Objective
Systemic lupus erythematosus (SLE) is a highly heritable complex disorder with heterogeneous clinical manifestations. In this study, we aimed to identify the genetic risk load using ...clinical and serological manifestations in SLE patients.
Methods
We genotyped a total of 1,655 Korean patients with SLE (n = 1,243 as a discovery set and n = 412 as a replication set) using a customized genome‐wide single‐nucleotide polymorphism (SNP) array, KoreanChip. A weighted genetic risk score (wGRS) for an individual was calculated from 112 well‐validated non‐HLA SNPs and HLA haplotypes of SLE‐risk loci. We analyzed associations between individual wGRS and clinical SLE subphenotypes and autoantibodies using multivariable linear or logistic regression adjusted by onset age, sex, and disease duration.
Results
Childhood‐onset SLE (<16 years) conferred the highest genetic risk compared with adult‐onset (16–50 years) or late‐onset (>50 years) SLE (P = 6.8 × 10−6). High wGRS significantly increased associations with SLE manifestations, regardless of onset age, sex, and disease duration. Individual wGRS significantly correlated positively with more clinical American College of Rheumatology criteria (β = 0.143, P = 1.8 × 10−6). Subphenotype analysis revealed significant associations between the highest and lowest wGRS quartile with risk of renal disorder (hazard ratio HR 1.74, P = 2.2 × 10−8) and anti–Sm antibody production (HR 1.85, P = 2.8 × 10−5). Higher wGRS markedly modulated the pathogenesis of proliferative and membranous lupus nephritis class III or IV (HR 1.98, P = 1.6 × 10−5) and class V (HR 2.79, P = 1.0 × 10−3), but especially lupus nephritis class V in anti–Sm‐positive SLE (area under the curve 0.68, P = 1.8 × 10−4).
Conclusion
Patients with SLE and high wGRS tended to have earlier age of SLE onset, higher anti–Sm antibody positivity, and more diverse clinical phenotypes. Genetic profiling may predict high risk for lupus nephritis and a diverse clinical course in SLE patients.
The rapid and sensitive classification of bacteria is the first step of bacterial community research and the treatment of infection. Herein, a fluorescent probe BacGO is presented, which shows the ...best universal selectivity for Gram‐positive bacteria among known probes with a minimum staining procedure for sample detection and enrichment of the live bacteria. BacGO could also be used to assess of the Gram status in the bacterial community from wastewater sludge. Furthermore, BacGO could sensitively and selectively detect a Gram‐positive bacterial infection, not only in vitro but also using an in vivo keratitis mouse model. BacGO provides an unprecedented research tool for the study of dynamic bacterial communities and for clinical application.
BacGO, a novel Gram‐positive bacterial probe, was developed from a library of fluorescent molecules with a boronic‐acid motif that binds to peptidoglycan on the Gram‐positive bacterial cell wall. BacGO can be used to identify Gram‐positive bacteria in diverse, highly complex samples, and is an attractive alternative to Gram staining.
Summary
Background
Asthma‐chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS), which has received much attention, has not been unanimously defined.
Objective
In this study, we tried ...to demonstrate that longitudinally defined ACOS is more useful in the real world than blending patients with asthma and COPD.
Methods
The study patients had undergone two consecutive pulmonary function tests measured at least 3 months apart (n = 1889). We selected the patients who had positive bronchodilator response or methacholine provocation tests (n = 959). Next, we defined ACOS as a patient with a persistent airflow obstruction forced expiratory volume in 1 second (FEV1)/forced vital capacity <0.7 that was identified twice consecutively by an interval of at least 3 months (n = 228).
Results
The proportions of patients who were older, male and smokers were significantly higher, and baseline lung function was lower in patients with ACOS. In the longitudinal analysis, the mean change in lung function was high, and a greater decline in FEV1 was observed in patients with ACOS. In addition, we compared ACOS and severe asthma, and we also performed a cluster analysis and compared the results with our definition of ACOS. According to our definition, ACOS is an independent subtype with distinctive characteristics. Finally, a genome‐wide association study (GWAS) was performed to identify genetic variations associated with ACOS, but no significant single nucleotide polymorphisms were identified.
Conclusion
Our findings suggest that ACOS should be defined longitudinally and considered as an independent subgroup distinguished by inherited environmental factors rather than as a genetically distinct independent group.
Background
While the clinical characteristics and outcomes of asthma‐chronic obstructive pulmonary disease (COPD) overlap (ACO) have been frequently compared with those of COPD or asthma, the ...prevalence and features of ACO in patients with severe asthma are unclear.
Objectives
Evaluation of the prevalence and clinical features of ACO using the Korean severe asthma registry.
Methods
At the time of registration, ACO was determined in patients with severe asthma by attending specialists. Patients were classified into ACO and non‐ACO groups, and the demographic and clinical characteristics of these two groups were compared.
Results
Of 482 patients with severe asthma, 23.7% had ACO. Patients in the ACO group were more likely to be male (P < .001), older (P < .001), and ex‐ or current smokers (P < .001) compared with those in the non‐ACO group. Patients in the ACO group had lower mean forced expiratory volume in 1 second (P < .001) and blood eosinophil percentage (P = .006), but higher blood neutrophil percentage (P = .027) than those in the non‐ACO group. The ACO group used more inhaled long‐acting muscarinic antagonist (P < .001), methylxanthine (P = .001), or sustained systemic corticosteroid (P = .002). In addition, unscheduled emergency department visits due to exacerbation were more frequent in the ACO group (P = .006).
Conclusion
Among patients with severe asthma, those with ACO were older, predominantly male, and were more likely to have a smoking history than those with asthma only. Patients with ACO used more systemic corticosteroid and had more frequent exacerbations related to emergency department visits than those with severe asthma only.
We found that about one‐fourth of patients with severe asthma was diagnosed with ACO by specialists. The most common reason for ACO diagnosis was smoking history. ACO patients were predominantly male, older, and had more smoking history compared with non‐ACO patients. ACO patients had higher blood neutrophil count, but lower lung function. ACO patients used more LAMA, methylxanthine, and systemic corticosteroid and had more frequent exacerbations related to ER visits compared with those with severe asthma only. Abbreviations: ACO, asthma‐COPD overlap; ER, emergency room; FEV1, forced expiratory volume in one second.
The settling of microplastics (MPs) is crucial for their removal from municipal wastewater treatment plants (WWTPs) and sedimentation in static waterbodies, where they can accumulate in bottom ...sediments. Biofilm formation on MPs enhances their aggregation with other particles, thereby changing their density and size and altering their settling rates. However, only a few studies have investigated the settling of MPs of different sizes and materials. Specifically, the settling of small-sized MPs (<150 μm) has been poorly documented. In this study, cylindrical and fragmented particles of four polymer types (high-density polyethylene (HDPE), polypropylene (PP), polystyrene (PS), and poly(ethylene terephthalate) (PET)) were used to investigate the settling or floating of reference MPs (20–130 μm) in a custom-made column that simulated a primary sedimentation tank in a typical WWTP before and after incubation in wastewater influent. The settling velocity of the reference MP particles was strongly influenced by the particle size and density. The settled fractions of all the cylindrical reference MPs increased significantly (up to 5 times) due to biofilm formation at overflow velocities of 0.15, 0.26, and 0.40 mm s−1. This was observed even for HDPE and PP (density <1 g cm−3) after biofilm formation. The fragmented reference MPs showed complex and rather unpredictable behavior, possibly due to their irregular shape. Generally, the settling of pristine PS and PET in the laboratory tests was consistent with the theoretical predictions obtained using Stokes’ law. The experimental findings of this study can be used to develop models that predict the removal efficiencies of MPs in WWTPs and to estimate the sinking of MPs to bottom sediments of static waterbodies.
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•Vertical transport of 4 polymer types of MPs (<150 μm) was evaluated.•Settling rate of reference MPs increased with increasing size and density.•Biofilm formation on MP surfaces greatly enhanced settling of MPs in waterbody.•Experimental results coincided with the prediction by Stokes' law.•The results can be used to evaluate the sedimentation of MPs in static waterbodies.
Incorporating bioactive molecules into synthetic ceramic scaffolds is challenging. In this study, to enhance bone regeneration, a magnesium phosphate (MgP) ceramic scaffold was incorporated with a ...novel indene compound, KR-34893. KR-34893 induced the deposition of minerals and expression of osteoblast marker genes in primary human bone marrow mesenchymal stem cells (BMSCs) and a mouse osteoblastic MC3T3-E1 cell line. Analysis of the mode of action showed that KR-34893 induced the phosphorylation of MAPK/extracellular signal-regulated kinase and extracellular signal-regulated kinase, and subsequently the expression of bone morphogenetic protein 7, accompanied by SMAD1/5/8 phosphorylation. Accordingly, KR-34893 was incorporated into an MgP scaffold prepared by 3D printing at room temperature, followed by cement reaction. KR-34893-incorporated MgP (KR-MgP) induced the expression of osteoblast differentiation marker genes in vitro. In a rat calvaria defect model, KR-MgP scaffolds enhanced bone regeneration and increased bone volume compared with MgP scaffolds, as assessed by micro-computed tomography and histological analyses. In conclusion, we developed a method for producing osteoinductive MgP scaffolds incorporating a bioactive organic compound, without high temperature sintering. The KR-MgP scaffolds enhanced osteoblast activation in vitro and bone regeneration in vivo.
Genome-wide association studies (GWAS) in rheumatoid arthritis (RA) have discovered over 100 RA loci, explaining patient-relevant RA pathogenesis but showing a large fraction of missing heritability. ...As a continuous effort, we conducted GWAS in a large Korean RA case-control population.
We newly generated genome-wide variant data in two independent Korean cohorts comprising 4068 RA cases and 36 487 controls, followed by a whole-genome imputation and a meta-analysis of the disease association results in the two cohorts. By integrating publicly available omics data with the GWAS results, a series of bioinformatic analyses were conducted to prioritise the RA-risk genes in RA loci and to dissect biological mechanisms underlying disease associations.
We identified six new RA-risk loci (
,
,
,
,
and
) with p
<5×10
and consistent disease effect sizes in the two cohorts. A total of 122 genes were prioritised from the 6 novel and 13 replicated RA loci based on physical distance, regulatory variants and chromatin interaction. Bioinformatics analyses highlighted potentially RA-relevant tissues (including immune tissues, lung and small intestine) with tissue-specific expression of RA-associated genes and suggested the immune-related gene sets (such as CD40 pathway, IL-21-mediated pathway and citrullination) and the risk-allele sharing with other diseases.
This study identified six new RA-associated loci that contributed to better understanding of the genetic aetiology and biology in RA.
This current study aimed to elucidate the effects and possible underlying mechanisms of long-term supplementation with dietary luteolin (LU)-enriched artichoke leaf (AR) in high-fat diet ...(HFD)-induced obesity and its complications (e.g., dyslipidemia, insulin resistance, and non-alcoholic fatty liver disease) in C57BL/6N mice. The mice were fed a normal diet, an HFD, or an HFD plus AR or LU for 16 weeks. In the HFD-fed mice, AR decreased the adiposity and dyslipidemia by decreasing lipogenesis while increasing fatty acid oxidation, which contributed to better hepatic steatosis. LU also prevented adiposity and hepatic steatosis by suppressing lipogenesis while increasing biliary sterol excretion. Moreover, AR and LU prevented insulin sensitivity by decreasing the level of plasma gastric inhibitory polypeptide and activity of hepatic glucogenic enzymes, which may be linked to the lowering of inflammation as evidenced by the reduced plasma interleukin (IL)-6, IL-1β, and plasminogen activator inhibitor-1 levels. Although the anti-metabolic syndrome effects of AR and LU were similar, the anti-adiposity and anti-dyslipidemic effects of AR were more pronounced. These results in mice with diet-induced obesity suggest that long-term supplementation with AR can prevent adiposity and related metabolic disorders such as dyslipidemia, hepatic steatosis, insulin resistance, and inflammation.
Plastic pollution is a significant environmental concern because microplastics (MPs) accumulate in various ecosystems; therefore, the accurate identification and quantification of MPs in ...environmental samples is crucial. This study presents a new sequential analytical method that combines Fourier-transform infrared spectroscopy (FTIR) and pyrolysis-gas chromatography/mass spectrometry (Pyr-GC/MS) to characterize and quantify MPs. FTIR with a microscope allows the identification of the polymer type and physical dimensions of MPs, whereas Pyr-GC/MS enables determining the chemical composition of MPs with plastic additives. Pretreated wastewater influent samples spiked with reference MPs were filtered through an Al2O3 disk for FTIR analysis, and the surface contents were collected and subjected to Pyr-GC/MS analysis. The mass of the reference MPs estimated using FTIR were in good agreement but were slightly lower than those obtained using Pyr-GC/MS. This finding supports the notion that the proposed sequential method can be used to determine both the number and the mass of MPs in environmental samples.
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•A sequential analytical method using FTIR and Pyr-GC/MS was proposed.•The method was able to provide both the number and the mass of MPs in a sample.•Masses of MPs estimated using FTIR agreed well with those using Pyr-GC/MS.•Slightly greater mass obtained using Pyr-GC/MS is likely via contribution of smaller MPs.
For consistent and effective CO2 reduction, many countries need to improve not only the technical efficiency of CO2 mitigation, but also environmental responsibility. In this study, we examine both ...the technical efficiency and voluntary environmental consciousness (VEC) of 12 European countries using a two-stage data envelopment analysis (DEA). In the first stage, we measured the technical efficiency of green energy technologies (GET) associated with fossil fuels, renewable energy, and storage technologies of each country for energy generation with regard to CO2 emissions by surveying GET-related patents. Using the logarithmic mean Divisia index (LMDI), we decomposed CO2 emissions into the following technological factors: energy intensity, fuel mix, and CO2 emission coefficient. In the second stage, we quantified the VEC in each country by investigating GET patent changes via research and development (R&D) investment at given changes in CO2 emissions. The results show different aspects for each country in terms of technical efficiency and VEC, suggesting potential levels of both efficient CO2 reductions and desirable GET development by using reference countries as a benchmark. Our study methodology and results can contribute to establishing effective national technology policy and aid in calls for common responsibility and the active participation of nations in addressing climate change.
•Technical efficiency for CO2 reduction and voluntary environmental consciousness (VEC) of 12 EU countries were evaluated.•We use the two-stage DEA using technological factors decomposed by the logarithmic mean Divisia index.•The 12 European countries were classified into four groups, based on technical efficiency and VEC.•Our findings can help managing effective and consistent reduction of CO2emissions.
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