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Carbapenem-resistant and hypervirulent K. pneumoniae (CR-HvKP) strains that have emerged recently have caused infections of extremely high mortality in various countries. In this study, we discovered a conjugative plasmid that encodes carbapenem resistance and hypervirulence in a clinical ST86 K2 CR-HvKP, namely 17ZR-91. The conjugative plasmid (p17ZR-91-Vir-KPC) was formed by fusion of a non-conjugative pLVPK-like plasmid and a conjugative blaKPC-2-bearing plasmid and is present dynamically with two other non-fusion plasmids. Conjugation of p17ZR-91-Vir-KPC to other K. pneumoniae enabled them to rapidly express the carbapenem resistance and hypervirulence phenotypes. More importantly, genome analysis provided direct evidence that p17ZR-91-Vir-KPC could be directly transmitted from K2 CR-HvKP strain, 17ZR-91, to ST11 clinical K. pneumoniae strains to convert them into ST11 CR-HvKP strains, which explains the evolutionary mechanisms of recently emerged ST11 CR-HvKP strains., Carbapenem-resistant and hypervirulent Klebsiella pneumoniae strains are emerging. Here Xie et al. show that these phenotypes are carried on a plasmid formed from the fusion of a virulence plasmid with a conjugative plasmid.

Colistin is recognized as a last-resort treatment option against multi-drug resistant bacteria including carbapenem-resistant Enterobacteriaceae (CRE). However, the plasmid-mediated colistin-resistance gene mcr-1 has been reported globally resulting in an increase of colistin-resistant bacteria. A quick and accurate method for determining the pathogen resistance of colistin is therefore crucial in the clinic. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is a potential tool forto be applied for antimicrobial susceptibility testing. We compared the growth of Escherichia coli strains in the presence or absence of colistin. Automated analyses of the spectra were performed with a prototype software tool written with package R. Three mcr-1-positive and six mcr-1-negative E. coli were used for establishing the model to obtain the optimal incubation time, the breakpoint concentration of colistin and cut-off of the relative growth (RG) value. The distinction between susceptible and resistant strains was already noticeable after 2 h of incubation. The best separation between the susceptible and resistant strains was achieved at a concentration of 4 µg ml-1 and a relative growth cut-off value of 0.6. Application of the model for the analysis of 128 E. coli isolates, a sensitivity of 97.4% and a specificity of 88.2% were achieved compared with colistin MIC results. The rapid MALDI-TOF MS-based method approach is simple to set-up, uses a short incubation time, and had excellent outcomes with respect to sensitivity and specificity for colistin sensitivity testing in Escherichia coli.

A rectal swab sample was collected from a patient with Guillain–Barré syndrome and enriched in lysogeny broth. Carbapenem-resistant bacteria were selected by China Blue agar plates containing 0.3 μg/ml meropenem. Carbapenemase-producing Klebsiella michiganensis was identified and characterized by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF), immune colloidal gold technique, a conjugation experiment, PCR analysis, and antimicrobial susceptibility testing. The genome of K. michiganensis was determined by whole genome sequencing. Antimicrobial susceptibility testing showed that the K. michiganensis was resistant to imipenem, meropenem, ertapenem, cefmetazole, ceftazidime, cefotaxime, piperacillin/tazobactam, sulbactam/cefoperazone, ceftazidime/avibactam, cefepime, and aztreonam while susceptible to polymyxin B, ciprofloxacin, tigecycline, and amikacin. Immune colloidal gold technique suggested that this strain co-produced three different carbapenemases [Klebsiella pneumoniae carbapenemase (KPC), New Delhi metallo-beta-lactamase (NDM), and Imipenem (IMP)]. Whole genome sequencing analysis indicated that this strain belonged to ST91, and blaKPC–2, blaNDM–1, and blaIMP–4 were carried on different conjugative plasmids. Besides, the co-existence and transferability of blaKPC–2, blaNDM–1, and blaIMP–4 in K. michiganensis facilitates the potential horizontal dissemination and nosocomial spread of resistance genes among multidrug-resistant organisms.

The acquisition of resistance to one antibiotic sometimes leads to collateral sensitivity to a second antibiotic. Here, we show that vancomycin resistance in Enterococcus faecium is associated with a remarkable increase in susceptibility to pleuromutilin antibiotics (such as lefamulin), which target the bacterial ribosome. The trade-off between vancomycin and pleuromutilins is mediated by epistasis between the van gene cluster and msrC, encoding an ABC-F protein that protects bacterial ribosomes from antibiotic targeting. In mouse models of vancomycin-resistant E. faecium colonization and septicemia, pleuromutilin treatment reduces colonization and improves survival more effectively than standard therapy (linezolid). Our findings suggest that pleuromutilins may be useful for the treatment of vancomycin-resistant E. faecium infections.

Background: Carbapenem-resistant K. pneumoniae (CRKP) is the leading cause of hospital infections. The prevalence of CRKP in human and the risk factors that predispose occurrence of CRKP infections need to be determined. Methods: We conducted a retrospective, cross-sectional study of K. pneumoniae strains collected in a hospital in Zhejiang Province, China, from Jan 2014 to Dec 2017. The strains were characterized by antimicrobial susceptibility tests and whole genome sequencing. Then we investigated risk factors of CRKP infections and depicted the likely disease outcomes. Findings: 804 patients tested positive for intestinal CRKP or carbapenem susceptible strains (CSKP) in total. Ninety-seven patients were positive for both intestinal and extra-intestinal CRKP and had significantly (P

A heterogeneous nanocomposite (NC) of g-C 3 N 4 /W 18 O 49 based on the coupling of W 18 O 49 nanorods (NRs) with the graphitic carbon nitride (g-C 3 N 4 ) sheets has been synthesised via a solvothermal method. The as-synthesised products were characterised by X-ray diffraction, X-ray photoelectron spectrometry, and transmission electron microscopy. The g-C 3 N 4 /W 18 O 49 NC exhibited very strong adsorption ability towards the methylene blue (MB) dye and demonstrated a high removal efficiency of 99.14% after 0.5 h equilibration in dark. Compared to the g-C 3 N 4 sheets and W 18 O 49 NRs, the g-C 3 N 4 /W 18 O 49 NC exhibited higher removal efficiencies towards both the MB and methyl orange (MO) dyes via a combination of adsorption and degradation. The photocatalytic process of the g-C 3 N 4 /W 18 O 49 NC followed the Z-scheme photocatalytic mechanism. This work provides an efficient strategy for the synthesis of g-C 3 N 4 -based heterogeneous photocatalysts.

Summary Background Hypervirulent Klebsiella pneumoniae strains often cause life-threatening community-acquired infections in young and healthy hosts, but are usually sensitive to antibiotics. In this study, we investigated a fatal outbreak of ventilator-associated pneumonia caused by a new emerging hypervirulent K pneumoniae strain. Methods The outbreak occurred in the integrated intensive care unit of a new branch of the Second Affiliated Hospital of Zhejiang University (Hangzhou, China). We collected 21 carbapenem-resistant K pneumoniae strains from five patients and characterised these strains for their antimicrobial susceptibility, multilocus sequence types, and genetic relatedness using VITEK-2 compact system, multilocus sequence typing, and whole genome sequencing. We selected one representative isolate from each patient to establish the virulence potential using a human neutrophil assay and Galleria mellonella model and to establish the genetic basis of their hypervirulence phenotype. Findings All five patients had undergone surgery for multiple trauma and subsequently received mechanical ventilation. The patients were aged 53–73 years and were admitted to the intensive care unit between late February and April, 2016. They all had severe pneumonia, carbapenem-resistant K pneumoniae infections, and poor responses to antibiotic treatment and died due to severe lung infection, multiorgan failure, or septic shock. All five representative carbapenem-resistant K pneumoniae strains belonged to the ST11 type, which is the most prevalent carbapenem-resistant K pneumoniae type in China, and originated from the same clone. The strains were positive on the string test, had survival of about 80% after 1 h incubation in human neutrophils, and killed 100% of wax moth larvae ( G mellonella ) inoculated with 1 × 10 6 colony-forming units of the specimens within 24 h, suggesting that they were hypervirulent K pneumoniae . Genomic analyses showed that the emergence of these ST11 carbapenem-resistant hypervirulent K pneumoniae strains was due to the acquisition of a roughly 170 kbp pLVPK-like virulence plasmid by classic ST11 carbapenem-resistant K pneumoniae strains. We also detected these strains in specimens collected in other regions of China. Interpretation The ST11 carbapenem-resistant hypervirulent K pneumoniae strains pose a substantial threat to human health because they are simultaneously hypervirulent, multidrug resistant, and highly transmissible. Control measures should be implemented to prevent further dissemination of such organisms in the hospital setting and the community. Funding Chinese National Key Basic Research and Development Program and Collaborative Research Fund of Hong Kong Research Grant Council.

Rare-earth-doped WO 2.72 microspheres (RE-WO 2.72 MSs) have been successfully synthesized by using a facile solvothermal route with tungsten salt as precursor, RE (RE=Ce, La, and Y) metal salts as dopants, and ethanol as solvent. Results of X-ray diffraction (XRD), X-ray photoelectron spectrometry (XPS), and energy dispersive spectroscopy (EDS) showed that the solvothermal process allowed for the homogeneous doping of WO 2.72 while maintaining the original crystal structure. The RE doping could effectively engineer the bandgap of WO 2.72 , which could not only enhance the light-harvesting ability but also deduce up-shift of both the conduction band and valence band. Compared to the undoped WO 2.72 nanorods (NRs), the RE-WO 2.72 MSs exhibited highly enhanced photocatalytic properties for the degradation of methylene blue (MB) under full spectrum light irradiation. This work provides a versatile strategy for the synthesis of RE-doped tungsten oxides and can be extended to the doping of other oxide semiconductors.

In this study, a CRISPR/Cas9-mediated genome editing method was used to study the functions of the mgrB , tetA , and ramR genes in mediating colistin and tigecycline resistance in carbapenem-resistant Klebsiella pneumoniae (CRKP). Inactivation of the tetA or ramR gene or the mgrB gene by CRISPR/Cas9 affected bacterial susceptibility to tigecycline or colistin, respectively.

Gastrointestinal carriage is regarded as a major reservoir of K. pneumoniae infections, especially in intensive care patients. A total of 101 (95.3%) KPC-producing carbapenem-resistant K. pneumoniae (CRKP) isolates were identified among 106 CRKP isolates collected from stool samples of inpatients performing active rectal screening for carbapenem-resistant Enterobacteriaceae during hospitalization in the ICUs of a tertiary hospital between 2016 and 2017. Among them, six KPC-producing CRKP isolates from three patients (two isolates for each patient) were identified with distinct antibacterial susceptibility. Our findings showed that: (1) blaKPC–2 gene is predominant in CRKP strains isolated from the intensive care patients and can be incorporated into various plasmids that are transmissible among multiple bacterial hosts in the human gastrointestinal tract; (2) the human gastrointestinal tract has a capacity to dynamically colonize multiple clones of CRKP strains with varied plasmids, diverse antimicrobial resistance genes and virulence genes. K. pneumoniae colonization is an important step in progression to extraintestinal infection, which provides the rationale for establishing intervention measures to prevent subsequent infection. Thus, close surveillance on CRKP colonization, together with effective infection prevention and control measures, should be put into practice.

A novel hybrid nanocomposite composed of AgCl nanoparticles and W 18 O 49 nanorods was fabricated through a facile, clean, efficient deposition route. The AgCl–W 18 O 49 nanocomposite has been found to exhibit excellent antibacterial activity, which may arise from the high-density loading of the AgCl nanoparticles on the W 18 O 49 nanorods and the strongly-coupled interaction between the two components. Under light irradiation, partially photoreduction of the AgCl nanoparticles could convert the AgCl–W 18 O 49 nanocomposite to the plasmonic Ag–AgCl–W 18 O 49 nanophotocatalyst with enhanced antibacterial activity. The AgCl–W 18 O 49 nanocomposite is promising candidate for potential application in the field of marine antifouling coatings.

In this work, we successfully synthesized the silver-reduced graphene oxide (Ag-rGO) composites based on the in situ growth of Ag nanoparticles (NPs) on the surfaces of the GO sheets through a one-pot solvothermal method without using any surfactants or modifiers. The as-synthesized Ag-rGO composites have been characterized by X-ray diffraction, X-ray photoelectron spectrometry and electron microscopy. Results showed that high-density Ag NPs and dots with uniform size distribution were grown on the surfaces of the GO sheets, accompanied by the reduction of GO to rGO. By simply changing the concentration of Ag + ions in the solvothermal reaction system, the size and distribution of the Ag nanocrystals could be controlled. The antibacterial properties of the Ag-rGO composites were investigated by combined techniques of inhibition zone method, plate colony-counting method and bacterial growth curve. The Ag-rGO composites have been found to exhibit excellent antibacterial properties with long-term effects, which could effectively inhibit the growth of bacteria of Vibrio natriegens and Bacillus sp. 1NLA3E . The strongly-coupled interaction between the Ag nanocrystals and the rGO supports as well as the presence of the Ag dots contributed equally to the prominent long-term antibacterial performance of the Ag-rGO composites. The present Ag-rGO composites may find important environmental applications.

A series of ZnO-based heterogeneous photocatalysts, including Ag-ZnO, ZnO- and Ag-ZnO-reduced graphene oxide (rGO) nanocomposites, was successfully synthesized by a one-pot solvothermal route. The as-synthesized products were systematically characterized using combined techniques of X-ray diffraction, X-ray photoelectron spectrometry, electron microscopy, and energy dispersive spectrometry. The resulting ZnO-based photocatalysts exhibited selective photocatalytic behavior towards the degradation of different organic dyes under solar light irradiation. Compared with plain ZnO nanoparticles, the heterogeneous nanocomposite photocatalysts of Ag-ZnO, ZnO- and Ag-ZnO-rGO showed significantly improved photocatalytic activities. The Ag-ZnO nanocomposite exhibited the highest photocatalytic efficiency, which can be ascribed to its core-shell structure with strong interfacial coupling between the Ag shell and the ZnO core as well as the surface plasmon resonance effect of the Ag. The ZnO- and Ag-ZnO-rGO nanocomposites displayed excellent recyclability, due to the strongly coupled interactions between the ZnO or Ag nanoparticles and the rGO support. The ZnO-rGO nanocomposite is the most promising candidate for photocatalysis application with excellent comprehensive performance. This study will not only provide guidance for the selection of ZnO-based heterogeneous photocatalysts, but also open new opportunities for the synthesis of other heterogeneous photocatalysts. Keywords: ZnO, Photocatalyst, Heterogeneous, Solvothermal, Reduced graphene oxide

Summary Background Until now, polymyxin resistance has involved chromosomal mutations but has never been reported via horizontal gene transfer. During a routine surveillance project on antimicrobial resistance in commensal Escherichia coli from food animals in China, a major increase of colistin resistance was observed. When an E coli strain, SHP45, possessing colistin resistance that could be transferred to another strain, was isolated from a pig, we conducted further analysis of possible plasmid-mediated polymyxin resistance. Herein, we report the emergence of the first plasmid-mediated polymyxin resistance mechanism, MCR-1, in Enterobacteriaceae. Methods The mcr-1 gene in E coli strain SHP45 was identified by whole plasmid sequencing and subcloning. MCR-1 mechanistic studies were done with sequence comparisons, homology modelling, and electrospray ionisation mass spectrometry. The prevalence of mcr-1 was investigated in E coli and Klebsiella pneumoniae strains collected from five provinces between April, 2011, and November, 2014. The ability of MCR-1 to confer polymyxin resistance in vivo was examined in a murine thigh model. Findings Polymyxin resistance was shown to be singularly due to the plasmid-mediated mcr-1 gene. The plasmid carrying mcr-1 was mobilised to an E coli recipient at a frequency of 10 −1 to 10 −3 cells per recipient cell by conjugation, and maintained in K pneumoniae and Pseudomonas aeruginosa . In an in-vivo model, production of MCR-1 negated the efficacy of colistin. MCR-1 is a member of the phosphoethanolamine transferase enzyme family, with expression in E coli resulting in the addition of phosphoethanolamine to lipid A. We observed mcr-1 carriage in E coli isolates collected from 78 (15%) of 523 samples of raw meat and 166 (21%) of 804 animals during 2011–14, and 16 (1%) of 1322 samples from inpatients with infection. Interpretation The emergence of MCR-1 heralds the breach of the last group of antibiotics, polymyxins, by plasmid-mediated resistance. Although currently confined to China, MCR-1 is likely to emulate other global resistance mechanisms such as NDM-1. Our findings emphasise the urgent need for coordinated global action in the fight against pan-drug-resistant Gram-negative bacteria. Funding Ministry of Science and Technology of China, National Natural Science Foundation of China.

The rapid dissemination of non-conjugative virulence plasmids among non-K1/K2 types of Klebsiella pneumoniae poses an unprecedented threat to human health, yet the underlying mechanisms governing dissemination of such plasmids is unclear. In this study, a novel 68 581 bp IncFIA plasmid is discovered that can be fused to a hypervirulence-encoding plasmid to form a hybrid conjugative virulence plasmid in conjugation experiments; such fusion events involve homologous recombination between a 241 bp homologous region located in each of the two plasmids. The fusion hypervirulence-encoding plasmid can be conjugated to both classic and blaKPC-2 -bearing carbapenem-resistant K. pneumoniae strains through conjugation, enabling such strains to acquire the ability to express the hypervirulence phenotype. Dissemination of this fusion virulence plasmid will impose an enormous burden on current efforts to control and treat infections caused by multidrug resistant and hypervirulent K. pneumoniae.

Gastrointestinal carriage is regarded as a major reservoir of K. pneumoniae infections, especially in intensive care patients. A total of 101 (95.3%) KPC-producing carbapenem-resistant K. pneumoniae (CRKP) isolates were identified among 106 CRKP isolates collected from stool samples of inpatients performing active rectal screening for carbapenem-resistant Enterobacteriaceae during hospitalization in the ICUs of a tertiary hospital between 2016 and 2017. Among them, six KPC-producing CRKP isolates from three patients (two isolates for each patient) were identified with distinct antibacterial susceptibility. Our findings showed that: (1) blaKPC–2 gene is predominant in CRKP strains isolated from the intensive care patients and can be incorporated into various plasmids that are transmissible among multiple bacterial hosts in the human gastrointestinal tract; (2) the human gastrointestinal tract has a capacity to dynamically colonize multiple clones of CRKP strains with varied plasmids, diverse antimicrobial resistance genes and virulence genes. K. pneumoniae colonization is an important step in progression to extraintestinal infection, which provides the rationale for establishing intervention measures to prevent subsequent infection. Thus, close surveillance on CRKP colonization, together with effective infection prevention and control measures, should be put into practice.

A rapid, sensitive, and accurate Vitek MS assay was developed to distinguish clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) from clinical isolates of methicillin-sensitive Staphylococcus aureus (MSSA) by developing an in-house knowledgebase of SuperSpectra. Three unique peaks, including peaks at 2305.6 and 3007.3 Da specific to MRSA, and 6816.7 Da specific to MSSA, were selected for differentiating MRSA and MSSA. This assay accurately identified 84 and 91% of clinical MRSA and MSSA strains out of the total 142 clinically acquired S. aureus strains that were tested. This method will greatly improve the efficiency of single clinical sample identification of MRSA, thereby facilitating a reduction in the transmission of MRSA in clinical settings.

Well-exfoliated graphene oxide sheets were initially fabricated through a modified pressurized oxidation method with powdered flake graphite as raw material. A variety of inorganic-reduced graphene oxide composites have been then successfully synthesized through a general solvothermal strategy with the graphene oxide sheets as supports, ethanol as solvent, and metal salts as precursors. After the solvothermal reactions, Ni(OH)2 nanoparticles, Fe2O3 nanorods, W18O49 nanowires, ZnO nanoparticles, and Ag nanoparticles were in situ grown on the surfaces of the graphene oxide sheets, accompanied by effective reduction of graphene oxide to reduced graphene oxide. The as-prepared products have been systematically characterized by electron microscopy, X-ray diffraction, X-ray photoelectron spectrometry, and Raman spectroscopy. The present work opens up a versatile route for preparing the reduced graphene oxide-based composites.

We report the emergence of five carbapenem-resistant K1 hypervirulent Klebsiella pneumoniae (hvKP) strains which caused fatal infections in hospital patients in Zhejiang Province, China, upon entry through surgical wounds. Genotyping results revealed the existence of three genetically related strains which exhibited a new sequence type, ST1797, and revealed that all strains harbored the magA and wcaG virulence genes and a plasmid-borne bla KPC-2 gene. These findings indicate that K1 hvKP is simultaneously hypervirulent, multidrug resistant, and transmissible.

We report the genetic and functional characterization of a novel CTX-M-199 β-lactamase, which was encoded by a bla CTX-M-64 variant gene found in a conjugative mcr-1 -bearing IncI2 plasmid and exhibited resistance to β-lactamase inhibitors, tazobactam, and sulbactam.

We report the genetic and functional characterization of a novel CTX-M-199 β-lactamase, which was encoded by a blaCTX-M-64 variant gene found in a conjugative mcr-1-bearing IncI2 plasmid and exhibited resistance to β-lactamase inhibitors, tazobactam, and sulbactam.

A novel sandwich-like MnO

One hundred and thirty-six bla OXA-51-negative strains were identified from 1,067 Acinetobacter calcoaceticus-A. baumannii complex (ACB complex) isolates, which were collected during October 2010 to March 2013 from 15 general hospitals in 10 cities throughout Zhejiang Province, China. Seven of the 136 bla OXA-51-negative ACB complex isolates were New Delhi metallo-β-lactamase-1 (NDM-1)-positive, among which three were identified as A. nosocomialis and four were identified as A. pittii strains using 16S-23S rRNA gene intergenic spacer (ITS) sequencing and partial RNA polymerase β-subunit (rpoB) sequencing. Pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) analysis showed that the seven NDM-positive isolates belonged to three clonal strains with three novel sequence types (STs). Polymerase chain reaction (PCR) assays and DNA sequence analysis of the carbapenemase and other β-lactamase genes indicated that all the isolates harbored the bla NDM-1 gene, and that only one strain of A. nosocomialis isolates harbored both bla NDM-1 and bla OXA-23. All of them were positive for bla ADC, from which three novel bla ADC genes (designated as bla ADC-69, bla ADC-70, and bla ADC-71) were detected for the first time. The presence of ISAba125 upstream of bla NDM-1 was identified through genetic environment analysis. Carbapenem resistance can be transferred from A. nosocomialis and A. pittii to Escherichia coli EC600 by the conjugation experiment. Plasmid analysis, DNA hybridization, and extraction experiments indicated that bla NDM-1 was located on a plasmid of approximately 50 kb. In conclusion, we characterized the dissemination of NDM-1-positive A. pittii strains in Zhejiang Province, China, and reported the NDM-producing A. nosocomialis for the first time.

In recent years, antimicrobial resistance has increasingly been recognized as a significant problem that transcends international boundaries. With the global increase in the prevalence of carbapenem-resistant Enterobacteriaceae, polymyxins have been resurrected as a last-resort treatment option ([1

The origin of pathogenic Enteroaggregative Escherichia coli (EAEC), a major causative agent of childhood diarrhea worldwide, remains ill-defined. The objective of this study was to determine the relative prevalence of EAEC in clinical and non-clinical sources and compare their genetic characteristics in order to identify strains that rarely and commonly cause human diarrhea. The virulence gene astA was commonly detectable in both clinical and non-clinical EAEC, while clinical isolates, but not the non-clinical strains, were consistently found to harbor other virulence factors such as aap (32%), aatA (18%) and aggR (11%). MLST analysis revealed the extremely high diversity of EAEC ST types, which can be grouped into three categories including: (i) non-clinical EAEC that rarely cause human infections; (ii) virulent strains recoverable in diarrhea patients that are also commonly found in the non-clinical sources; (iii) organisms causing human infections but rarely recoverable in the non-clinical setting. In addition, the high resistance in these EAEC isolates in particular resistance to fluoroquinolones and cephalosporins raised a huge concern for clinical EAEC infection control. The data from this study suggests that EAEC strains were diversely distributed in non-clinical and clinical setting and some of the clinical isolates may originate from the non-clinical setting.

The enhanced permeability and retention (EPR) effect of tumors is much more complex than initially defined, and it alone is not sufficient for targeted delivery of nanosized agents. Meanwhile, poor tumor penetration is another major challenge for the treatment of solid tumors using nanoparticles. Development of delivery systems for SN38, the active metabolite of CPT-11 in human and a very potent anticancer molecule, has become an attractive research area. PEGx -p(HEMASN38)y (x and y are viable), a prodrug synthesized by using polyethylene glycol (PEG) as initiator and SN38 as monomer through atom transfer radical polymeration (ATRP) method, is previously reported. Using PEG2.4K -p(HEMASN38)3K as a model prodrug, herein an active-targeted strategy decorated with cys-arg-gly-asp-lys (CRGDK), a peptide specifically binds to neuropilin-1 overexpressed by tumor vessels and tumor cells, is successfully established to further improve the delivery and efficacy of SN38. CRGDK-functionalized PEG2.4K -p(HEMASN38)3K (C-SN38) nanoparticles and nonfunctionalized control (B-SN38) are prepared with two distinct sizes, 30 and 100 nm. Their physiochemical and biological characteristics are investigated in vitro and in vivo with multiple tumor models. It is demonstrated for the first time that CRGDK functionalization can be a promising strategy for efficient delivery of SN38, and C-SN38 is a potent drug candidate for the treatment of neuropilin-1 overexpressing tumors.

Hypervirulent strains of Klebsiella pneumoniae (hvKP) are genetic variants of Klebsiella pneumoniae which can cause life-threatening community-acquired infection in healthy individuals. Currently, methods for efficient differentiation between classic K. pneumoniae (cKP) and hvKP strains are not available, often causing delay in diagnosis and treatment of hvKP infections. To address this issue, we devised a Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) approach for rapid identification of K1 hvKP strains. Four standard algorithms, genetic algorithm (GA), support vector machine (SVM), supervised neural network (SNN), and quick classifier (QC), were tested for their power to differentiate between K1 and non-K1 strains, among which SVM was the most reliable algorithm. Analysis of the receiver operating characteristic curves of the interest peaks generated by the SVM model was found to confer highly accurate detection sensitivity and specificity, consistently producing distinguishable profiles for K1 hvKP and non-K1 strains. Of the 43 K. pneumoniae modeling strains tested by this approach, all were correctly identified as K1 hvKP and non-K1 capsule type. Of the 20 non-K1 and 17 K1 hvKP validation isolates, the accuracy of K1 hvKP and non-K1 identification was 94.1% and 90.0% respectively according to the SVM model. In summary, the MALDI-TOF MS approach can be applied alongside the conventional genotyping techniques to provide rapid and accurate diagnosis, and hence prompt treatment of infections caused by hvKP.

In this work, a novel nanocomposite (NC) based on the decoration of Ag nanoparticles (NPs) and W[Formula: see text]O[Formula: see text] nanorods (NRs) on the GO surfaces was prepared using combined techniques of solvothermal method and photochemical process. Compared with the Ag-GO NC, the Ag-W[Formula: see text]O[Formula: see text]-GO NC exhibited enhanced long-term antibacterial activity against the bacterium of Bacillus sp.1NLA3E (Bacillus sp.). The antibacterial mechanisms of both the Ag-GO and Ag-W[Formula: see text]O[Formula: see text]-GO NCs were distinctly revealed by observation of the direct interaction between the Ag NPs, W[Formula: see text]O[Formula: see text] NRs, or GO sheets and the bacterial cells. Results showed that the GO sheets in the NCs mainly acted as supports for trapping or wrapping the bacterial cells, and it was the Ag NPs or W[Formula: see text]O[Formula: see text] NRs grown on the GO surfaces that caused direct damage to the cells. The synergistic effects between the Ag NPs or W[Formula: see text]O[Formula: see text] NRs and the GO sheets resulted in the prominent long-term antibacterial effect of the Ag-W[Formula: see text]O[Formula: see text]-GO NC. This work provides in-depth understanding of the mechanism regarding the antibacterial activity of the GO-based NCs.

A novel sandwich-like MnO2/g-C3N4 nanocomposite (NC) based on the integration of high-density MnO2 nanorods (NRs) onto the surfaces of two-dimensional (2D) g-C3N4 sheets has been successfully fabricated through a facile soft chemical route at low temperature. The MnO2/g-C3N4 NC electrode enhanced the supercapacitor (SC) performance, benchmarked against both the bare MnO2 NRs electrode and the MnO2/graphene oxide (GO) NC electrode, exhibiting high specific capacitance of 211 F/g at a current density of 1 A/g, with good rate capacity and cycling stability. The sandwich-like hybrid structure, the unique 2D structure of the g-C3N4 sheets and the presence of nitrogen in the g-C3N4 all contributed to the promising SC performance of the MnO2/g-C3N4 NC. This work demonstrated the advantages of the g-C3N4 sheets over the commonly-used GO sheets in the design of novel hybrid composite for enhanced capacitance performance of MnO2-based electrochemical SCs, and the results could be extended to other electrode materials for SCs.

CTX-M-type extended-spectrum β-lactamases (ESBLs) did not become dominant until the early 2000s, when extreme diversification of these enzymes was observed. The evolution of CTX-M-type ESBLs has been based mainly on amino acid substitutions. However, several chimeras of the CTX-M-1 and CTX-M-9

A collection of 1159 enterococcal isolates from five Chinese hospitals were screened for the presence of the novel oxazolidinone resistance gene optrA, which was found in 34 (2.9%) isolates. Pulsed-field gel electrophoresis (PFGE) typing of 29 optrA-carrying Enterococcus faecalis isolates revealed 25 PFGE patterns, and multilocus sequence typing yielded 20 sequence types. Routine surveillance of optrA-positive enterococci in hospitals should be conducted to monitor and counteract their further dissemination. The data of this study may be used as a baseline from which to judge future decreases or increases in optrA-positive enterococci.