Angelicin improves osteoporosis in ovariectomized rats by reducing ROS production in osteoclasts through regulation of the KAT6A/Nrf2 signalling pathway.

Background: Angelicin, which is found in Psoralea, can help prevent osteoporosis by stopping osteoclast formation, although the precise mechanism remains unclear.

Methods: We evaluated the effect of angelicin on the oxidative stress level of osteoclasts using ovariectomized osteoporosis model rats and RAW264.7 cells.

Restoring colistin sensitivity in colistin-resistant and : combinatorial use of berberine and EDTA with colistin.

Unlabelled: The appearance and prevalence of multidrug-resistance (MDR) Gram-negative bacteria (GNB) have limited our antibiotic capacity to control bacterial infections. The clinical efficacy of colistin (COL), considered as the "last resort" for treating GNB infections, has been severely hindered by its increased use as well as the emergence and prevalence of mobile colistin resistance (MCR)-mediated acquired drug resistance. Identifying promising compounds to restore antibiotic activity is becoming an effective strategy to alleviate the crisis of increasing MDR.

Upregulation of outer membrane porin gene contributed to enhancement of azithromycin susceptibility in multidrug-resistant .

The outer membrane (OM) in gram-negative bacteria contains proteins that regulate the passive or active uptake of small molecules for growth and cell function, as well as mediate the emergence of antibiotic resistance. This study aims to explore the potential mechanisms for restoring bacteria to azithromycin susceptibility based on transcriptome analysis of bacterial membrane-related genes. Transcriptome sequencing was performed by treating multidrug-resistant T28R with azithromycin or in combination with colistin and confirmed by reverse transcription-quantitative PCR (RT-qPCR).

Robust and dynamic underwater adhesives enabled by catechol-functionalized poly(disulfides) network.

Developing molecular approaches to the creation of robust and water-resistant adhesive materials promotes a fundamental understanding of interfacial adhesion mechanisms as well as future applications of biomedical adhesive materials. Here, we present a simple and robust strategy that combines natural thioctic acid and mussel-inspired iron-catechol complexes to enable ultra-strong adhesive materials that can be used underwater and simultaneously exhibit unprecedentedly high adhesion strength on diverse surfaces. Our experimental results show that the robust crosslinking interaction of the iron-catechol complexes, as well as high-density hydrogen bonding, are responsible for the ultra-high interfacial adhesion strength.

Synergistic antibacterial activity of baicalin and EDTA in combination with colistin against colistin-resistant Salmonella.

The emergence and rapid spread of multidrug resistant (MDR) Gram-negative bacteria have posed a serious threat to global health and security. Because of the time-consuming, high cost and high risk of developing new antibiotics, a significant method is to use antibiotic adjuvants to revitalize the existing antibiotics. The purpose of the study is to research the traditional Chinese medicine baicalin with the function of inhibiting the efflux pump and EDTA whether their single or combination can increase the activity of colistin against colistin-resistant Salmonella in vitro and in vivo, and to explore its molecular mechanisms.

A Dynamic Supramolecular H-bonding Network with Orthogonally Tunable Clusteroluminescence.

Enabling dynamically tunable emissive systems offers opportunities for constructing smart materials. Clusteroluminescence, as unconventional luminescence, has attracted increasing attention in both fundamental and applied sciences. Herein, we report a supramolecular poly(disulfides) network with tunable clusteroluminescence.

Decreased cyclic-AMP caused by ATP contributes to fosfomycin heteroresistance in avian Escherichia coli.

Background: Fosfomycin is an important broad-spectrum bactericidal antibiotic to treat multidrug-resistant bacteria infections. It is generally accepted that heteroresistant bacteria are an intermediate stage in the formation of drug resistance, but there are few studies on the formation mechanism underlying fosfomycin heteroresistance (FHR).

Objectives: To reveal the characteristics and formation mechanisms of FHR in Escherichia coli isolates obtained from chickens.

Characterization of IncI1/ST71 and IncF18:A-:B1 multidrug-resistance plasmids from an avian Escherichia coli isolate.

To characterize IncI1 and IncF18:A-:B1 multidrug-resistance plasmids from an avian Escherichia coli isolate, antibiotic susceptibility testing, conjugation assays, transformation assays, S1-PFGE, and WGS analysis were performed. The 119,457-bp plasmid pEC014-1 with a multidrug-resistance region (MRR) containing four different segments interspersed with six IS26 elements, belonged to incompatibility group I1 and sequence type 71. The 154,516-bp plasmid pEC014-2 with two replicons, typed as FII-18 and FIB-1, carried 14 resistance determinants including bla, bla, oqxAB, dfrA17, aac(6')-Ib-cr, sul1, sul2, tet(A), floR, catB3, hph(aph(4)-Ia), aacC4(aac(3)-IV), aadA5, arr-3, and a merEDACPTR loci in MRR, and additionally encoded three virulence loci: iroNEDCB, sitABCD, and iucABCD-iutA.

Multidrug Resistance Genes Carried by a Novel Transposon Tn and a Genomic Island Named MMGI-4 in a Pathogenic Morganella morganii Isolate.

Antimicrobial resistance in Morganella morganii is increasing in recent years, which is mainly introduced via extra genetic and mobile elements. The aim of our study is to analyze the multidrug resistance (MDR) and characterize the mobile genetic elements (MGEs) in M. morganii isolates.

Characterization of a Novel Linezolid Resistance Gene and Bacitracin Resistance Locus-Carrying Multiple Antibiotic Resistant Integrative and Conjugative Element ICE1112S in .

Streptococcus suis strain 1112S was isolated from a diseased pig in a feedlot from Henan, China, in 2019. The isolate harbored a linezolid resistance gene . WGS data revealed that the gene was associated with a single copy ETAf IS, in tandem with (B) and (O), located in a novel 72,587 bp integrative and conjugative element (ICE).

BRD4 inhibition induces synthetic lethality in ARID2-deficient hepatocellular carcinoma by increasing DNA damage.

Hepatocellular carcinoma (HCC) has emerged as the third cause of cancer-related death owing to lacking effective systemic therapies. Genomic DNA sequencing revealed the high frequency of loss-of-function mutations in ARID2, which encodes a subunit of SWI/SNF chromatin remodeling complex, however, the therapeutic strategy for the HCC patients with ARID2 mutations is still completely unclear. In this study, we first performed a high-throughput screening approach using a compound library consisting of 2 180 FDA-approved drugs and other compounds, to elicit the potential drugs for synthetic lethality to target ARID2-deficient HCC cells.

ARID1A deficiency weakens BRG1-RAD21 interaction that jeopardizes chromatin compactness and drives liver cancer cell metastasis.

ARID1A, encoding a subunit of SWI/SNF chromatin remodeling complex, is widely recognized as a tumor suppressor gene in multiple tumor types including liver cancer. Previous studies have demonstrated that ARID1A deficiency can cause liver cancer metastasis, possibly due to the altered chromatin organization, however the underlying mechanisms remain poorly understood. To address the effect of Arid1a deficiency on chromatin organization, we generated chromatin interaction matrices, and exploited the conformation changes upon Arid1a depletion in hepatocytes.

Double deletion of cpxR and tolC significantly increases the susceptibility of Salmonella enterica serovar Typhimurium to colistin.

Background: The increasing use of colistin causes a serious breach in our last line of defence against MDR Gram-negative pathogens. Our previous study showed that CpxR overexpression increases the susceptibility of acrB and cpxR double-deleted Salmonella enterica serovar Typhimurium to colistin.

Objectives: To identify the mechanism of CpxAR and efflux pumps that synergistically enhance the susceptibility of S.

The Formation of Two Hybrid Plasmids Mediated by IS and Tn in Serotype .

To characterize the formation mechanism and characteristics of two cointegrate plasmids in serotype strain S13, plasmids from strain S13 and three corresponding transconjugants were subjected to whole genome sequencing and analyzed using bioinformatics tools. The traits of two fusion plasmids in transconjugants were characterized by stability and conjugation experiments. Sequence analysis indicated that strain S13 contained four plasmids, including -bearing pS13-1, -carrying pS13-2, (M)-bearing pS13-3, and -carrying pS13-4.

Characterization of bla-carrying IncC and rmtB-carrying IncI1/ST136 plasmids in an avian Escherichia coli ST224 strain.

To analyze characteristics and underlying evolutionary processes of IncC and IncI1 plasmids in a multidrug-resistant avian E. coli strain, antibiotic susceptibility testing, PCR, conjugation assays, and next-generation sequencing were performed. The type 1 IncC plasmid pEC009.

Molecular Characterization of a Novel Integrative Conjugative Element ICE in .

ICE was identified in the genome of a serovar 8 ST288 isolate YHP170504 from a case of swine lower respiratory tract infection. The aim of the present study was to characterize the integrative conjugative element ICE and its multiresistance region. Susceptibility testing was determined by broth microdilution and the complete ICE was identified by WGS analysis.

Characterization of pTS14, an IncF2:A1:B1 Plasmid Carrying (M) in a Isolate.

The objective of this study was to explore the genetic and biological features of the (M)-harboring plasmid pTS14 in strain S14 isolated from a chicken fecal sample. Plasmid pTS14 was identified by conjugation, S1-pulsed-field gel electrophoresis (PFGE), Southern hybridization, and plasmid sequencing. The biological characteristics of pTS14 were assessed via stability, growth kinetics, and starvation survival experiments.

CpxR regulates the colistin susceptibility of Salmonella Typhimurium by a multitarget mechanism.

Background: The two-component signalling systems PmrAB and PhoPQ of Salmonella have been extensively studied with regard to colistin resistance. We previously showed that overexpressed CpxR could significantly increase the colistin susceptibility (16-fold compared with the WT strain) of Salmonella enterica serovar Typhimurium (Salmonella Typhimurium) through PmrAB and PhoPQ.

Objectives: To identify the potential target genes of CpxR in PmrAB- and PhoPQ-related signalling pathways.

Let-7f-5p suppresses Th17 differentiation via targeting STAT3 in multiple sclerosis.

T helper 17 (Th17) cells are regarded as key factors in the pathogenesis of multiple sclerosis (MS). Although the involvement of certain microRNAs (miRNAs) in the development of MS has been reported, their roles in Th17 cell differentiation and MS pathogenesis remain elusive. In this study, we identified that let-7f-5p expression is significantly downregulated in CD4 T cells from MS patients and during the process of Th17 differentiation.

P450 enzymes-based metabolic interactions between monarch drugs and the other constituent herbs: A strategy to explore compatibility mechanism of Sangju-Yin.

Background: Herbal compatibility of compound formulas can enhance therapeutic effects or reduce side effects of the monarch drugs, but majority of compatibility mechanisms are still unknown. Sangju-Yin, a well-known Chinese compound formula, is currently used to treat common cold in clinical.

Purpose: In this study, we proposed a strategy to explore the compatibility mechanism of Sangju-Yin by investigating P450 enzymes-based metabolic interactions between monarch drugs and the other constituent herbs.

Antimicrobial resistance-encoding plasmid clusters with heterogeneous MDR regions driven by IS26 in a single Escherichia coli isolate.

Background: IS26-flanked transposons played an increasingly important part in the mobilization and development of resistance determinants. Heterogeneous resistance-encoding plasmid clusters with polymorphic MDR regions (MRRs) conferred by IS26 in an individual Escherichia coli isolate have not yet been detected.

Objectives: To characterize the complete sequence of a novel blaCTX-M-65- and fosA3-carrying IncZ-7 plasmid with dynamic MRRs from an E.