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To demonstrate the detailed genetic characteristics of a bla NDM–1-carrying multidrug-resistant Aeromonas caviae strain, the complete genome of the A. caviae strain K433 was sequenced by Illumina HiSeq and Oxford nanopore platforms, and mobile genetic elements associated with antibiotic resistance genes were analyzed by a series of bioinformatics methods. A. caviae K433 which was determined to produce class B carbapenemase, was resistant to most antibiotics tested except amikacin. The genome of K433 consisted of a chromosome cK433 (6,482-kb length) and two plasmids: pK433-qnrS (7.212-kb length) and pK433-NDM (200.855-kb length), the last being the first investigated bla NDM-carrying plasmid from Aeromonas spp. By comparison of the backbone and MDR regions from the plasmids studied, they involved a highly homologous sequence structure. This study provides in-depth genetic insights into the plasmids integrated with bla NDM-carrying genetic elements from Aeromonas spp. [ABSTRACT FROM AUTHOR]

In this study, a detailed genetic dissection of the huge and complex bla NDM-carrying genetic elements and their related mobile genetic elements was performed in Enterobacteriaceae. An extensive comparison was applied to 12 chromosomal genetic elements, including six sequenced in this study and the other six from GenBank. These 12 genetic elements were divided into five groups: a novel IME Tn 6588 ; two related IMEs Tn 6523 (SGI1) and Tn 6589 ; four related ICEs Tn 6512 (R391), Tn 6575 (ICE Pvu ChnBC22), Tn 6576 , and Tn 6577 ; Tn 7 and its derivatives Tn 6726 and 40.7-kb Tn 7 -related element; and two related IMEs Tn 6591 (GI sul2) and Tn 6590. At least 51 resistance genes, involved in resistance to 18 different categories of antibiotics and heavy metals, were found in these 12 genetic elements. Notably, Tn 6576 carried another ICE Tn 6582. In particular, the six bla NDM-carrying genetic elements Tn 6588 , Tn 6589 , Tn 6575 , Tn 6576 , Tn 6726 , and 40.7-kb Tn 7 -related element contained large accessory multidrug resistance (MDR) regions, each of which had a very complex mosaic structure that comprised intact or residual mobile genetic elements including insertion sequences, unit or composite transposons, integrons, and putative resistance units. Core bla NDM genetic environments manifested as four different Tn 125 derivatives and, notably, two or more copies of relevant Tn 125 derivatives were found in each of Tn 6576 , Tn 6588 , Tn 6589 , and 40.7-kb Tn 7 -related element. The huge and complex bla NDM-carrying genetic elements were assembled from complex transposition and homolog recombination. Firstly identified were eight novel mobile elements, including three ICEs Tn 6576 , Tn 6577 , and Tn 6582 , two IMEs, Tn 6588 and Tn 6589 , two composite transposons Tn 6580a and Tn 6580b , and one integron In1718. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a common disease with a significant mortality, and there is no effective treatment for advanced patients. Growing evidence indicates that circRNAs are closely related to HCC progression, may be used as biomarkers and targets for the diagnosis and treatment of HCC. Recent researches have shown that circPUM1 may play an oncogene role in a variety of human cancers, but its role in HCC development has not been reported. Our study found that circPUM1 could promote the proliferation, migration and invasion of HCC cells in vitro. In addition, in vivo studies showed that circPUM1 could increase the development of HCC tumours and regulate the expression of EMT‐related proteins. Furthermore, we demonstrated that circPUM1 could promote the development of HCC by up‐regulating the expression of MAP3K2 via sponging miR‐1208. Our study suggested that circPUM1 may be a potential therapeutic target for HCC. [ABSTRACT FROM AUTHOR]

The purpose of the present study is to investigate the prevalence of Th17 and regulatory T (Treg) cells in children with allergic rhinitis (AR) accompanying with bronchial asthma (BA). 24 children with AR, 22 children with BA, 18 children with AR accompanying with BA, and 20 healthy controls were recruited. The prevalence of peripheral blood Th17 and Treg cells were determined by flow cytometry. mRNA expression of retinoid-acid receptor-related orphan receptor (ROR)-γt and forkhead box P3 (Foxp3) were determined by realtime polymerase chain reaction. Cytokine expressions in plasma were determined by enzyme linked immunosorbent assay. The frequency of Th17 cells, ROR-γt mRNA expression, and the plasma levels of IL-17 were significantly higher, while Treg cells and Transforming growth factor (TGF)-β1 were significantly lower in children with AR accompanying with BA compared with those in children with AR or BA alone or control subjects. In children with allergic airway disease, total IgE levels were positively correlated to the frequency of Th17 cells (r=0.607, p<0.01), plasma IL-17 levels, and negatively correlated to the frequency of Treg cells (r=-0.429, p<0.01) and TGF-β1 levels (r=-0.224, p<0.01). While Forced expiratory volume in one second (FEV1) (% predicted) was negatively correlated to the frequency of Th17 cells (r=-0.602, p<0.01), plasma IL-17 levels (r=-0.577, p<0.01), and positively correlated to the frequency of Treg cells r=0.504, p<0.01) and TGF-β1 levels (r=0.231, p<0.05). Our results demonstrate that the imbalance of peripheral Th17/Treg cells plays an important role in the pathogenesis of AR accompanying with BA. [ABSTRACT FROM AUTHOR]

Objective: The emergence of clinical Klebsiella pneumoniae strains harboring acrAB-tolC genes in the chromosome, along with the presence of two repetitive tandem core structures for bla KPC-2 and bla CTX-M-65 genes on a plasmid, has presented a significant clinical challenge., Methods: In order to study the detailed genetic features of K. pneumoniae strain SC35, both the bacterial chromosome and plasmids were sequenced using Illumina and nanopore platforms. Furthermore, bioinformatics methods were employed to analyze the mobile genetic elements associated with antibiotic resistance genes., Results: K. pneumoniae strain SC35 was found to possess a class A beta-lactamase and demonstrated resistance to all tested antibiotics. This resistance was attributed to the presence of efflux pump genes, specifically acrAB-tolC , on the SC35 chromosome. Additionally, the SC35 plasmid p1 carried the two repetitive tandem core structures for bla KPC-2 and bla CTX-M-65 , as well as bla TEM-1 with rmtB , which shared overlapping structures with mobile genetic elements as In413, Tn 3 , and Tn As3 . Through plasmid transfer assays, it was determined that the SC35 plasmid p1 could be successfully transferred with an average conjugation frequency of 6.85 × 10 -4 ., Conclusion: The structure of the SC35 plasmid p1 appears to have evolved in correlation with other plasmids such as pKPC2&#95;130119, pDD01754-2, and F4&#95;plasmid pA. The infectious strain SC35 exhibits no susceptibility to tested antibioticst, thus effective measures should be taken to prevent the spread and epidemic of this strain., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 He, Wang, Ma, Wang and Long.)

Background: Today, the bla NDM gene is widely distributed on several plasmids from a variety of Gram-negative bacteria, primarily in transposons and gene cassettes within their multidrug-resistant (MDR) regions. This has led to the global dissemination of the bla NDM gene., Methods: The determination of class A beta-lactamase, class B and D carbapenemases was performed according to the recommendations of the Clinical and Laboratory Standards Institute (CLSI). Antimicrobial susceptibility testing was performed using both the BioMerieux VITEK2 system and antibiotic paper diffusion methods. Plasmid transfer was then evaluated by conjugation experiments and plasmid electroporation assays. To comprehensively analyze the complete genome of K. pneumoniae strain F11 and to investigate the presence of mobile genetic elements associated with antibiotic resistance and virulence genes, Nanopore and Illumina sequencing platforms were used, and bioinformatics methods were applied to analyze the obtained data., Results: Our findings revealed that K. pneumoniae strain F11 carried class A beta-lactamase and classes B+D carbapenemases, and exhibited resistance to commonly used antibiotics, particularly tigecycline and ceftazidime/avibactam, due to the presence of relevant resistance genes. Plasmid transfer assays demonstrated successful recovery of plasmids pA&#95;F11 and pB&#95;F11, with average conjugation frequencies of 2.91×10 -4 and 1.56×10 -4 , respectively. However, plasmids pC&#95;F11 and pD&#95;F11 failed in both conjugation and electroporation experiments. The MDR region of plasmid pA&#95;F11 contained rare In1765, Tn As2 , and Tn As3 elements. The MDR2 region of plasmid pB&#95;F11 functioned as a mobile genetic "island" and lacked the bla NDM-1 gene, serving as a "bridge" connecting the early composite structure of ble MBL and bla NDM-1 to the recent composite structure. Additionally, the MDR1 region of plasmid pB&#95;F11 comprised In27, Tn As1 , Tn As3 , and Tn 2 ; and plasmid pC&#95;F11 harbored the recent composite structure of ble MBL and bla NDM-1 within Tn 3000 which partially contained partial Tn 125 ., Conclusion: This study demonstrated that complex combinations of transposons and integron overlaps, along with the synergistic effects of different drug resistance and virulence genes, led to a lack of effective therapeutic agents for strain F11, therefore its dissemination and prevalence should be strictly controlled., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ma, Qu, Wang and Wang.)

Objective: Today, the emergence of Klebsiella pneumoniae with the tmexCD1-toprJ1 gene cassette in patients has presented a significant clinical challenge., Methods: To present the detailed genetic features of the tmexCD1-toprJ1 gene cassette of K. pneumoniae strain F4&#95;plasmid pA, the whole bacterial genome was sequenced by Illumina and nanopore platforms, and mobile genetic elements related to antibiotic resistance genes were analyzed with a series of bioinformatics methods., Results: K. pneumoniae strain F4 was determined to be a class A+C beta-lactamase, and was resistant to routinely used antibiotics, especially tigecycline, because of the oqxAB gene localized on the F4&#95;chromosome and tmexCD1-toprJ1 on F4&#95;plasmid A. After plasmid transfer assays, the F4&#95;plasmid pA or F4&#95;plasmid pB could be recovered with an average conjugation frequencies of 3.42×10 -4 or 4.19×10 -4 . F4&#95;plasmid pA carried tmexCD1-toprJ1 and bla DHA-1 accompanied by genetic intermixing of Tn As1 , Tn 5393 , Tn As3 , and In641, while F4&#95;plasmid pB, bearing bla CTX-M-174 , had structural overlap of Tn As3 and In641., Conclusions: We suggested that plasmids carrying tmexCD1- toprJ1 might be strongly related to IS 26 -integrated loop intermediates. This study showed that due to the structural evolution of F4 and related strains, their resistances were so strong that effective antibiotics were virtually unavailable, therefore their spread and prevalence should be strictly controlled., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Qu, Wang, Lu, Qiu, Wang and Ma.)

To demonstrate the detailed genetic characteristics of a bla NDM-1 -carrying multidrug-resistant Aeromonas caviae strain, the complete genome of the A. caviae strain K433 was sequenced by Illumina HiSeq and Oxford nanopore platforms, and mobile genetic elements associated with antibiotic resistance genes were analyzed by a series of bioinformatics methods. A. caviae K433 which was determined to produce class B carbapenemase, was resistant to most antibiotics tested except amikacin. The genome of K433 consisted of a chromosome cK433 (6,482-kb length) and two plasmids: pK433-qnrS (7.212-kb length) and pK433-NDM (200.855-kb length), the last being the first investigated bla NDM -carrying plasmid from Aeromonas spp. By comparison of the backbone and MDR regions from the plasmids studied, they involved a highly homologous sequence structure. This study provides in-depth genetic insights into the plasmids integrated with bla NDM -carrying genetic elements from Aeromonas spp., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Luo, Mu, Zhao, Zhang, Qu, Hu, Jia, Dai, Weng, Wang and Yu.)

Purpose: We intended to preliminarily find differentially expressed proteins that play crucial roles in proliferative diabetic retinopathy (PDR), and lay the foundation for subsequent further research on the mechanism., Experimental Design: Here, we developed a new strategy integrated the sequential windowed acquisition of all theoretical fragment ion (SWATH) mass spectra (MS) with multi-dataset joint analysis to screen for the PDR plasma biomarker. The annotation of the given gene list was performed with ClueGO function analysis. Additionally, the protein-protein interaction relationship was also revealed by the STRING database., Results: In SWATH-MS assays, we identified 23 upregulated and 13 downregulated proteins in PDR plasma. In the mRNA database analysis, 375 genes were identified as differentially expressed genes in GSE102485. Only three genes (FCGR3A, DPEP2, and ADGRF5) were characterized as upregulated in both the dataset and the SWATH-MS list. The area under the ROC curve (AUC) of FCGR3A, DPEP2, and ADGRF5 in distinguishing PDR from others was 0.739, 0.770, and 0.739., Conclusions and Clinical Relevance: We provide a novel strategy for biomarker screening and identified plasma FCGR3A, DPEP2, and ADGRF5 as potential biomarkers for patients with PDR. Identifying the key molecules of the disease is essential for the development of new therapeutic molecules and new uses of existing drugs., (© 2021 Wiley-VCH GmbH.)

In this study, a detailed genetic dissection of the huge and complex bla NDM -carrying genetic elements and their related mobile genetic elements was performed in Enterobacteriaceae. An extensive comparison was applied to 12 chromosomal genetic elements, including six sequenced in this study and the other six from GenBank. These 12 genetic elements were divided into five groups: a novel IME Tn 6588 ; two related IMEs Tn 6523 (SGI1) and Tn 6589 ; four related ICEs Tn 6512 (R391), Tn 6575 (ICE Pvu ChnBC22), Tn 6576 , and Tn 6577 ; Tn 7 and its derivatives Tn 6726 and 40.7-kb Tn 7 -related element; and two related IMEs Tn 6591 (GI sul2 ) and Tn 6590 . At least 51 resistance genes, involved in resistance to 18 different categories of antibiotics and heavy metals, were found in these 12 genetic elements. Notably, Tn 6576 carried another ICE Tn 6582 . In particular, the six bla NDM -carrying genetic elements Tn 6588 , Tn 6589 , Tn 6575 , Tn 6576 , Tn 6726 , and 40.7-kb Tn 7 -related element contained large accessory multidrug resistance (MDR) regions, each of which had a very complex mosaic structure that comprised intact or residual mobile genetic elements including insertion sequences, unit or composite transposons, integrons, and putative resistance units. Core bla NDM genetic environments manifested as four different Tn 125 derivatives and, notably, two or more copies of relevant Tn 125 derivatives were found in each of Tn 6576 , Tn 6588 , Tn 6589 , and 40.7-kb Tn 7 -related element. The huge and complex bla NDM -carrying genetic elements were assembled from complex transposition and homolog recombination. Firstly identified were eight novel mobile elements, including three ICEs Tn 6576 , Tn 6577 , and Tn 6582 , two IMEs, Tn 6588 and Tn 6589 , two composite transposons Tn 6580a and Tn 6580b , and one integron In1718., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Luo, Yin, Zeng, Hu, Jiang, Jing, Chen, Wang, Song, Yang and Zhou.)