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ObjectiveA method of ultra performance liquid chromatography-mass spectrometry （UPLC-MS） was established for the determination of octylphenol ethoxylates （OPEO） and nonylphenol ethoxylates （NPEO） in coating agent.MethodsSamples were extracted with water， and purified by solid phase extraction column. And Thermo Acclaim RSLC 120 C18 （2.1 mm×100 mm， 2.2 μm） chromatographic column was used for separation. Acetonitrile and 0.1% formic acid water were mobile phase， gradient elution and quantification was performed in SIM mode with positive ion mode of electrospray ionization.ResultsOctylphenol ethoxylates （OPEO） and nonylphenol ethoxylates （NPEO） were in the range of 0-400 μg/L， and the linear relationships was good （r2>0.996）. The recoveries at three spiked levels （0.12， 0.24 mg/kg， 1.2 mg/kg） were 88.5%-96.9% with the relative standard deviation of 2.9%-7.0%， and the limits of quantitative was 0.12 mg/kg.ConclusionThe method was simple， rapid and accurate. Its sensitivity， accuracy and precision were suitable for the quantitative analysis and determination of alkylphenol ethoxylates in coating agent.

Abstract Protein-protein interactions are a key component of life processes. The knowledge of the three-dimensional structure of these interactions is important for understanding protein function. Genome-Wide Docking Database (http://gwidd.bioinformatics.ku.edu) offers an extensive source of data for structural studies of protein-protein complexes on genome scale. The current release of the database combines the available experimental data on the structure and characteristics of protein interactions with structural modeling of protein complexes for 771 organisms spanned over the entire universe of life from viruses to humans. The interactions are stored in a relational database with user-friendly interface that includes various search options. The search results can be interactively previewed; the structures, downloaded, along with the interaction characteristics.

Abstract Background The new field of metagenomics studies microorganism communities by culture-independent sequencing. With the advances in next-generation sequencing techniques, researchers are facing tremendous challenges in metagenomic data analysis due to huge quantity and high complexity of sequence data. Analyzing large datasets is extremely time-consuming; also metagenomic annotation involves a wide range of computational tools, which are difficult to be installed and maintained by common users. The tools provided by the few available web servers are also limited and have various constraints such as login requirement, long waiting time, inability to configure pipelines etc. Results We developed WebMGA, a customizable web server for fast metagenomic analysis. WebMGA includes over 20 commonly used tools such as ORF calling, sequence clustering, quality control of raw reads, removal of sequencing artifacts and contaminations, taxonomic analysis, functional annotation etc. WebMGA provides users with rapid metagenomic data analysis using fast and effective tools, which have been implemented to run in parallel on our local computer cluster. Users can access WebMGA through web browsers or programming scripts to perform individual analysis or to configure and run customized pipelines. WebMGA is freely available at http://weizhongli-lab.org/metagenomic-analysis. Conclusions WebMGA offers to researchers many fast and unique tools and great flexibility for complex metagenomic data analysis.

Pemphigus vulgaris (PV) stands as a rare autoimmune bullous disease, while the precise underlying mechanism remains incompletely elucidated. High‐throughput proteomic methodologies, such as LC‐MS/MS, have facilitated the quantification and characterisation of proteomes from clinical skin samples, enhancing our comprehension of PV pathogenesis. The objective of this study is to elucidate the signalling mechanisms underlying PV through proteomic analysis. Proteins and cell suspension were extracted from skin biopsies obtained from both PV patients and healthy volunteers and subsequently analysed using LC‐MS/MS and scRNA‐seq. Cultured keratinocytes were treated with PV serum, followed by an assessment of protein expression levels using immunofluorescence and western blotting. A total of 880, 605, and 586 differentially expressed proteins (DEPs) were identified between the lesion vs. control, non‐lesion vs. control, and lesion vs. non‐lesion groups, respectively. The oxidative phosphorylation (OXPHOS) pathway showed activation in PV. Keratinocytes are the major cell population in the epidermis and highly expressed ATP5PF, ATP6V1G1, COX6B1, COX6A1, and NDUFA9. In the cellular model, there was a notable increase in the expression levels of OXPHOS‐related proteins (V‐ATP5A, III‐UQCRC2, II‐SDHB, I‐NDUFB8), along with STAT1, p‐STAT1, and p‐JAK1. Furthermore, both the OXPHOS inhibitor metformin and the JAK1 inhibitor tofacitinib demonstrated therapeutic effects on PV serum‐induced cell separation, attenuating cell detachment. Metformin notably reduced the expression of V‐ATP5A, III‐UQCRC2, II‐SDHB, I‐NDUFB8, p‐STAT1, p‐JAK1, whereas tofacitinib decreased the expression of p‐STAT1 and p‐JAK1, with minimal impact on the expression of V‐ATP5A, III‐UQCRC2, II‐SDHB, and I‐NDUFB8. Our results indicate a potential involvement of the OXPHOS and JAK‐STAT1 pathways in the pathogenesis of PV. [ABSTRACT FROM AUTHOR]

The purpose of this study is to utilize three machine learning models—random forest, logistic regression and extreme gradient boosting—to assess the landslide susceptibility of Wushan County and compare the predictive performance of each algorithm. To achieve this, the database was randomly divided into training (80%) and testing (20%) datasets. We considered the impact of soil thickness, which has rarely been explored in previous research. A spatial database of 19 conditioning factors related to the occurrence of a landslide was constructed to develop the landslide susceptibility maps. Thereafter, three models were estimated and compared using metrics such as accuracy, recall, F1 score and area under the receiver operating characteristic curve (AUC). The results show that the random forest model with the testing dataset has higher accuracy (0.848), F1 score (0.740) and AUC (0.904) values. Soil thickness is found to play a significant role in the occurrence of a landslide. The quantitative analysis of landslide susceptibility maps indicates the superiority of the random forest model. Finally, the outcomes of the random forest model incorporating multicollinearity analysis and factor selection were thoroughly discussed. In conclusion, the random forest is the recommended algorithm for evaluating landslide susceptibility to aid in disaster management in Wushan County. [ABSTRACT FROM AUTHOR]

Swin Transformers have been designed and used in various image super-resolution (SR) applications. One of the recent image restoration methods is RSTCANet, which combines Swin Transformer with Channel Attention. However, for some channels of images that may carry less useful information or noise, Channel Attention cannot automatically learn the insignificance of these channels. Instead, it tries to enhance their expression capability by adjusting the weights. It may lead to excessive focus on noise information while neglecting more essential features. In this paper, we propose a new image SR method, RSVTCANet, based on an extension of Swin2SR. Specifically, to effectively gather global information for the channel of images, we modify the Residual SwinV2 Transformer blocks in Swin2SR by introducing the coordinate attention for each two successive SwinV2 Transformer Layers (S2TL) and replacing Multi-head Self-Attention (MSA) with Efficient Multi-head Self-Attention version 2 (EMSAv2) to employ the resulting residual SwinV2 Transformer coordinate attention blocks (RSVTCABs) for feature extraction. Additionally, to improve the generalization of RSVTCANet during training, we apply an optimized RandAugment for data augmentation on the training dataset. Extensive experimental results show that RSVTCANet outperforms the recent image SR method regarding visual quality and measures such as PSNR and SSIM. [ABSTRACT FROM AUTHOR]

Abstract Background The new field of metagenomics studies microorganism communities by culture-independent sequencing. With the advances in next-generation sequencing techniques, researchers are facing tremendous challenges in metagenomic data analysis due to huge quantity and high complexity of sequence data. Analyzing large datasets is extremely time-consuming; also metagenomic annotation involves a wide range of computational tools, which are difficult to be installed and maintained by common users. The tools provided by the few available web servers are also limited and have various constraints such as login requirement, long waiting time, inability to configure pipelines etc. Results We developed WebMGA, a customizable web server for fast metagenomic analysis. WebMGA includes over 20 commonly used tools such as ORF calling, sequence clustering, quality control of raw reads, removal of sequencing artifacts and contaminations, taxonomic analysis, functional annotation etc. WebMGA provides users with rapid metagenomic data analysis using fast and effective tools, which have been implemented to run in parallel on our local computer cluster. Users can access WebMGA through web browsers or programming scripts to perform individual analysis or to configure and run customized pipelines. WebMGA is freely available at http://weizhongli-lab.org/metagenomic-analysis. Conclusions WebMGA offers to researchers many fast and unique tools and great flexibility for complex metagenomic data analysis.

None film surface of TFT glass will be damaged varying degrees due to physical contact with array equipment, which will seriously reduce the strength of none film surface. In this paper, we clarified the physical damage caused by the dry etch equipment on none film surface of TFT and its impact on the strength reduction through multiple verifications in array process. It is proved that strength reduction is mainly related to the back electrode material of dry etch. By changing the back electrode material from M to N(code name), the strength of the acrylic ball drop increased by more than 500%, and the strength of the cell ROR increased by 57%. This research has greatly improved the strength of none film surface of LCD, which is great significant to product performance improvement and new product certification. [ABSTRACT FROM AUTHOR]

Depression is a complex clinical disorder associated with poor outcomes. Electroacupuncture (EA) has been demonstrated to have an important role in both clinical and pre-clinical depression investigations. Evidence has suggested that the P2X7 receptor (P2X7R), NLRP3, and IL-1β play an important role in depressive disorder. Our study is aimed at exploring the role of EA in alleviating depression-like behaviors in rats. We therefore investigated the effects of EA on the prefrontal cortex and liver of rats subjected to chronic unpredictable mild stress (CUMS) through behavior tests, transmission electron microscopy, Nissl staining, HE staining, immunohistochemistry and Western blotting. Five weeks after exposure to CUMS, Sprague-Dawley (SD) rats showed depression-like behavior. Three weeks after treatment with brilliant blue G (BBG) or EA, depressive symptoms were significantly improved. Liver cells and microglia showed regular morphology and orderly arrangement in the BBG and EA groups compared with the CUMS group. Here we show that EA downregulated P2X7R/NLRP3/IL-1β expression and relieved depression-like behavior. In summary, our findings demonstrated the efficacy of EA in alleviating depression-like behaviors induced by CUMS in rats. This suggests that EA may serve as an adjunctive therapy in clinical practice, and that P2X7R may be a promising target for EA intervention on the liver–brain axis in treatment of depression. [ABSTRACT FROM AUTHOR]

In this paper, we proposed a novel e‐Privacy LCD, based on the smart viewing angle controllable (SVC) cell with IPS electrode structure, which can be electrically switched between the wide viewing angle (share mode) and the narrow viewing angle (privacy mode). The path of the collimated light emitted from collimated microstructural LGP BLU is not be changed when the SVC cell is off state, it is privacy mode; the light will be scattered when it pass through the SVC cell that be applied voltage, it is share mode. This phenomenon is very consistent with the simulated results. We also study the influence of the operating voltage or the cell gap on share performance. With the increase of the operating voltage or the cell gap of the SVC cell, the share performance is obviously improved. [ABSTRACT FROM AUTHOR]

The failure of large-scale resettlement policies has been largely determined by the collective resistance of residents. For migrants who must leave their original residence and get resettled, mass media and interpersonal communication are important sources to get policy information, which affects their attitudes and responses to resettlement policies. Existing studies have provided two pathways to explain the influencing mechanism between information sources and people's collective resistance intention. One of these pathways focuses on trust in government and the other highlights perceived benefits. However, it is still unclear how to predict migrants' collective resistance intention based on different information sources within these two pathways. By concentrating on the policy domain of Chinese resettlement projects, this study aims to develop an integrated, theoretical framework to explore the causal paths between information sources and migrants' collective resistance intention. Based on a survey of three towns in Ankang, China, we tested the causal mechanism with a structural equation model. The results demonstrate that the pathway that involves trust in government is more explanatory in illustrating the causal mechanism than the pathway of perceived benefits, and interpersonal communication yields stronger effects than mass media in mitigating migrants' collective resistance intention. The implications for resettlement policy publicity and trust-building in China are discussed. Points for practitioners: Public communication is a critical competency for public managers. Public managers are recommended to flexibly apply various information sources to communicate with migrants in order to eventually mitigate their collective resistance intention by strengthening their trust in government, as well as their perceived benefits. In the early stages of policy publicity, a variety of mass media are needed to inform the migrants of resettlement policies. Then, at the stage of policy implementation, the primary focus becomes interpersonal communication that offers sufficiently detailed information. In this regard, local government managers should carry out more programs that entail face-to-face information sharing to help participants understand the resettlement policy, and encourage them to explain it to their family and friends. [ABSTRACT FROM AUTHOR]

In order to improve the strength of TFT glass, especially the surface strength of array side, we have studied the failure mechanism and influence factors of glass strength in this paper. The relationship between film stress and glass strength is proposed for the first time. By optimizing the parameters of array process and introducing negative (compressive) stress into passivation (PVX) layer, the surface strength of TFT glass could be increased substantially, and the degree of COG Mura can also be improved. Finally, a high‐performance and high‐strength TFT glass could be obtained. [ABSTRACT FROM AUTHOR]

Stability assessment of cracked clay slopes has been a research hotspot in geotechnical engineering in recent years. The assessment work should include crack initiation/development and stability evaluation. However, there has been no universal method for predicting crack evolution until now. In addition, scholars have paid little attention to the coupling relationship between the evolution of cracks and the progressive failure process of macroscopic clay slopes and have seldom studied the ubiquitous diagonal cracks in clay slopes. In this work, the stress mechanism for initiation and development of major cracks was derived based on unsaturated soil mechanics and critical state soil mechanics considering the tensile, compression, and shear properties of clay. The correctness of the proposed theory was verified by constructing a large-scale, arc-shaped slip surface clay slope model. In the model test, earth pressure cells and displacement gauge were employed to monitor development of stresses within the clay slope and horizontal displacement of the slope shoulder, respectively, under the set load sequence. The results showed that the stress mechanism proposed in this paper could judge not only vertical cracks but also diagonal cracks. Horizontal stresses near the primary crack appeared as a result of stress saltation. The locations and depths of the major cracks could be determined by analyzing the differences in horizontal stress between adjacent measuring points under the same load step. The development of major crack–horizontal stress–displacement had intrinsic consistency, and the initiation and development of major cracks aggravated changes in displacement and horizontal stresses. The perspective of major crack–stress–displacement is helpful to wholly grasp the progressive failure process of cracked clay slopes and provide a reference for prediction of clay landslides. [ABSTRACT FROM AUTHOR]

China's emergency management (EM) system has undergone a series of reforms and organizational changes since the SARS epidemic in 2003. However, institutional segmentation, unbalanced power for the Emergency Management Office, pervasive internal corruption, and state monopoly control are threats to the administration's goal of resilient and modern EM systems. The new round of 2018 reforms was intended to promote integration through the establishment of the Ministry of Emergency Management and related institutional restructuring involving power redistribution. The reforms are nevertheless likely to face some potential problems like the operation of a super‐ministry, interorganizational integration, state‐society relations, and supervision. Through field interviews, the article investigates and uncovers issues in China's EM system and the perception from government sectors at different levels. The article suggests that cooperative governance in coping with state‐society relations and decentralization of power could be of great significance for future EM reform in China. Related Articles: Ash, John. 2010. "New Nuclear Energy, Risk, and Justice: Regulatory Strategies for an era of Limited Trust." Politics & Policy 38 (2): 255‐284. https://doi.org/10.1111/j.1747‐1346.2010.00237.x Brogan, Michael James. 2017. "Evaluating Risk and Natural gas Pipeline Safety." Politics & Policy 45 (4): 657‐680. https://doi.org/10.1111/polp.12211 Neill, Katharine A., and John C. Morris. 2012. "A Tangled web of Principals and Agents: Examining the Deepwater Horizon oil Spill through a Principal–Agent Lens." Politics & Policy 40 (4): 629‐656. http://onlinelibrary.wiley.com/doi/10.1111/j.1747‐1346.2012.00371.x/full [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by abnormal activation of T cells and caused by an imbalance in the production and clearance of apoptotic cells. We previously showed that the transcription regulator Bach2 regulated abnormal B‐cell activation in SLE. Here, we investigated whether Bach2 was also involved in Th9 cell differentiation in SLE. We found that the proportion of Th9 cells was enhanced in the peripheral blood mononuclear cells (PBMC) of SLE patients. The PBMC and CD4+ T cells of SLE patients exhibited a decrease of Bach2 expression and an increase of IL‐9 expression. Furthermore, Bach2 overexpression significantly repressed the levels of PU.1, IRF4, IL‐9, and Th9 cells in the CD4+ T cells of SLE patients and healthy volunteers. In addition, Bach2 overexpression inhibited the levels of IL‐9 and Th9 cells, whereas IRF4 upregulation enhanced the levels of IRF4 and IL‐9 and Th9 cells in the CD4+ T cells of SLE patients and healthy volunteers. The effect of IRF4 up‐regulation was abolished by Bach2 overexpression. In summary, our work suggests that Bach2 overexpression represses Th9 cell differentiation by suppressing IRF4 expression in SLE, and thus, Bach2 may be a novel potential target for SLE treatment. [ABSTRACT FROM AUTHOR]

Recently, there has been growing interest in improving the efficiency and accuracy of the Indoor Positioning System (IPS). The Received Signal Strength- (RSS-) based fingerprinting technique is essential for indoor localization. However, it is challenging to estimate the indoor position based on RSS's measurement under the complex indoor environment. This paper evaluates three machine learning approaches and Gaussian Process (GP) regression with three different kernels to get the best indoor positioning model. The hyperparameter tuning technique is used to select the optimum parameter set for each model. Experiments are carried out with RSS data from seven access points (AP). Results show that GP with a rational quadratic kernel and eXtreme gradient tree boosting model has the best positioning accuracy compared to other models. In contrast, the eXtreme gradient tree boosting model could achieve higher positioning accuracy with smaller training size and fewer access points. [ABSTRACT FROM AUTHOR]

Objective: Genome‐wide association studies have identified many susceptibility loci for systemic lupus erythematosus (SLE). However, most of these loci are located in noncoding regions of the genome. Long noncoding RNAs (lncRNAs) are pervasively expressed and have been reported to be involved in various diseases. This study aimed to explore the genetic significance of lncRNAs in SLE. Methods: A genome‐wide survey of SLE risk variants in lncRNA gene loci was performed in Han Chinese subjects (4,556 with SLE and 9,451 healthy controls). The functional relevance of an SLE risk variant in one of the lncRNA genes was explored using biochemical and molecular cell biology analyses. In vitro loss‐of‐function and gain‐of‐function strategies were used to clarify the functional and phenotypic relevance of this SLE susceptibility lncRNA. Moreover, correlation of this lncRNA with the degree of apoptosis in the peripheral blood of SLE patients was evaluated. Results: A novel SLE susceptibility locus in a lncRNA gene, designated SLEAR (for SLE‐associated RNA), was identified at the single‐nucleotide polymorphism rs13259960 (odds ratio 1.35, Pcombined = 1.03 × 10−11). The A>G variation at rs13259960, located in an intronic enhancer, was found to impair STAT1 recruitment to the enhancer that loops to the SLEAR promoter, resulting in decreased SLEAR production in peripheral blood mononuclear cells from patients with SLE (3 with the G/G genotype, 22 with A/G, and 103 with A/A at rs13259960; P = 0.0241). Moreover, SLEAR interacted with the RNA binding proteins interleukin enhancer binding factor 2, heterogeneous nuclear RNP F, and TATA‐binding protein–associated factor 15, to form a complex for transcriptional activation of the downstream antiapoptotic genes. In addition, SLEAR regulated apoptosis of Jurkat cells in vitro, and its expression level was correlated with the degree of cell death in the peripheral blood of patients with SLE (r = 0.824, P = 2.15 × 10−8; n = 30). Conclusion: These findings suggest a mechanism by which the risk variant at rs13259960 modulates SLEAR expression and confers a predisposition to SLE. Taken together, these results may give insights into the etiology of SLE. [ABSTRACT FROM AUTHOR]

Single‐nucleotide polymorphisms (SNPs) in the UHRF gene have been shown to be associated with systemic lupus erythematosus (SLE) in European and Hong Kong Chinese, but statistically significant evidence for association has not been found in a mainland Han Chinese population. Therefore, we selected SNP rs13205210 located in UHRF1BP1 as a candidate association from our previously published genome‐wide association study (GWAS) data of SLE (1,047 cases and 1,205 controls from a mainland Han Chinese population) to explore the association between the UHRF1BP1 gene and SLE. We conducted a large‐scale replication study in an additional independent sample of 3,509 cases and 8,246 controls from a mainland Han Chinese population. Real‐time PCR was used to determine gene expression differences in peripheral blood mononuclear cells (PBMCs) from cases and controls. As a result, we replicated the association between the UHRF1BP1 gene and SLE (rs13205210, missense, Pmeta = 2.26E‐17, odds ratio = 1.41) by a meta‐analysis of our previous GWAS and this replication study involving a total of 4,556 cases and 9,451 controls. The UHRF1BP1 mRNA expression level in PBMCs was significantly decreased in patients with SLE compared with that in healthy controls. SNP rs13205210 exhibited an expression quantitative trait loci effect on the UHRF1BP1 gene in PBMCs from patients. In conclusion, this study not only suggests that the UHRF1BP1 gene was associated with SLE in a mainland Han Chinese population, but also implied that it might be a common genetic factor contributing to SLE susceptibility in multiple populations. [ABSTRACT FROM AUTHOR]

Lithology identification is an indispensable part in geological research and petroleum engineering study. In recent years, several mathematical approaches have been used to improve the accuracy of lithology classification. Based on our earlier work that assessed machine learning models on formation lithology classification, we optimize the boosting approaches to improve the classification ability of our boosting models with the data collected from the Daniudi gas field and Hangjinqi gas field. Three boosting models, namely, AdaBoost, Gradient Tree Boosting, and eXtreme Gradient Boosting, are evaluated with 5-fold cross validation. Regularization is applied to the Gradient Tree Boosting and eXtreme Gradient Boosting to avoid overfitting. After adapting the hyperparameter tuning approach on each boosting model to optimize the parameter set, we use stacking to combine the three optimized models to improve the classification accuracy. Results suggest that the optimized stacked boosting model has better performance concerning the evaluation matrix such as precision, recall, and f1 score compared with the single optimized boosting model. Confusion matrix also shows that the stacked model has better performance in distinguishing sandstone classes. [ABSTRACT FROM AUTHOR]

This study was aimed to investigate whether NFKB1 participates in the pathogenesis of psoriasis by mediating Th1/Th17 cells. In this study, expression of NFKB1 was assessed in skin tissues from psoriasis patients and the healthy controls through Western blot and Immunohistochemistry. Enzyme-linked immunosorbent assay (ELISA) was used to analyze the serum levels of IFN-γ, IL-17 (IL-17A) and IL-17RA. The imiquimod-induced psoriasis mouse model was employed to examine the role of NFKB1 in psoriasis via the assessment of psoriasis area and severity index (PASI), including erythema, thickness and scales. The effects of NFKB1 on Th1/Th17 cells in were examined by flow cytometry. In vitro co-culture of Th1/Th17 cells isolated from different mice with HaCat cells was conducted to elucidate the effect of Th1/Th17 cells-mediated by NFKB1 on HaCat cells by MTT, wound healing and transwell invasion assay, respectively. The results showed that NF-κB p105/p50 expression in skin tissues was significantly increased in psoriasis (n = 21) compared to the healthy controls (n = 16), as well as levels of serum INF-γ and IL-17. Additionally, NF-κB p105/p50 expression in lesional skin tissues was much higher than that in non-lesional skin tissues of the same patients. In the psoriasis mouse model, NFKB1 overexpression significantly elevated the scores of erythema, thickness and scales. Besides, NFKB1 up-regulated the level of NF-κB p105/p50, INF-γ, T-bet, IL-17 and RORγt, as well as Th1/Th17 cells in skin tissues of psoriasis mice. Finally, in vitro assay confirmed that the activation of Th1 and Th17 mediated by NFKB1 in psoriasis promoted the proliferation, migration and invasion of keratinocytes. These findings suggest a critical role for NFKB1 in the regulation of Th1 and Th17 in psoriasis. [ABSTRACT FROM AUTHOR]

Abstract: The polymorphism of PRKCB has been proven to be associated with systemic lupus erythematosus (SLE) in our previous study. We aimed to investigate the relationship between expression of PRKCB mRNA and the Disease Activity Index (SLEDAI) and manifestations of SLE. Quantitative reverse transcription polymerase chain reaction (RT‐PCR) was applied to examine the expression of PRKCB mRNA in peripheral blood mononuclear cells of 60 patients with SLE and 62 controls. The Sequenom MassArray System was used to detect genotype SNP rs16972959. The expression levels of PRKCB mRNA in SLE cases were significantly increased compared with those in healthy controls (P < 0.001). In addition, PRKCB mRNA expression levels were negatively correlated with the SLEDAI (P < 0.05, r = –0.322), with lower mRNA expression levels of PRKCB in patients found with higher SLEDAI, presence of a new rash (P < 0.01), and proteinuria (P < 0.05). No association evidence was observed between the genotype of the variant rs16972959 and PRKCB mRNA expression levels; however, SNP rs16972959 was found to be an expression quantitative trait loci for PRKCB with the SLE risk allele correlated with increased expression in naïve monocytes (PFDR = 9.12 × 10–13) and stimulated monocytes (9.24 × 10–6 > PFDR > 2.75 × 10–17). On the other hand, SNP rs16972959 of PRKCB was found to have suggestive significant associations with vasculitis (P = 0.00718) of SLE. These results indicated that expression of PRKCB mRNA may be correlated with the pathogenesis of SLE; however, more investigation is still needed. [ABSTRACT FROM AUTHOR]

Objectives: Systemic lupus erythematosus (SLE) is a prototype autoimmune disease with a strong genetic component in its pathogenesis. Through genome-wide association studies (GWAS), we recently identified 10 novel loci associated with SLE and uncovered a number of suggestive loci requiring further validation. This study aimed to validate those loci in independent cohorts and evaluate the role of SLE genetics in drug repositioning.Methods: We conducted GWAS and replication studies involving 12 280 SLE cases and 18 828 controls, and performed fine-mapping analyses to identify likely causal variants within the newly identified loci. We further scanned drug target databases to evaluate the role of SLE genetics in drug repositioning.Results: We identified three novel loci that surpassed genome-wide significance, including ST3AGL4 (rs13238909, pmeta=4.40E-08), MFHAS1 (rs2428, pmeta=1.17E-08) and CSNK2A2 (rs2731783, pmeta=1.08E-09). We also confirmed the association of CD226 locus with SLE (rs763361, pmeta=2.45E-08). Fine-mapping and functional analyses indicated that the putative causal variants in CSNK2A2 locus reside in an enhancer and are associated with expression of CSNK2A2 in B-lymphocytes, suggesting a potential mechanism of association. In addition, we demonstrated that SLE risk genes were more likely to be interacting proteins with targets of approved SLE drugs (OR=2.41, p=1.50E-03) which supports the role of genetic studies to repurpose drugs approved for other diseases for the treatment of SLE.Conclusion: This study identified three novel loci associated with SLE and demonstrated the role of SLE GWAS findings in drug repositioning. [ABSTRACT FROM AUTHOR]

Objective This study was aimed to explore the effect of Bach2 on B cells in systemic lupus erythematosus (SLE), as well as the underlying mechanisms. Methods Expression of Bach2, phosphorylated-Bach2 (p-Bach2), Akt, p-Akt and BCR-ABL (p210) in B cells isolated from SLE patients and the healthy persons were assessed by Western blot. Immunofluorescence staining was performed to assess the localization of Bach2 in B cells. Enzyme-linked immunosorbent assay (ELISA) was employed to detect IgG produced by B cells. Cell counting kit-8 (CCK-8) and Annexin-V FITC/PI double staining assay were adopted to evaluate cell proliferation and apoptosis in B cells, respectively. Results Compared to the healthy controls, Bach2, p-Akt and p210 were significantly decreased, while nuclear translocation of Bach2, IgG, CD40 and CD86 obviously up-regulated in B cells from SLE patients. Bach2 significantly inhibited the proliferation, promoted apoptosis of B cells from SLE patients, whereas BCR-ABL dramatically reversed cell changes induced by Bach2. Besides, BCR-ABL also inhibited nuclear translocation of Bach2 in B cells from SLE patients. Further, LY294002 treatment had no effect on decreased expression of Bach2 induced by BCR-ABL, but significantly eliminated BCR-ABL-induced phosphorylation of Bach2 and restored reduced nuclear translocation of Bach2 induced by BCR-ABL in B cells from SLE. Conclusions Bach2 may play a suppressive role in B cells from SLE, and BCR-ABL may inhibit the nuclear translocation of Bach2 via serine phosphorylation through the PI3K pathway. [ABSTRACT FROM AUTHOR]