spines (20%) and somata (11%) in neocortical layers 2-3.

Dual ferroptosis induction in N2-TANs and TNBC cells via FTH1 targeting: A therapeutic strategy for triple-negative breast cancer.

Tumor-associated neutrophils (TANs) play a critical role in the progression and prognosis of triple-negative breast cancer (TNBC), with N2-type TANs known for their pro-tumor characteristics. This study introduces CT-1, a derivative of cryptotanshinone that effectively suppresses TNBC growth while selectively reducing the proportion of N2-type TANs within tumor tissue. Notably, CT-1 induces simultaneous ferroptosis in both N2-type TANs and TNBC cells, a dual mechanism that enhances its therapeutic efficacy.

Advanced applications of two-dimensional liquid chromatography in quantitative analysis of natural products.

Two-dimensional liquid chromatography (2D-LC) separation systems, based on two independent columns with different separation mechanisms, have exhibited strong resolving power for complex samples. Therefore, in recent years, the exceptional resolution of 2D-LC has significantly advanced the chemical separation of natural products, such as complex herbs, greatly facilitating their qualitative and quantitative analysis. This paper aims to review the latest strategies of 2D-LC in the quantitative analysis of complex chemical compositions in natural products.

New quinazolone-sulfonate conjugates with an acetohydrazide linker as potential antimicrobial agents: design, synthesis and molecular docking simulations.

A novel molecular design based on a quinazolinone scaffold was developed the attachment of aryl alkanesulfonates to the quinazolinone core through a thioacetohydrazide azomethine linker, leading to a new series of quinazolinone-alkanesulfonates 5a-r. The antimicrobial properties of the newly synthesized quinazolinone derivatives 5a-r were investigated to examine their bactericidal and fungicidal activities against bacterial pathogens like , (Gram-positive), , , (Gram-negative), in addition to (unicellular fungal). The tested compounds demonstrated reasonable bactericidal activities compared to standard drugs.

Design, synthesis, , and studies of novel isatin-hybrid hydrazones as potential triple-negative breast cancer agents.

Recent advances in cancer therapy have been made possible by monoclonal antibodies, domain antibodies, antibody drug conjugates, The most impact has come from controlling cell cycle checkpoints through checkpoint inhibitors. This manuscript explores the potential of a series of novel -benzyl isatin based hydrazones (5-25), which were synthesized and evaluated as anti-breast cancer agents. The synthesized hydrazones of -benzyl isatin were screened against two cell lines, the MDA-MB-231 breast cancer cell line and the MCF-10A breast epithelial cell line.

Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition.

The tumor microenvironment (TME) is integral to cancer progression, impacting metastasis and treatment response. It consists of diverse cell types, extracellular matrix components, and signaling molecules that interact to promote tumor growth and therapeutic resistance. Elucidating the intricate interactions between cancer cells and the TME is crucial in understanding cancer progression and therapeutic challenges.

Preclinical and First-in-Human Study of a Compact Radionuclide Labeled Self-Assembly Nanomedicine for Chemo-Radio-Theranostics of Cancer.

The emerging combination of chemotherapy and radionuclide therapy has been actively investigated to overcome the limitations of monotherapy and augment therapeutic efficacy. However, it remains a challenge to design a single delivery vehicle that can incorporate chemotherapeutics and radionuclides into a compact structure. Here, a chelator DOTA- or NOTA-modified Evans blue conjugated camptothecin molecule (EB-CPT) nanoprodrug was synthesized, which could self-assemble into nanoparticles due to its inherent amphiphilicity.

Neutrophil adhesion to vessel walls impairs pulmonary circulation in COVID-19 pathology.

Microthrombus formation is associated with COVID-19 severity; however, the detailed mechanism remains unclear. In this study, we investigated mouse models with severe pneumonia caused by SARS-CoV-2 infection by using our in vivo two-photon imaging system. In the lungs of SARS-CoV-2-infected mice, increased expression of adhesion molecules in intravascular neutrophils prolonged adhesion time to the vessel wall, resulting in platelet aggregation and impaired lung perfusion.

Structural characterization of polysaccharides from Polygonatum Sibiricum and effect on alleviating hyperlipidemia in egg yolk emulsion-induced mice.

Polysaccharides are the major bioactive composition of Polygonatum sibiricum (P. sibiricum). However, the structural and functional identifications of these polysaccharides were still limited.

Automated and Efficient Sampling of Chemical Reaction Space.

Machine learning interatomic potentials (MLIPs) promise quantum-level accuracy at classical force field speeds, but their performance hinges on the quality and diversity of training data. An efficient and fully automated approach to sample chemical reaction space without relying on human intuition, addressing a critical gap in MLIP development is presented. The method combines the speed of tight-binding calculations with selective high-level refinement, generating diverse datasets that capture both equilibrium and reactive regions of potential energy surfaces.

Preparation, Modification, Quantitation, and Dentin Biomodification Activity of Selectively Enriched Proanthocyanidins.

To date, quantitative analysis of proanthocyanidin (PAC) containing materials including plant extracts and fractions depends on colorimetric assays or phloroglucinolysis/thiolysis combined with UV-HPLC analysis. Such assays are of limited accuracy, particularly lack specificity, require extensive sample preparation and degradation, and need appropriate physical reference standards. To address this analytical challenge and toward our broader goal of developing new plant-sourced biomaterials that chemically and mechanically modulate the properties of dental tissue for clinical interventions, we have characterized 12 different PAC DESIGNER (Depletion and Enrichment of Select Ingredients Generating Normalized Extract Resources) materials.

Statin Use and the Risk of Graves' Orbitopathy: A Nationwide Population-Based Cohort Study.

Statin use is reported to reduce the risk of Graves' orbitopathy (GO) in Western populations. However, study regarding the protective effect of statins against GO in Asians with Graves' disease (GD) is scarce. This study aims to investigate the efficacy of statins in preventing GO in Asian GD patients.

4-O-Methylglucuronoxylan from Hygrophila Ringens var. Ringens Seeds: Chemical Composition and Anti-Inflammatory Activity.

Hygrophila ringens var. ringens is a medicinal plant of the Acanthaceae family. A soluble polysaccharide is extracted from H.

Recent trends in the elucidation of complex triterpene biosynthetic pathways in horticultural trees.

Triterpene (C30 isoprene compounds) represents the most structurally diverse class of natural products and has been extensively exploited in the food, medicine, and industrial sectors. Decades of research on medicinal triterpene biosynthetic pathways have revealed their roles in stress tolerance and shaping microbiota. However, the biological function and mechanism of triterpenes are not fully identified.

Hyaluronic Acid-Based Hybrid Nanoparticles as Promising Carriers for the Intranasal Administration of Dimethyl Fumarate.

Purpose: Dimethyl fumarate (DMF), the first-line oral therapy for relapsing-remitting multiple sclerosis, is rapidly metabolized into monomethyl fumarate. The DMF oral administration provokes gastrointestinal discomfort causing treatment withdrawal. The present study aimed to develop an innovative formulation for DMF nasal administration.

Overweight, obesity, and cardiovascular disease in heterozygous familial hypercholesterolaemia: the EAS FH Studies Collaboration registry.

Background And Aims: Overweight and obesity are modifiable risk factors for atherosclerotic cardiovascular disease (ASCVD) in the general population, but their prevalence in individuals with heterozygous familial hypercholesterolaemia (HeFH) and whether they confer additional risk of ASCVD independent of LDL cholesterol (LDL-C) remains unclear.

Methods: Cross-sectional analysis was conducted in 35 540 patients with HeFH across 50 countries, in the EAS FH Studies Collaboration registry. Prevalence of World Health Organization-defined body mass index categories was investigated in adults (n = 29 265) and children/adolescents (n = 6275); and their association with prevalent ASCVD.

A Small-Molecule Drug for the Self-Checking of Mitophagy.

Mitophagy, particularly in the context of drugs that disrupt mitochondrial membrane potential (MMP), represents a critical focus in pharmacology. However, the discovery and evaluation of MMP-disrupting drugs are often hampered using commercially available marker molecules that target similar or identical zones. These markers can significantly interfere with, obscure, or amplify the functional effects of MMP-targeting drugs, frequently leading to clinical failures.

A sensitive post-column derivatization approach for enhancing hydroxyl metabolites detection.

Background: Chemical derivatization is a common technique in liquid chromatography-mass spectrometry (LC-MS) metabolomics used to improve the ionizability and chromatographic properties of metabolites in complex biological samples. This process facilitates better detection and separation of a wide array of compounds. The reagent 2-(4-boronobenzyl) isoquinolin-2-ium bromide (BBII), developed as a glucose labeling reagent for matrix-assisted laser desorption/ionization MS, enhances ionization for glucose and other hydroxyl metabolites.

Blarcamesine for the treatment of Early Alzheimer's Disease: Results from the ANAVEX2-73-AD-004 Phase IIB/III trial.

Background: There are no approved oral disease-modifying treatments for Alzheimer's disease (AD).

Objectives: The objective of this study was to assess efficacy and safety of blarcamesine (ANAVEX®2-73), an orally available small-molecule activator of the sigma-1 receptor (SIGMAR1) in early AD through restoration of cellular homeostasis including autophagy enhancement.

Design: ANAVEX2-73-AD-004 was a randomized, double-blind, placebo-controlled, 48-week Phase IIb/III trial.

Inhibited peroxidase activity of peroxiredoxin 1 by palmitic acid exacerbates nonalcoholic steatohepatitis in male mice.

Reactive oxygen species exacerbate nonalcoholic steatohepatitis (NASH) by oxidizing macromolecules; yet how they promote NASH remains poorly understood. Here, we show that peroxidase activity of global hepatic peroxiredoxin (PRDX) is significantly decreased in NASH, and palmitic acid (PA) binds to PRDX1 and inhibits its peroxidase activity. Using three genetic models, we demonstrate that hepatic PRDX1 protects against NASH in male mice.

Dietary purslane (Portulaca oleracea L.) leaf powder maintains growth and intestinal health in Oreochromis niloticus under chronic water-borne cadmium exposure by strengthening the gut barriers, modulating the intestinal nutrient transporters, and relieving oxidative stress.

High cadmium (Cd) concentrations pose a threat to aquatic life globally. This study examined the efficiency of adding purslane (Portulaca oleracea L.) leaf powder (PLP) to Oreochromis niloticus diets on Cd's negative effects.

Synthesis and Physico-Chemical Analysis of Dextran from Maltodextrin via pH Controlled Fermentation by .

Dextran is an exopolysaccharide (EPS) with multifunctional applications in the food and pharmaceutical industries, primarily synthesized from . Dextran can be produced from dextrin through fermentation, utilizing its dextran dextrinase activity. This study examined how jar fermentor conditions impact the growth and enzyme activity of , with a focus on the effects of pH on dextran synthesis via bioconversion (without pH control, pH 4.

Comparative Analysis of Five Moroccan Thyme Species: Insights into Chemical Composition, Antioxidant Potential, Anti-Enzymatic Properties, and Insecticidal Effects.

This study aimed to investigate the chemical composition and bioactivities of essential oils (EOs) from five Moroccan thyme species: subsp. , , subsp. , and .

Unveiling the Mineral and Sugar Richness of Moroccan Honeys: A Study of Botanical Origins and Quality Indicators.

This study comprehensively analyzes the mineral and heavy metal profiles of seven honey types, focusing on the contents of potassium (K), calcium (Ca), magnesium (Mg), iron (Fe), zinc (Zn), manganese (Mn), copper (Cu), cadmium (Cd), and lead (Pb), with particular emphasis on honey produced in eastern Morocco. Multifloral honey was found to have the highest total mineral content (661 mg/kg), while rosemary honey had the lowest (201.31 mg/kg), revealing the strong influence of floral and botanical origin.