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Enterohemorrhagic Escherichia coli (EHEC) strains cause serious gastrointestinal disease, which can lead to potentially life-threatening systemic complications such as hemolytic uremic syndrome. Although the ehx gene is established as a major virulence factor of EHEC, the role of this gene in colonization and biofilm formation remains to be elucidated. We constructed recombinant isogenic mutants of the ehxA locus of E. coli HLJ1122 (serotype O82) using the λ Red homologous recombination system. Significantly higher levels of adherence to human epithelial cells (HEp-2) cells were observed for strain HLJ1122 compared with the mutant strain HLJ1122-Δ ehxA ( P < 0.05). Strain HLJ1122 also exhibited significantly higher levels of biofilm formation than strain HLJ1122-Δ ehxA ( P < 0.05). Mice infected with strain HLJ1122 showed severe destruction of the intestinal and gastric mucosa; in contrast, mice infected with HLJ1122-Δ ehxA showed limited intestinal pathology, displaying minimal inflammatory infiltrates compared with mock-infected mice. These results showed the multifunctional role of Ehx in E. coli virulence. [ABSTRACT FROM AUTHOR]

Abstract: A novel and practical procedure was developed for the preparation of D-ring unsaturated 17-alkynyl steroids by Pd(PPh3)4/AgOAc-catalyzed coupling of steroidal 17-triflates and alkynes. Firstly treatment of the steroid-17-ones with PhN(Tf)2 and KHMDS in dried THF at −78°C for 2h gives the corresponding steroidal 17-triflates products in high yields (97–98%), following the coupling of steroidal 17-triflates and various 1-alkynes by Pd(PPh3)4/AgOAc-catalyzed in the presence of DIPEA for 24h to yield the desired D-ring unsaturated 17-alkynyl steroids (86–97%). Moreover, it was found that the coupling reaction catalyzed by Pd[(C6H5)3P]4/AgOAc system is selective for aryl triflates or vinyl triflates. By optimizing the reaction conditions, the sole C17-coupling products from steroidal bistriflates were obtained in satisfactory yields. Since D-ring unsaturated 17-alkynyl steroids with conjugated double and triplet bond can be subsequently converted into pentacyclic steroids and 17-oxosteroid derivatives at the side chain of D-ring, this general method provides a highly efficient route to these biologically important compounds. [ABSTRACT FROM AUTHOR]

High-frequency oscillatory activity in cognition-related neural circuits during wakefulness consistently induces the growth of dendritic spines and axonal terminals. Although these structural changes are essential for cognitive functions, it is hypothesized that if these newly expanded structures fail to establish functional connections, they may become superfluous. Sleep is believed to facilitate the reduction of such redundant structures to maintain neural homeostasis. However, the mechanisms underlying this pruning process during sleep remain poorly understood. In this study, that melatonin type 3 receptors (MT 3 Rs) are selectively expressed in the stellate neurons of the medial entorhinal cortex (MEC) is demonstrated, an area where high melatonin levels are detected during sleep. Activation of MT 3 Rs during sleep initiates the shrinkage of dendritic spines in stellate neurons by downregulating neural network activity and dephosphorylating synaptic proteins in the MEC. This process is disrupted when MT 3 R expression is knocked down or when MT 3 Rs are blocked during sleep. Notably, interference with MT 3 Rs in the MEC during sleep impairs the acquisition of spatial memory but does not affect object memory acquisition following sleep. These findings reveal novel molecular mechanisms involving melatonin and MT 3 Rs in the regulation of dendritic spine shrinkage during sleep, which is crucial for the acquisition and consolidation of spatial memory., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Rationale and Objectives: This study aims to assess the prognostic value of Cyclin-dependent kinases 6 (CDK6) expression levels and establish a machine learning-based radiomics model for predicting the expression levels of CDK6 in high-grade gliomas (HGG)., Materials and Methods: Clinical parameters and genomic data were extracted from 310 HGG patients in the Cancer Genome Atlas (TCGA) database and 27 patients in the Repository of Molecular Brain Neoplasia Data (REMBRANDT) database. Univariate and multivariate Cox regression, as well as Kaplan-Meier analysis, were performed for prognosis analysis. The correlation between immune cell Infiltration with CDK6 was assessed using spearman correlation analysis. Radiomic features were extracted from contrast-enhanced magnetic resonance imaging (CE-MRI) in the Cancer Imaging Archive (TCIA) database (n = 82) and REMBRANDT database (n = 27). Logistic regression (LR) and support vector machine (SVM) were employed to establish the radiomics model for predicting CDK6 expression. Receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA) were utilized to assess the predictive performance of the radiomics model. Generate radiomic scores (RS) based on the LR model. An RS-based nomogram was constructed to predict the prognosis of HGG., Results: CDK6 was significantly overexpressed in HGG tissues and was related to lower overall survival. A significant elevation in infiltrating M0 macrophages was observed in the CDK6 high group (P < 0.001). The LR radiomics model for the prediction of CDK6 expression levels (AUC=0.810 in the training cohort, AUC = 0.784 after cross-validation, AUC=0.750 in the testing cohort) was established utilizing three radiomic features. The predictive efficiencies of the RS-based nomogram, as measured by AUC, were 0.769 for 1-year, 0.815 for 3-year, and 0.780 for 5-year, respectively., Conclusion: The expression level of CDK6 can impact the prognosis of patients with HGG. The expression level of HGG can be noninvasively prognosticated utilizing a radiomics model., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Introduction: Glioblastoma (GBM) presents significant challenges due to its malignancy and limited treatment options. Precision treatment requires subtyping patients based on prognosis. Disulfidptosis, a novel cell death mechanism, is linked to aberrant glucose metabolism and disulfide stress, particularly in tumors expressing high levels of SLC7A11. The exploration of disulfidptosis may provide a new perspective for precise diagnosis and treatment of glioblastoma., Methods: Transcriptome sequencing was conducted on samples from GBM patients treated at Tiantan Hospital (January 2022 - December 2023). Data from CGGA and TCGA databases were collected. Consensus clustering based on disulfidptosis features categorized GBM patients into two subtypes (DRGclusters). Tumor immune microenvironment, response to immunotherapy, and drug sensitivity were analyzed. An 8-gene disulfidptosis-based subtype predictor was developed using LASSO machine learning algorithm and validated on CGGA dataset., Results: Patients in DRGcluster A exhibited improved overall survival (OS) compared to DRGcluster B. DRGcluster subtypes showed differences in tumor immune microenvironment and response to immunotherapy. The predictor effectively stratified patients into high and low-risk groups. Significant differences in IC50 values for chemotherapy and targeted therapy were observed between risk groups., Discussion: Disulfidptosis-based classification offers promise as a prognostic predictor for GBM. It provides insights into tumor immune microenvironment and response to therapy. The predictor aids in patient stratification and personalized treatment selection, potentially improving outcomes for GBM patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yang, Cai, Wang, Jiang, Li, Chen and Li.)

The utility of flexidentate pyridyl-substituted formazanate ligands for assembling dinuclear coordination complexes with iridium(III) and/or platinum(II) building blocks is demonstrated herein. The dinuclear complexes are prepared either via a stepwise strategy, adding one metal unit at a time, or via one-pot self-assembly. Eight of the new complexes, including both mononuclear precursors and dinuclear products, are structurally characterized by single-crystal X-ray diffraction and NMR spectroscopy, revealing several distinct binding modes of the formazanates. All complexes are characterized by UV/Vis absorption spectroscopy and cyclic voltammetry. The frontier orbitals are primarily localized on the formazanate ligand, and a characteristic, intense formazanate-centered π→π* absorption band is observed in the absorption spectra., (© 2020 Wiley-VCH GmbH.)

Non-amphiphilic WIQPKTKVIPYVRYL (WI-6) derived from bovine α s2 -casein f (193-207) was modified by a defined mutation method to obtain five engineered peptides with mirror symmetry structures. The five engineered peptide sequences were WF-1 (WFQVKTRVRTKVQFW), FW-2 (FWRRYKKVKKYRRWF), FW-3 (FWQVIKKVKKIVQWF), FK-4 (FKQFYRRVRRYFQKF), and FR-5 (FRQWYRRVRRYWQRF). However, FW-2, FW-3, FK-4, and FR-5 had obvious XXYXX sequences. Among these, FW-3 was demonstrated to have the highest antibacterial activity, which indicates that the non-perfectly amphipathic α-helical structure containing the XXYXX sequence has a better bactericidal effect. Therefore, peptide FW-3 could be widely used as a substitute for antibiotics in food, medicine, and other fields. These findings provide a potential method for designing novel antimicrobial peptides.

The primary objective of this study was to improve our understanding of the antimicrobial mechanism of protein-derived peptides and to provide evidence for protein-derived peptides as food bio-preservatives by examining the antimicrobial activities, low cytotoxicity, stabilities, and mechanism of Cp1 (LRLKKYKVPQL). In this study, the protein-derived peptide Cp1 was synthesized from bovine α S1 -casein, and its potential use as a food biopreservative was indicated by the higher cell selectivity shown by 11-residue peptide towards bacterial cells than human RBCs. It also showed broad-spectrum antimicrobial activity, with minimum inhibitory concentrations (MICs) of 64⁻640 μM against both gram-positive and gram-negative bacteria. The peptide had low hemolytic activity (23.54%, 512 μM) as well as cytotoxicity. The results of fluorescence spectroscopy, flow cytometry, and electron microscopy experiments indicated that Cp1 exerted its activity by permeabilizing the microbial membrane and destroying cell membrane integrity. We found that Cp1 had broad-spectrum antimicrobial activity, low hemolytic activity, and cytotoxicity. The results also revealed that Cp1 could cause cell death by permeabilizing the cell membrane and disrupting membrane integrity. Overall, the findings presented in this study improve our understanding of the antimicrobial potency of Cp1 and provided evidence of the antimicrobial mechanisms of Cp1. The peptide Cp1 could have potential applications as a food biopreservative., Competing Interests: The authors declare no conflict of interest.

The objective of the study is to analyze the biological characteristics and stability of the linear derivative Bac2a from bactenecin, compared with the control peptide melittin. The secondary structure, antibacterial activity, hemolytic activity, cell toxicity and stability of the Bac2a were determined by circular dichroism spectroscopy, broth micro-dilution method and MTT assay. The results showed that Bac2a was a nonregular curl in aqueous solution, however, it was an α-helix structure in the hydrophobic environment. The minimal inhibitory concentration (MIC) of Bac2a ranged from 2 to 32 μmol/L, so the bacteriostatic activity of Bac2a was strong. The hemolytic rate was only 14.81% when the concentration of Bac2a was 64 μmol/L, which showed that the hemolytic rate of Bac2a was low. The therapy index of Bac2a was 3.26, and the cytotoxicity was relatively low, thus the cell selectivity was relatively high. In addition, with the heating treatment of 100℃ for 1 h, Bac2a still possessed rather a high antibacterial activity and showed a good heating stability. In a word, Bac2a has good application prospects in food, medicine and other fields, and is expected as a substitute for traditional antibiotics.