587 research outputs found
Autoantibodies against eukaryotic translation elongation factor 1 delta in two patients with autoimmune cerebellar ataxia
BackgroundAutoantibodies are useful biomarkers for the early detection and diagnosis of autoimmune cerebellar ataxia (ACA).ObjectiveTo identify novel autoantibody candidates in ACA patients.MethodsPatients with cerebellar ataxia of unknown cause were recruited from July 2018 to February 2023. Anti-neural autoantibodies in patient samples were detected by tissue-based indirect immunofluorescence assay (TBA) on rat cerebellum sections. TBA-positive samples were further screened for well-established anti-neural autoantibodies using commercial kits. Tissue-immunoprecipitation (TIP) and subsequent mass spectrometric (MS) analysis were used to explore the target antigens of autoantibodies in samples that were TBA-positive but negative for known autoantibodies. The specific binding between autoantibodies and the identified target antigen was confirmed by neutralization experiments, recombinant cell-based indirect immunofluorescence assay (CBA), and western blotting experiments.ResultsThe eukaryotic translation elongation factor 1 delta (EEF1D) protein was identified as a target antigen of autoantibodies in samples from a 43-year-old female ACA patient, while the specific binding of autoantibodies and EEF1D was confirmed by subsequent experiments. A second anti-EEF1D autoantibody-positive ACA patient, a 59-year-old female, was detected in simultaneous screening. The main clinical manifestations in each of the two patients were cerebellar syndrome, such as unsteady walking and limb ataxia. Both patients received immunotherapy, including corticosteroids, intravenous immunoglobulin, and mycophenolate mofetil. Their outcomes provided evidence to support the effectiveness of immunotherapy, but the cerebellar atrophy that occurred before treatment may be irreversible.ConclusionIn the current study, we identified anti-EEF1D autoantibody as a novel autoantibody candidate in ACA. Its pathological roles and diagnostic value need to be further verified in larger-scale studies
A comprehensive review of computation-based metal-binding prediction approaches at the residue level
Clear evidence has shown that metal ions strongly connect and delicately tune the dynamic homeostasis in living bodies. They have been proved to be associated with protein structure, stability, regulation, and function. Even small changes in the concentration of metal ions can shift their effects from natural beneficial functions to harmful. This leads to degenerative diseases, malignant tumors, and cancers. Accurate characterizations and predictions of metalloproteins at the residue level promise informative clues to the investigation of intrinsic mechanisms of protein-metal ion interactions. Compared to biophysical or biochemical wet-lab technologies, computational methods provide open web interfaces of high-resolution databases and high-throughput predictors for efficient investigation of metal-binding residues. This review surveys and details 18 public databases of metal-protein binding. We collect a comprehensive set of 44 computation-based methods and classify them into four categories, namely, learning-, docking-, template-, and meta-based methods. We analyze the benchmark datasets, assessment criteria, feature construction, and algorithms. We also compare several methods on two benchmark testing datasets and include a discussion about currently publicly available predictive tools. Finally, we summarize the challenges and underlying limitations of the current studies and propose several prospective directions concerning the future development of the related databases and methods
The Combination of Molecular Adjuvant CCL35.2 and DNA Vaccine Significantly Enhances the Immune Protection of Carassius auratus gibelio against CyHV-2 Infection
Cyprinid herpesvirus 2 (CyHV-2) infection results in huge economic losses in gibel carp (Carassius auratus gibelio) industry. In this study, we first constructed recombinant plasmids pcORF25 and pcCCL35.2 as DNA vaccine and molecular adjuvant against CyHV-2, respectively, and confirmed that both recombinant plasmids could be effectively expressed in vitro and in vivo. Then, the vaccination and infection experiments (n = 50) were set as seven groups. The survival rate (70%) in ORF25/CCL35.2 group was highest. The highest specific antibody levels were found in ORF25/CCL35.2 group in major immune tissues by qRT-PCR, and confirmed in serum by ELISA assay, antibody neutralization titer, and serum incubation-infection experiments. Three crucial innate immune indices, namely C3 content, lysozyme, and total superoxide dismutase (TSOD) activities, were highest in ORF25/CCL35.2 group in serum. pcORF25/pcCCL35.2 can effectively up-regulate mRNA expressions of some important immune genes (IL-1β, IL-2, IFN-γ2, and viperin), and significantly suppress CyHV-2 replication in head kidney and spleen tissues. The minimal tissue lesions can be seen in ORF25/CCL35.2 group in gill, spleen, and trunk kidney tissues by histopathological examination. The results indicated that the combination of DNA vaccine pcORF25 and molecular adjuvant pcCCL35.2 is an effective method against CyHV-2 infection, suggesting a feasible strategy for the control of fish viral diseases
Research on Users’ Exercise Behaviors of Online Exercise Community Based on Social Capital Theory
Online exercise communities play an important role in their users’ self-health management. The willingness of users to interact and create user-generated content in online communities reflects the vitality of the online exercise community and the positive impact it has on offline users’ health performance. Therefore, based on social capital theory, we study the relationship between three types of social capital and users’ offline exercise behaviors and add off-topics in the community in the model. We select the KEEP health community user group as the research setting and conduct the regression analysis. The results show that owned centrality and reciprocity have a significant positive relationship with users’ exercise behaviors; accessed centrality and trust have a significant negative relationship with users’ exercise behaviors; and common topics and off-topics show a partly significant correlation. As a moderating variable, off-topics have a negative moderating effect on owned centrality and betweenness centrality, but a positive moderating effect on reciprocity and trust among group members. The results enrich and expand social capital theory, deepen the research on users’ exercise behaviors in the online exercise community, and provide a good reference for online exercise community management
Prediction of complete regression in fertility-sparing patients with endometrial cancer and apical hyperplasia: the GLOBAL model in a large Chinese cohort
Abstract Background Fertility preservation treatment is increasingly essential for patients with apical endometrial hyperplasia (AEH) and early endometrial cancer (EEC) worldwide. Complete regression (CR) is the main endpoint of this treatment. Accurately predicting CR and implementing appropriate interventions during treatment are crucial for these patients. Methods We conducted a retrospective study involving 193 patients diagnosed with atypical AEH or EEC, enrolled from January 2012 to March 2022 at our center. We evaluated 24 clinical parameters as candidate predictors and employed LASSO regression to develop a prediction model for CR. Subsequently, a nomogram was constructed to predict CR after the treatment. We evaluated the performance of the nomogram using receiver operator characteristic (ROC) curve and decision curve analysis (DCA) to assess its predictive accuracy. Additionally, we employed cumulative curves to determine the CR rate among patients. Results Out of the 193 patients, 173 achieved CR after undergoing fertility preservation treatment. We categorized features with similar properties and provided a list of formulas based on their coefficients. The final model, named GLOBAL (including basic information, characteristics, blood pressure, glucose metabolism, lipid metabolism, immunohistochemistry, histological type, and medication), comprised eight variables identified using LASSO regression. A nomogram incorporating these eight risk factors was developed to predict CR. The GLOBAL model exhibited an AUC of 0.907 (95% CI 0.828–0.969). Calibration plots demonstrated a favorable agreement between the predicted probability by the GLOBAL model and actual observations in the cohort. The cumulative curve analysis revealed varying cumulative CR rates among patients in the eight subgroups. Categorized analysis demonstrated significant diversity in the effects of the GLOBAL model on CR among patients with different total points (p < 0.05). Conclusion We have developed and validated a model that significantly enhances the predictive accuracy of CR in AEH and EEC patients seeking fertility preservation treatment
Analysis on Pigment and Photosynthetic Characteristics of Leaves of New Strain of Rehmannia glutinosa
Through the analysis on the leaf color and photosynthetic characteristics of new strains and main cultivars of Rehmannia glutinosa, it is expected to provide theoretical basis for breeding of new varieties. Chlorophyll, anthocyanin, and net photosynthetic rate (Pn), stomatal conductance (Cond), transpiration rate (Tr), and intercellular CO2 concentration (Ci) in 8 varieties of Rehmannia glutinosa were measured by spectrophotometer and LI-6400XT Portable Photosynthesis System. The results showed that the chlorophyll content of Huaidijin 8 (2.84 mg/g), Huaidi 81 (2.71 mg/g), Huaidi 85-5 (2.69 mg/g), Jinjiu (2.66 mg/g) and Huaidi 83 (2.63 mg/g) was higher; the anthocyanin content of Jinjiu (0.169) and Huaidijin 8 (0.165) was higher, while the anthocyanin content Huaidi 83(0.060) was the lowest; Pn of Huaidi 81 [2.41 μmol/(m2·s)], Huaidi 83 [2.37 μmol/(m2·s)] and Huaidijin 8 [2.25 μmol/(m2·s)] was higher, and the anthocyanin content was positively correlated with Pn, while the anthocyanin content was negatively correlated with Pn; Huaidijin 8 and Huaidi 83 showed dominant advantages in single plant fresh weight, indicator component, and resistance over the main cultivars. This indicates that the new variety Huaidijin 8 and Huaidi 83 have excellent comprehensive traits and can be properly popularized
2-Amino-5-methylpyridinium nitrate
In the title salt, C6H9N2+&#183;NO3&#8722;, the 2-amino-5-methylpyridinium cation and the nitrate anion are cyclically linked through pyridinium and amine N&#8212;H...O hydrogen bonds [graph set R43(12)]. These units are extended into a zigzag chain structure lying parallel to the a axis, through a second cyclic R22(8) association involving amine N&#8212;H...O and aromatic C&#8212;H...O hydrogen bonds to nitrate O-atom acceptors
The Circular RNA Profiles of Colorectal Tumor Metastatic Cells
Circular RNAs (circRNAs) have been reported that can be used as biomarkers for colorectal cancers (CRC) and other types of tumors. However, a limited number of studies have been performed investigating the potential role of circRNAs in tumor metastasis. Here, we examined the circRNAs in two CRC cell lines (a primary tumor cell SW480 and its metastasis cell SW620), and found a large set of circRNA (2,919 ncDECs) with significantly differential expression patterns relative to normal cells (NCM460). In addition, we uncovered a set of 623 pmDECs that differ between the primary CRC cells and its metastasis cells. Both differentially expressed circRNA (DEC) sets contain many previously unknown putative CRC-related circRNAs, thereby providing many new circRNAs as candidate biomarkers for CRC development and metastasis. These studies are the first large-scale identification of metastasis-related circRNAs for CRC and provide valuable candidate biomarkers for diagnostic and a starting point for additional investigations of CRC metastasis
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