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Coumarin Analogues as Promising Anti-Obesity Agents: In Silico Design, Synthesis, and In Vitro Pancreatic Lipase Inhibitory Activity.

Chem Biol Drug Des

January 2025

Laboratory of Natural Product Chemistry, Department of Pharmacy, Birla Institute of Technology and Science, Pilani (BITS Pilani), Pilani, Rajasthan, India.

A set of coumarin-3-carboxamide analogues were designed, synthesized, and evaluated for their ability to impede pancreatic lipase (PL) activity. Out of all the analogues, 5dh and 5de demonstrated promising inhibitory activity against PL, as indicated by their respective IC values of 9.20 and 11.

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Hydroxylation, an extensive post-translational modification on proline, is critical for the modulation of protein structures, further dominating their functions in life systems. However, current mass spectrometry-based identification, could hardly distinguish hydroxylation from neighboring oxidation due to the same mass shifts, as well as challenges posed by low abundance and exogenous oxidation during sample preparation. To address these, an engineered nanopore was designed, capable of discriminating single hydroxyl group, to achieve the identification of proline hydroxylation on individual native peptides directly in the mixture.

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The architectural characteristics of metal-organic frameworks (MOFs) can be examined through their net topology, which consists of nodes and linkers. A node's connectivity and site symmetry are likely the key elements influencing the net topology of MOFs. Metal-organic polyhedra (MOPs) function effectively as nodes when used as supermolecular building blocks (SBBs).

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Three new pyridine derivatives, irpelactedines A-C (1-3), and a new furan derivative, irpelactedine D (5), along with two structurally related known compounds, irpexidine A (4) and 5-carboxy-2-furanpropanoic acid (6), were isolated from the medicinal fungus Irpex lacteus SY1002. Their structures were elucidated through NMR and mass spectral analyses, combined with density functional theory calculations of ECD data. Evaluation of angiotensin-converting enzyme (ACE) inhibitory activity revealed that compounds 1 and 3 displayed moderate inhibition, with IC50 values of 31.

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Aim: To implement and evaluate an Advanced Practice Nurse-led transitional care model (AdvantAGE) to reduce rehospitalisation rates in frail older adults discharged from a Swiss geriatric hospital.

Design: The study adopts an effectiveness-implementation hybrid design (Type 1) to simultaneously evaluate the effectiveness of the care model and explore the implementation process.

Methods: The primary outcome, the 90-day rehospitalisation rate, will be evaluated using a matched-cohort design with a prospective intervention group and a retrospective control group.

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