646 research outputs found

    New Hepatitis E Virus Genotype in Bactrian Camels, Xinjiang, China, 2013

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    Switching of pyruvate kinase isoform L to M2 promotes metabolic reprogramming in hepatocarcinogenesis

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    Hepatocellular carcinoma (HCC) is an aggressive tumor, with a high mortality rate due to late symptom presentation and frequent tumor recurrences and metastasis. It is also a rapidly growing tumor supported by different metabolic mechanisms; nevertheless, the biological and molecular mechanisms involved in the metabolic reprogramming in HCC are unclear. In this study, we found that pyruvate kinase M2 (PKM2) was frequently over-expressed in human HCCs and its over-expression was associated with aggressive clinicopathological features and poor prognosis of HCC patients. Furthermore, knockdown of PKM2 suppressed aerobic glycolysis and cell proliferation in HCC cell lines in vitro. Importantly, knockdown of PKM2 hampered HCC growth in both subcutaneous injection and orthotopic liver implantation models, and reduced lung metastasis in vivo. Of significance, PKM2 over-expression in human HCCs was associated with a down-regulation of a liver-specific microRNA, miR-122. We further showed that miR-122 interacted with the 3UTR of the PKM2 gene. Re-expression of miR-122 in HCC cell lines reduced PKM2 expression, decreased glucose uptake in vitro, and suppressed HCC tumor growth in vivo. Our clinical data and functional studies have revealed a novel biological mechanism involved in HCC metabolic reprogramming.published_or_final_versio

    Virulence determinants, drug resistance and mobile genetic elements of Laribacter hongkongensis: a genome-wide analysis

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    <p>Abstract</p> <p>Background</p> <p><it>Laribacter hongkongensis </it>is associated with community-acquired gastroenteritis and traveler's diarrhea. In this study, we performed an in-depth annotation of the genes in its genome related to the various steps in the infective process, drug resistance and mobile genetic elements.</p> <p>Results</p> <p>For acid and bile resistance, <it>L. hongkongensis </it>possessed a urease gene cassette, two <it>arc </it>gene clusters and bile salt efflux systems. For intestinal colonization, it possessed a putative adhesin of the autotransporter family homologous to those of diffusely adherent <it>Escherichia coli </it>(<it>E. coli</it>) and enterotoxigenic <it>E. coli</it>. To evade from host defense, it possessed superoxide dismutase and catalases. For lipopolysaccharide biosynthesis, it possessed the same set of genes that encode enzymes for synthesizing lipid A, two Kdo units and heptose units as <it>E. coli</it>, but different genes for its symmetrical acylation pattern, and nine genes for polysaccharide side chains biosynthesis. It contained a number of CDSs that encode putative cell surface acting (RTX toxin and hemolysins) and intracellular cytotoxins (patatin-like proteins) and enzymes for invasion (outer membrane phospholipase A). It contained a broad variety of antibiotic resistance-related genes, including genes related to β-lactam (n = 10) and multidrug efflux (n = 54). It also contained eight prophages, 17 other phage-related CDSs and 26 CDSs for transposases.</p> <p>Conclusions</p> <p>The <it>L. hongkongensis </it>genome possessed genes for acid and bile resistance, intestinal mucosa colonization, evasion of host defense and cytotoxicity and invasion. A broad variety of antibiotic resistance or multidrug resistance genes, a high number of prophages, other phage-related CDSs and CDSs for transposases, were also identified.</p

    Development of a multi-locus sequence typing scheme for Laribacter hongkongensis, a novel bacterium associated with freshwater fish-borne gastroenteritis and traveler's diarrhea

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    <p>Abstract</p> <p>Background</p> <p>Laribacter hongkongensis is a newly discovered, facultative anaerobic, Gram-negative, motile, sea gull-shaped rod associated with freshwater fish borne gastroenteritis and traveler's diarrhea. A highly reproducible and discriminative typing system is essential for better understanding of the epidemiology of <it>L. hongkongensis</it>. In this study, a multilocus sequence typing (MLST) system was developed for <it>L. hongkongensis</it>. The system was used to characterize 146 <it>L. hongkongensis </it>isolates, including 39 from humans and 107 from fish.</p> <p>Results</p> <p>Fragments (362 to 504 bp) of seven housekeeping genes were amplified and sequenced. Among the 3068 bp of the seven loci, 332 polymorphic sites were observed. The median number of alleles at each locus was 34 [range 22 (<it>ilvC</it>) to 45 (<it>thiC</it>)]. All seven genes showed very low <it>d</it><sub><it>n</it></sub>/<it>d</it><sub><it>s </it></sub>ratios of < 0.04, indicating that no strong positive selective pressure is present. A total of 97 different sequence types (STs) were assigned to the 146 isolates, with 80 STs identified only once. The overall discriminatory power was 0.9861. eBURST grouped the isolates into 12 lineages, with six groups containing only isolates from fish and three groups only isolates from humans. Standardized index of association (<it>I</it><sup><it>S</it></sup><sub><it>A</it></sub>) measurement showed significant linkage disequilibrium in isolates from both humans and fish. The <it>I</it><sup><it>S</it></sup><sub><it>A </it></sub>for the isolates from humans and fish were 0.270 and 0.636, indicating the isolates from fish were more clonal than the isolates from humans. Only one interconnected network (<it>acnB</it>) was detected in the split graphs. The P-value (P = 0) of sum of the squares of condensed fragments in Sawyer's test showed evidence of intragenic recombination in the <it>rho, acnB </it>and <it>thiC </it>loci, but the P-value (P = 1) of maximum condensed fragment in these gene loci did not show evidence of intragenic recombination. Congruence analysis showed that all the pairwise comparisons of the 7 MLST loci were incongruent, indicating that recombination played a substantial role in the evolution of <it>L. hongkongensis</it>. A website for <it>L. hongkongensis </it>MLST was set up and can be accessed at <url>http://mlstdb.hku.hk:14206/MLST_index.html</url>.</p> <p>Conclusion</p> <p>A highly reproducible and discriminative MLST system was developed for <it>L. hongkongensis</it>.</p

    Folate cycle enzyme MTHFD1L confers metabolic advantages in hepatocellular carcinoma

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    LP-INDEX: Explore the Best Practice of LPWAN Technologies in Smart City

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    Internet of Things (IoT) based infrastructures and applications are essential parts in smart city establishment. The low power wide area network (LPWAN) plays a key role in IoT techniques due to the characteristics of wide coverage and low power consumption. However, it is hard to decide which one of the LPWAN techniques to be implemented in a specific application for best practice. Considering this, we discussed the main characteristics of the three popular LPWAN technologies, LoRaWAN, NB-IoT, and Sigfox, and proposed an LP-INDEX to weighting them according to application requirements. To further distinguish their difference, a comparison test based on parking detection sensors using the three different techniques was implemented as a use case

    Load Forecasting based on Deep Long Short-term Memory with Consideration of Costing Correlated Factor

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    Guangdong University of Technology, Guangzhou, China, Grant from the Financial and Education Department of Guangdong Province 2016[202]: Key Discipline Construction Programme; Education Department of Guangdong Province: New and integrated energy system theory and technology research group, project number 2016KCXTD022; National Science Foundation of China: A Time-Based-Demand- Response Program of Compensated Multiple-Shape Pricing Scheme, Grant No. 51707041; State Grid Technology Project: the Smart Monitoring Techniques Research in Self- Correlated Framework for Power Utility (Grant No. 5211011600RJ); Education Department of Guangdong Province: The Power Market Advanced Service for Load Monitoring Technologies, 2016KQNCX047

    Omicron variant susceptibility to neutralizing antibodies induced in children by natural SARS-CoV-2 infection or COVID-19 vaccine

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    The novel SARS-CoV-2 Omicron variant may increase the risk of re-infection and vaccine breakthrough infections as it possesses key mutations in the spike protein that affect neutralizing antibody response. Most studies on neutralization susceptibility were conducted using specimens from adult COVID-19 patients or vaccine recipients. However, since the paediatric population has an antibody response to SARS-CoV-2 infection that is distinct from the adult population, it is critical to assess the neutralization susceptibility of pediatric serum specimens. This study compared the neutralization susceptibility of serum specimens collected from 49 individuals of <18 years old, including 34 adolescent BNT162b2 (Pfizer-BioNTech) vaccine recipients, and 15 recovered COVID-19 patients aged between 2 and 17. We demonstrated that only 38.2% of BNT162b2 vaccine recipients and 26.7% of recovered COVID-19 patients had their serum neutralization titre at or above the detection threshold in our live virus microneutralization assay. Furthermore, the neutralizing antibody titer against the Omicron variant was substantially lower than those against the ancestral virus or the Beta variant. Our results suggest that vaccine recipients and COVID-19 patients in the pediatric age group will likely be more susceptible to vaccine breakthrough infections or reinfections due to the Omicron variant than previous variants
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