4-Hydroxybenzyl-substituted glutathione derivatives from <i>Gastrodia elata</i>

<div><p>Seven new 4-hydroxybenzyl-substituted glutathione derivatives (<b>2</b>–<b>8</b>), together with a known analogue (<b>1</b>), were isolated from the aqueous extract of <i>Gastrodia elata</i> Blume rhizomes. Their structures were determined by using spectroscopic and chemical methods. The absolute configurations of <b>1</b>–<b>8</b> were assigned by using Marfey's method, combined with comparing the NMR and CD spectroscopic data of sulfoxide moieties in <b>3</b>–<b>6</b> with those of <i>S</i>-(4-hydroxybenzyl)cysteine sulfoxide stereoisomers (<b>9</b>–<b>12</b>) synthesized as authentic samples. The configurations of <b>9</b>–<b>12</b> were confirmed by electronic CD calculations based on the quantum-mechanical time-dependent density functional theory. Furthermore, the structures of <b>1</b>, <b>3</b>, <b>5</b>, <b>7</b>, and <b>8</b> were verified by synthesis. Compound <b>3</b> was active against serum deprivation-induced PC12 cell damage and synthetic <b>9</b>–<b>14</b> exhibited activity against Fe²⁺-cysteine induced rat liver microsomal lipid peroxidation.</p></div

High normal alanine aminotransferase is an indicator for better response to antiviral therapy in chronic hepatitis B

BackgroundEvidence shows people living with CHB even with a normal ALT (40U/L as threshold) suffer histological disease and there is still little research to evaluate the potential benefit of antiviral benefits in them.MethodsWe retrospectively examined 1352 patients who underwent liver biopsy from 2017 to 2021 and then obtained their 1-year follow-up data to analyze.ResultsALT levels were categorized into high and low, with thresholds set at &gt;29 for males and &gt;15 for females through Youden’s Index. The high normal ALT group showed significant histological disease at baseline (56.43% vs 43.82%, p&lt; 0.001), and better HBV DNA clearance from treatment using PSM (p=0.005). Similar results were obtained using 2016 AASLD high normals (male &gt;30, female &gt;19). Further multivariate logistic analysis showed that high normal ALT (both criterias) was an independent predictor of treatment (OR 1.993, 95% CI 1.115-3.560, p=0.020; OR 2.000, 95% CI 1.055-3.793, p=0.034) Both of the models had higher AUC compared with current scoring system, and there was no obvious difference between the two models (AUC:0.8840 vs 0.8835)ConclusionMale &gt;30 or female &gt;19 and Male &gt;29 or female&gt;15 are suggested to be better thresholds for normal ALT. Having a high normal ALT in CHB provides a potential benefit in antiviral therapy

Gd-Dots with Strong Ligand–Water Interaction for Ultrasensitive Magnetic Resonance Renography

Magnetic resonance imaging contrast agents with both significantly enhanced relaxivity and minimal safety risk are of great importance for sensitive clinical diagnosis, but have rarely been reported. Herein, we present a simple strategy to improve relaxivity by introducing surface ligands with strong interaction to water molecules. As a proof of concept, NaGdF₄ nanoparticles (NPs) capped by poly­(acrylic acid) (PAA) show superior relaxivity to those capped by polyethylenimine and polyethylene glycol, which is attributed to the strong hydrogen-bond capacity of PAA to water molecules as revealed by theoretical calculation. Furthermore, benefiting from PAA and ultrasmall particle size, Gd-dots, namely PAA-capped GdOF NPs (2.1 ± 0.2 nm), are developed as a high-performance contrast agent, with a remarkable ionic relaxivity of ∼75 mM^–1 s^–1 in albumin solution at 0.5 T. These Gd-dots also exhibit efficient renal clearance with <3% of injected amount left 12 h post-injection. Ultrasensitive MR renography achieved with Gd-dots strongly suggests their great potential for practical applications