A membrane-targeting magnolol derivative for the treatment of methicillin-resistant Staphylococcus aureus infections.

Multidrug-resistant bacterial infections are a major global health challenge, especially the emergence and rapid spread of methicillin-resistant Staphylococcus aureus (MRSA) urgently require alternative treatment options. Our study has identified that a magnolol derivative 6i as a promising agent with significant antibacterial activity against S. aureus and clinical MRSA isolates (MIC = 2-8 µg/mL), showing high membrane selectivity. Unlike traditional antibiotics, 6i demonstrated rapid bactericidal efficiency and a lower propensity for inducing bacterial resistance. Compound 6i also could inhibit biofilm formation and eradicate bacteria within biofilms. Mechanistic studies further revealed that 6i could target bacterial cell membranes, disrupting the integrity of the cell membrane and leading to increased DNA leakage, resulting in potent antibacterial effects. Meanwhile, 6i also showed good plasma stability and excellent biosafety. Notably, 6i displayed good in vivo antibacterial activity in a mouse skin abscess model of MRSA-16 infection, which was comparable to the positive control vancomycin. These findings indicated that the magnolol derivative 6i possessed the potential to be a novel anti-MRSA infection agent.

Molecular characterization of hybrid virulence plasmids in ST11-KL64 KPC-2-producing multidrug-resistant hypervirulent Klebsiella pneumoniae from China.

Introduction: Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-HvKP) strains combining virulence and multidrug resistance (MDR) features pose a great public health concern. The aim of this study is to explore the evolutionary characteristics of virulence in CR-HvKP by investigating the genetic features of resistance and virulence hybrid plasmids. Methods: The resistance and virulence phenotypes were determined by using antimicrobial susceptibility testing and the mouse bacteremia infection model, respectively. Plasmid profiles were investigated by S1 nuclease pulsed-field gel electrophoresis (S1-PFGE) and Southern blotting, conjugation assay, and whole genome sequencing (WGS). Bioinformatics tools were used to uncover the genetic features of the resistance and virulence hybrid plasmids. Results: Two ST11-KL64 CRKP clinical isolates (KP18-3-8 and KP18-2079), which exhibited enhanced virulence compared with the classic CRKP, were detected positive for blaKPC-2 and rmpA2. The virulence level of the hypermucoviscous strain KP18-3-8 was higher than that of KP18-2079. S1-PFGE, Southern hybridization and WGS analysis identified two novel hybrid virulence plasmids in KP18-3-8 (pKP1838-KPC-vir, 228,158 bp) and KP18-2079 (pKP1838-KPC-vir, 182,326 bp), respectively. The IncHI1B/repB-type plasmid pKP1838-KPC-vir co-harboring blaKPC-2 and virulence genes (rmpA2, iucABCD and iutA) but lacking type IV secretion system could transfer into non-hypervirulent ST11 K. pneumoniae with the assistance of a helper plasmid in conjugation. The IncFII/IncR-type virulence plasmid pKP18-2079-vir may have been generated as a result of recombination between a typical pLVPK-like virulence plasmid and an MDR plasmid. Conclusion: Our studies further highlight co-evolution of the virulence and resistance plasmids in ST11-CRKP isolates. Close surveillance of such hybrid virulence plasmids in clinical K. pneumoniae should be performed.

PCA-WRKNN-assisted label-free SERS serum analysis platform enabling non-invasive diagnosis of Alzheimer's disease.

Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative brain disorder with significant economic and societal impacts, whereas early AD diagnosis remains a considerable challenge. Here, a robust and convenient surface-enhanced Raman scattering (SERS) analysis platform was fabricated on a microarray chip to dissect the variation in serum composition for AD diagnosis, eliminating the invasive cerebrospinal fluid (CSF)-based and costly instrument-dependent diagnostic methods. AuNOs array prepared by self-assembly at liquid-liquid interface enabled the acquirement of SERS spectra with excellent reproducibility. Moreover, a finite-difference time-domain (FDTD) simulation suggested the significant plasmon hybridization generated by AuNOs aggregation, resulting in high signal-to-noise ratio SERS spectra. We established an AD mice model with Aß1-40 induction followed by recording the serum SERS spectra at different stages. A multivariate analysis method of principal component analysis (PCA)-weighted representation-based k-nearest neighbor (WRKNN) was applied for the characteristics extraction to improve the classification performance, with an accuracy of over 95 %, an AUC of over 90 %, a sensitivity of over 80 %, and a specificity of over 96.7 %. The results of this study demonstrate the potential of SERS application as a diagnostic screening method, following further validation and optimization, which may open up new exciting opportunities for future biomedical applications.

Validation of iScore and PLAN Score for Death in Thrombectomy in Acute Stroke Due to Anterior Circulation Large Artery Occlusion.

BACKGROUND: To validate iScore and PLAN score in acute anterior circulation large vessel occlusion stroke patients undergoing thrombectomy. METHODS: iScore and PLAN score were calculated for consecutive acute ischemic stroke undergoing thrombectomy were included and death at 1 month and death at 3 months were recorded. The area under the receiver operating characteristic curve was used to assess the discrimination ability of the scales for death. RESULTS: Two hundred and twenty-nine patients were included, 25.3% (58 of 229) of patient died at 1 month after thrombectomy and 25.8% (59 of 229) of them died at 3 months after thrombectomy. The receiver operator curve analysis found that iScore (area under the curve [AUC] = .76, 95% confidence interval [CI] .69-.83) was numerically better than PLAN score (AUC = .73, 95% CI .66-.81) for predicting death at day 90. The cut-off for iScore is 193, with sensitivity 64%, specificity 79%, positive predictive value 75% and negative predictive value 69%. CONCLUSIONS: The iScore scale is a valid predictive tool for death in anterior circulation large vessel occlusions undergoing thrombectomy.

Characterization of Teicoplanin Nonsusceptible Staphylococcus epidermidis Clinical Isolates Belonging Predominantly to ST267.

Staphylococcus epidermidis is the main cause of bacteremia and infections of indwelling catheters, glycopeptide antibiotics are often considered as the choice of empirical drugs for the treatment of staphylococcal infections. In the present study, 12 teicoplanin nonsusceptible S. epidermidis isolates were collected between January and October 2013. All strains carried the mecA gene, displayed multiple drug resistance, and showed heterogeneous resistance to vancomycin using the population analysis profiling/area under the curve method. Multilocus sequence typing revealed four different sequence types among these isolates; eight isolates belonged to the same ST type (ST267). Pulsed-field gel electrophoresis (PFGE) with SmaI endonuclease showed four distinct pulsotypes. Six isolates that belonged to ST267 shared the same PFGE bands, indicating that they were clonally related. In addition, cell wall thickening and decreased autolysis were found in these isolates. Our study demonstrated that ST267 was the most epidemic clone among teicoplanin nonsusceptible S. epidermidis and identified a potential endemic clone in this region, which was believed to be the first report that the ST267 clone has spread in China. Our findings revealed that strengthened monitoring of S. epidermidis for drug resistance to glycopeptide antibiotics is urgently needed, and heightened measures should be taken to control the further spread of the ST267 clone.

Preparation of γ-Fe2O3@C@MoO3 core/shell nanocomposites as magnetically recyclable catalysts for efficient and selective epoxidation of olefins.

Magnetic γ-Fe2O3@C@MoO3 core-shell structures were fabricated via a general approach and characterized by several techniques such as XRD, XPS, ICP-AES, Raman etc. The catalytic performance of them has been demonstrated in heterogeneously catalyzed oxidation of cyclooctene with tert-butyl hydroperoxide (tBuOOH) as an oxidant, and high conversion (100%) and selectivity (over 99%) were achieved with relatively low catalyst dosage under mild conditions. It should be emphasized that the hybrid catalyst could be easily separated by an external magnet and reused up to 9 times with no significant loss of activity and selectivity. The reaction mechanism over MoO3 is also discussed on the basis of the FTIR and XPS measurements. It is suggested that the high catalytic activity is related to the formation of the transition state, a Mo-alkyl peroxide and olefin complex, which is beneficial for an efficient oxygen atom transfer by converting the intermolecular process directly into an intramolecular process.