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Hg-based compounds show abundant structural diversity and distinguished properties. Herein, a new phase transition compound CsHg2I5 was reported. The high-temperature phase ß-CsHg2I5 with rare [Hg2I5] dimers was synthesized by the flux method at 573 K, and it shows a reversible phase transition at a low temperature of â¼100 K to form the low-temperature phase α-CsHg2I5. The two phases crystallize in the same P21/c space group, with different crystal structures. ß-CsHg2I5 is composed of rare [Hg2I5] dimers and [CsI11] polyhedral units, while α-CsHg2I5 is composed of [Hg4I11] and [CsI10] units. The experimental band gap of ß-CsHg2I5 was found to be 2.58 eV. Owing to the presence of [Hg2I5]∞ pseudo-layers, ß-CsHg2I5 exhibits large optical anisotropy with a calculated birefringence of 0.132@1064 nm. Meanwhile, ß-CsHg2I5 is a congruent compound and the congruent point is â¼481 K. Theoretical calculations indicate that the rare [Hg2I5] dimer is a nonlinear active unit, which can be used as a new fundamental building block for the design of advanced nonlinear optical materials. Moreover, a CsI-HgI2 pseudo-binary diagram was drawn. The results enrich the structural diversity of Hg-based halides and give some insights into the development of new functional materials based on rare [Hg2I5] dimers.
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Introduction: In the era of the Internet, online digital traces have become a new way to study the online attention of scenic spots and tourists' purchase behavior. The public's information search on major search platforms is a series of manifestations of potential tourists' attention and interest in scenic spots, but there are few studies on how attention, interest and information search affect potential tourists to generate real purchase behavior. Method: This paper selects four dimensions of short video platform, travel website, search engine and social media to comprehensively measure the online attention of high-quality scenic spots in Yunnan Province, and then establishes a gray association analytic hierarchy process based on the relevant variables of the AISAS model to empirically analyze the primary and secondary factors affecting tourists' purchase behavior. Results: (1) From the perspective of the online attention of scenic spots on different platforms, the intensity of the public's scenic spots online attention on the four types of media platforms is in the order of travel websites, search engines, short videos and social media (2) From the perspective of spatial distribution characteristics, the online attention of high-quality scenic spots in Yunnan Province is unevenly distributed, that is, there is a big difference between the attention of higher star scenic spots and their star rating and popularity, while the attention of low-star scenic spots is not much different from their star rating and popularity (3) From the perspective of spatial agglomeration characteristics, the comprehensive online attention of high-quality scenic spots in Yunnan Province presents the spatial agglomeration characteristics of "the multi-core linkage of high-density in the east and north, and sub-high-density in the south" (4) The factors influencing the purchase behavior of potential tourists are sharing experience, attracting attention, generating interest and searching information. Discussion: By exploring the formation mechanism of high-quality scenic spots online attention in Yunnan Province and the mechanism of its spatial differentiation, this study not only enriches the logical chain of "tourism information source â potential tourists â demand driven â tourism information search â travel preference â destination selection â purchase decision â travel experience â real tourists â feelings after traveling â focus on feedback â tourism information source," but also broadens the application scenarios and application boundaries of travel preference theory and AISAS behavior model to a certain extent.
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Human Ureaplasma species are being increasingly recognized as opportunistic pathogens in human genitourinary tract infections, infertility, adverse pregnancy, neonatal morbidities, and other adult invasive infections. Although some general reviews have focused on the detection and clinical manifestations of Ureaplasma spp., the molecular epidemiology, antimicrobial resistance, and pathogenesis of Ureaplasma spp. have not been adequately explained. The purpose of this review is to offer valuable insights into the current understanding and future research perspectives of the molecular epidemiology, antimicrobial resistance, and pathogenesis of human Ureaplasma infections. This review summarizes the conventional culture and detection methods and the latest molecular identification technologies for Ureaplasma spp. We also reviewed the global prevalence and mechanisms of antibiotic resistance for Ureaplasma spp. Aside from regular antibiotics, novel antibiotics with outstanding in vitro antimicrobial activity against Ureaplasma spp. are described. Furthermore, we discussed the pathogenic mechanisms of Ureaplasma spp., including adhesion, proinflammatory effects, cytotoxicity, and immune escape effects, from the perspectives of pathology, related molecules, and genetics.
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Raoultella planticola is an emerging bacterial pathogen responsible for causing infections in both humans and animals. Unfortunately, sporadic reports of carbapenem-resistant R. planticola (CRRP) have been documented worldwide. Here we first reported the complete genome sequence of a CRRP isolate RP_3045 co-carrying blaIMP-4 and blaSHV-12, recovered from a patient in China, and its genetic relatedness to 82 R. planticola strains deposited in the NCBI GenBank database, sourced from humans, animals, and the environment. Whole-genome sequencing was performed using the Illumina NovaSeq 6000 and Oxford Nanopore MinION platforms. Phylogenetic analysis was also performed and visualized using a single nucleotide polymorphism (SNP)-based strategy. The complete genome of R. planticola strain RP_3045 was determined to be 6,312,961 bp in length, comprising five contigs that included one chromosome and four plasmids. RP_3045 was found to be multidrug-resistant and harbored several antimicrobial resistance genes, including both blaIMP-4 and blaSHV-12 genes located on a single plasmid. The most closely related strain was hkcpe63, recovered from humans in Hong Kong, China, in 2014, with 506 SNP differences. R. planticola strains were distributed globally and exhibited strong associations among isolates obtained from different sectors. This study provides evidence for the potential of R. planticola to disseminate carbapenem resistance across different sectors, highlighting the critical need for active and continuous surveillance of CRRP.
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Mycoplasma hominis, a commensal bacterium that commonly inhabits the genital tract, leading to infections in both the genitourinary and extragenital regions. However, the antimicrobial resistance and pathogenic mechanisms of M. hominis isolated from extra-urogenital cystic abscess is largely unknown. This study reports the genomic epidemiological characteristics of a M. hominis isolate recovered from a pelvic abscess sample in China. Genomic DNA was extracted and sequenced using Illumina HiSeq X Ten platform. De novo assembly was performed and in silico analysis was accomplished by multiple bioinformatics tools. For phylogenomic analysis, publicly available M. hominis genomes were retrieved from NCBI GenBank database. Whole genome sequencing data showed that the genome size of M. hominis MH4246 was calculated as 679,746 bp, with 558 protein-coding sequences and a G + C content of 26.9%. M. hominis MH4246 is resistant to fluoroquinolones and macrolides, harboring mutations in the quinolone resistance-determining regions (QRDRs) (GyrA S153L, ParC S91I and ParE V417I) and 23S rRNA gene (G280A, C1500T, T1548C and T2218C). Multiple virulence determinants, such as tuf, hlyA, vaa, oppA, MHO_0730 and alr genes, were identified. Phylogenetic analysis showed that the closest relative of M. hominis MH4246 was the strain MH-1 recovered from China, which differed by 3490 SNPs. Overall, this study contributes to the comprehension of genomic characteristics, antimicrobial resistance patterns, and the mechanisms underlying the pathogenicity of this pathogen.
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Abscesso , Mycoplasma hominis , Humanos , Mycoplasma hominis/genética , Filogenia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Fluoroquinolonas/farmacologia , Fluoroquinolonas/uso terapêuticoRESUMO
As an important chemical raw material, hydrazine brings convenience to people's lives and provides opportunities for human development. However, the misuse or leakage of hydrazine has brought pollution to the environment, including water, soil and living organisms. At the same time, hydrazine poses a potential threat to human health as a carcinogen. Despite the enormous challenges, it is crucial to develop an effective method to detect hydrazine in environmental samples. In this work, we have synthesized a series of probes based on phenothiazine fluorophore by the introduction of different substituents and developed a novel probe for the detection of hydrazine. The probe is capable of detecting hydrazine in aqueous solutions with high sensitivity and selectivity, and can be easily fabricated into paper test strips for use in in situ samples. In addition, the probe is effective in detecting hydrazine in water, soil, cells, and zebrafish, providing an excellent tool for detecting hydrazine in the environment.
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Corantes Fluorescentes , Peixe-Zebra , Animais , Humanos , Corantes Fluorescentes/química , Hidrazinas/química , Fenotiazinas , Água , Solo , Espectrometria de FluorescênciaRESUMO
BACKGROUND: Motor neuron disease (MND) is a fatal neurodegenerative disorder that leads to progressive loss of motor neurons. Chlamydia psittaci (C. psittaci) is a rare etiology of community-acquired pneumonia characterized primarily by respiratory distress. We reported a case of C. psittaci pneumonia complicated with motor neuron disease (MND). CASE PRESENTATION: A 74-year-old male was referred to the Shaoxing Second Hospital at January, 2022 complaining of fever and fatigue for 2 days. The patient was diagnosed of MND with flail arm syndrome 1 year ago. The metagenomic next-generation sequencing (mNGS) of sputum obtained through bedside fiberoptic bronchoscopy showed C. psittaci infection. Then doxycycline was administrated and bedside fiberoptic bronchoscopy was performed to assist with sputum excretion. Computed Tomography (CT) and fiberoptic bronchoscopy revealed a significant decrease in sputum production. On day 24 after admission, the patient was discharged with slight dyspnea, limited exercise tolerance. One month later after discharge, the patient reported normal respiratory function, and chest CT showed significant absorption of sputum. CONCLUSIONS: The mNGS combined with bedside fiberoptic bronchoscopy could timely detect C. psittaci infection. Bedside fiberoptic bronchoscopy along with antibiotic therapy may be effective for C. psittaci treatment.
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Chlamydophila psittaci , Doença dos Neurônios Motores , Pneumonia , Psitacose , Masculino , Humanos , Idoso , Psitacose/complicações , Psitacose/diagnóstico , Psitacose/tratamento farmacológico , Brônquios , Doença dos Neurônios Motores/complicações , Doença dos Neurônios Motores/diagnóstico , DispneiaRESUMO
A new mixed anionic compound Cd2TeO3Cl2 with unprecedented [Cd2O6Cl4] octahedral dimers has been synthesized, and millimeter-scale single crystals of Cd2TeO3Cl2 have been grown by the vertical Bridgman method with CdCl2 as the flux. Cd2TeO3Cl2 crystallizes in the centrosymmetric P1Ì (no. 2) space group, and shows a mixed cationic layer structure constituted by distorted [TeO3] motifs, mixed anionic [Cd2O6Cl4] chains, and [Cd2O6Cl4] octahedral dimers. Experimental and theoretical results show that Cd2TeO3Cl2 is a direct band gap compound with an experimental band gap of â¼4.25 eV. Meanwhile, the compound has good optical transmittance in the 3-5 µm atmospheric window. The results indicate that Cd2TeO3Cl2 could be used as a promising mid-IR window material, and could enrich the chemical and structural diversity of oxides.
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Prevalence of carbapenem-resistant Klebsiella pneumoniae (CRKP) has compromised antimicrobial efficacy against severe infections worldwide. To monitor global spread, we conducted a comprehensive genomic epidemiologic study comparing sequences from 21 blaOXA-232-carrying CRKP isolates from China with K. pneumoniae sequence type (ST) 15 strains from 68 countries available in GenBank. Phylogenetic and phylogeographic analyses revealed all blaOXA-232-carrying CRKP isolates belonged to ST15 lineage and exhibited multidrug resistance. Analysis grouped 330 global blaOXA-232-carrying ST15 CRKP strains into 5 clades, indicating clonal transmission with small genetic distances among multiple strains. The lineage originated in the United States, then spread to Europe, Asia, Oceania, and Africa. Most recent common ancestor was traced back to 2000; mutations averaged ≈1.7 per year per genome. Our research helps identify key forces driving global spread of blaOXA-232-carrying CRKP ST15 lineage and emphasizes the importance of ongoing surveillance of epidemic CRKP.
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Enterobacteriáceas Resistentes a Carbapenêmicos , Infecções por Klebsiella , Humanos , Carbapenêmicos/farmacologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Klebsiella pneumoniae , Filogeografia , Plasmídeos , Filogenia , Genômica , Infecções por Klebsiella/epidemiologia , Infecções por Klebsiella/tratamento farmacológico , beta-Lactamases/genética , Testes de Sensibilidade MicrobianaRESUMO
INTRODUCTION AND OBJECTIVES: Dysphagia is common among older patients, affecting their nutritional status, hospital readmission, length of hospital stay, and hospitalization costs. Nurses can play a key role in early identification of dysphagia through systematic screening. This project sought to (i) achieve 80% compliance among nurses in using the 4-point questionnaire test (4QT) swallow screening test on patients and (ii) ensure all patients screening positive for dysphagia were referred to a speech therapist within 1 day. METHODS: A short swallow screening tool was adapted from an evidence-based screening tool, the 4QT, by a team of speech therapists, a geriatrician, and a geriatric trained nurse. Ward nurses were then trained on using the tool to screen older patients upon admission or transfer to another ward. The project used the JBI Evidence Implementation Framework, which involved pre and post audits and feedback to evaluate compliance with best practice. RESULTS: Compliance increased in the use of the short swallow screening tool, rising from 64% ( n â=â25) in the baseline audit to 71% ( n â=â34) in the follow-up audit. However, there was a decrease in the referral of patients who screened positive for dysphagia to speech therapists, with the rate dropping from 92% ( n â=â12) to 86% ( n â=â12). All patients ( n â=â12) from both baseline and follow-up audits were referred to a speech therapist within 1 day of admission/transfer post-implementation compared with 70% ( n â=â7) at pre-implementation. CONCLUSIONS: This project applied evidence-based recommendations to clinical practice and improved patient outcomes. The nurses facilitated timely referrals to speech therapists for further assessment and intervention, which was useful in the clinical context. The nurses continue to use the screening tool routinely to prevent dysphagia complications among geriatric patients.
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Transtornos de Deglutição , Humanos , Idoso , Transtornos de Deglutição/diagnóstico , Papel do Profissional de Enfermagem , Fala , Hospitalização , Encaminhamento e ConsultaRESUMO
Colistin is considered as one of the last-resort antimicrobial agents for treating multidrug-resistant bacterial infections. Multidrug-resistant E. asburiae has been increasingly isolated from clinical patients, which posed a great challenge for antibacterial treatment. This study aimed to report a mcr-10 and blaNDM-1 co-carrying E. asburiae clinical isolate 5549 conferred a high-level resistance against colistin. Antibiotic susceptibility testing was performed using the microdilution broth method. Transferability of mcr-10 and blaNDM-1-carrying plasmids were investigated by conjugation experiments. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was used to identify modifications in lipid A. Whole genome sequencing and phylogenetic analysis between strain 5549 and a total of 301 E. asburiae genomes retrieved from NCBI database were performed. The genetic characteristics of mcr-10 and blaNDM-1-bearing plasmids were also analyzed. Our study indicated that strain 5549 showed extensively antibiotic-resistant trait, including colistin and carbapenem resistance. The mcr-10 and blaNDM-1 were carried by IncFIB/IncFII type p5549_mcr-10 (159417 bp) and IncN type p5549_NDM-1 (63489 bp), respectively. Conjugation assays identified that only the blaNDM-1-carrying plasmid could be successfully transferred to E. coli J53. Interestingly, mcr-10 did not mediate colistin resistance when it was cloned into E. coli DH5α. Mass spectrometry analysis showed the lipid A palmitoylation of the C-lacyl-oxo-acyl chain to the chemical structure of lipid A at m/z 2063 in strain 5549. In summary, this study is the first to report a mcr-10 and blaNDM-1 co-occurrence E. asburiae recovered from China. Our investigation revealed the distribution of different clonal lineage of E. asburiae with epidemiology perspective and the underlying mechanisms of colistin resistance. Active surveillance is necessary to control the further dissemination of multidrug-resistant E. asburiae.
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The rapid global dissemination of Salmonella enterica sequence type 34 (ST34) has sparked significant concern due to its resistance to critical antimicrobials and its ability to spread across various sectors. In order to investigate the evolution and transmission dynamics of this epidemic clonal lineage, as well as the horizontal transfer of mcr-carrying plasmids within the One Health framework, we conducted a comprehensive genomic epidemiological study. This study focused on the 11 mcr-carrying S. enterica isolates obtained from clinical settings in China, while also considering 2337 publicly available genomes of mcr-carrying S. enterica collected from 20 countries and diverse sources spanning over a 22-year period. Among the mcr-positive Salmonella isolates, ST34 was found to be the predominant lineage, comprising 30.12 % (704/2337) of the total collection. These isolates were identified as either serovar Typhimurium or its monophasic variant, which were obtained from both clinical and non-clinical sources. Phylogeographic analyses traced the global spread of the mcr-carrying ST34 lineage, which was divided into three distinct clusters, with 83.10 % of them carrying mcr-1 or/and mcr-9 genes. Notably, the mcr-1 positive ST34 isolates were primarily found in China (190/298, 63.76 %), with only four from the United States. Conversely, mcr-9 positive ST34 isolates were predominantly identified in the United States (261/293, 89.08 %), while none were observed in China. The mcr-1 positive ST34 isolates was predicted to have originated from clinical sources in United Kingdom, whereas mcr-9 positive ST34 isolates was likely derived from environmental sources in Germany. The most recent common ancestor for mcr-1 and mcr-9 carrying ST34 S. enterica was estimated to have emerged around 1983 and 1951. These findings provided thorough and intuitive insights into the intercontinental spread of mcr-carrying S. enterica ST34 lineage in a One Health context. Ongoing surveillance is crucial for effectively monitoring the worldwide dissemination of this multidrug-resistant high-risk clone.
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Saúde Única , Salmonella enterica , Salmonella typhimurium/genética , Sorogrupo , Salmonella enterica/genética , Plasmídeos , Genômica , Antibacterianos/farmacologia , Testes de Sensibilidade MicrobianaRESUMO
BACKGROUND: l-Theanine (LTA) is a biologically active ingredient in tea that shows great potential for regulating lipid metabolism. Bile acids (BA), an important end-product of cholesterol catabolism, participate in the regulation of lipid metabolism and gut microbiota. Here, we investigated the effect of LTA on lipid metabolism and the mechanism by which it regulates BA metabolism and gut microbiota. Male BALB/c mice were treated with LTA for 28 days. RESULTS: Daily LTA doses of 100 and 300 mg kg-1 d-1 altered the gut microbiota in mice, predominantly by decreasing Lactobacillus, Streptococcus, Bacteroides, Clostridium and Enterorhabdus microbes associated with bile-salt hydrolase (BSH) activity, thereby decreasing the activity of BSH and increasing the levels of ileum conjugated BA (such as glycocholic acid (GCA) and lithocholic acid), thereby inhibiting the intestinal farnesoid X receptor (FXR)-fibroblast growth factor 15 (FGF15) signaling pathway. Inhibition of FXR-FGF15 signaling was accompanied by upregulation of cholesterol 7α-hydroxylase (CYP7A1) mRNA and protein expression and increased hepatic production of cholic acid, deoxycholic acid, GCA, glycine cholic acid and glycine ursodeoxycholic acid. Meanwhile, increasing hepatic unconjugated BA upregulated the mRNA and protein expression of liver 3-hydroxy-3-methylglutaryl-CoA reductase and downregulated the mRNA and protein expression of stearoyl-CoA desaturase-1, liver low-density lipoprotein receptor and type B scavenger receptor. Therefore, the serum levels of cholesterol and triglycerides decreased. CONCLUSION: Our findings indicate that LTA regulates lipid metabolism by modulating the gut microbiota and BA metabolism via the FXR-FGF15-CYP7A1 pathway. © 2022 Society of Chemical Industry.
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Microbioma Gastrointestinal , Metabolismo dos Lipídeos , Masculino , Camundongos , Animais , Ácidos e Sais Biliares/metabolismo , Fígado/metabolismo , Colesterol/metabolismo , RNA Mensageiro/metabolismo , Camundongos Endogâmicos C57BL , Colesterol 7-alfa-Hidroxilase/genética , Colesterol 7-alfa-Hidroxilase/metabolismoRESUMO
Ureaplasma spp. and Mycoplasma hominis, frequent colonizers in the lower urogenital tract, have been implicated in various infections, with antibiotic resistance growing and varying regionally. This study aims to investigate the prevalence and antibiotic resistance profiles of Ureaplasma spp. and M. hominis in outpatients in Hangzhou, China, from 2013 to 2019. A total of 135,263 outpatients were examined to determine the prevalence of Ureaplasma spp. and M. hominis, including 48,638 males and 86,625 females. Furthermore, trends in antibiotic susceptibility of Ureaplasma spp. and M. hominis during 1999-2019 were analyzed. The cultivation, identification, and antibiotic susceptibility of the bacteria (ofloxacin, ciprofloxacin, erythromycin, clarithromycin, azithromycin, josamycin, tetracycline, doxycycline, and pristinamycin) were determined using the Mycoplasma IST2 kit. Our study indicated that the overall prevalence of total Ureaplasma spp./M. hominis was 38.1% from 2013 to 2019. Ureaplasma spp. were the most frequently isolated species (overall prevalence, 31.3%), followed by Ureaplasma spp./M. hominis coinfection (6.0%) and single M. hominis infection (0.8%). The prevalence of Ureaplasma spp. and M. hominis was significantly higher in females than in males, and the highest positive rates of total Ureaplasma spp./M. hominis were observed in both female and male outpatients aged 14-20 years. During 2013-2019, josamycin, tetracycline, doxycycline, and pristinamycin maintained exceptionally high activity (overall resistance rates, <5%) against both Ureaplasma spp. and M. hominis, but ofloxacin and ciprofloxacin showed limited activity (overall resistance rates, >70%). During 1999-2019, the rates of resistance to ofloxacin and ciprofloxacin increased against both Ureaplasma spp. and M. hominis but decreased to erythromycin, clarithromycin, azithromycin, tetracycline, and doxycycline against Ureaplasma spp. In conclusion, our study demonstrates a high prevalence of Ureaplasma spp. compared to M. hominis and Ureaplasma spp./M. hominis, and their distribution was associated with sex and age. Josamycin, doxycycline, and tetracycline are promising antibiotics that have remarkable activity against Ureaplasma species and M. hominis.
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The improper use of phosgene, either as a chemical warfare agent or a leak during chemical production, causes significant risks to human life and property. Therefore, it is particularly important to develop a rapid and highly selective method for the detection of phosgene. In this article, a highly selective fluorescent sensor ONB with a BODIPY unit as a fluorophore and o-aminophenol as a reactive site was constructed for the selective and rapid detection of phosgene in solution. The ONB-containing nanofibers were sprayed onto a non-woven fabric by electrostatic spinning and cut into test films, which can be used well for the detection of gaseous phosgene. While, there were no reported bio-imaging applications for phosgene detection. In this work, nasal mucosa and lung samples from the mice exposed to gaseous phosgene after dropping the ONB solution through the nasal cavity achieved bio-imaging applications successfully.
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Substâncias para a Guerra Química , Fosgênio , Animais , Compostos de Boro , Substâncias para a Guerra Química/toxicidade , Gases/química , Pulmão , Camundongos , Mucosa Nasal , Fosgênio/química , Fosgênio/toxicidadeRESUMO
The in vitro activity of two new fluoroquinolones, delafloxacin and finafloxacin, were evaluated against M. hominis and Ureaplasma spp. The MICs of delafloxacin, finafloxacin, and two classical fluoroquinolones (moxifloxacin and levofloxacin) were tested against 29 M. hominis and 67 Ureaplasma spp. isolates using the broth microdilution method. The molecular mechanisms underlying fluoroquinolone resistance were also investigated. Delafloxacin exhibited low MICs against M. hominis and Ureaplasma spp., including the levofloxacin-resistant isolates. For M. hominis, delafloxacin showed low MIC90 value of 1 µg/mL (MIC range, <0.031 -1 µg/mL) compared to 8 µg/mL for finafloxacin, 16 µg/mL for moxifloxacin, and 32 µg/mL for levofloxacin. For U. parvum and U. urealyticum, delafloxacin had low MIC90 values (U. parvum, 2 µg/mL; U. urealyticum, 4 µg/mL) compared to 16 -32 µg/mL for finafloxacin, 16 µg/mL for moxifloxacin, and 32 - >32 µg/mL for levofloxacin. The two mutations GyrA S153L and ParC S91I were commonly identified in fluoroquinolone-resistant M. hominis, and ParC S83L was the most frequent mutation identified in fluoroquinolone-resistant Ureaplasma spp. Delafloxacin displayed lower MICs against fluoroquinolone-resistant isolates of both M. hominis and Ureaplasma spp. that have mutations in the quinolone resistance determining regions (QRDRs) than the two classical fluoroquinolones. Delafloxacin is a promising fluoroquinolone with low MICs against fluoroquinolone-resistant M. hominis and Ureaplasma spp. Our study confirms the potential clinical use of delafloxacin in treating antimicrobial-resistant M. hominis and Ureaplasma spp. infections. IMPORTANCE Fluoroquinolone resistance in Mycoplasma hominis and Ureaplasma spp. is on the rise globally, which has compromised the efficacy of the currently available antimicrobial agents. This study evaluated the antimicrobial activity of two new fluoroquinolones, delafloxacin and finafloxacin, for the first time, against M. hominis and Ureaplasma spp. clinical isolates. Delafloxacin and finafloxacin displayed different antimicrobial susceptibility profiles against M. hominis and Ureaplasma spp. in vitro. Delafloxacin was found to be more effective against M. hominis and Ureaplasma spp. than three classical fluoroquinolones (finafloxacin, moxifloxacin, and levofloxacin). Finafloxacin displayed activity similar to moxifloxacin but superior to levofloxacin against M. hominis and Ureaplasma spp. Our findings demonstrate that delafloxacin is a promising fluoroquinolone with outstanding activity against fluoroquinolone-resistant M. hominis and Ureaplasma spp.
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Mycoplasma hominis , Infecções por Ureaplasma , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Fluoroquinolonas/farmacologia , Humanos , Levofloxacino/farmacologia , Levofloxacino/uso terapêutico , Testes de Sensibilidade Microbiana , Moxifloxacina/farmacologia , Moxifloxacina/uso terapêutico , Ureaplasma , Infecções por Ureaplasma/tratamento farmacológicoRESUMO
OBJECTIVES: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is increasingly reported worldwide and has posed a serious challenge for public health. Here we report the complete genome sequence of a multidrug-resistant (MDR) K. pneumoniae carrying one blaNDM-1 and two copies of blaKPC-2 genes isolated from a cerebrospinal fluid specimen in China. METHODS: The minimal inhibitory concentrations (MICs) of 26 antimicrobial agents against K. pneumoniae strain KP46 were measured. The complete genome sequence of KP46 was determined using Illumina and Nanopore platforms. The derived short and long reads were assembled using Unicycler. Multilocus sequence typing (MLST), antimicrobial resistance genes, virulence genes, and plasmid replicons were predicted in silico using the BacWGSTdb server. The phylogenetic relationship between KP46 and 454 ST15 K. pneumoniae strains obtained from NCBI GenBank database was analysed based on a core genome MLST (cgMLST) strategy. RESULTS: K. pneumoniae strain KP46 was resistant to all antimicrobial agents tested, except for tigecycline, colistin, cefiderocol, and fosfomycin. The genome sequence of KP46 belonged to sequence type 15 (ST15), which contained seven circularized contigs comprising 5 674 521 bp, including one chromosome and six plasmids. Serval antimicrobial resistance genes were identified, including a blaNDM-1 gene located in a 53 096 bp IncX3 plasmid, and two copies of blaKPC-2 gene located both in a 103 807 bp IncX6 and an 88 164 bp IncFII plasmid, respectively. The most closely related strain was another ST15 strain also isolated from China with five cgMLST loci differences. CONCLUSION: We reported the first complete genome sequence of a K. pneumoniae ST15 clinical isolate coharbouring blaNDM-1 and two copies of blaKPC-2 in China. This study will provide insight into the antimicrobial resistance mechanisms and phylogeny of carbapenem-resistant ST15 K. pneumoniae.
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Infecções por Klebsiella , Klebsiella pneumoniae , Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Farmacorresistência Bacteriana Múltipla , Humanos , Infecções por Klebsiella/líquido cefalorraquidiano , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/genética , Tipagem de Sequências Multilocus , Filogenia , beta-LactamasesRESUMO
Pseudorabies virus (PRV) infection could cause severe histopathological damage via releasing multiple factors, including cytokines, peptides, etc. Here, peptidomic results showed that 129 peptides were identified in PRV-infected mouse lungs and were highly involved in the process of PRV infection. The role of one down-regulated biological peptide (designated as AGDP) during PRV infection was investigated. To verify the expression profiles of AGDP in response to PRV infection, the expression level of the precursor protein of AGDP mRNA was significantly decreased in PRV-infected mouse lungs and cells. The synthesized AGDP-treating cells were less susceptible to PRV challenges than the controls, as demonstrated by the decreased virus production and gE expression. AGDP not only inhibited the expression of TNF-α and IL-8 but also appeared to suppress the extracellular release of high-mobility group box 1 (HMGB1) by inhibiting the output of nuclear HMGB1 in cells. AGDP could also inhibit the degradation of IκBα and the phosphorylation levels of P65 after PRV infection. In total, our results revealed many meaningful peptides involved in PRV infection, thereby enhancing the current understanding of the host response to PRV infection, and how AGDP may serve as a promising candidate for developing novel anti-PRV drugs.
Assuntos
Proteína HMGB1 , Herpesvirus Suídeo 1 , Pseudorraiva , Animais , Citocinas , Pulmão/patologia , Camundongos , Pseudorraiva/tratamento farmacológicoRESUMO
The presence and dissemination of carbapenem-resistant Klebsiella pneumoniae (CRKP) often cause life-threatening infections worldwide, but the therapeutic option is limited. In this study, whole-genome sequencing (WGS) was applied to assess the epidemiological characteristics and transmission dynamics of CRKP isolates recovered from two fetal outbreaks of nosocomial infections. Between April 2016 and March 2018, a total of 70 isolates of K. pneumoniae were collected from sterile samples in a tertiary hospital in Hangzhou, China. The minimal inhibitory concentrations (MICs) of 21 antimicrobial agents were determined using the broth microdilution methods. Pulsed-field gel electrophoresis (PFGE) was performed on 47 CRKP isolates, and 16 clonally related isolates were further characterized by Illumina sequencing. In addition, the complete genome sequences of three representative isolates (KP12, KP36, and KP37) were determined by Oxford Nanopore sequencing. The K. pneumoniae isolates were recovered from patients diagnosed with pulmonary infection, cancer, or encephalopathy. For all CRKP isolates, PFGE separated three clusters among all strains. The most predominant PFGE cluster contained 16 isolates collected from patients who shared close hospital units and represented a potential outbreak. All 16 isolates showed an extremely high resistance level (≥87.5%) to 18 antimicrobials tested but remain susceptible to colistin (CST). Multiple antimicrobial resistance and virulence determinants, such as the carbapenem resistance gene bla KPC-2, and genes encoding the virulence factor aerobactin and the regulator of the mucoid phenotype (rmpA and rmpA2), were observed in the 16 CRKP isolates. These isolates belonged to sequence type 11 (ST11) and capsular serotype KL64. A core genome single nucleotide polymorphism (cgSNP)-based phylogenetic analysis indicated that the 16 CRKP isolates could be partitioned into two separate clades (≤15 SNPs), suggesting the two independent transmission scenarios co-occurred. Moreover, a high prevalence of IncFIB/IncHI1B type virulence plasmid with the iroBCDN locus deleted, and an IncFII/IncR type bla KPC-2-bearing plasmid was co-harbored in ST11-KL64 CRKP isolates. In conclusion, our data indicated that the nosocomial dissemination of ST11-KL64 CRKP clone is a potential threat to anti-infective therapy. The development of novel strategies for surveillance, diagnosis, and treatment of this high-risk CRKP clone is urgently needed.