Background and Aims
Autoimmune hepatitis (AIH) is a rare and chronic autoimmune liver disease. While genetic factors are believed to play a crucial role in the etiopathogenesis of AIH, our understanding of these genetic risk factors is still limited. In this study, we aimed to identify susceptibility loci to further understand the pathogenesis of this disease.
Approach and Results
We conducted a case–control association study of 1,622 Chinese patients with AIH type 1 and 10,466 population controls from two independent cohorts. A meta‐analysis was performed to ascertain variants associated with AIH type 1. A single‐nucleotide polymorphism within the human leukocyte antigen (HLA) region showed the strongest association with AIH (rs6932730: OR = 2.32; p = 9.21 × 10−73). The meta‐analysis also identified two non‐HLA loci significantly associated with AIH: CD28/CTLA4/ICOS on 2q33.3 (rs72929257: OR = 1.31; p = 2.92 × 10−9) and SYNPR on 3p14.2 (rs6809477: OR = 1.25; p = 5.48 × 10−9). In silico annotation, reporter gene assays, and CRISPR activation experiments identified a distal enhancer at 2q33.3 that regulated expression of CTLA4. In addition, variants near STAT1/STAT4 (rs11889341: OR = 1.24; p = 1.34 × 10−7), LINC00392 (rs9564997: OR = 0.81; p = 2.53 × 10−7), IRF8 (rs11117432: OR = 0.72; p = 6.10 × 10−6), and LILRA4/LILRA5 (rs11084330: OR = 0.65; p = 5.19 × 10−6) had suggestive association signals with AIH.
Conclusions
Our study identifies two novel loci (CD28/CTLA4/ICOS and SYNPR) exceeding genome‐wide significance and suggests four loci as potential risk factors. These findings highlight the importance of costimulatory signaling and neuro‐immune interaction in the pathogenesis of AIH.
Recently, a series of urban diseases have seriously impacted the development of large and medium cities. The development of urban underground space (UUS) is widely regarded as an effective solution. Due to the irreversibility of underground space resources, it is important to formulate scientific and reasonable development planning based on evaluation of the development potential of urban underground space (DPUUS). In this work, from the perspective of society, economy, and environment, an evaluation model of the DPUUS was established, and nine indexes were selected, including population density, vehicle possessive quantity per 100 capita, policy support, GDP per capita, GDP per km2, land price, geographical position, geological conditions, and natural disasters. The comprehensive weight method (CWM) combined with subjective and objective weights was used to determine the final weight of the evaluation index. Set pair analysis (SPA) and the credible degree recognition criterion (CDRC) were applied to determine the DPUUS grade of each city, which can provide a new idea for DPUUS.
Quasi‐2D perovskite light‐emitting diodes (PeLEDs) are promising candidates to realize superior luminescent. However, the poorly controlled phase distribution and surface defects hinder the improvement of the device's performance. Here, by introducing rubidium bromide (RbBr) to tune the crystallization kinetics of quasi‐2D perovskites, more uniform phase distribution is achieved through the suppression of medium‐n phases, resulting in narrower emission spectrum and more efficient energy transfer. Meanwhile, the defects are effectively passivated by the addition of RbBr. As a result, the photoluminescence quantum yield (PLQY) of quasi‐2D perovskite films increases significantly from 45.6% to 81.3%, and the maximum external quantum efficiency (EQE) of PeLEDs reaches 18.92%. This finding provides a new insight into the phase distribution control of quasi‐2D perovskites and the further improvement of PeLEDs.
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