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Hypervirulent carbapenem-resistant Klebsiella pneumoniae (hv-CRKP) has been widely reported and poses a global threat. However, the comprehensive genetic structure of ST11-KL64 hv-CRKP and the possible evolutionary mechanisms from a genetic structure perspective of this high-risk clone remain unclear. Here, a bla KPC-2 - bla NDM-1 -positive ST11-KL64 hv-CRKP isolate was obtained from a human bloodstream infection (BSI). Whole-genome sequencing and bioinformatics analyses revealed that it contained a fusion plasmid, pKPTCM2–1. pKPTCM2–1 is a conjugative plasmid composed of an oriT -positive pLVPK-like virulence plasmid and a type IV secretion system-produced bla NDM-1 -bearing IncX3 plasmid mediated by IS 26 -based co-integration. This progress generated 8-bp target site duplications (TGAAAACC) on both sides. The fusion plasmid possessed self-transferability and could be transferred to bla KPC-2 -harboring ST11-KL64 CRKP to form the ST11-KL64 hv-CRKP clone. The pLVPK-like-positive ST11-KL64 strain exhibited virulence levels similar to those of the typical hypervirulent K. pneumoniae NTUH-2044. The mutation, Tet(A) (A276S), which was believed to lead to tigecycline resistance was observed. Overall, this high-risk clone has emerged as a tremendous threat in fatal BSIs and thus, targeted surveillance is an urgent need to contain the hv-CRKP clones. • One bla KPC-2 - bla NDM-1 -positive ST11-KL64 hv-CRKP in human bloodstream infection. • oriT -positive pLVPK-like virulence plasmid and bla NDM-1 -bearing IncX3 plasmid fusion. • One mutation of Tet(A) (A276S) maybe lead to tigecycline resistance. [ABSTRACT FROM AUTHOR]

Background. Triple-negative breast cancer (TNBC) is a subtype of breast cancer with limited therapeutic options. Eupalinolide O (EO) was reported to inhibit tumor growth. This study is aimed at exploring the role of EO on TNBC both in vivo and in vitro. Methods. In in vitro experiments, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and clonogenic assay were conducted to measure the impact of EO on TNBC cell growth at different concentrations and time points. Flow cytometry was conducted to evaluate cell apoptosis. Mitochondrial membrane potential (MMP) loss, caspase-3 activity, and reactive oxygen species (ROS) generation were assessed. The expressions of apoptosis-related mRNAs and Akt/p38 MAPK signaling pathway-related proteins were measured. In in vivo experiments, by injecting TNBC cells into the nude mice to induce xenograft tumor, mice were treated with EO for 20 days. Then, in vivo bioluminescence imaging system was utilized to monitor the growth and distribution of TNBC cells. Tumor volume and weight were also recorded. Hematoxylin-eosin (HE) staining and ELISA assay were applied to observe tumor tissue morphology and ROS levels. Furthermore, western blotting was conducted to observe the expression of apoptosis-related proteins and Akt/p38 MAPK signaling pathway-associated proteins. Results. EO inhibited the cell viability and proliferation of TNBC cells but not normal epithelial cells. Furthermore, EO induced apoptosis, decreased MMP, and elevated caspase-3 activity and ROS content in TNBC cells. Meanwhile, the expression of apoptosis-related mRNAs and Akt/p38 MAPK pathway-related proteins was regulated by EO treatment. Besides, in vivo experiments demonstrated EO not only suppressed tumor growth, Ki67 expression, ROS generation, and Akt phosphorylation but also upregulated caspase-3 expression and p-38 phosphorylation. Conclusion. EO may induce cell apoptosis in TNBC via regulating ROS generation and Akt/p38 MAPK pathway, indicating EO may be a candidate drug for TNBC. [ABSTRACT FROM AUTHOR]

An efficient synthesis of indolizines with a thioether group is developed through employing [4+2]-annulation of N-substituted pyrrole-2-carboxaldehydes and prop-2-ynylsulfonium salts, forming a wide variety of target compounds with various substituents and functionalities in moderate to good yields. The success of this transformation makes it an alternative approach to previous protocols, and pharmaceutical and biomedical applications of the investigated compounds are expected with further development. [ABSTRACT FROM AUTHOR]

Chrysanthemum morifolium cv. Hang-ju (HJ) is considered as a healthy food supplement for a long time in Asia. But until now, there are few reports on the biological activity of HJ leaves, which is the main by-products of HJ. In this study, HJ leaves was extracted by water, ethanol and water: ethanol (30: 70), respectively. The results showed that the total polyphenol content of water extract, hydroalcoholic extract and ethanol extract was 75.1 ± 6.9 mg GAE/g, 162.2 ± 5.6 mg GAE/g and 128.5 ± 1.9 mg GAE/g, respectively. However, the ethanol extract has the highest antibacterial activity against the tested strains with a MIC of 0.25 mg/mL compared to water extract (MIC > 8.0 mg/mL) and ethanol extract (MIC = 0.50 mg/mL). The essential oil was extracted from HJ leaves by water distillation (0.5%), which showed higher antibacterial effect on gram-positive bacteria (MIC = 0.125 mg/mL) than ethanol extract. GC–MS was used for the preliminary identification of essential oil composition. The compound (1S,4aS,7R,8aS)-1,4a-dimethyl-7-(prop-1-en-2-yl)decahydronaphthalen-1-ol was first identified from HJ and found to be the most dominant compound. Furthermore, essential oil can significantly deform cell morphology and damage cell wall structure, which was confirmed by LIVE/DEAD® BacLight Viability Kit and scanning electron microscopy observations. The mentioned findings indicated that HJ leaves could be utilized as a natural additive in food industry with significant antimicrobial potential. [ABSTRACT FROM AUTHOR]

This study aimed to isolate, prepare and identify the main flavonoids from a standardized Smilax glabra flavonoids extract (SGF) using preparative HPLC, MS, 1H NMR and 13C NMR, determine the contents of these flavonoids using UPLC, then compare their pharmacological activities in vitro. We obtained six flavonoids from SGF: astilbin (18.10%), neoastilbin (11.04%), isoastilbin (5.03%), neoisoastilbin (4.09%), engeletin (2.58%) and (−)-epicatechin (1.77%). The antioxidant activity of six flavonoids were evaluated by determining the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical and 2,2′-Azinobis (3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt (ABTS+) radical scavenging activity and ferric reducing antioxidant power (FRAP). In addition, the anti-inflammatory activity of six flavonoids were evaluated by determining the production of cytokines (IL-1β, IL-6), nitric oxide (NO) using enzyme linked immunosorbent assay and the NF-κB p65 expression using Western blotting in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. The results showed that (−)-epicatechin, astilbin, neoastilbin, isoastilbin and neoisoastilbin had strong antioxidant activities, not only in DPPH and ABTS+ radicals scavenging capacities, but in FRAP system. Furthermore, all the six flavonoids could significantly inhibit the secretion of IL-1β, IL-6, NO (p < 0.01) and the protein expression of NF-κB p-p65 (p < 0.01) in LPS-stimulated RAW264.7 cells. This study preliminarily verified the antioxidant and anti-inflammatory activities of six flavonoids in S. glabra. [ABSTRACT FROM AUTHOR]