Objective
To demonstrate the immune landscape of blood and synovial cells in the setting of ankylosing spondylitis (AS) through the analysis of both single‐cell transcriptome and surface protein ...expression, and to unveil the molecular characteristics of pathogenic Th17 cells.
Methods
This study included 40 individuals with active AS, 20 individuals with stable AS, 40 patients with active rheumatoid arthritis, and 20 healthy controls. Surface phenotype and intracellular staining were assessed using flow cytometry after peripheral blood mononuclear cells and synovial fluid mononuclear cells were stimulated with T cell receptor. Single‐cell transcriptomes of 6 patients with active AS were studied along with cellular indexing of transcriptomes and epitopes by sequencing. We also assessed the outcome of targeting OX40 and glucocorticoid‐induced tumor necrosis factor receptor (GITR) on the surface of Th17 cells in a mouse model of curdlan‐injected SKG mice in which anti‐GITR ligand and/or anti‐OX40 ligand were used.
Results
We identified pathogenic Th17 cells as polyfunctional interleukin‐17A (IL‐17A)– and interferon‐γ (IFNγ)–producing memory CD4+ T cells, with clinically supportive evidence for their pathogenic roles at sites of inflammation in AS. Transcriptome and flow cytometric analyses revealed that the coexpression of TNFRSF4 (OX40) and TNFRSF18 (GITR) is increased in pathogenic Th17 cells. Suppression of ligand receptor interactions in vivo through OX40 and GITR effectively suppressed clinical arthritis and decreased pathogenic Th17 cells in the curdlan‐injected SKG mouse model.
Conclusion
Our results have implications for the understanding of pathogenic Th17 cells in AS patients and suggest potential therapeutic targets.
Lithium‐sulfur (Li‐S) batteries have garnered considerable interest as a promising alternative to current state‐of‐the‐art Li‐ion batteries. However, the shuttle effect poses a formidable challenge ...to development of Li‐S batteries. Considering that all ions in electrolytes move through separators between electrodes, significant attention should be paid to separators to prevent the shuttle effect. Here, a new class of spiderweb‐mimicking, anion‐exchanging separators based on polyionic liquids (“spiderweb separators”) is demonstrated to address the aforementioned issue. The spiderweb separator consists of sandwich‐type functional nanomats (top/bottom layers = multi‐walled carbon nanotube‐wrapped polyetherimide nanomats, middle layer = poly(1‐ethyl‐3‐methylimidazolium) bis(trifluoromethanesulfonyl)imide (PVImTFSI, polyionic liquid)/poly(vinylidene fluoride‐co‐hexafluoropropylene) (PVdF‐HFP) nanomat) on polyethylene separator. The middle nanomat layer enables (discharge voltage‐dependent) reversible trap/release of polysulfides via an anion exchange reaction between TFSI−anions (from PVImTFSI) and polysulfides. The top/bottom nanomat layers respectively act as an upper current collector and a blocking layer to prevent crossover of polysulfides to Li anodes. Driven by its unique morphology and chemical functionalities, the spiderweb separator prevents the shuttle effect while ensuring facile ion transport, leading to exceptional improvement in the electrochemical performance (capacity = 819 mAh g−1 and cycling retention = 72% (at 2.0 C/2.0 C) after 300 cycles) of Li‐S batteries.
Spiderweb‐mimicking anion‐exchanging separators are presented as membrane‐driven strategy for the developing high‐performance Li–S batteries. The polyionic liquid (poly(1‐ethyl‐3‐methylimidazolium) bis(trifluoromethanesulfonyl)imide, (PVImTFSI))–based nanomat in the spiderweb separator enables discharge voltage–dependent, reversible trap/release of polysulfides via an anion exchange reaction between TFSI− anions and polysulfides. Eventually, the spiderweb separator prevents the shuttle effect with ensuring facile ion transport.
This study proposes the use of genetic analysis as a complementary method for species identification in the genus Pinus, particularly in cases where anatomical identification is challenging. Pinus ...species were grouped based on anatomical similarities, and the efficacy of using ycf1b, which is the most variable for Pinus species identification, and rbcL, which is a suggested DNA barcode for land plants, was evaluated within each group. Sequences for each species were obtained from the National Center for Biotechnology Information database and were used to perform phylogenetic analysis. Among the species in Group 1 (P. echinata, P. elliottii, P. ponderosa, P. radiata, P. rigida, P. taeda, and P. virginiana), rbcL was only effective in identifying P. radiata and P. ponderosa, while ycf1b classified five species. An additional DNA barcode, trnH-psbA, was needed to identify P. radiata and P. taeda. In Group 2 (P. densiflora, P. sylvestris, and P. thunbergii), most species were identified using both rbcL and ycf1b, with the exception of possible hybrids of P. densiflora and P. sylvestris. In Group 3 (P. koraiensis and P. strobus), two species were identified using rbcL and ycf1b. Combining genetic species identification with anatomical identification can accurately identify species of the genus Pinus.
While previous research has identified populations susceptible to non-optimal temperatures, disability has been largely overlooked. Given the growing number of persons with disabilities (PwD) and ...their social and health disadvantages, understanding how disability intersects with temperature-related health effects is crucial. This study aimed to investigate the associations between non-optimal temperatures and cardiovascular disease (CVD) hospitalization and examine how these associations vary over time considering the existence of disability.
We used the National Health Insurance Service-National Sample Cohort to investigate the association between non-optimal temperatures and CVD hospitalization in South Korea, 2002–2019. We obtained daily mean temperature from the Korea Meteorological Administration's automated synoptic observing system. We applied a space-time-stratified case-crossover design using a conditional quasi-Poisson regression with a distributed lag non-linear model, adjusting for relative humidity, wind speed, and public holidays. We examined temporal variations in temperature-CVD hospitalization associations using a time window approach. All analyses used the minimum hospitalization temperature (20.0 °C) as reference and were stratified by disability status.
The cumulative exposure-response curve in persons without disabilities showed a J-shape with a relative risk (RR) of 1.07 (95 % confidence interval CI: 0.99, 1.15) at extreme heat (99th percentile) and 1.09 (95 % CI: 0.97, 1.23) at extreme cold (1st percentile). The cumulative exposure-response curve in PwD showed an M-shape with the highest RR at chill (1.22 95 % CI: 1.13, 1.32) and moderate cold temperature (1.11 95 % CI: 1.01, 1.21), defined as the 30th and 5th percentiles, respectively. The impacts of heat and cold decreased over time for persons without disabilities but increased for PwD.
Our study found differential temperature-related impacts on CVD hospitalization based on disability status, and PwD were maladapted to heat and cold over time. This suggests the importance of considering disability when investigating temperature-related health disparity and adopting disability-inclusive adaptation strategies.
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•Persons with disabilities (PwD) more susceptible to less extreme temperatures•Heat and cold effects decreased in non-disabled but increased in PwD over time.•A disability-inclusive approach is needed for effective adaptation strategies.
This study aims to investigate the association of particulate matter with an aerodynamic diameter smaller than 10 μm (PM
) and greenness with cause-specific mortality and their interactions in seven ...Korean metropolitan cities. We obtained the annual standardized cause-specific mortality rates, annual mean concentration of PM
, and annual Normalized Difference Vegetation Index (NDVI) for 73 districts for the period 2008-2016. We used negative binomial regression with city-specific random effects to estimate the association of PM
and greenness with mortality. The models were adjusted for potential confounders and spatial autocorrelation. We also conducted stratified analyses to investigate whether the association between PM
and mortality differs by the level of greenness. Our findings suggest an increased risk of all causes examined, except respiratory disease mortality, with high levels of PM
and decreased risk of cardiovascular-related mortality with a high level of greenness. In the stratified analyses, we found interactions between PM
and greenness, but these interactions in the opposite direction depend on the cause of death. The effects of PM
on cardiovascular-related mortality were attenuated in greener areas, whereas the effects of PM
on non-accidental mortality were attenuated in less green areas. Further studies are needed to explore the underlying mechanisms.
Lag is one of the major uncertainties in the heterogeneity of short-term effects of particulate matter with aerodynamic diameter <10 μm (PM10) on mortality. This study aimed to explore spatial ...variations in extended lag effects of PM10 on all-cause mortality, cardiovascular mortality and respiratory mortality in seven major South Korean cities over a period spanning 2006–2013. We did time-series analysis using generalized linear models and adjusted for temporal trend, day of the week, holiday, influenza epidemic, and weather. Single lag models and distributed lag models were extensively compared, specifically in terms of lag interval, and adjustment for temporal trend. We also conducted a time-stratified case-crossover analysis. Multivariate meta-regressions with city characteristic variables were conducted in order to assess spatial variation in the lag structure. When considering up to previous 45 days of exposure, we found longer lag associations between PM10 and mortality, particularly in all-cause mortality and respiratory mortality. SO2, the ratio of SO2 to PM10 and gross regional domestic product were all found to positively contribute towards the associations between PM10 and all-cause mortality and cardiovascular mortality. Ulsan (Korea's largest industrial city) was found to have the strongest cumulative percentage increases in all-cause mortality and cardiovascular mortality per 10 μg/m3 increase of PM10: 4.9% (95% CI: 2.5, 7.3) and 4.3% (95% CI: −0.9, 9.7) respectively. Busan (Korea's largest seaport city) was found to have the highest cumulative percentage increase in respiratory mortality with an 8.2% increase (95% CI: 2.8, 13.8). In summary, the short-term effects of PM10 on mortality may persist over a period of not just few weeks but longer than a month, and may differ according to regional economy. This study provides public health implication that, in order to minimize the health effects of PM, air quality interventions should focus on not only particulate pollution but also gaseous pollution, such as SO2.
•We found the lag effects of PM10 on mortality up to 45 days of exposure•The effect on cardiovascular mortality was immediate•The effect on respiratory mortality persisted over 45 days•Cities with higher SO2 level and GRDP per capita had greater PM10 risk
The association between temperature and health outcome has been studied in worldwide. However, studies for mild diseases such as AR, with high prevalence and considerable economic burden, are lacking ...compared to other relatively severe respiratory diseases. We aimed to assess the trend of hospital visit by AR and estimate the cold temperature effect on hospital visit by allergic rhinitis in Seoul, Korea, 2003–2011.
We fitted generalized additive model with quasi-poisson distribution, controlling for humidity, long-term trend, day of week, national holiday, and influenza epidemic. We estimated the cumulative cold temperature effect (10%, −1.7°C) referent to 7.9°C for the considered lag periods using distributed lag non-linear model: vary from the day of hospital visit to 10days before. Stratified analysis by season was also conducted. To adjust for possible confounding effect of air pollutants, we additionally adjusted for PM10, O3 and NO2 respectively.
Hospital visit counts and rates per 1,000,000 show increasing trend especially in elderly population (over 65years). Hospital visit rate is higher in children population (age<13years). Statistically significant cold temperature effects were found in the total (1.094(95%CI: 1.037, 1.153)), male (1.100 (95%CI: 1.010, 1.163)), female (1.088 (95%CI: 1.059, 1.170)) and adult (1.113 (95%CI: 1.059, 1.170)) population with consideration of 3-day lag period. In the stratified analysis by the season, the strongest effect was shown in the autumn (Sep–Nov) season. Confounding effects by air pollutants were not found.
In this study, we found significant increasing trend of hospital visit by AR. This study provides suggestive evidence of cold temperature effect on hospital visit by AR. To reduce the growing burden of AR, it is important to find possible related environmental risk factors. More studies should be conducted for better understanding of temperature effect on AR.
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•Studies for assessing cold temperature effect on AR are scarce.•Cold temperature effect on hospital visit by AR was assessed.•Hospital visit by AR has steadily increased especially for the elderly population.•We found cold temperature effect on AR and the strongest effect found in autumn season.•More studies should be conducted for better understanding of temperature effect on AR.
WNT16 is critical for bone homeostasis, but the effect of WNT16 in ankylosing spondylitis (AS) is still unknown. Here, we investigated whether WNT16 influences bone formation and pathophysiological ...changes of AS in an in vitro model.
The bone tissue from the facet joints was obtained from seven disease control and seven AS patients. Primary osteoprogenitor cells of the facet joints were isolated using an outgrowth method. Isolated osteoprogenitor cells from both control and AS tissues were analyzed by microarray, RT-qPCR, immunoblotting, and immunohistochemistry. The bone-forming activity of osteoprogenitor cells was assessed by various in vitro assays. β-galactosidase staining and senescence-associated secretory phenotype (SASP) using RT-qPCR were used to assess cell senescence.
In microarray analysis, WNT16 expression was significantly elevated in AS osteoprogenitor cells compared to the control. We also validated that WNT16 expression was elevated in AS-osteoprogenitor cells and human AS-bone tissues. WNT16 treatment inhibited bone formation in AS-osteoprogenitor cells but not in the control. Intriguingly, AS-osteoprogenitor cells were stained markedly with β-galactosidase for cell senescence in WNT16 treatment. Furthermore, in an H
O
stress-induced premature senescence condition, WNT16 treatment increased cell senescence in AS-osteoprogenitor cells and WNT16 treatment under the H
O
stress condition showed an increase in p21 protein and SASP mRNA expression. The WNT16-induced SASP expression in AS-osteoprogenitor cells was reduced in WNT16 knockdown cultures.
WNT16 is highly expressed in AS and WNT16 treatment facilitated cell senescence in AS-osteoprogenitor cells during osteoblast differentiation accompanied by suppression of bone formation. The identified role of WNT16 in AS could influence bone loss in AS patients.
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