Results:  All isolates harboured the bla(KPC-2) gene. Seven sequence types (STs) were obtained. The dominant clone was ST11 (61/95), which was identified in isolates from Zhejiang province (four hospitals in Hangzhou and one hospital in Ningbo), Jiangsu province (one hospital in Nanjing) and Anhui province (one hospital in Hefei). Isolates with ST11 showed >80% similarity in PFGE patterns. Plasmids from 14 selected transformants, their original isolates representing different STs and/or regions, had a diversity of HindIII restriction maps.

Yaping Jin, a bovine veterinarian at Northwest A&F who led the experiment, told the Global Times that cloning will help revitalize China's agricultural sector. Jin said his team's experiment produced more than 100 cloned embryos that were implanted into the surrogates with a pregnancy rate of about 18% after 200 days.


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This is a very delayed follow up to the kit parts review I made a few months ago. Shipping of the printed parts from TriangleLAB got set back by over 2 months due to pandemic, and they had to be shipped from china on a boat instead of an airplane. However, I now have the printer assembled and working, so we can finally talk about it.

Antimicrobial resistance of Shigella sonnei has become a global concern. Here, we report a phylogenetic group of S. sonnei with extensive drug resistance, including a combination of multidrug resistance, coresistance to ceftriaxone and azithromycin (cefRaziR), reduced susceptibility to fluoroquinolones, and even colistin resistance (colR). This distinct clone caused six waterborne shigellosis outbreaks in China from 2015 to 2020. We collect 155 outbreak isolates and 152 sporadic isolates. The cefRaziR isolates, including outbreak strains, are mainly distributed in a distinct clade located in global Lineage III. The outbreak strains form a recently derived monophyletic group that may have emerged circa 2010. The cefRaziR and colR phenotypes are attributed to the acquisition of different plasmids, particularly the IncB/O/K/Z plasmid coharboring the blaCTX-M-14, mphA, aac(3)-IId, dfrA17, aadA5, and sul1 genes and the IncI2 plasmid with an mcr-1 gene. Genetic analyses identify 92 accessory genes and 60 single-nucleotide polymorphisms associated with the cefRaziR phenotype. Surveillance of this clone is required to determine its dissemination and threat to global public health.

Antimicrobials, especially fluoroquinolones (e.g., ciprofloxacin and norfloxacin), third-generation cephalosporins (e.g., ceftriaxone), and macrolides (e.g., azithromycin), are recommended by the World Health Organization (WHO) for the treatment of shigellosis to accelerate recovery, prevent complications, and reduce onward transmission6. Unfortunately, a pandemic clone of multidrug-resistant (MDR) S. sonnei has been found to be globally distributed in recent years, and this pandemic clone is located within global Lineage III, which recently emerged from Europe and underwent contemporary global dispersal and localized clonal expansion3,7. Accordingly, the WHO and US Centers for Disease Control and Prevention (CDC) have declared MDR Shigella a serious threat2,8. Moreover, resistance to fluoroquinolones has been increasingly detected among MDR S. sonnei, and studies have shown that South Asia acts as a reservoir for a single clone of ciprofloxacin-resistant S. sonnei, which has caused travel-associated infections and even large outbreaks in many countries9,10.

In this work, we perform whole-genome sequencing (WGS) of the outbreak and sporadic S. sonnei isolates with this distinct resistance profile to determine the origin, spread, and local establishment of these extensively drug-resistant (XDR) S. sonnei isolates. We find that most of these isolates are located in Lineage III and form a distinct clade. The cefRaziR isolates, including the outbreak strains, are mainly distributed in this clade and the outbreak strains form a recently derived monophyletic group that may have emerged circa 2010. The cefRaziR and colR phenotypes are attributed to the acquisition of different plasmids, particularly the IncB/O/K/Z plasmid coharboring the blaCTX-M-14, mphA, aac(3)-IId, dfrA17, aadA5, and sul1 genes and the IncI2 plasmid with an mcr-1 gene. Ninety-two accessory genes and 60 single-nucleotide polymorphisms (SNPs) are associated with the cefRaziR phenotype, supporting the divergent evolution of S. sonnei via the accumulation of genomic signatures. Heavy precipitation and floods may be relevant to the prevalence of the XDR clone. Continued surveillance and further genomic epidemiological studies are urgently required to determine the potential dissemination and consequent risk to global public health of this clone.

We drew a maximum-likelihood phylogenetic tree based on 462 genomes (155 outbreak isolates, 152 sporadic isolates, and 155 globally distributed isolates described previously3,12, as detailed in Supplementary Table S3) to investigate the population structure and evolutionary position of the Chinese S. sonnei isolates, including the cefRaziR isolates, within the global S. sonnei phylogeny. The phylogenetic tree (Fig. 1c) showed that the 462 genomes were divided into four distinct lineages as described by Holt KE et al.4, and the Chinese isolates were distributed within two of the four lineages (Lineage I and Lineage III). The majority of the Chinese isolates were located in Lineage III and formed a distinct Chinese clade (main Chinese clade). Further genotyping of the main Chinese clade strains showed that they belonged to the 3.7.6 genotype, corresponding to global Lineage III (Fig. 1c). Multilocus sequence typing (MLST) analysis showed that all of the strains belonged to ST152, as described by Hawkey et al.13. It is estimated that the main Chinese S. sonnei clade shares a most recent common ancestor (MRCA) that existed circa 1987 (Fig. 1c), suggesting a recently derived clone of S. sonnei circulating in China. The cefRaziR isolates were mainly distributed in the main Chinese clade, which was traced back to 1999 by Bayesian phylogenetic analysis (Fig. 1c). The outbreak isolates formed a recently derived monophyletic group that may have emerged circa 2010 (Figs. 1c, 2).

As shown in Supplementary Table S3, our dataset contains genome sequences with different spatiotemporal and phenotypic contexts, offering an opportunity to explore the microevolution and phylogeography of cefRaziR isolates, especially the outbreak strains, within China. A total of 215 cefRaziR isolates were screened, including 205 Chinese cefRaziR isolates and ten UK cefRaziR isolates. The Chinese cefRaziR isolates were recovered from nine of the 11 monitored regions of China from 2008 to 2020 (Supplementary Table S3). The Shanghai isolates were widely distributed among the cefRaziR groups (Fig. 2), revealing Shanghai as a hub for the transmission of cefRaziR isolates within China. A total of 159 SNPs were identified among the six outbreak isolates, and 7, 18, 20, 7, 9, and 17 SNPs were identified among the Yulin, Baise, Nanning, Guigang, Wuzhou, and Huainan outbreaks, respectively (Fig. 2). The strains in the Huainan outbreak were closer to those in the Yulin outbreak, with 46 SNPs in the 49 strains. The strains from Baise were closer to those from Guigang, with 22 SNPs in 44 strains, and the strains from Nanning were closer to those from Wuzhou, with 32 SNPs among the 62 strains. The geographical locations of the five outbreaks in Guangxi from west to east are in the order Baise, Nanning, Guigang, Yulin, and Wuzhou (Fig. 1a and Supplementary Fig. S2). These five cities are located in the Pearl River Basin, and the Pearl River flows from southwest to northeast. The location of Huainan is near the Yangtze River Basin and Huaihe Basin. Moreover, in the Yulin, Baise, Nanning, and Guigang outbreaks, the cefRaziR isolates recovered from water samples and outbreak patients were similar, with only one to three different SNPs, suggesting that the contaminated water supply may have been the cause of the outbreaks. These results indicated that the cefRaziR isolates have been prevalent in diverse regions of China, undergone clonal expansion, and then caused shigellosis outbreaks, and the outbreak clone probably originated from an MRCA.

Shigellosis outbreaks caused by MDR S. sonnei are now being commonly reported18,19. Nevertheless, outbreaks caused by MDR S. sonnei with cefRaziR resistance have rarely been reported14,16. To date, no outbreaks have been reported as being caused by MDR S. sonnei with colR. Concerningly, here, we report the prevalence and outbreaks of shigellosis caused by S. sonnei with a combination of MDR, cefRaziR, reduced susceptibility to fluoroquinolones, and even colR. S. sonnei clones belonging to Lineage III appear to be more easily transmitted from person to person and spread across regions12 and to be highly proficient at acquiring resistance to additional antimicrobials, such as fluoroquinolones, macrolides, third-generation cephalosporins, and polymyxins, when they are introduced into new locations20,21. Thus, the clone in this study belonging to Lineage III seemingly has the potential to develop into a superbug, posing the risk of nearly untreatable shigellosis.

To our knowledge, this is one of the few studies that has used WGS to explore the microevolution and phylogeography of Chinese S. sonnei isolates, especially those with cefRaziR and even colR. Our data showed that the Chinese S. sonnei isolates formed a main Chinese clade within the global Lineage III that may have emerged circa 1987. The cefRaziR isolates were mainly located in the main Chinese clade, which was probably derived from the non-cefRaziR S. sonnei ancestor that existed circa 1999 and then spread and localized into a more recently emerged clone of S. sonnei with XDR. This distinct clone has now disseminated to diverse regions of China, possibly with Shanghai acting as a major transport hub for the spread of the cefRaziR S. sonnei clone. Shanghai, an international metropolis, is the largest economic and trade center of China, with a resident population of 24 million and a floating population of ~10 million, possibly facilitating the spread of this specific clone. These analyses indicated that Shanghai may act as a hub for the spread of the cefRaziR S. sonnei in China, and this clone has spread successfully within diverse regions of China as a single, rapidly evolving clone, establishing new, local populations and causing large-scale shigellosis outbreaks. be457b7860

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