Abstract Sepsis is a devastating condition characterized by a systemic inflammatory response. Recently, high mobility group box 1 (HMGB1) was identified as a necessary and sufficient mediator of the lethal systemic inflammation caused by sepsis. However, despite its clinical importance, the mechanism of HMGB1 release has remained to be elusive. In this study, we demonstrate that the IFN-β-mediated JAK/STAT pathway is essential for LPS or Escherichia coli-induced HMGB1 release, which is dependent on Toll/IL-1R domain-containing adapter-inducing IFN-β adaptor. Additionally, we show that NO acts as a downstream molecule of the IFN-β signaling. Furthermore, the JAK inhibitor treatment as well as the STAT-1 or IFN-β receptor deficiency reduced HMGB1 release in a murine model of endotoxemia. Our results suggest that HMGB1 release in sepsis is dependent on the IFN-β signaling axis; thus, therapeutic agents that selectively inhibit IFN-β signaling could be beneficial in the treatment of sepsis.
Dominik Bartmanski, Seonju Kim, Martina Löw, Timothy Pape und Jörg Stollmann widmen sich in ihrem Beitrag der Planstadt Songdo, die, von Grund auf als Smart City konzipiert, lange als Vorzeigeprojekt und Testfall für umfassende Digitalisierung galt. Heute lockt die engmaschig überwachte und von unzähligen Sensoren gesteuerte Stadt vor allem Koreas Mittelschicht an. Doch ihre Beliebtheit bei Immobilienkäufern hat wenig mit innovativer HighTech zu tun, sondern mehr mit den planerischen Glaubenssätzen der koreanischen Spätmoderne. Songdo ist ein Musterbeispiel dafür, wie hypermoderne Smart Cities soziale Unterschiede entlang der modernen Dreifaltigkeit von Effizienz, Sicherheit und Überwachung reproduzieren. Das digitale Substrat der Stadt erhöht die Vermarktbarkeit und Wertigkeit der urbanen Gebilde ohne neue Werte zu schaffen. Die Enthüllung eines gewöhnlichen Developmentalismus hinter der scheinbar außergewöhnlichen, smarten Idealstadt entmystifiziert diese. Das Zusammenspiel von Technologieunternehmen und Staat führt zu einer weiteren Kommerzialisierung neuen Wohnraums und zu einer ausgeprägten Raumorientierung der koreanischen Mittelschicht. Die umfassende Digitalisierung bleibt eher unterschwellig präsent, deren Funktionalität im Hintergrund. Gleichzeitig produziert Songdo als neuartiges Wohnumfeld Räume, die das Verhältnis zwischen öffentlich und privat, zwischen Inklusion und Exklusion neu ordnen. Die enge Verflechtung unterschiedlicher Kontexte und Texturen erschafft Wohnräume mit einer polykontexturalen Struktur. Im Falle Songdos impliziert dies eher graduelle, nicht substanzielle Veränderungen des Lebensalltags.
This study investigated association between smoking habit change and cancer-related mortality risk in Korean women. Materials and MethodsStudy population were women aged ≥40 years who underwent two biennial cancer screenings during 2009-2012 and were followed up until 2020.Participants were grouped into sustained nonsmokers, sustained quitters, new quitters, relapsers/smoking initiators, and sustained smokers.Outcomes included all-cause and cancer-related deaths.Cox regression and competing risk analysis was used to assess association between smoking habit change and mortality risk. ResultsOf 2,892,590 women, 54,443 death cases were recorded (median follow-up of 9.0 years).Compared with sustained non-smokers, mortality risk from all causes and cancer-related causes increased in all other smoking groups.Cancer-related risk increased 1.22-fold among sustained quitters (95% CI 1.10-1.36),1.56-fold (95% CI 1.40-1.75) in new quitters, 1.40-fold (95% CI 1.21-1.62) in relapsers/smoking initiators, and 1.61-fold (95% CI 1.46-1.78) in sustained smokers compared with sustained non-smokers.Women who were sustained smokers with higher smoking intensity had a higher mortality risk in terms of HR compared to non-smokers (<5 pack-years 2.12fold, 5-10 pack-years 2.15-fold, and >10 pack-years 2.27-fold). ConclusionQuitting smoking earlier is critical for preventing death from all causes and cancer among female smokers.
Abstract: This study was undertaken to investigate the potential toxicity and establish the no observed adverse effect level (NOAEL) and target organ(s) of negatively charged colloidal silica particles of different sizes, ie, SiO 2 EN,20(-) (20 nm) or SiO 2 EN,100(-) (100 nm), administered by gavage in Sprague-Dawley rats. After verification of the physicochemical properties of the SiO 2 particles to be tested, a preliminary dose range-finding study and 90-day repeated dose study were conducted according to the Organisation for Economic Cooperation and Development test guideline. Based on the results of the 14-day dose range-finding study, a high dose was determined to be 2,000 mg/kg, and middle and low doses were set at 1,000 and 500 mg/kg, respectively. In the 90-day toxicity study, there were no animal deaths in relation to administration of SiO 2 particles of either size. In addition, no treatment-related clinical changes or histopathological findings were observed in any of the experimental groups. Moreover, no difference in toxic effects from chronic exposure to SiO 2 EN,20(-) (20 nm) or SiO 2 EN,100(-) (100 nm) was observed. The results of this study indicate that the NOAEL for SiO 2 EN,20(-) and SiO 2 EN,100(-) would most likely be 2,000 mg/kg, and no target organ was identified in rats of either sex. Keywords: silica nanoparticles, particle size, 90-day oral dose toxicity, no observed adverse effect level
In the present paper, a numerical study was carried out to simulate ground expansion induced by an application of pulse discharge technology. Based on laboratory pulse discharge tests, the characteristics of shockwave were investigated, and then the laboratory tests were numerical1y simulated using underwater explosion model implemented in a coupled acoustic-structural finite element analysis. In addition, for clayey soils, the expansion of ground was also studied using soil properties obtained from empirical correlations with SPT N values. It was found that the calculation results well agreed with the field test results.
The purpose of this study is to investigate the opinions of teachers, directors, and parents about childcare teachers' facial expression language. We performed in-depth interviews based on literature and previous studies, which consisted of ten childcare teachers, ten directors, and ten parents. From the in-depth interviews, we are able to mainly conclude that all groups think that a childcare teacher's facial expression language is very important, and strongly influences interpersonal problems and work performance. Mostly, childcare teachers aim to have pleasant facial expressions. However they complain that in some situations it is difficult to do so, which causes severe stress. They argued that the facial expressions of both the director of the childcare center and the parents are also very important for children. However, the directors thought that teachers' facial expressions affect children and their parents' impressions of the teachers and quality of childcare. The parents are usually highly satisfied with the childcare when the teacher has a pleasant facial expression, which motivates the parents to have a positive impression of the teacher. Taken together, childcare teachers' facial expression language is critical for children and the childcare environment. Thus, developing an education program for facial expression language would be helpful for improving the quality of child care. Plus, childcare environments should be developed so that teachers do not experience difficulty in having pleasant facial expressions. This result might have the limitation of being collected from only female childcare teachers, directors, and parents.
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