Yuanyuan Wang

Background: Depression is a serious mental disorder and the most prevalent cause of disability and suicide worldwide. Chronic unpredictable mild stress (CUMS) can lead to a significant acceleration of depression development. Quercetin (Que) is a flavonoid compound with a wide range of pharmacological effects. Recent studies have shown that quercetin can improve CUMS‐induced depression‐like behavior, but the mechanism of its improvement is still unclear. α2δ‐1 is a regulatory subunit of voltage‐gated calcium channel, which can interact with N‐methyl‐D‐aspartate receptor (NMDAR) to form a complex.Objective: In this study, we found that Que could inhibit the increase of α2δ‐1 and NMDAR expression in rat hypothalamus induced by CUMS. In pain, chronic hypertension and other studies have shown that α2δ‐1 interacts with the NMDAR to form a complex, which subsequently affects the expression level of NMDAR. Consequently, the present study aimed to investigate the antidepressant effect of Que in vivo and in vitro and to explore its mechanism of action in terms of the interaction between α2δ‐1 and NMDAR.Methods: Rats were randomly exposed to two stressors every day for 4 weeks to establish a CUMS rat model, then sucrose preference test (SPT), forced swimming test (FST), tail suspension test (TST), and open field test (OFT) were performed to detect the behavior of CUMS rats, so as to evaluate whether the CUMS rat model was successfully established and the improvement effect of Que on CUMS‐induced depression‐like behavior in rats. Experimental techniques such as serum enzyme‐linked immunosorbent assay (ELISA), immunofluorescence, Western blot, and co‐immunoprecipitation, as well as in vitro experiments, were used to investigate the mechanisms by which Que exerts its antidepressant effects.Results: Behavioral and ELISA test results showed that Que could produce a reduction in the excitability of the hypothalamic–pituitary–adrenal (HPA) axis in CUMS rats and lead to significant improvements in their depressive behavior. Western blot, immunofluorescence, and co‐immunoprecipitation experiments showed that Que produced a decrease in NMDAR1 and α2δ‐1 expression levels and interfered with α2δ‐1 and NMDAR1 binding. In addition, the neural regulation mechanism of Que on antidepressant effect in PC12 cells knocked out α2δ‐1 gene was further verified. Cellular experiments demonstrated that Que led to a reversal of up‐regulation of NMDAR1 and α2δ‐1 expression levels in corticosterone‐injured PC12 cells, while Que had no effects on NMDAR1 expression in PC12 cells with the α2δ‐1 gene knockout.Conclusions: Que has a good antidepressant effect and can significantly improve the depression‐like behavior caused by CUMS. It exerts antidepressant effects by inhibiting the expression level of α2δ‐1, interfering with the interaction between α2δ‐1 and NMDAR, and then reducing the excitability of the HPA axis.

To control the dimension of the supramolecular system was of great significance. We construct a two component self-assembly system, in which the gelator LHC18 and achiral azobenzene carboxylic acid could co-assembly and form gels. By modulating the stoichiometric ratio of the two components, not only the morphology could be transformed from 1D nanaotube to 0D nanospheres but also the supramolecualr chirality could be tuned. This work could provide some insights to the control of dimension and the supramolecular chirality in the two-component systems by simply modulating the stoichiometric ratio.

To analyze pesticide residues, GC coupled with quadrupole‐Orbitrap MS (GC‐Orbitrap‐MS) has become a powerful tool because of its unique characteristics of accurate mass full‐spectrum acquisition, high resolution, fast acquisition rates, and overcoming matrix interference. This paper presents an efficiency evaluation of GC‐Orbitrap‐MS for identification and quantitation in the 352 pesticide residues analysis of chrysanthemum flowers in full‐scan mode. A streamlined pretreatment approach using one‐step extraction and dilution was used, which provided high‐throughput processing and excellent recovery. The samples were extracted using acetonitrile. The extracted solution was purified by a Sin‐QuEChERS Nano column to suppress the matrix in chrysanthemum flowers and determined by GC‐Orbitrap‐MS. The calibration curves for the 352 pesticides obtained by GC‐Orbitrap‐MS were linear in the range of 0.5–200 μg·kg⁻¹, with the correlation coefficients higher than 0.99. The limits of detection (LODs) and the limits of quantification (LOQs) for the 352 pesticide residues were 0.3–3.0 μg·kg⁻¹ and 1.0–10.0 μg·kg⁻¹, respectively. The average recoveries in chrysanthemum flower at three levels were 95.2%, 88.6%, and 95.7%, respectively, with relative standard deviations (RSDs) of 7.1%, 7.5%, and 7.2%, respectively. Lastly, the validated method and retrospective analysis was applied to a total of 200 chrysanthemum flower samples bought in local pharmacies. The proposed method can simultaneously detect multipesticide residues with a good performance in qualitative and quantitative detection.

Human nuclear protein positive cofactor PC4 is a DNA-binding protein, and plays an important role in the early response to DNA damage by recognizing single-stranded oligodeoxynucleotide domain and facilitating the subsequent steps of DNA repair. Our group previously discovered that PC4 selectively binds to a double-stranded oligodeoxynucleotide (dsODN) damaged by a trans-platinum anticancer complex, trans-[PtCl2(NH3)(thiazole)] (trans-PtTz). However, the molecular basis of this unique recognition and interaction remained unclear. In this work, amide hydrogen/deuterium exchange mass spectrometry (HDX-MS) was applied to dissect the interaction interface between PC4 and a 15-mer double-stranded oligodeoxynucleotide crosslinked by trans-PtTz (trans-PtTz-dsODN). Global deuterium uptake suggested a 1:1 binding stoichiometry of PC4 to trans-PtTz-dsODN. Local deuterium uptake revealed that the flexible N-terminal loop and the β3 – β5-sheet played key roles in the recognition and interaction between PC4 and trans-PtTz-dsODN. In order to locate the key amino acid residues, molecular dynamics simulation was employed, demonstrating that PC4 binds to the trans-PtTz-dsODN at the minor groove via strong H-bonds with the nucleobases of the complementary strand. The minor groove width was broadened to adapt for the binding of PC4. Arg86 residue in PC4 was shown to dominate the recognition and interaction, which was verified by electrophoretic mobility shift assays. This work profiles the detailed interaction mechanism of PC4 with trans-PtTz damaged dsODN, and the combination use of HDX-MS and molecular dynamics simulation provides a new paradigm for the future research of the cellular response to the platinum induced DNA damage.