Monitoring the long-term spatiotemporal transmission dynamics and ecological surveillance of multidrug-resistant Salmonella enterica serovar Goldcoast: A multicenter genomic epidemiology study.

The emergence of multidrug-resistant Salmonella enterica serovar Goldcoast poses a significant threat to the effective treatment and control of salmonellosis within the ecological environment. Here, we conducted a genomic epidemiological study delineate the global dissemination scenarios of the multidrug-resistant S. Goldcoast originated from 11 countries for over 20 years. The population structure and evolutionary history of multidrug-resistant S. Goldcoast was investigated through phylogenomic and long-term spatiotemporal transmission dynamic analysis. ST358 and ST2529 are the predominant lineages of S. Goldcoast. Multidrug-resistant S. Goldcoast strains have mainly been identified in the ST358 lineage from human and the ST2529 lineage from livestock. ST358 S. Goldcoast was estimated to have emerged in the United Kingdom in 1969, and then spread to China, with both countries serve as centers for the global dissemination of the ST358 lineage. After its emergence and subsequent spread in Chinese clinical and environmental samples, occasional instances of this lineage have been reported in Canada, the United Kingdom, and Ireland. Clonal transmission of ST358 and ST2529 S. Goldcoast have occurred not only on an international and intercontinental scale but also among clinical, environmental and livestock samples. These data indicated that international circulation and local transmission of S. Goldcoast have occurred for over a decade. Continued surveillance of multidrug-resistant S. Goldcoast from a global "One Health" perspective is urgently needed to facilitate monitoring the spread of the antimicrobial resistant high-risk clones.

Global Phylogeography and Genomic Epidemiology of Carbapenem-Resistant blaOXA-232-Carrying Klebsiella pneumoniae Sequence Type 15 Lineage.

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.

Genomic Characteristics of Extended Spectrum ß-Lactamase Producing Escherichia coli Isolates Recovered from a District Hospital in China.

Purpose: The isolation rate of extended spectrum ß-lactamase (ESBL)-producing Escherichia coli is increasing, posing a challenge to clinical anti-infective therapy. This study aims to provide new insight into the genomic characteristics and antimicrobial resistance mechanisms of extended spectrum ß-lactamase producing E. coli isolates recovered from a district hospital in China. Methods: A total of 36 ESBL-producing E. coli isolates were collected from body fluid samples from a Chinese district hospital. All isolates were subjected to whole genome sequencing to identify their antimicrobial resistance genes, virulence genes, serotypes, sequence types, and phylogenetic relationships by BacWGSTdb 2.0 webserver. Results: Among these isolates, all were resistant to cefazolin, cefotaxime, ceftriaxone, ampicillin, 24 (66.7%) were resistant to aztreonam, 16 (44.4%) were resistant to cefepime, and 15 were resistant (41.7%) to ceftazidime. The blaCTX-M gene was detected in all ESBL-producing E. coli isolates. Two isolates carrying two different types of blaCTX-M genes simultaneously. The carbapenem resistance gene blaKPC-2 was detected in one (2.8%) isolate. A total of 17 sequence types (STs) were found, with ST131 accounting for the majority (n =13; 36.1%). The most common serotype was O16:H5 associated with seven ST131 strains, followed by O25:H4/ST131 (n = 5) and O75:H5/ST1193 (n = 5). Evaluation of clonal relatedness revealed that all blaCTX-M gene-carrying E. coli had a difference of SNPs range from 7 to 79,198, which could be divided into four clusters. Only 7 SNPs could be found between EC266 and EC622, indicating that they are variants of the same clonal lineage. Conclusion: This study investigated the genomic characteristics of ESBL-producing E. coli isolates recovered from a district hospital in China. Continuous surveillance of ESBL-producing E. coli infections is imperative to create efficient strategies for controlling the transmission of these multi-drug resistant bacteria in clinical and community settings.

Genomic Characteristics of a Multidrug-Resistant ST648 Escherichia coli Isolate Co-Carrying blaKPC-2 and blaCTX-M-15 Genes Recovered from a Respiratory Infection in China.

Background: The transmission of carbapenem-resistant Enterobacterales pose a significant threat to global public health, which weakens the effectiveness of most antimicrobial agents. The aim of this study is to present the genomic characteristics of a multidrug-resistant Escherichia coli, which contains both blaKPC-2 and blaCTX-M-15 genes, discovered from a respiratory infection in China. Methods: The antimicrobial susceptibility of E. coli isolate 488 was measured by using the broth microdilution method. The Oxford Nanopore MinION and Illumina NovaSeq 6000 platforms were applied to determine the whole-genome sequence of this isolate. De novo assembly of short Illumina reads and long MinION reads were performed by Unicycler. In silico multilocus sequence typing (MLST), antimicrobial resistance genes and plasmid replicon types were determined using the genome sequencing data. Additionally, a pairwise core genome single nucleotide polymorphism (cgSNP) comparison between E. coli 488 and all ST648 E. coli strains retrieved from NCBI GenBank database were conducted using the BacWGSTdb 2.0 server. Results: E. coli 488 was resistant to aztreonam, levofloxacin, cefepime, fosfomycin, amikacin, imipenem, cefotaxime, and meropenem. The complete genome sequence of E. coli 488 (belong to ST648) is made up of eleven contigs totaling 5,573,915 bp, including one chromosome and ten plasmids. Eight antimicrobial resistance genes were identified, including blaKPC-2 located in a 46,161 bp IncI1-type plasmid and the blaCTX-M-15 gene situated in the chromosome. Other two E. coli S617-2 and R616-1 isolates, recovered from China in 2018, are the closest relatives of E. coli 488, with only 52 SNPs difference. The genome also contains at least 57 genomic islands and several IS elements. Conclusion: Our study reveals the first ST648 E. coli isolate containing both blaKPC-2 and blaCTX-M-15 in China. These results could provide valuable insights into the genetic characteristics, antimicrobial resistance mechanisms, and transmission dynamics of carbapenem-resistant Enterobacterales in clinical settings.

Taxonomic structure in a set of abstract concepts.

A large portion of human knowledge comprises "abstract" concepts that lack readily perceivable properties (e.g., "love" and "justice"). Since abstract concepts lack such properties, they have historically been treated as an undifferentiated category of knowledge in the psychology and neuropsychology literatures. More recently, the categorical structure of abstract concepts is often explored using paradigms that ask participants to make explicit judgments about a set of concepts along dimensions that are predetermined by the experimenter. Such methods require the experimenter to select dimensions that are relevant to the concepts and further that people make explicit judgments that accurately reflect their mental representations. We bypassed these requirements by collecting two large sets of non-verbal and implicit judgments about which dimensions are relevant to the similarity between pairs of 50 abstract nouns to determine the representational space of the concepts. We then identified categories within the representational space using a clustering procedure that required categories to replicate across two independent data sets. In a separate experiment, we used automatic semantic priming to further validate the categories and to show that they are an improvement over categories that were defined within the same set of abstract concepts using explicit ratings along predetermined dimensions. These results demonstrate that abstract concepts can be characterized beyond their negative relation to concrete concepts and that categories of abstract concepts can be defined without using a priori dimensions for the concepts or explicit judgments from participants.

A functional parcellation of the whole brain in individuals with autism spectrum disorder reveals atypical patterns of network organization.

BACKGROUND: Researchers studying autism spectrum disorder (ASD) lack a comprehensive map of the functional network topography in the ASD brain. We used high-quality resting state functional MRI (rs-fMRI) connectivity data and a robust parcellation routine to provide a whole-brain map of functional networks in a group of seventy individuals with ASD and a group of seventy typically developing (TD) individuals. METHODS: The rs-fMRI data were collected using an imaging sequence optimized to achieve high temporal signal-to-noise ratio (tSNR) across the whole-brain. We identified functional networks using a parcellation routine that intrinsically incorporates stability and replicability of the networks by keeping only network distinctions that agree across halves of the data over multiple random iterations in each group. The groups were tightly matched on tSNR, in-scanner motion, age, and IQ. RESULTS: We compared the maps from each group and found that functional networks in the ASD group are atypical in three seemingly related ways: 1) whole-brain connectivity patterns are less stable across voxels within multiple functional networks, 2) the cerebellum, subcortex, and hippocampus show weaker differentiation of functional subnetworks, and 3) subcortical structures and the hippocampus are atypically integrated with the neocortex. CONCLUSIONS: These results were statistically robust and suggest that patterns of network connectivity between the neocortex and the cerebellum, subcortical structures, and hippocampus are atypical in ASD individuals.

Maladaptive Laterality in Cortical Networks Related to Social Communication in Autism Spectrum Disorder.

Neuroimaging studies of individuals with autism spectrum disorders (ASDs) consistently find an aberrant pattern of reduced laterality in brain networks that support functions related to social communication and language. However, it is unclear how the underlying functional organization of these brain networks is altered in ASD individuals. We tested four models of reduced laterality in a social communication network in 70 ASD individuals (14 females) and a control group of the same number of tightly matched typically developing (TD) individuals (19 females) using high-quality resting-state fMRI data and a method of measuring patterns of functional laterality across the brain. We found that a functionally defined social communication network exhibited the typical pattern of left laterality in both groups, whereas there was a significant increase in within- relative to across-hemisphere connectivity of homotopic regions in the right hemisphere in ASD individuals. Furthermore, greater within- relative to across-hemisphere connectivity in the left hemisphere was positively correlated with a measure of verbal ability in both groups, whereas greater within- relative to across-hemisphere connectivity in the right hemisphere in ASD, but not TD, individuals was negatively correlated with the same verbal measure. Crucially, these differences in patterns of laterality were not found in two other functional networks and were specifically correlated to a measure of verbal ability but not metrics of other core components of the ASD phenotype. These results suggest that previous reports of reduced laterality in social communication regions in ASD is because of the two hemispheres functioning more independently than seen in TD individuals, with the atypical right-hemisphere network component being maladaptive.SIGNIFICANCE STATEMENT A consistent neuroimaging finding in individuals with ASD is an aberrant pattern of reduced laterality of the brain networks that support functions related to social communication and language. We tested four models of reduced laterality in a social communication network in ASD individuals and a TD control group using high-quality resting-state fMRI data. Our results suggest that reduced laterality of social communication regions in ASD may be because of the two hemispheres functioning more independently than seen in TD individuals, with atypically greater within- than across-hemisphere connectivity in the right hemisphere being maladaptive.

Multicenter Investigation of the Initial Hemodialysis Vascular Access and Its Related Factors in Hangzhou of China.

OBJECTIVE: To investigate the initial hemodialysis vascular access in Hangzhou and provide evidence for improving the use of autologous arteriovenous fistula by identifying factors associated with the choice of initial vascular access. METHODS: We retrospectively studied the initial hemodialysis vascular access of 257 patients in five hemodialysis units in Hangzhou of China during a 21-month period (January 2018 to September 2019). A logistic regression was used to identify the risk factors of failing to use an arteriovenous fistula at the initiation of hemodialysis. RESULTS: (1) 257 participants with mean age 67.65 ± 13.43 years old were reviewed, including 165 males (64.2%) and 92 females (35.8%). The etiologies of end-stage renal disease included diabetic nephropathy (37.35%), chronic glomerulonephritis (31.13%), hypertensive nephropathy (14.01%), and other diseases (17.51%). Only 51 patients (19.84%) received arteriovenous fistula, whereas the remaining 206 patients (80.16%) initiated dialysis with a central venous catheter. (2) Logistic regression analysis revealed that the independent risk factors for central venous catheter at the initial hemodialysis were age >70 years old (OR = 4.827, p < 0.01 versus ≤70 years old), chronic glomerulonephritis as the primary etiology (OR = 2.565, p < 0.05 versus nonchronic glomerulonephritis) and eGFR <8.5 mL/min/1.73m2 (OR = 2.283, p < 0.05 versus eGFR ≥8.5 mL/min/1.73m2). CONCLUSION: The proportion of patients using arteriovenous fistula as the initial hemodialysis vascular access in Hangzhou was still low. The choice of vascular access for the first hemodialysis was related to age, eGFR, and the primary etiology of end-stage renal disease. Increasing the proportion of planned vascular access and arteriovenous fistula at the initiation of hemodialysis is still our current goal.

Engineered Human Cathelicidin Antimicrobial Peptides Inhibit Ebola Virus Infection.

The 2014-2016 West Africa Ebola virus (EBOV) outbreak coupled with the most recent outbreaks in Central Africa underscore the need to develop effective treatment strategies against EBOV. Although several therapeutic options have shown great potential, developing a wider breadth of countermeasures would increase our efforts to combat the highly lethal EBOV. Here we show that human cathelicidin antimicrobial peptide (AMP) LL-37 and engineered LL-37 AMPs inhibit the infection of recombinant virus pseudotyped with EBOV glycoprotein (GP) and the wild-type EBOV. These AMPs target EBOV infection at the endosomal cell-entry step by impairing cathepsin B-mediated processing of EBOV GP. Furthermore, two engineered AMPs containing D-amino acids are particularly potent in blocking EBOV infection in comparison with other AMPs, most likely owing to their resistance to intracellular enzymatic degradation. Our results identify AMPs as a novel class of anti-EBOV therapeutics and demonstrate the feasibility of engineering AMPs for improved therapeutic efficacy.

Role of microRNA-29b in angiotensin II-induced epithelial-mesenchymal transition in renal tubular epithelial cells.

Angiotensin II (Ang II) has been proven to induce epithelial-mesenchymal transition (EMT). The aim of the present study was to determine the role of microRNA-29b (miR-29b) during Ang II-induced EMT. For this purpose, we used spontaneously hypertensive rats (SHRs) and age-matched Wistar-Kyoto (WKY) rats. The levels of Ang II and its receptor in the kidneys of the SHRs are significantly higher than those in the age-matched WKY rats. As shown by RT-qPCR, the expression of miR-29b in the renal cortex was lower in the SHRs than in the WKY rats. For in vitro experiments, NRK-52E renal tubular epithelial cells were treated with 10(-7) M Ang II; we found that the expression of miR-29b was decreased in the cells treated with Ang II. In addition, transfection of the NRK-52E cells with miR-29b inhibitor led to the downregulation of miR-29b in these cells, and increased the expression of transforming growth factor (TGF)-ß, α-smooth muscle actin (α-SMA) and collagen I (Col I). Similar results were observed with the induction of Ang II expression in the NRK-52E cells. By contrast, the upregulation of miR-29b by transfection with miR-29b mimics inhibited the overexpression of these genes induced by Ang II. These results suggest that miR-29b plays an important role in Ang II-induced EMT.