Axial spondyloarthritis (axSpA) is a globally prevalent and challenging autoimmune disease. Characterised by insidious onset and slow progression, the absence of specific clinical manifestations and ...biomarkers often leads to misdiagnosis, thereby complicating early detection and diagnosis of axSpA. Furthermore, the high heterogeneity of axSpA, its complex pathogenesis and the lack of specific drugs means that traditional classification standards and treatment guidelines struggle to meet the demands of personalised treatment. Recently, machine learning (ML) has seen rapid advancements in the medical field. By integrating large-scale data with diverse algorithms and using multidimensional data, such as patient medical records, laboratory examinations, radiological data, drug usage and molecular biology information, ML can be modelled based on real-world clinical issues. This enables the diagnosis, stratification, therapeutic efficacy prediction and prognostic evaluation of axSpA, positioning it as an emerging research topic. This study explored the application and progression of ML in the diagnosis and therapy of axSpA from five perspectives: early diagnosis, stratification, disease monitoring, drug efficacy evaluation and comorbidity prediction. This study aimed to provide a novel direction for exploring rational diagnostic and therapeutic strategies for axSpA.
This study aimed to validate the mechanism of triptolide in treating ankylosing spondylitis (AS) through network pharmacology, molecular docking, and in vitro experiments.
We gathered AS-related ...genes using databases including DrugBank, OMIM, GeneCards, TTD and DisGeNET. TCMSP database was used to collect Tripterygium wilfordii (TWHF)-related data. Additionally, the potential targets of TWHF in treating AS were predicted by consulting databases such as Venny, String, Cytoscape, and Cytohubba. Subsequently, a protein-protein interaction network was created and the gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed by metascape database. After selecting the most active ingredient of TWHF, molecular docking was performed to confirm the predicted results. Furthermore, we explore the potential mechanism of the most active ingredient of TWHF in the treatment of AS in vitro.
By integrating the results of network pharmacological analysis, 62 genes were found to be strongly associated with AS, such as STAT3, TNF, MMP9, VEGFA, CXCL8, PTGS2, etc. Triptolide (TP) is one of the most active ingredients in TWHF. The enrichment analysis indicated that 292 biological processes and 132 signaling pathways were involved, with the T helper 17 cells cell differentiation pathway as the key pathway. TP was selected for molecular docking and in vitro experiments. The molecular docking results indicated that TP had excellent affinity with 6 key targets. Further, flow cytometry, cell counting assay, and ELISA demonstrated that the serum level of IL-17 was higher in AS patients compared to XXX, and 25 μg/mL TP was the optimal intervention concentration. RT-qPCR and Western blotting further verified that TP could inhibit the activation of RORγt and the JAK2/STAT3 signaling pathway.
In conclusion, based on network pharmacology, molecular docking, and experimental verification in vitro, we proposed that the TP can inhibit the activation of RORγt and the JAK2/STAT3 signaling pathway and inhibit the differentiation of T helper 17 cells cells. The article provide a theoretical basis for further development and utilization of TWHF in AS management.
Ankylosing spondylitis (AS) is a common chronic progressive inflammatory autoimmune disease. T helper 17 (Th17) cells are the major effector cells mediating AS inflammation. Histone 3 Lys 27 ...trimethylation (H3K27me3) is an inhibitory histone modification that silences gene transcription and plays an important role in Th17 differentiation. The objective of this study was to investigate the expression of H3K27me3 in patients with AS and to explore its epigenetic regulation mechanism of Th17 differentiation during AS inflammation. We collected serum samples from 45 patients with AS at various stages and 10 healthy controls to measure their Interleukin-17 (IL-17) levels using ELISA. A quantitative polymerase chain reaction was used to quantify the mRNA levels of RORc and the signaling molecules of the JAK2/STAT3 pathway, JMJD3, and EZH2. Additionally, Western blot analysis was performed to quantify the protein levels of H3K27me3, RORγt, JAK2, STAT3, JMJD3, and EZH2 in cell protein extracts. The results showed that H3K27me3 expression in peripheral blood mononuclear cells (PBMCs) was significantly lower in patients with active AS compared to both the normal control groups and those with stable AS. Moreover, a significant negative correlation was observed between H3K27me3 expression and the characteristic transcription factor of Th17 differentiation, RORγt. We also discovered that patients with active AS exhibited significantly higher levels of JMJD3, an inhibitor of H3K27 demethylase, compared to the normal control group and patients with stable AS, while the expression of H3K27 methyltransferase (EZH2) was significantly lower. These findings suggest that H3K27me3 may be a dynamic and important epigenetic modification in AS inflammation, and JMJD3/EZH2 regulates the methylation level of H3K27me3, which may be one of the key regulatory factors in the pathogenesis of AS. These findings contribute to our understanding of the role of epigenetics in AS and may have implications for the development of novel therapeutic strategies for AS.
The aim of this study was to investigate the status of health-related quality of life in Chinese patients with ankylosing spondylitis (AS) and to analyze factors associated with the Assessment of ...SpondyloArthritis international Society Health Index (ASAS-HI) in AS and its relationship with disease activity and psychological status.OBJECTIVEThe aim of this study was to investigate the status of health-related quality of life in Chinese patients with ankylosing spondylitis (AS) and to analyze factors associated with the Assessment of SpondyloArthritis international Society Health Index (ASAS-HI) in AS and its relationship with disease activity and psychological status.A cross-sectional study of 484 patients with AS attending 10 hospitals in China from March 2021 to September 2023 was recruited. The ASAS-HI assessed general health and functional status; the Depression Anxiety Stress Scales (DASS-21) assessed psychological disorders such as anxiety, depression, and stress; and the Functional Assessment of Chronic illness Therapy-Fatigue Scale (FACIT-F) assessed patients' fatigue symptoms; the Ankylosing Spondylitis Disease Activity Score-C-Reactive Protein (ASDAS-CRP), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and Bath Ankylosing Spondylitis Measurement Index (BASMI) were used to assess patients' disease activity and functional impairment. The correlation between ASAS-HI and the ASDAS, poor psychological status, and fatigue symptoms was observed. Univariate and multivariate logistic regression analyses were used to explore the relevant influencing factors of ASAS-HI.METHODSA cross-sectional study of 484 patients with AS attending 10 hospitals in China from March 2021 to September 2023 was recruited. The ASAS-HI assessed general health and functional status; the Depression Anxiety Stress Scales (DASS-21) assessed psychological disorders such as anxiety, depression, and stress; and the Functional Assessment of Chronic illness Therapy-Fatigue Scale (FACIT-F) assessed patients' fatigue symptoms; the Ankylosing Spondylitis Disease Activity Score-C-Reactive Protein (ASDAS-CRP), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and Bath Ankylosing Spondylitis Measurement Index (BASMI) were used to assess patients' disease activity and functional impairment. The correlation between ASAS-HI and the ASDAS, poor psychological status, and fatigue symptoms was observed. Univariate and multivariate logistic regression analyses were used to explore the relevant influencing factors of ASAS-HI.A total of 484 patients were included in this study of whom 162 were in poor health, 139 in moderate health, and 183 in good health. On univariate analysis, disease activity is an important factor affecting ASAS-HI. People with extremely high disease activity (ASDAS ≥ 3.5) had a 12 times elevated risk of having poor health status (OR = 12.53; P < 0.001). Other significant covariates included age ≥ 36 (OR = 1.58; P = 0.015), BMI ≥ 24 kg/m2 (OR = 2.93; P = 0.013), smoke (OR = 1.96; P = 0.002), BASFI (OR = 1.49; P < 0.001), BASMI (OR = 1.22; P < 0.001), fatigue (OR = 6.28; P < 0.001), and bad psychological conditions such as depression (OR = 10.86; P < 0.001), anxiety (OR = 3.88; P < 0.001), and stress (OR = 4.65; P < 0.001). The use of bMARDs is inversely associated with the appearance of adverse health status (OR = 0.54; P = 0.012). There was no significant relationship between HLA-B27 and sex. Multivariable logistic regression showed that higher disease activity (ASDAS ≥ 3.5) (OR = 5.14; P = 0.005), higher scores of BASMI (OR = 1.10; P = 0.009), self-reported depression (OR = 3.68; P = 0.007), and fatigue (OR = 2.76; P < 0.001) were factors associated with adverse health status.RESULTSA total of 484 patients were included in this study of whom 162 were in poor health, 139 in moderate health, and 183 in good health. On univariate analysis, disease activity is an important factor affecting ASAS-HI. People with extremely high disease activity (ASDAS ≥ 3.5) had a 12 times elevated risk of having poor health status (OR = 12.53; P < 0.001). Other significant covariates included age ≥ 36 (OR = 1.58; P = 0.015), BMI ≥ 24 kg/m2 (OR = 2.93; P = 0.013), smoke (OR = 1.96; P = 0.002), BASFI (OR = 1.49; P < 0.001), BASMI (OR = 1.22; P < 0.001), fatigue (OR = 6.28; P < 0.001), and bad psychological conditions such as depression (OR = 10.86; P < 0.001), anxiety (OR = 3.88; P < 0.001), and stress (OR = 4.65; P < 0.001). The use of bMARDs is inversely associated with the appearance of adverse health status (OR = 0.54; P = 0.012). There was no significant relationship between HLA-B27 and sex. Multivariable logistic regression showed that higher disease activity (ASDAS ≥ 3.5) (OR = 5.14; P = 0.005), higher scores of BASMI (OR = 1.10; P = 0.009), self-reported depression (OR = 3.68; P = 0.007), and fatigue (OR = 2.76; P < 0.001) were factors associated with adverse health status.The health status of AS patients is related to age, BMI, smoking, disease activity, poor psychological status, and fatigue and is influenced by a combination of multiple factors such as emotional state, economic level, pain, and dysfunction. Therefore, clinicians should pay attention to the early assessment of ASAS-HI in order to improve the prognosis of the disease. Key Points •Ankylosing spondylitis (AS) is a chronic inflammatory autoimmune disease with a long course and heavy disease burden, which greatly affects patients' quality of life. Therefore, this study aims to evaluate the health status of ankylosing spondylitis in the Chinese population and its influencing factors. •This is a multi-center cross-sectional study in China, which can better reflect the overall situation of the Chinese population.CONCLUSIONThe health status of AS patients is related to age, BMI, smoking, disease activity, poor psychological status, and fatigue and is influenced by a combination of multiple factors such as emotional state, economic level, pain, and dysfunction. Therefore, clinicians should pay attention to the early assessment of ASAS-HI in order to improve the prognosis of the disease. Key Points •Ankylosing spondylitis (AS) is a chronic inflammatory autoimmune disease with a long course and heavy disease burden, which greatly affects patients' quality of life. Therefore, this study aims to evaluate the health status of ankylosing spondylitis in the Chinese population and its influencing factors. •This is a multi-center cross-sectional study in China, which can better reflect the overall situation of the Chinese population.
UDP-glucose pyrophosphorylase (UGPase) is an important pyrophosphatase that reversibly catalyzes the synthesis of UDP-glucose during glucose metabolism. We previously found that the deletion of ...UGPase may affect structure, growth, the virulence of Brucella, and the activation of cellular NF-κB. However, the exact mechanism of activation of NF-κB regulated by Brucella UGPase is still unclear. Here, we found for the first time that UGPase can regulate the expression of virB proteins (virB3, virB4, virB5, virB6, virB8, virB9, virB10, and virB11) of type IV secretion system (T4SS) as well as effectors (vceC, btpA, btpB, ricA, bspB, bspC, and bspF) of Brucella by promoting the expression of ribosomal S12 protein (rpsL), BMEI1825, and quinone of 2,4,5-trihydroxyphenylalanine (topA) proteins, and further inhibits the activation of cellular NF-κB and affects the virulence of Brucella. Our findings provide new insights into the mechanism used by Brucella to escape the immune recognition, which is expected to be of great value in the designing of Brucella vaccines and the screening of drug targets.
Organic light-emitting diodes (OLEDs) device capable of stored charges with poly (methyl methacrylate) (PMMA) layer is studied by transient electroluminescence measurements. The mechanism and optical ...application of stored carriers are elucidated. A spike after a driven pulse is found in the device with PMMA layer, which is attributed to the drifting back of accumulated electrons and trapped ones in shallow states, and the detrapping of latter may result in a long decay tail. A reversed post-pulse is applied to release the electrons in deep traps as they are immobile unless under a strong reversed field. Since the stored charges can lead to a great loss of carriers and weaken the performance of device, we find a way to use them in the form of light emitting with an enhanced intensity more than 3 times as against steady-state. So we have a good reason to believe if in a proper way, we can make full use of the stored charges in optical application.
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•Preparation of device capable of stored charges with insulator PMMA in OLEDs.•Mechanism analysis with transient EL measurement.•Realize the optical application of stored charges by transient method, and few related papers have been reported.
AC-driven organic light-emitting diodes (OLEDs) can overcome some reliability-related drawbacks to traditional DC-OLEDs. They imply the use of insulating layers in the device. In this work OLEDs ...containing an insulating layer of poly (methyl methacrylate) (PMMA) in storing charges with the thickness of 2, 6, 8, 10 nm have been prepared and investigated. The emission mechanisms of the device are analyzed considering transient and AC electroluminescence (EL) measurements. We show that charges are stored in the PMMA layer as surface charges and bulk charges. The former contribute to the occurrence of EL spike after the driving pulse with a decay tail for about 80 μs to 10nm PMMA device, and the latter can be released to emit light under reversed voltage more than 2 V because they are immobile unless under the stronger reversed field. Stored charges commonly are harmful for the performance of OLEDs devices due to quenching, nonradiative transition and the thermal energy accumulation even degradation. Whereas when operating under alternating current (AC) stress, we not only obtain the EL peak from injection charges under forward voltage, but also obtain another peak below the built-in voltage 4.3 V, whose peak point lies in −0.2 V. It turns to originate from stored charges so they become beneficial instead of weakening EL for reusing to produce light. All the results pave the way to realize AC driven OLEDs devices using these stored charges, to uncover the AC EL mechanisms and to improve their EL performance.
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•Preparation of device capable of stored charges with insulator PMMA in OLEDs.•Mechanism analysis with transient EL measurement.•Realize the stored charges induced AC-EL which is distinct from other similar ELs.•Demonstrate AC-EL induced by stored charges with series of pulses in transient way.
Organic integrated circuits based on organic thin film transistors (OTFT) are gaining more and more attention nowadays, the availability of accurate spice-like device model for OTFTs suitable for ...Electronic design automation (EDA) applications is particularly attractive. In this paper, we demonstrate the applicability of the accurate direct-current (DC) model for OTFTs suitable for EDA, the parameters in the unified model all can be extracted in a simple and direct way from the experimental measurements. Two types of top source and drain contact (TC) pentacene TFTs with different gate dielectrics are researched on, simulation results based Simulation Program with Integrated Circuit Emphasis (SPICE) are obtained with this model and parameters extracted, which show a very good agreement with measured curves in both transfer and output characteristics, so the DC model and the extracted parameters are verified.
The Internet and the Web are the dominant communication methods nowadays. There is also a trend in using web technology to replace or supplant the more traditional communication methods, for example ...using the internet to make Voice over IP telephone calls. This thesis proposes an efficient solution to integrate VoIP/SIP call controlfunctionality into Web containers. It presents the communication convergence of Web technology, VoIP networks, and PSTN circuit switched (CS) networks. The Web Call Software Development Kit (SDK) is the implementation of thissolution. It consists of three sub-projects: a SIP Call Control Component, a web application, and a Java ME Client Application. Using the SDK it is possible to easily implement SIP call functionality in Java EE web containers and other Java applications.
