Rheumatoid meningitis: a rare neurological complication of rheumatoid arthritis

ObjectiveTo describe the clinical and neuroimaging characteristics of rheumatoid meningitis (RM) in Chinese patients. MethodsThe patients admitted to our hospital with the diagnosis of RM in the past 8 years were retrospectively analyzed. ResultsSix patients with RM were identified among 933 patients admitted with rheumatoid arthritis (RA). The symptoms of meningitis occurred after onset of arthritis in five patients and before onset in one. Headache (n=6), hyperacute focal neurological deficits (n=4) and seizures (n=3) were the most prevalent symptoms. The nadir modified Rankin Scale score was ≥3 in five patients. Rheumatoid factor was elevated in all patients, and interleukin-6 levels in cerebrospinal fluid were dramatically elevated in three of four tested patients. Magnetic resonance imaging of the brain revealed that the meninges were affected in all patients and the cerebral parenchyma was affected in one patient. The lesions were generally located in the frontoparietal region and showed restricted diffusion along the adjacent subarachnoid space. RM occurred during disease-modifying therapy in four patients. In the acute episode, three patients improved on tocilizumab and the other three improved on pulse corticosteroids. For maintenance therapy, two patients received combined therapy of tocilizumab and other immunosuppressive agents, one received adalimumab and methotrexate, and two received low-dose oral corticosteroids with an immunosuppressive agent. Five patients had a good outcome, and one died of Pneumocystis jirovecii pneumonia after stabilization of his neurologic conditions. No relapse of RM occurred on immunotherapy during follow-up. ConclusionsChinese patients with RM share some remarkable clinical and neuroimaging features and respond well to appropriate immunotherapy. Tocilizumab could be a treatment option for this severe complication of RA

Prevalence and diagnostic value of non-criteria antiphospholipid antibodies for antiphospholipid syndrome in Chinese patients

BackgroundThe presence of antiphospholipid antibodies (aPLs) plays a pivotal role in the pathogenesis of antiphospholipid antibody syndrome (APS). This study aimed to examine the diagnostic value of a set of non−criteria aPLs and their relevance with APS-related criteria and extra-criteria manifestations.MethodsFrom a prospectively constructed database, consecutive APS patients consisting of 114 primary APS (PAPS group), 54 with APS secondary to SLE (SAPS group), 9 seronegative APS (SNAPS), as well as 209 patients with systemic lupus erythematosus (SLE) and 88 healthy controls were included in this study. Levels of criteria aPLs, baseline information, and APS-related criteria and extra-criteria features were extracted from the database. Serum levels of non-criteria aPLs including aPC IgG/IgM, aPI IgG/IgM, aPE IgG/IgM/IgA, aPG IgG/IgM/IgA, anti-phosphatidic acid (aPA) IgG/IgM, aSM IgG/IgM, and aPS/PT IgG/IgM were analyzed with AESKULISA® ELISA Test Kits.ResultsThe addition of aPC IgG/M, aPI IgG/M, aPE IgG/M/A, aSM IgG/M, and aPA IgG/M to aCL or aβ2GPI IgG/M could significantly increase diagnostic sensitivity and accuracy. A significant difference between PAPS or SAPS and HC was presented in all non-criteria aPLs except for aSM IgM and aPG IgA. Eight out of nine SNAPS patients were positive for at least 1 aPL. Pregnancy morbidity was associated with aSM IgM (r = 0.22) and aSM IgG (r = 0.15). Pre-eclampsia or premature birth was associated with aSM IgG (r = 0.16), aPI IgG (r = 0.22), aPC IgG (r = 0.16), and aPG IgG (r = 0.18). Stroke was associated with aPI IgG (r = 0.2). The clinical association was also observed in DVT with aPS/PT IgG (r = 0.17). Valve lesion was positively associated with aSM IgM (Fisher test p = 0.039), APS nephropathy was associated with aPC IgG (OR 3.797), and livedo reticularis was associated with aPE IgM (OR 15.391).ConclusionAdditional detection of non-criteria aPLs including aPC IgG/M, aPE IgG/M/A, aPI IgG/M, aSM IgG/M, and aPA IgG/M could assist in APS diagnosis. The positivity of certain aPLs was statistically associated with both criteria and extra-criteria APS clinical manifestations

Acetylation Regulates Gluconeogenesis by Promoting PEPCK1 Degradation via Recruiting the UBR5 Ubiquitin Ligase

Protein acetylation has emerged as a major mechanism in regulating cellular metabolism. Whereas most glycolytic steps are reversible, the reaction catalyzed by pyruvate kinase is irreversible and the reverse reaction requires phosphoenolpyruvate carboxykinase (PEPCK1) to commit for gluconeogenesis. Here we show that acetylation regulates the stability of the gluconeogenic rate limiting enzyme PEPCK1, thereby modulating cellular response to glucose. High glucose destabilizes PEPCK1 by stimulating its acetylation. PEPCK1 is acetylated by the P300 acetyltransferase and this acetylation stimulates the interaction between PEPCK1 and UBR5, a HECT domain containing E3 ubiquitin ligase, therefore promoting PEPCK1 ubiquitinylation and degradation. Conversely, SIRT2 deacetylates and stabilizes PEPCK1. These observations represent an example that acetylation targets a metabolic enzyme to a specific E3 ligase in response to metabolic condition changes. Given that increased levels of PEPCK is linked with type II diabetes, this study also identifies potential therapeutic targets for diabetes

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

SOMOphilic Alkynylation of Unreactive Alkenes Enabled by Iron-Catalyzed Hydrogen Atom Transfer

We report an efficient and practical iron-catalyzed hydrogen atom transfer protocol for assembling acetylenic motifs into functional alkenes. Diversities of internal alkynes could be obtained from readily available alkenes and acetylenic sulfones with excellent Markovnikov selectivity. An iron hydride hydrogen atom transfer catalytic cycle was described to clarify the mechanism of this reaction

Immune Thrombocytopenia Could be an Independent Clinical Phenotype of Antiphospholipid Syndrome: A Prospective Cohort Study

Abstract Background Patients with persistent positive antiphospholipid antibodies (aPLs) and immune thrombocytopenia (ITP) hardly develop thrombosis but share many similar characteristics with antiphospholipid syndrome (APS). Methods This is a prospective cohort study consecutively enrolling thrombocytopenic patients with continuous positive aPLs. Patients developing thrombotic events are classified as the APS group. Then we compare the clinical characteristics and prognosis between aPLs carriers and patients with APS. Results This cohort included 47 thrombocytopenic patients with continuous positive aPLs and 55 with diagnosed primary APS. The proportion of smoking and hypertension are higher in the APS group (p = 0.03, 0.04, 0.03, respectively). The platelet count of aPLs carriers at admission was lower than APS patients [26 × 109/l (9 × 109/l, 46 × 109/l) vs. 64 × 109/l (24 × 109/l, 89 × 109/l), p = 0.0002]. Triple aPLs positivity is more common in primary APS patients with thrombocytopenia [24 (51.1%) vs. 40 (72.7%), p = 0.04]. Regarding the treatment response, the complete response (CR) rate is similar between aPLs carriers and primary APS patients with thrombocytopenia (p = 0.2). Nonetheless, the proportion of response, no response, and relapse differed significantly between the two groups [13 (27.7%) vs. 4 (7.3%), p < 0.0001; 5 (10.6%) vs. 8 (14.5%), p < 0.0001; 5 (10.6%) vs. 8 (14.5%), p < 0.0001, respectively]. In Kaplan–Meier analysis, primary APS patients had significantly more thrombotic events than aPLs carriers (p = 0.0006). Conclusions In the absence of other high-risk factors for thrombosis, thrombocytopenia could be an independent and long-lasting clinical phenotype of APS

Identification of potential susceptibility genes in patients with primary Sjögren’s syndrome-associated pulmonary arterial hypertension through whole exome sequencing

Abstract Background Pulmonary arterial hypertension (PAH) is a rare complication of primary Sjögren’s syndrome (pSS). Several genes have proven to be associated with pSS and PAH. However, there is no study specifically addressing the genetic susceptibility in pSS combined with PAH. Methods Thirty-four unrelated patients with pSS-PAH were recruited from April 2019 to July 2021 at Peking Union Medical College Hospital. Demographic and clinical data were recorded in detail, and peripheral blood samples were collected for whole-exome sequencing (WES). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to predict the functional effect of mutant genes. Genetic variants identified by WES were confirmed by polymerase chain reaction (PCR)-Sanger sequencing. Results We totally identified 141 pathogenic variant loci of 129 genes in these 34 pSS-PAH patients, using WES analysis. Patients with a family history of rheumatic diseases are more likely to carry FLG mutations or carry gene variations related to the biosynthesis of the amino acids pathway (p  T, BCR c.3275_3278dupCCGG, GIGYF2 c.3463C > A, ITK c.1741C > T, and SLC26A4 c.919-2A > G. Conclusion Our findings provide preliminary data of exome sequencing to identify susceptibility loci for pSS-PAH and enriched our understanding of the genetic etiology for pSS-PAH. The candidate pathogenic genes may be the potential genetic markers for early warning of this disease

A Method of Noise Reduction for Radio Communication Signal Based on RaGAN

Radio signals are polluted by noise in the process of channel transmission, which will lead to signal distortion. Noise reduction of radio signals is an effective means to eliminate the impact of noise. Using deep learning (DL) to denoise signals can reduce the dependence on artificial domain knowledge, while traditional signal-processing-based denoising methods often require knowledge of the artificial domain. Aiming at the problem of noise reduction of radio communication signals, a radio communication signal denoising method based on the relativistic average generative adversarial networks (RaGAN) is proposed in this paper. This method combines the bidirectional long short-term memory (Bi-LSTM) model, which is good at processing time-series data with RaGAN, and uses the weighted loss function to construct a noise reduction model suitable for radio communication signals, which realizes the end-to-end denoising of radio signals. The experimental results show that, compared with the existing methods, the proposed algorithm has significantly improved the noise reduction effect. In the case of a low signal-to-noise ratio (SNR), the signal modulation recognition accuracy is improved by about 10% after noise reduction

Classifier-guided multi-style tile image generation method

Image generative models for ceramic tile design lack style diversity and controllability of high-quality generated styles. It is difficult to find a series of ceramic tiles with the same texture but distinct styles, that makes it a challenging for users to select from a limited number of tiles with a single style. Although, Generative Adversarial Networks (GANs) can slightly increase the style diversity of tile images, the style controllability remains very weak. Additionally, concatenating generated tile image blocks to obtain a larger texture region can easily result in seams at the boundaries that decrease image quality. In this paper, we propose a style transfer method for ceramic tiles texture generation that combines a classifier-guided StyleGAN with AdaIN-GAN to overcome the above limitations. Firstly, we introduce a new conditional classifier-guided module into the StyleGAN. With the guidance of the input condition vector, the output image is made to have the tile style characteristics that match the vector. At the same time, the fusion of the condition vectors realizes the style gradient effect of the tile image to expand the style diversity. Secondly, we use the AdaIN-GAN to color the original texture in tile style. The style images generated by StyleGAN are then used as a dataset for model training to enhance the generalization ability of the model and achieve a style transfer effect with fixed texture features but significantly diverse styles. Finally, a linear weighted image stitching method is adopted, which uses an adaptive kernel linear weighted matrix to cover and splice arbitrary seams with image blocks, thereby successfully eliminating seams and enhancing image continuity. When this method is applied to high-resolution tile image generation, the method still maintains higher continuity and clearer image quality. Extensive experiments and human evaluation confirm the superior performance of the proposed method compared with other SOTA methods. The experimental results also verify that the new tile images generated by the proposed algorithm have diverse styles and meet the design requirements for tile style diversity

The Lncrna-TUG1/EZH2 Axis Promotes Pancreatic Cancer Cell Proliferation, Migration and EMT Phenotype Formation Through Sponging Mir-382

Background/Aims: Pancreatic carcinoma (PC) is the one of the most common and malignant cancers worldwide. LncRNA taurine upregulated gene 1 (TUG1) was initially identified as a transcript upregulated by taurine, and the abnormal expression of TUG1 has been reported in many cancers. However, the biological role and molecular mechanism of TUG1 in PC still needs further investigation. Methods: Quantitative real-time PCR (qRT-PCR) was performed to measure the expression of TUG1 in PC cell lines and tissues. MTT and colony formation assays were used to measure the effect of TUG1 on cell proliferation. A wound healing assay, transwell assay and western blot assay were employed to determine the effect of TUG1 on cell migration and the epithelial mesenchymal transition (EMT) phenotype. RNA-binding protein immunoprecipitation (RIP) and a biotin-avidin pulldown system were performed to confirm the interaction between miR-328 and TUG1. A gene expression array analysis using clinical samples and RT-qPCR suggested that enhancer of zeste homolog 2 (EZH2) was a target of miR-382 in PC. Results: In this study, we reported that TUG1 was overexpressed in PC tissues and cell lines, and high expression of TUG1 predicted poor prognosis. Further experiments revealed that overexpressed TUG1 promoted cell proliferation, migration and contributed to EMT formation, whereas silenced TUG1 led to opposing results. Additionally, luciferase reporter assays, an RIP assay and an RNA-pulldown assay demonstrated that TUG1 could competitively sponge miR-382 and thereby regulate EZH2. Conclusion: Collectively, these findings revealed that TUG1 functions as an oncogenic lncRNA that promotes tumor progression, at least partially, by functioning as an endogenous ‘sponge’ and competing for miR-382 binding to the miRNA target EZH2