Roles of the spiA gene from Salmonella enteritidis in biofilm formation and virulence

Salmonella enteritidis has emerged as one of the most important food-borne pathogens for humans, and the formation of biofilms by this species may improve its resistance to disadvantageous conditions. The spiA gene of Salmonella typhimurium is essential for its virulence in host cells. However, the roles of the spiA gene in biofilm formation and virulence of S. enteritidis remain unclear. In this study we constructed a spiA gene mutant with a suicide plasmid. Phenotypic and biological analysis revealed that the mutant was similar to the wild-type strain in growth rate, morphology, and adherence to and invasion of epithelial cells. However, the mutant showed reduced biofilm formation in a quantitative microtitre assay and by scanning electron microscopy, and significantly decreased curli production and intracellular proliferation of macrophages during the biofilm phase. In addition, the spiA mutant was attenuated in a mouse model in both the exponential growth and biofilm phases. These data indicate that the spiA gene is involved in both biofilm formation and virulence of S. enteritidis

Anti-Tumor Effect of Rutin on Human Neuroblastoma Cell Lines through Inducing G2/M Cell Cycle Arrest and Promoting Apoptosis

Aims. To further investigate the antineuroblastoma effect of rutin which is a type of flavonoid. Methods. The antiproliferation of rutin in human neuroblastoma cells LAN-5 were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Chemotaxis of LAN-5 cells was assessed using transwell migration chambers and scratch wound migration assay. The cell cycle arrest and apoptosis in a dose-dependent manner was measured by flow cytometric and fluorescent microscopy analyses. The apoptosis-related proteins BAX and BCL2 as well as MYCN mRNA express were determined by RT-PCR analysis. Secreted TNF-α level were determined using specific enzyme-linked immunosorbent assay kits. Results. Rutin significantly inhibited the growth of LAN-5 cells and chemotactic ability. Flow cytometric analysis revealed that rutin induced G2/M arrest in the cell cycle progression and induced cell apoptosis. The RT-PCR showed that rutin could decrease BCL2 expression and BCL2/BAX ratio. In the meantime, the MYCN mRNA level and the secretion of TNF-α were inhibited. Conclusion. These results suggest that rutin produces obvious antineuroblastoma effects via induced G2/M arrest in the cell cycle progression and induced cell apoptosis as well as regulating the expression of gene related to apoptosis and so on. It supports the viability of developing rutin as a novel therapeutic prodrug for neuroblastoma treatment, as well as providing a new path on anticancer effect of Chinese traditional drug

DIACHRONOUS EVOLUTION OF BACK-ARC BASINS IN THE SOUTH TIANSHAN: INSIGHTS FROM STRUCTURAL, GEOCHRONOLOGICAL AND GEOCHEMICAL STUDIES OF THE WUWAMEN OPHIOLITE MÉLANGE

The South Tianshan is located to the north of the Tarim block and defines the southern margin of the Paleozoic Central Asian Orogenic Belt (CAOB). This study presents new structural data, geochronological and geochemical results for the Wuwamen ophiolite mélange in the Chinese segment of the South Tianshan. In the south, the Wuwamen ophiolite mélange shows typical block-in-matrix fabrics and occurs in the footwall of a south-dipping thrust fault, hanging wall of which is composed of weakly metamorphosed and deformed Lower Paleozoic marine to deep marine sequences from the South Tianshan. In the north, a southdipping thrust fault juxtaposes the Wuwamen ophiolite mélange in its hanging wall against the high-grade and strongly deformed metasedimentary rocks from the Central Tianshan in its footwall.The South Tianshan is located to the north of the Tarim block and defines the southern margin of the Paleozoic Central Asian Orogenic Belt (CAOB). This study presents new structural data, geochronological and geochemical results for the Wuwamen ophiolite mélange in the Chinese segment of the South Tianshan. In the south, the Wuwamen ophiolite mélange shows typical block-in-matrix fabrics and occurs in the footwall of a south-dipping thrust fault, hanging wall of which is composed of weakly metamorphosed and deformed Lower Paleozoic marine to deep marine sequences from the South Tianshan. In the north, a southdipping thrust fault juxtaposes the Wuwamen ophiolite mélange in its hanging wall against the high-grade and strongly deformed metasedimentary rocks from the Central Tianshan in its footwall

Estudo e Desenvolvimento de Uma Carga Eletronica Regenerativa, Baseada em Inversor Nao-Autonomo, Aplicada a...

Apresenta-se nesse estudo uma nova proposta de carga eletrônica regenerativa (CERE) para testes em equipamentos elétricos que permite que laboratórios de eletrônica de potência realizem ensaios com baixas perdas de energia; nesse caso, o fluxo de potência fornecida pelo equipamento em teste é dirigido quase que totalmente de volta para a rede elétrica, minimizando a dissipação de energia por efeito Joule, diferente do que acontece com o uso de resistores ou cargas eletrônicas convencionais. Do ponto de vista técnico, tais ensaios poderão ter suas características variadas segundo a necessidade de análise do equipamento sob teste, permitindo submetê-os a diferentes condições de funcionamento. O objetivo do protótipo da CERE-CA aqui desenvolvida é apenas comprovar os resultados teóricos e de simulação apresentados na dissertação. Neste primeiro momento, não haverá preocupação com a qualidade da energia que é regenerada para a rede CA, e nem com a precisão do controle do fluxo de corrente drenado da fonte CA. Estas e outras melhorias deverão ser implantadas em pesquisas futuras nessa área de eletrônica de potência

Enhancing Literacy Education with Narrative Richness in the Metaverse

Through an education-centric metaverse learning application, this research aims to assess the use of narrative richness to deliver media, language, and sustainability literacy education. The 21st-century learning needs require teaching and learning resources to be shared and managed more effectively across institutions. The use of metaverse features can help to manage varying narrative richness to boost learning reflection and attitude. Despite its potential, it is unclear how narrative richness in the metaverse can enhance teaching and learning. The study proposed in this research, which includes institutions from four Asian countries, is driven by this knowledge and evidence gap. Module leaders conceptualize and evaluate a purpose-built metaverse-learning application to produce rich and realistic learning experiences. We utilize narratives to enhance the realism of learning experiences and will assess the effects of narrative richness on learning reflection and attitude

Transforming growth factor β-activated kinase 1 transcriptionally suppresses hepatitis B virus replication

Hepatitis B Virus (HBV) replication in hepatocytes is restricted by the host innate immune system and related intracellular signaling pathways. Transforming growth factor β-activated kinase 1 (TAK1) is a key mediator of toll-like receptors and pro-inflammatory cytokine signaling pathways. Here, we report that silencing or inhibition of endogenous TAK1 in hepatoma cell lines leads to an upregulation of HBV replication, transcription, and antigen expression. In contrast, overexpression of TAK1 significantly suppresses HBV replication, while an enzymatically inactive form of TAK1 exerts no effect. By screening TAK1-associated signaling pathways with inhibitors and siRNAs, we found that the MAPK-JNK pathway was involved in TAK1-mediated HBV suppression. Moreover, TAK1 knockdown or JNK pathway inhibition induced the expression of farnesoid X receptor α, a transcription factor that upregulates HBV transcription. Finally, ectopic expression of TAK1 in a HBV hydrodynamic injection mouse model resulted in lower levels of HBV DNA and antigens in both liver and serum. In conclusion, our data suggest that TAK1 inhibits HBV primarily at viral transcription level through activation of MAPK-JNK pathway, thus TAK1 represents an intrinsic host restriction factor for HBV replication in hepatocytes

Mechanism of Beraprost Effects on Pulmonary Hypertension: Contribution of Cross-Binding to PGE2 Receptor 4 and Modulation of O2 Sensitive Voltage-Gated K+ Channels

Background: The purpose of this study is to elucidate mechanism(s) by which the orally active PGI2 analog, Beraprost (BPS), ameliorates pulmonary hypertension (PH). Prostaglandins are an important treatment for PH. Mechanisms of their action are not fully elucidated in relation to receptor subtype and effects on O2 sensitive Kv channels.Methods: Distal (3rd order and beyond) pulmonary arteries from chronically hypoxic rats and from humans with established PH were studied. Measurements included pulmonary haemodynamics and histology, vascular reactivity, prostanoid receptor expression and activity of the O2 sensitive Kv channels.Results: Prostacyclin receptor (IP), prostaglandin receptor E3 (EP3) and prostaglandin receptor E4 (EP4) are the main pulmonary artery receptor subtypes in both rat and human pulmonary arteries. Circulating levels of PGI2 and PGE2 were reduced in PH. PH was also associated with reduced receptor expression of IP but not of EP4. The effects on IP expression were overcome with BPS. Dilatory responses in PH to BPS were reduced in the presence of EP4 blockade. Expression and activity of oxygen sensitive Kv channels were reduced in pulmonary artery smooth muscle cell from rats with PH and humans with PAH and were also overcome by administration of BPS. Effects of BPS on oxygen sensitive Kv channels were reduced in the presence of EP4 blockade implicating the EP4 receptor, as well as the IP receptor, in mediating BPS effects.Conclusion: Reduced expression of pulmonary IP receptors and reduced activity of O2 sensitive Kv channels are found in PH in both humans and rats. The orally active prostacyclin analogue, BPS, is able to reverse these changes, partly through binding to the EP4 receptor

Utility of S100A12 as an Early Biomarker in Patients With ST-Segment Elevation Myocardial Infarction

Importance: S100A12 is a calcium binding protein which is involved in inflammation and progression of atherosclerosis. Objective: We sought to investigate the utility of S100A12 as a biomarker for the early diagnosis and prognostication of patients presenting with ST-segment elevation myocardial infarction (STEMI). Design, Setting, and Participants: S100A12 was measured in 1023 patients presenting to the emergency department with acute chest pain between June 2012 and November 2015. An independent cohort of 398 patients enrolled at 3 different hospitals served as a validation cohort. Main Outcomes and Measures: The primary clinical endpoint of interest was major adverse cardiac and cerebral events (MACCE) defined as a composite of all-cause death, MI, stroke, or hospitalization for heart failure. Results: A total of 438/1023 patients (42.8%) in the diagnosis cohort were adjudicated as STEMI, among whom plasma S100A12 levels increased within 30 min and peaked 1–2 h after symptom onset. Compared with high-sensitivity cardiac troponin T and creatine kinase-MB isoenzyme, S100A12 more accurately identified STEMI, especially within the first 2 h after symptom onset (area under the curve 0.963 compared with 0.860 for hscTnT and 0.711 for CK-MB, both P \u3c 0.05). These results were consistent in the 243-patient validation cohort. The 1-year rate of MACCE was greatest in patients in the highest peak S100A12 tertile, intermediate in the middle tertile and least in the lowest tertile (9.3 vs. 5.7 vs. 3.0% respectively, Ptrend = 0.0006). By multivariable analysis the peak plasma concentration of S100A12 was an independent predictor of MACCE within 1 year after STEMI (HR, 1.001, 95%CI, 1.000–1.002; P = 0.0104). Zhang et al. S100A12 as a STEMI Biomarker Conclusions and Relevance: S100A12 rapidly identified patients with STEMI, more accurately than other cardiac biomarkers, especially within the first 2 h after symptom onset. The peak plasma S100A12 level was a strong predictor of 1-year prognosis after STEMI

Global climate forcing of aerosols embodied in international trade

International trade separates regions consuming goods and services from regions where goods and related aerosol pollution are produced. Yet the role of trade in aerosol climate forcing attributed to different regions has never been quantified. Here, we contrast the direct radiative forcing of aerosols related to regions’ consumption of goods and services against the forcing due to emissions produced in each region. Aerosols assessed include black carbon, primary organic aerosol, and secondary inorganic aerosols, including sulfate, nitrate and ammonium. We find that global aerosol radiative forcing due to emissions produced in East Asia is much stronger than the forcing related to goods and services ultimately consumed in that region because of its large net export of emissions-intensive goods. The opposite is true for net importers such as Western Europe and North America: global radiative forcing related to consumption is much greater than the forcing due to emissions produced in these regions. Overall, trade is associated with a shift of radiative forcing from net importing to net exporting regions. Compared to greenhouse gases such as carbon dioxide, the short atmospheric lifetimes of aerosols cause large localized differences between consumption- and production-related radiative forcing. International efforts to reduce emissions in the exporting countries will help alleviate trade-related climate and health impacts of aerosols while lowering global emissions

Transboundary health impacts of transported global air pollution and international trade

Millions of people die every year from diseases caused by exposure to outdoor air pollution1, 2, 3, 4, 5. Some studies have estimated premature mortality related to local sources of air pollution6, 7, but local air quality can also be affected by atmospheric transport of pollution from distant sources8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18. International trade is contributing to the globalization of emission and pollution as a result of the production of goods (and their associated emissions) in one region for consumption in another region14, 19, 20, 21, 22. The effects of international trade on air pollutant emissions23, air quality14 and health24 have been investigated regionally, but a combined, global assessment of the health impacts related to international trade and the transport of atmospheric air pollution is lacking. Here we combine four global models to estimate premature mortality caused by fine particulate matter (PM2.5) pollution as a result of atmospheric transport and the production and consumption of goods and services in different world regions. We find that, of the 3.45 million premature deaths related to PM2.5 pollution in 2007 worldwide, about 12 per cent (411,100 deaths) were related to air pollutants emitted in a region of the world other than that in which the death occurred, and about 22 per cent (762,400 deaths) were associated with goods and services produced in one region for consumption in another. For example, PM2.5 pollution produced in China in 2007 is linked to more than 64,800 premature deaths in regions other than China, including more than 3,100 premature deaths in western Europe and the USA; on the other hand, consumption in western Europe and the USA is linked to more than 108,600 premature deaths in China. Our results reveal that the transboundary health impacts of PM2.5 pollution associated with international trade are greater than those associated with long-distance atmospheric pollutant transport