Identification of key interferon-stimulated genes for indicating the condition of patients with systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with highly heterogeneous clinical symptoms and severity. There is complex pathogenesis of SLE, one of which is IFNs overproduction and downstream IFN-stimulated genes (ISGs) upregulation. Identifying the key ISGs differentially expressed in peripheral blood mononuclear cells (PBMCs) of patients with SLE and healthy people could help to further understand the role of the IFN pathway in SLE and discover potential diagnostic biomarkers.The differentially expressed ISGs (DEISG) in PBMCs of SLE patients and healthy persons were screened from two datasets of the Gene Expression Omnibus (GEO) database. A total of 67 DEISGs, including 6 long noncoding RNAs (lncRNAs) and 61 messenger RNAs (mRNAs) were identified by the “DESeq2” R package. According to Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, those DEISGs were mainly concentrated in the response to virus and immune system processes. Protein-protein interaction (PPI) network showed that most of these DEISGs could interact strongly with each other. Then, IFIT1, RSAD2, IFIT3, USP18, ISG15, OASL, MX1, OAS2, OAS3, and IFI44 were considered to be hub ISGs in SLE by “MCODE” and “Cytohubba” plugins of Cytoscape, Moreover, the results of expression correlation suggested that 3 lncRNAs (NRIR, FAM225A, and LY6E-DT) were closely related to the IFN pathway.The lncRNA NRIR and mRNAs (RSAD2, USP18, IFI44, and ISG15) were selected as candidate ISGs for verification. RT-qPCR results showed that PBMCs from SLE patients had substantially higher expression levels of 5 ISGs compared to healthy controls (HCs). Additionally, statistical analyses revealed that the expression levels of these ISGs were strongly associated to various clinical symptoms, including thrombocytopenia and facial erythema, as well as laboratory indications, including the white blood cell (WBC) count and levels of autoantibodies. The Receiver Operating Characteristic (ROC) curve demonstrated that the IFI44, USP18, RSAD2, and IFN score had good diagnostic capabilities of SLE.According to our study, SLE was associated with ISGs including NRIR, RSAD2, USP18, IFI44, and ISG15, which may contribute to the future diagnosis and new personalized targeted therapies

Proposed clinical phases for the improvement of personalized treatment of checkpoint inhibitor–related pneumonitis

BackgroundCheckpoint inhibitor–related pneumonitis (CIP) is a lethal immune-related adverse event. However, the development process of CIP, which may provide insight into more effective management, has not been extensively examined.MethodsWe conducted a multicenter retrospective analysis of 56 patients who developed CIP. Clinical characteristics, radiological features, histologic features, and laboratory tests were analyzed. After a comprehensive analysis, we proposed acute, subacute, and chronic phases of CIP and summarized each phase’s characteristics.ResultsThere were 51 patients in the acute phase, 22 in the subacute phase, and 11 in the chronic phase. The median interval time from the beginning of CIP to the different phases was calculated (acute phase: ≤4.9 weeks; subacute phase: 4.9~13.1 weeks; and chronic phase: ≥13.1 weeks). The symptoms relieved from the acute phase to the chronic phase, and the CIP grade and Performance Status score decreased (P<0.05). The main change in radiologic features was the absorption of the lesions, and 3 (3/11) patients in the chronic phase had persistent traction bronchiectasis. For histologic features, most patients had acute fibrinous pneumonitis in the acute phase (5/8), and most had organizing pneumonia in the subacute phase (5/6). Other histologic changes advanced over time, with the lesions entering a state of fibrosis. Moreover, the levels of interleukin-6, interleukin-10 and high-sensitivity C-reactive protein (hsCRP) increased in the acute phase and decreased as CIP progressed (IL-6: 17.9 vs. 9.8 vs. 5.7, P=0.018; IL-10: 4.6 vs 3.0 vs. 2.0, P=0.041; hsCRP: 88.2 vs. 19.4 vs. 14.4, P=0.005).ConclusionsThe general development process of CIP can be divided into acute, subacute, and chronic phases, upon which a better management strategy might be based devised

Study on Damage Characteristics of Water-Bearing Coal Samples under Cyclic Loading–Unloading

For underground water reservoirs in coal mines, the complex water-rich environment and changing overburden stress can damage coal pillar dams. In this paper, the coal samples from coal seam 22 of Shangwan coal mine were taken as research objects and the damage mechanism and characteristics of coal samples with different moisture content and wetting-drying cycles under cyclic loading were investigated. The results show that as the moisture content and wetting-drying cycles increase, the post-peak stage of the coal samples under cyclic stress becomes obvious, and the hysteresis loop changes from dense to sparse. Compared to the uniaxial compression experiment, when w = 5.28% (the critical water content), mechanical parameters such as peak strength and modulus of elasticity decrease the most. Under cyclic loading, the damage mode of both sets of coal samples was tensile damage, but the increase in wetting-drying cycles promotes the development of shear fractures. For evaluating fracture types, the RA-AF density map is more applicable to wetting-drying cycle coal samples, whereas for the coal samples with different moisture contents this should be carried out with caution. This study can provide some theoretical basis for the stability evaluation of coal pillar dams in underground water reservoirs

Serological and clinical associations of autoantibodies in Chinese patients with new-onset systemic lupus erythematosus

Abstract To study the clinical significance of autoantibodies in Chinese patients with new-onset systemic lupus erythematosus (SLE), we enrolled 526 new-onset patients who met the 1997 Updated American College of Rheumatology SLE Classification Criteria for a retrospective cohort study. Chi-square test and Wilcoxon rank-sum test were used to detect the relationship of autoantibodies with clinical manifestations and serological results respectively. Our results demonstrated that the positive rate of anti-ribosomal P protein (anti-P) antibody in female patients was higher than that in male patients (41.2% vs. 22%, P = 0.008). Patients with anti-SSB (43.95 ± 73.12 vs. 40.92 ± 75.75, P = 0.004; 63.93 ± 103.56 vs. 55.06 ± 120.84, P = 0.008 respectively) antibodies had higher levels of alanine aminotransferase (ALT) and aspartate transaminase (AST), whereas those with anti-P antibody (28.90 ± 25.70 vs. 50.08 ± 93.00, P = 0.014; 38.51 ± 48.19 vs. 69.95 ± 142.67, P = 0.047, respectively) had lower levels of them. Anti-dsDNA antibody (P = 0.021) was associated with pulmonary arterial hypertension (PAH). The patients with anti-Ro60 (P = 0.044), anti-P (P = 0.012) and anti-dsDNA (P = 0.013) antibodies were less likely to develop Interstitial lung disease. Anti-SmRNP antibody was correlated to lower prevalence of neuropsychiatric symptoms (P = 0.037), and patients with anti-centromere antibody (ACA) were more likely to develop serositis (P = 0.016).We identified five clusters of SLE-related autoantibodies, confirmed previously reported associations of autoantibodies, and discovered new associations

Effects of Current and Ambient Temperature on Thermal Response of Lithium Ion Battery

Both operating current and ambient temperature have a great impact on heat generation and the available residual capacity of the lithium ion battery. The thermal response of the lithium ion battery is investigated under isothermal conditions. Six currents from 1 A to 6 A, with a 1 A interval, are investigated in order to discuss the effect of current under 25 °C; four temperatures from 10 °C to 55 °C, with a 15 °C interval, are investigated to study the effect of temperature under the current of 2 A. The heat generation rate increases with the current increasing during both the charge and discharge stage, but the charge capacity remains independent of current, while the discharge capacity decreases with increasing current. Heat generation decreases with increasing temperature in both the charge and discharge stage, while charge capacity and discharge capacity increase. with the temperature increasing from 10 °C to 55 °C. Heat generation of per charge/discharge capacity is also discussed, and in most cases, the heat generation of per charge capacity during the constant voltage charge stage is larger than that during the constant current charge stage. Heat generation increases at the expense of available capacity, during the discharge stage

Learning With Stochastic Guidance for Robot Navigation

Due to the sparse rewards and high degree of environmental variation, reinforcement learning approaches, such as deep deterministic policy gradient (DDPG), are plagued by issues of high variance when applied in complex real-world environments. We present a new framework for overcoming these issues by incorporating a stochastic switch, allowing an agent to choose between high- and low-variance policies. The stochastic switch can be jointly trained with the original DDPG in the same framework. In this article, we demonstrate the power of the framework in a navigation task, where the robot can dynamically choose to learn through exploration or to use the output of a heuristic controller as guidance. Instead of starting from completely random actions, the navigation capability of a robot can be quickly bootstrapped by several simple independent controllers. The experimental results show that with the aid of stochastic guidance, we are able to effectively and efficiently train DDPG navigation policies and achieve significantly better performance than state-of-the-art baseline models

Bradykinin contributes to immune liver injury via B2R receptor-mediated pathways in trichloroethylene sensitized mice: A role in Kupffer cell activation

We have previously shown trichloroethylene (TCE) induced occupational medicamentosa-like dermatitis due to TCE (OMLDT) with immune liver injury, and kallikrein-kinin system (KKS) activation as a probably mechanism underlying the immune damage. Bradykinin (BK) is an important active component of KKS system function, but the specific role of BK in the immune liver injury has never been examined. The present study aimed to explore the important role of BK and mechanisms of action in immune liver injury induced by TCE. TCE sensitization significantly increased the expression of BK receptor (B2R) in the liver. Compared to blank and vehicle control group, TCE sensitization positive mice developed exacerbated liver injury evidenced by elevated AST, ALT levels and hepatocyte damage. TCE sensitization also stimulated MAPK and STAT3 activation in liver tissue. B2R antagonist HOE140 ameliorated these changes. Kupffer cells (KCs) of the liver were also activated following TCE sensitization; both CD68+ KCs and CD16/CD32+ M1 type KCs were increased in TCE positive group. Further experiments isolated the KCs from the liver in each group and showed that TCE sensitization resulted activation of MAPK signal pathway which in turn caused release of the pro-inflammatory cytokines, IL-1β, IL-6, TNF-α, in KCs; the antagonist HOE140 again decreased these changes in KCs. These results uncover a novel role of BK and B2R cross-talk in KCs activation in TCE sensitized mice, mediated by pro-inflammatory cytokine release via MAPK and STAT3 activation, contributing to the immune liver injury

Different Tea Germplasms Distinctly Influence the Adaptability of <i>Toxoptera aurantii</i> (Hemiptera: Aphididae)

Aphids are typical phloem-sucking insect pests. A good understanding regarding their feeding behavior and population dynamics are critical for evaluating host adaptation and screening of aphid-resistant resources. Herein, the adaptability of Toxoptera aurantii (Boyer) (Hemiptera: Aphididae) to different hosts was evaluated via electropenetrography and an age-stage, two-sex life table on six tea germplasms: Zikui (ZK), Zhongcha108 (ZC108), Zhongcha111 (ZC111), Qianmei419 (QM419), Meitan5 (MT5), and Fudingdabaicha (FD). Our findings revealed that the feeding activities of T. aurantii differed considerably among the host plants. T. aurantii exhibited significantly more pathway activities on ZK and FD than on the other hosts. However, the duration of feeding of T. aurantii on ZK phloem considerably decreased compared with those of the other germplasms. Life parameters indicated that T. aurantii exhibited the highest intrinsic rate of increase (r), net reproductive rate (R0), and finite rate of increase (λ) on MT5, and the maximum values of total longevity and oviposition period were recorded on FD; these variables were reduced significantly on ZK. The results of our study demonstrate that T. aurantii can successfully survive on the six tea germplasms; however, ZK was less suitable for T. aurantii and should be considered as a potential source of resistance in breeding and Integrated Pest Management