Changes and significance of TLR7/9 and IFN-Ⅰ levels in children with severe mycoplasma pneumoniae pneumonia

Objective To investigate the changes and significance of Toll-like receptor 7 （TLR7）， TLR9 and type I interferon （IFN-Ⅰ） in children with severe mycoplasma pneumoniae pneumonia （SMPP）. Methods 80 children with mycoplasma pneumoniae pneumonia （MPP） were divided into the non-severe MPP （MPP group） and SMPP groups （SMPP group）. 26 healthy children who underwent outpatient physical examination were chosen as the control group. Serum samples in each group were collected. In the SMPP group， bronchoalveolar lavage fluid （BALF） on the affected and contralateral sides of 26 children with unilateral lung consolidation， atelectasis， lung abscess or lung tissue necrosis on imaging examination were collected. The levels of TLR7， TLR9， myeloid differentiation factor 88 （MyD88）， interferon-α （IFN-α） and IFN-β in the serum and BALF samples were determined by enzyme-linked immunosorbent assay （ELISA）. Results The serum levels of TLR7， TLR9， MyD88， IFN-α and IFN-β in the SMPP and MPP groups were significantly higher than those in the control group， and the levels of all cytokines in the SMPP group were significantly higher compared with those in the MPP group （all P < 0.05）. The levels of TLR7， TLR9， MyD88， IFN-α and IFN-β in the BALF on the affected side were significantly higher than those on the contralateral side （all P < 0.01）. The area under the receiver operating characteristic curve （AUC） of serum TLR7 and MyD88 levels for predicting SMPP was 0.709 and 0.723. Conclusions Over-induced and generated TLR7， TLR9， IFN-α and IFN-β may be pathogenic factors for the incidence of SMPP and severe local lung tissue injury in children with SMPP. TLR7 and MyD88 can be used as predictors of SMPP to guide clinical treatment

Research Progress on Microbial Source Tracking for Traceability of Pollution Sources in Food Chains

Fecal microbial contamination in the food chain is a significant concern in the field of food safety as it is one of the most important pathways causing foodborne diseases. Microbial source tracking (MST) is an effective approach to address this issue, which can track the sources and contamination of fecal microbes. MST methods can be categorized into two types: library-dependent methods (LDMs) and library-independent methods (LIMs), with LIMs including culture-dependent and culture-independent methods. The non-culture-dependent method using 16S rRNA and host-microbial interaction genes as specific molecular markers has been widely used to investigate microbial contamination in the food chain. This review provides an overview of the basic principle and characteristics of MST, and focuses on recent advances in MST methods based on host-specific molecular markers for tracing microbial contamination in the food chain. Furthermore, future prospects of MST are discussed based on its unique advantages and disadvantages

PHT427 as an effective New Delhi metallo-β-lactamase-1 (NDM-1) inhibitor restored the susceptibility of meropenem against Enterobacteriaceae producing NDM-1

IntroductionWith the increasingly serious problem of bacterial drug resistance caused by NDM-1, it is an important strategy to find effective inhibitors to assist β-lactam antibiotic treatment against NDM-1 resistant bacteria. In this study, PHT427 (4-dodecyl-N-1,3,4-thiadiazol-2-yl-benzenesulfonamide) was identified as a novel NDM-1 inhibitor and restored the susceptibility of meropenem against Enterobacteriaceae producing NDM-1.MethodsWe used a high throughput screening model to find NDM-1 inhibitor in the library of small molecular compounds. The interaction between the hit compound PHT427 and NDM-1 was analyzed by fluorescence quenching, surface plasmon resonance (SPR) assay, and molecular docking analysis. The efficacy of the compound in combination with meropenem was evaluated by determining the FICIs of Escherichia coli BL21(DE3)/pET30a(+)-blaNDM–1 and Klebsiella pneumoniae clinical strain C1928 (producing NDM-1). In addition, the mechanism of the inhibitory effect of PHT427 on NDM-1 was studied by site mutation, SPR, and zinc supplementation assays.ResultsPHT427 was identified as an inhibitor of NDM-1. It could significantly inhibit the activity of NDM-1 with an IC50 of 1.42 μmol/L, and restored the susceptibility of meropenem against E. coli BL21(DE3)/pET30a(+)-blaNDM–1 and K. pneumoniae clinical strain C1928 (producing NDM-1) in vitro. The mechanism study indicated that PHT427 could act on the zinc ions at the active site of NDM-1 and the catalytic key amino acid residues simultaneously. The mutation of Asn220 and Gln123 abolished the affinity of NDM-1 by PHT427 via SPR assay.DiscussionThis is the first report that PHT427 is a promising lead compound against carbapenem-resistant bacteria and it merits chemical optimization for drug development

Dynamic distribution and expression in vivo of the human interferon gamma gene delivered by adenoviral vector

<p>Abstract</p> <p>Background</p> <p>We previously found that r-hu-IFNγ exerts a potent anti-tumor effect on human nasopharyngeal carcinoma xenografts <it>in vivo</it>. Considering the fact that the clinical use of recombinant IFNγ is limited by its short half-life and systemic side effects, we developed a recombinant adenovirus, Ad-IFNγ.</p> <p>Methods</p> <p>Dynamic distribution of the adenovirus vector and expression of IFNγ were evaluated by Q-PCR and ELISA after intratumoral administration of Ad-IFNγ into CNE-2 xenografts.</p> <p>Results</p> <p>Ad-IFNγ DNA was mainly enriched in tumors where the Ad-IFNγ DNA was injected (<it>P </it>< 0.05, compared to blood or parenchymal organs), as well as in livers (<it>P </it>< 0.05). Concentrations of Ad-IFNγ DNA in other organs and blood were very low. Intratumoral Ad-IFNγ DNA decreased sharply at high concentrations (9 × 10⁵copies/μg tissue DNA), and slowly at lower concentrations (1.7–2.9 × 10⁵copies/μg tissue DNA). IFNγ was detected in the tumors and parenchymal organs. The concentration of IFNγ was highest in the tumor (<it>P </it>< 0.05), followed by the liver and kidney (<it>P </it>< 0.05). High-level intratumoral expression of IFNγ was maintained for at least 7 days, rapidly peaking on day 3 after injection of Ad-IFNγ DNA.</p> <p>Conclusion</p> <p>An IFNγ gene delivered by an adenoviral vector achieved high and consistent intratumoral expression. Disseminated Ad-IFNγ DNA and the transgene product were mainly enriched in the liver.</p

Minicircle-oriP-IFNγ: A Novel Targeted Gene Therapeutic System for EBV Positive Human Nasopharyngeal Carcinoma

) in which the transgene expression was under the transcriptional regulation of oriP promoter.. Immunohistochemistry was used to detect the expression and the activity of the IFNγ in tumor sections. Our results demonstrated that mc-oriP vectors mediated comparable gene expression and anti-proliferative effect in the EBV-positive NPC cell line C666-1 compared to mc-CMV vectors. Furthermore, mc-oriP vectors exhibited much lower killing effects on EBV-negative cell lines compared to mc-CMV vectors. The targeted expression of mc-oriP vectors was inhibited by EBNA1-siRNA in C666-1. This selective expression was corroborated in EBV-positive and -negative tumor models. as a safe and highly effective targeted gene therapeutic system for the treatment of EBV positive NPC

Rail-Induced Social Changes in Central Guangzhou, China

The economic benefits of rail development are well researched, but the social effects of rail are largely understudied, especially in China. We analyze the association between educational attainment level and urban rail development using the 2000 and 2010 census data from Central Guangzhou, China, and a linear mixed-effects modeling approach. Our results indicate that the change in education level is greater in rail neighborhoods than in non-rail neighborhoods in the central area of Guangzhou, and that the rail/metro-induced effect on educational attainment level is evidenced. This research contributes to the existing literature by exploring a new method for this line of research and providing empirical evidence of social changes in a city that has experienced rapid economic growth and pioneered rail development in China, a developing country. The limitations and implications of the research are discussed

Rail-Induced Social Changes in Central Guangzhou, China

The economic benefits of rail development are well researched, but the social effects of rail are largely understudied, especially in China. We analyze the association between educational attainment level and urban rail development using the 2000 and 2010 census data from Central Guangzhou, China, and a linear mixed-effects modeling approach. Our results indicate that the change in education level is greater in rail neighborhoods than in non-rail neighborhoods in the central area of Guangzhou, and that the rail/metro-induced effect on educational attainment level is evidenced. This research contributes to the existing literature by exploring a new method for this line of research and providing empirical evidence of social changes in a city that has experienced rapid economic growth and pioneered rail development in China, a developing country. The limitations and implications of the research are discussed

Titanium Dioxide Nanoparticles Induced Proinflammation of Primary Cultured Cardiac Myocytes of Rat

Titanium dioxide (TiO2) nanoparticles are widely used in electronics, biology, and medicine owing to their special properties. However, during TiO2 nanoparticles exposure, nanoparticles may enter the blood circulation and translocate to the heart, and they may result in negative effects on the cardiovascular system. In this study, we demonstrated that the anatase and rutile TiO2 nanoparticles had potential toxicological effects on primary cultured cardiac myocytes of rat. After incubating with the anatase and rutile TiO2 nanoparticles, the primary cultured cardiac myocytes had become elongated and appeared to detach from the surface of cell plate. After exposure to 50, 100, and 150 μg/mL anatase and rutile TiO2 nanoparticles for 2 days, the obvious decrease of cell viability was observed. And further studies showed that TiO2 nanoparticles exposure could induce the high expression of proinflammatory cytokines TNF-α and IL-6, especially in 150 μg/mL group. The long-rod rutile TiO2 had more strong effects on cell viability and proinflammatory cytokines induction than red-blood cells like anatase TiO2. Results indicated that TiO2 nanoparticles exposure could impair the function of primary cultured cardiac myocytes of rat. Therefore, these findings support the view that much more attention should be aroused on the application of these nanoparticles and their potential exposure effects on human beings

Heavy Metal Content and Pollution Assessment in Typical Check Dam Sediment in a Watershed of Loess Plateau, China

To understand historical trends and assess the ecological risk associated with heavy metal pollution, the concentration of eight species of heavy metals (vanadium (V), chromium (Cr), manganese (Mn), cobalt (Co), nickel (Ni), zinc (Zn), copper (Cu), and arsenic (As)) in typical silt dam sediments on the Loess Plateau were analyzed. The radionuclide 137Cs was used to quantify rates of erosion, deposition, and heavy metal contamination in the soils of a watershed that supplies a check dam. The sediment record revealed three time periods distinguished by trends in erosion and pollutant accumulation (1960&ndash;1967, 1968&ndash;1981, and 1985&ndash;1991). Heavy metal concentrations were highest but exhibited significant fluctuation in the first two periods (1960&ndash;1967 and 1968&ndash;1981). From 1985 to 1991, heavy metal pollution showed a downward trend and tended to be stable. The potential risks of heavy metals in silt dam sediments were explored by applying the geo-accumulation index and the potential ecological risk index. The results indicated medium risk associated with Cu and As accumulation, especially in 1963, 1971, and 1986 when the assessed values increased significantly from previous levels. Agricultural practices and high rates of slope erosion may be responsible for the enrichment of As and Cu in soil and the accompanying increase in risk. Land use optimization and the careful use of fertilizers could be used to control or intercept heavy metal pollutants in dammed lands. The results provide the basis for evaluating the current status and ecological risk of heavy metal contamination in dam sediments and for predicting possible heavy metal pollution in the future