Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of complex etiology that primarily affects women of childbearing age. The development of SLE is attributed to the breach of ...immunological tolerance and the interaction between SLE-susceptibility genes and various environmental factors, resulting in the production of pathogenic autoantibodies. Working in concert with the innate and adaptive arms of the immune system, lupus-related autoantibodies mediate immune-complex deposition in various tissues and organs, leading to acute and chronic inflammation and consequent end-organ damage. Over the past two decades or so, the impact of genetic susceptibility on the development of SLE has been well demonstrated in a number of large-scale genetic association studies which have uncovered a large fraction of genetic heritability of SLE by recognizing about a hundred SLE-susceptibility loci. Integration of genetic variant data with various omics data such as transcriptomic and epigenomic data potentially provides a unique opportunity to further understand the roles of SLE risk variants in regulating the molecular phenotypes by various disease-relevant cell types and in shaping the immune systems with high inter-individual variances in disease susceptibility. In this review, the catalogue of SLE susceptibility loci will be updated, and biological signatures implicated by the SLE-risk variants will be critically discussed. It is optimistically hoped that identification of SLE risk variants will enable the prognostic and therapeutic biomarker armamentarium of SLE to be strengthened, a major leap towards precision medicine in the management of the condition.
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.
Highlights
Based on the benefits of two-dimensional (2D) transition metal chalcogenides (TMC) materials, the operating concepts and basics of memristors for neuromorphic computing are introduced.
The ...prospects of 2D TMC materials and heterostructures are reviewed, as well as the state-of-the-art demonstration of 2D TMCs-based memristors for neuromorphic computing applications.
The most recent advances, current challenges, and future prospects for the manufacture and characterization of memristive neuromorphic devices based on 2D TMCs are discussed.
Two-dimensional (2D) transition metal chalcogenides (TMC) and their heterostructures are appealing as building blocks in a wide range of electronic and optoelectronic devices, particularly futuristic memristive and synaptic devices for brain-inspired neuromorphic computing systems. The distinct properties such as high durability, electrical and optical tunability, clean surface, flexibility, and LEGO-staking capability enable simple fabrication with high integration density, energy-efficient operation, and high scalability. This review provides a thorough examination of high-performance memristors based on 2D TMCs for neuromorphic computing applications, including the promise of 2D TMC materials and heterostructures, as well as the state-of-the-art demonstration of memristive devices. The challenges and future prospects for the development of these emerging materials and devices are also discussed. The purpose of this review is to provide an outlook on the fabrication and characterization of neuromorphic memristors based on 2D TMCs.
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.
Atomically thin two-dimensional materials such as MoS2, WS2, and graphene oxide (GO) are used as hole extraction layers (HEL) in organolead halide perovskites solar cells (PSCs) instead of ...poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) HEL. MoS2 and WS2 layers with a polycrystalline structure were synthesized by a chemical deposition method using a uniformly spin-coated (NH4)MoS4 and (NH4)WS4 precursor solution. GO was synthesized by the oxidation of natural graphite powder using Hummers' method. The work functions of MoS2, WS2, and GO are measured to be 5.0, 4.95, and 5.1 eV, respectively. The X-ray diffraction spectrum indicated that the synthesized perovskite material is CH3NH3PbI3−xClx. The PSCs with the p-n junction structure were fabricated based on the CH3NH3PbI3−xClx perovskite layer. The power conversion efficiencies of the MoS2, WS2, and GO-based PSCs were 9.53%, 8.02%, and 9.62%, respectively, which are comparable to those obtained from PEDOT:PSS-based devices (9.93%). These results suggest that two-dimensional materials such as MoS2, WS2, and GO can be promising candidates for the formation of HELs in the PSCs.
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•MoS2 and WS2 layers were prepared by chemical vapor deposition method.•Graphene oxide (GO) was synthesized by Hummers' method.•MoS2, WS2, and GO can be applied to the hole extraction layer for perovskite solar cell.
Aims/Introduction
It is not clear whether survival in kidney transplant recipients with pre‐transplant diabetes has improved over the past decades. We compared the rates of mortality and major ...adverse cardiovascular events (MACE) after renal transplantation in patients with and without pre‐transplant diabetes. Furthermore, we investigated whether transplant era and recipient age affected the association between diabetes status and adverse events.
Materials and Methods
This retrospective cohort study included 691 patients who underwent renal transplantation between 1994 and 2016 at a single tertiary center. We compared the incidences of post‐transplant mortality and four‐point MACE in patients with and without pre‐transplant diabetes using Kaplan–Meier analysis and the Cox proportional hazard model, and assessed the interactions between diabetes status and transplant era and recipient age.
Results
Of 691 kidney recipients, 143 (20.7%) had pre‐transplant diabetes. The mean follow‐up duration was 94.5 months. Kaplan–Meier analysis showed that patients with pre‐transplant diabetes had higher incidences of post‐transplant mortality and four‐point MACE compared with those without pre‐transplant diabetes (log–rank test, P < 0.001 for both). After adjusting for potential confounding factors, pre‐transplant diabetes was associated with an increased risk of post‐transplant mortality and four‐point MACE (hazard ratio 1.90, 95% confidence interval 1.05–3.44, P = 0.034; and hazard ratio 1.75; 95% confidence interval 1.02–3.00, P = 0.043, respectively). The associations between pre‐transplant diabetes status and all‐cause mortality and four‐point MACE were not affected by transplant era or recipient age.
Conclusions
Pre‐transplant diabetes remains a significant risk factor for mortality and four‐point MACE in kidney transplant recipients.
It is not clear whether survival in kidney transplant recipients with pre‐transplant diabetes has improved over the past decades. We compared the rates of mortality and major adverse cardiovascular events after kidney transplantation in patients with and without pre‐transplant diabetes. In this study, pre‐transplant diabetes remains a significant risk factor for mortality and four‐point major adverse cardiovascular events in kidney transplant recipients.
Perfect absorption (PA) of incident light is important for both fundamental light-matter interaction studies and practical device applications. PA studies so far have mainly used resonant ...nanostructures that require delicate structural patterning. Here, we realize tunable and broadband PA in the near-infrared region using relatively simple thin film coatings. We adjust the growth condition of an ITO film and control its epsilon-near-zero (ENZ) wavelength. We show that this results in highly tunable PA in the telecommunication window. Then, using an ITO multilayer of different ENZ wavelengths, we demonstrate broadband PA that covers a wide range of near-infrared wavelengths. The use of ENZ coatings makes PA adjustable during the film growth and does not require any structural patterning afterward. It also facilitates the chip-scale integration of perfect absorbers with other device components. Broadband PA relaxes the single wavelength condition in previous PA studies, and thus it is suitable for many practical device applications, including sensors, photodetectors, and energy harvesting devices.
A novel β-glucosidase was purified from pumpkin (Cucurbita moschata) seed by anion exchange chromatography and gel permeation chromatography, and its molecular mass was determined to be 42.8 kDa by ...gel permeation chromatography. The heterodimeric structure consisting of two subunits, free from disulfide bonds, was determined by native-PAGE analysis followed by zymography. The enzyme was maximally active at pH 4.0 and 70°C, and Vmax, Km, and kcat values were 0.078 units mg−1 protein, 2.22 mM, and 13.29 min−1, respectively, employing p-nitrophenyl-β-d-glucopyranoside as the substrate. The high content of glycine determined by amino acid analysis implies that the enzyme possesses flexible conformations and interacts with cell membranes and walls in nature. Circular dichroism studies revealed that the high stability of the enzyme within the pH range of 2.0–10.0 is due to its reversible pH-responsive characteristics for α-helix–antiparallel β-sheet interconversion.
•A novel β-glucosidase from pumpkin (Cucurbita moschata) seed was purified and characterized.•The heterodimeric structure of the enzyme was revealed by SDS-PAGE and GPC.•The enzyme was maximally active at pH 4.0 and stable within the pH range of 2.0–10.0.•Circular dichroism studies revealed that its reversible pH-responsive characteristics.
Systemic lupus erythematosus (SLE), an autoimmune disorder, has been associated with nearly 100 susceptibility loci. Nevertheless, these loci only partially explain SLE heritability and their ...putative causal variants are rarely prioritised, which make challenging to elucidate disease biology. To detect new SLE loci and causal variants, we performed the largest genome-wide meta-analysis for SLE in East Asian populations.
We newly genotyped 10 029 SLE cases and 180 167 controls and subsequently meta-analysed them jointly with 3348 SLE cases and 14 826 controls from published studies in East Asians. We further applied a Bayesian statistical approach to localise the putative causal variants for SLE associations.
We identified 113 genetic regions including 46 novel loci at genome-wide significance (p<5×10
). Conditional analysis detected 233 association signals within these loci, which suggest widespread allelic heterogeneity. We detected genome-wide associations at six new missense variants. Bayesian statistical fine-mapping analysis prioritised the putative causal variants to a small set of variants (95% credible set size ≤10) for 28 association signals. We identified 110 putative causal variants with posterior probabilities ≥0.1 for 57 SLE loci, among which we prioritised 10 most likely putative causal variants (posterior probability ≥0.8). Linkage disequilibrium score regression detected genetic correlations for SLE with albumin/globulin ratio (r
=-0.242) and non-albumin protein (r
=0.238).
This study reiterates the power of large-scale genome-wide meta-analysis for novel genetic discovery. These findings shed light on genetic and biological understandings of SLE.
Background: Increased serum uric acid is associated with prevalence and incidence of atrial fibrillation (AF), but there is a lack of studies on the association between serum uric acid and risk of AF ...in the general population. Methods and Results: We used the data from the Kangbuk Samsung Hospital health screening cohort recorded between 2002 and 2015. The primary outcome was incidence of AF diagnosed on 12-lead electrocardiography. We analyzed and compared the hazard ratios (HR) according to baseline serum uric acid quartiles. The present study involved 282,473 subjects without baseline AF. Mean follow-up was 5.4±3.6 years. During follow-up, AF was identified in 365 subjects (cumulative incidence, 0.13%). After multivariable adjustment, including that for C-reactive protein, the risk of AF was significantly higher in the upper 2 quartiles than in the lowest quartile in men (upper third quartile: adjusted HR, 1.53; 95% confidence interval CI: 1.11–2.89; highest quartile: HR, 1.60; 95% CI: 1.13–2.25). In women, even though AF incidence rate was very low (0.6 of 10,000 person-years), the risk of AF in the highest quartile was 6.93-fold that in the lowest quartile (95% CI: 1.53–31.29). Conclusions: Serum uric acid is significantly and positively associated with incident AF in the Korean general population.
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