Objective To investigate whether ultrasound (US)-targeted microbubble (MB) destruction (UTMD) can influence the biofilm and bacteria in morphology.Methods Twenty-hour biofilms of Staphylococcus epidermidis RP62A were treated with US or UTMD.The acoustic intensity was 0.5-1.5W/cm2,the duty cycle was 50％ and the duration was 10 minutes.After treatment,the absorbance values (A570) of biofilms stained with the crystal violet were measured to assess the biofilm density.The biofilms were observed with macroscopy and light microscopy.The biofilms were examined by confocal laserscanning microscopy (CLSM) and scanning electron microscopy (SEM).Results A thick and compact biofilm was observed in the untreated control group,and there were no obvious micropores in biofilms under macrology and light micrology.Although there were no significant changes under macroscopy in both biofilms treated with US only and UTMD with 0.5 W/cm2 acoustic intensity,interestingly,many micropores could be found under microscopy.The diameters of micropores increased with increasing acoustic intensity,and the micropores in biofilms treated with UTMD were bigger than those treated with US-only in the same condition of acoustic intensity (P ＜0.05).The largest diameters of micropores were up to 1 mm in biofilms treated with UTMD using 1.5 W/cm2 (P ＜0.05).The biofilm density (A570 value) decreased with increasing of the acoustic intensity,and the values in UTMD group of 1.5 W/cm2 were the lowest (P ＜ 0.05).Micropores also could be observed under CLSM.There were no obvious dead bacteria in biofilms treated with US and UTMD compared with untreated control group (P ＞0.05).Under SEM,the shape of bacteria in biofilms treated with US and UTMD became irregular,and many rounded projection could be observed in the surface of the bacteria treated with UTMD.Conclusions US and UTMD can produce micropores in biofilms,which might help to promote antibiotic activity against biofilms

OBJECTIVE To investigate the mechanisms of rutin in alleviating depressive symptoms associated with premenstrual dysphoric disorder （PMDD） characterized by liver qi stagnation syndrome. METHODS Network pharmacology was employed to identify the intersecting targets of action between PMDD and rutin. A protein-protein interaction network was constructed to screen core targets， followed by gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis. Molecular docking simulations validated rutin’s binding affinity to core targets. The bilateral ovaries of female Wistar rats were removed， followed by artificial hormone induction. The rats were then randomly divided into normal group （10 rats） and modeling group （50 rats）. PMDD rat model with liver qi stagnation syndrome was established via restraint stress. The successfully modeled rats were further divided into model group， fluoxetine group （positive control） and rutin group， with 12 rats in each group. The corresponding drug solutions or water were administered by gavage at 9：00 a.m. every day， continuing for two estrous cycles. The open-field test， forced swimming test and Y-maze test were utilized to evaluate the effects of rutin on the behavioral indexes of model rats. Additionally， the density of neuronal dendritic spines in the hippocampal tissues of the rats was observed. Serum brain-derived neurotrophic factor （BDNF） levels and the expressions of BDNF， tyrosine kinase receptor type B （TrkB）， synuclein （Syn）， and postsynaptic density protein 95 （PSD95） in hippocampal tissues were quantified， respectively. RESULTS Network pharmacology and molecular docking revealed the core targets through which rutin ameliorated PMDD characterized by liver qi stagnation syndrome included BDNF， TrkB， PSD65， Syn， etc. The results of experimental validation demonstrated that rutin significantly increased the spontaneous alternation behavior scores of PMDD model rats with liver qi stagnation syndrome during the non-receptive phase， shortened their immobility time during the forced swimming test， and enhanced the density of neuronal dendritic spines in the hippocampal tissues. Additionally， rutin upregulated the levels of serum BDNF and the protein expressions of BDNF， TrkB and Syn in the hippocampal tissues （P＜0.05）. However， it had no significant effect on the above indexes in model rats during the receptive phase （P＞0.05）. CONCLUSIONS Rutin ameliorates depressive symptoms， enhances spatial memory capabilities， and reduces neuronal damage in PMDD model rats with liver qi stagnation syndrome. These effects may be associated with the activation of BDNF/TrkB signaling pathway and upregulation of Syn protein expression.