Search

Rheumatoid arthritis (RA) is a common autoimmune disease worldwide. Neutrophils play critical roles in the onset and development of RA and are the promising target for RA treatment. Tetrandrine is a bis-benzyl isoquinoline alkaloid derived from the traditional Chinese herbal Stephania tetrandra S. Moore. Tetrandrine is effective in alleviating RA by inhibiting macrophage inflammatory response, fibroblast overproliferation, and pannus formation. However, whether tetrandrine regulates the activities of neutrophils in RA is largely unknown. In this study, we adopted adjuvant-induced arthritis (AA) murine model to explore the effect of tetrandrine on RA and neutrophils. Twenty-eight mice were divided into four groups. The control group was injected with PBS in the limbs and treated with PBS by intraperitoneal injection (i.p.) from Day 10 to Day 37. The arthritis murine model was induced by injecting FCA into the ankle joints of hind limbs. The AA group, the AA + TET group, and the AA + DEX group mice were treated with PBS, tetrandrine (6 mg/kg), or dexamethasone (1 mg/kg) i.p. daily, respectively. Arthritic scores were evaluated, and the joint diameter was measured every three days. A cytometric bead assay was performed to measure the concentrations of IFN-γ, TNF-α, and IL-6 in the serum. H&E staining and Safranin O-fast staining were adopted to monitor the tissue changes in the joint. Immunohistochemistry assays were applied to detect the MPO, NE, CitH3, and PAD4 expression levels. To assess the effect of tetrandrine on neutrophil activities in vitro, CCK8 tests were applied to determine cell viability. The qPCR and ELISA were performed to determine IL-1β and IL-6 expression levels. Immunofluorescence assays were performed to measure the formation of NETs. The results indicated that tetrandrine significantly alleviated the symptoms of RA in terms of the ankle diameter (from 4.629 ± 2.729 to 3.957 ± 0.257; P < 0.01 ) and ankle score (from 4.000 ± 0.000 to 3.286 ± 0.756; P < 0.05 ). Tetrandrine treatment significantly increased the cartilage areas and decreased serum IL-6 significantly (from 5.954 ± 2.127 to 2.882 ± 2.013; P < 0.01 ). The immunohistochemistry assays also showed decreased expression levels of NE, MPO, PAD4, and CitH3 induced by tetrandrine in comparison with the AA group ( P < 0.01 ). The qPCR assays and ELISAs showed that tetrandrine had an anti-inflammatory effect in vitro by significantly inhibiting IL-6 ( P < 0.01 ). The immunofluorescence assays showed that NET formation induced by PMA could be reduced by tetrandrine ( P < 0.01 ). In conclusion, tetrandrine has good efficacy in treating RA by regulating neutrophil-involved inflammation and NET formation.

The initial satellite telemetry data acquired by ground stations usually contain noise and outlier interference. In order to ensure the accurate analysis of satellite status, the telemetry data need to be filtered. In this paper, a sliding window optimal tracking differentiator filtering (SWOTDF) method for satellite telemetry data is proposed. Aiming at the problem of parameter selection during the filtering of the optimal tracking differentiator, the amplitude-frequency characteristics of the maximum tracking differentiator are analyzed by sine sweep frequency method, and the mapping relationship between tracking factors and filtering effects is established. On this basis, the telemetry data are divided by sliding windows, and the relationship between local stability of data in each window and tracking factors is further analyzed. The calculation method of local data tracking factor is given to realize dynamic optimal tracking differentiator filtering of telemetry data in each window. Experimental results show that the SWOTDF method can effectively avoid the limitations of traditional digital filters in processing nonlinear telemetry data, and can effectively filter out noise and outliers in satellite telemetry data.

Previous studies have reported that the -methyladenosine demethylase ALKBH5 can regulate adipogenesis in humans. However, its function in birds remains unclear. In this study we aimed to explore the expression and function of the gene in chicken adipose tissue. The results showed that is widely expressed in various chicken tissues, and the expression of is relatively higher in abdominal adipose tissue. In addition, the expression of in abdominal adipose tissue of lean broilers is higher than that in fat broilers at 2 and 3 weeks of age. Moreover, the proliferation and differentiation of preadipocytes are associated with reduced and increased expression of , respectively. We also found that knockout promotes preadipocyte proliferation, as evidenced by an increase in cell viability, DNA replication activity, G-S cell cycle progression, and the expressions of and . Furthermore, after knockout of , the lipid droplet accumulation and the expression of , , and are reduced significantly. Thus, our results indicated that ALKBH5 is a novel regulator of proliferation and differentiation of chicken preadipocytes.

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is known as a rare disease characterized by inflammatory lesions on bones and skin. Polymorphism of clinical manifestation and lack of molecular biomarkers have both limited its diagnosis. Our study performed RNA sequencing (RNA-seq) and integrative bioinformatics analysis of long noncoding RNA (lncRNA)-messenger RNA (mRNA) profile in patients with SAPHO syndrome and healthy controls. A total of 4,419 differentially expressed (DE) mRNAs and 2,713 lncRNAs were identified (p < 0.05, fold change > 2) and a coexpression network was constructed to further investigate their regulatory interactions. The DE lncRNAs were predicted to interact with mRNAs in both cis and trans manners. Functional prediction found that the lncRNA-targeted genes may function in SAPHO syndrome by participating in biological process such as adipocytokine signaling pathway, ErbB signaling pathway, FoxO signaling pathway, as well as production and function of miRNAs. The expression levels of three pairs of coexpressed lncRNA-mRNAs were validated by qRT-PCR, and their relative expression levels were consistent with the RNA-seq data. The deregulated RNAs GAS7 and lnc-CLLU1.1-1:2 may serve as potential diagnostic biomarkers, and the combined receiver operating characteristic (ROC) curve of the two showed more reliable diagnostic ability with an AUC value of 0.871 in distinguishing SAPHO patients from healthy controls. In conclusion, this study provides a first insight into long noncoding RNA transcriptome profile changes associated with SAPHO syndrome and inspiration for further investigation on clinical biomarkers and molecular regulators of this inadequately understood clinical entity.

BACKGROUND Norovirus is a contagious disease. The transmission of norovirus spreads quickly and easily in various ways. Because effective methods to prevent or treat norovirus have not been discovered, it is important to rapidly recognize and report norovirus outbreaks in the early phase. Internet search has been a useful method for people to access information immediately. With the precise record of internet search trends, internet search has been a useful tool to manifest infectious disease outbreaks. OBJECTIVE In this study, we tried to discover the correlation between internet search terms and norovirus infection. METHODS The internet search trend data of norovirus were obtained from Google Trends. We used cross-correlation analysis to discover the temporal correlation between norovirus and other terms. We also used multiple linear regression with the stepwise method to recognize the most important predictors of internet search trends and norovirus. In addition, we evaluated the temporal correlation between actual norovirus cases and internet search terms in New York, California, and the United States as a whole. RESULTS Some Google search terms such as gastroenteritis, watery diarrhea, and stomach bug coincided with norovirus Google Trends. Some Google search terms such as contagious, travel, and party presented earlier than norovirus Google Trends. Some Google search terms such as dehydration, bar, and coronavirus presented several months later than norovirus Google Trends. We found that fever, gastroenteritis, poison, cruise, wedding, and watery diarrhea were important factors correlated with norovirus Google Trends. In actual norovirus cases from New York, California, and the United States as a whole, some Google search terms presented with, earlier, or later than actual norovirus cases. CONCLUSIONS Our study provides novel strategy-based internet search evidence regarding the epidemiology of norovirus.

Neutrophils are a major member of the innate immune system and play pivotal roles in host defense against pathogens and pathologic inflammatory reactions. Neutrophils can be recruited to inflammation sites via the guidance of cytokines and chemokines. Overwhelming infiltration of neutrophils can lead to indiscriminate tissue damage, such as in rheumatoid arthritis (RA). Neutrophils isolated from peritoneal exudate respond to a defined chemoattractant, N-formyl-Met-Leu-Phe (fMLP), in vitro in Transwell or Zigmond chamber assays. The air pouch experiment can be used to evaluate the chemotaxis of neutrophils towards lipopolysaccharide (LPS) in vivo. The adjuvant-induced arthritis (AA) mouse model is frequently used in RA research, and immunohistochemical staining of joint sections with anti-myeloperoxidase (MPO) or anti-neutrophil elastase (NE) antibodies is a well-established method to measure neutrophil infiltration. These methods can be used to discover promising therapies targeting neutrophil migration.

To effectively detect and identify the anomaly data in massive satellite telemetry data sets, the novel detection and identification method based on the pseudo-period was proposed in this paper. First, the raw data were compressed by extracting the shape salient points. Second, the compressed data were symbolized by the tilt angle of the adjacent data points. Based on this symbolization, the pseudo-period of the data was extracted. Third, the phase-plane trajectories corresponding to the pseudo-period data were obtained by using the pseudo-period as the basic analytical unit, and then, the phase-plane was divided into statistical regions. Finally, anomaly detection and identification of the raw data were achieved by analyzing the statistical values of the phase-plane trajectory points in each partition region. This method was verified by a simulation test that used the measured data of the satellite momentum wheel rotation. The simulation results showed that the proposed method could achieve the pseudo-period extraction of the measured data and the detection and identification of the anomalous telemetry data.

Bioactive compounds from medicinal plants with anti-inflammatory and immunosuppressive effects have been emerging as important sources of drugs for the treatment of inflammatory disorders. Triptolide, a diterpene triepoxide, is a pharmacologically active compound isolated from Tripterygium wilfordii Hook F (TwHF) that is used as a remedy for inflammatory and autoimmune diseases. As the most promising bioactive compound obtained from TwHF, triptolide has attracted considerable interest recently, especially for its potent anti-inflammatory and immunosuppressive activities. Over the past few years, an increasing number of studies have been published emphasizing the value of triptolide in the treatment of diverse inflammatory disorders. Here, we systematically review the mechanism of action and the therapeutic properties of triptolide in various inflammatory diseases according to different systematic organs, including lupus nephritis, inflammatory bowel disease, asthma, and rheumatoid arthritis with pubmed and Embase. Based on this review, potential research strategies might contribute to the clinical application of triptolide in the future.

Considering the difficulty in identifying the in-orbital spacecraft weak anomaly, a spacecraft anomaly state recognition method based on Morphological variational mode decomposition and JRD distance is proposed. First of all, the telemetry data of the spacecraft is decomposed into multi-scale modal functions with different frequencies via morphological variational modal decomposition. Then the Rényi entropy of each modal function is extracted, which is regarded as the feature of telemetry data. Finally, the recognition of spacecraft anomaly state is realized by comparing the JRD distance between the sample data and the measured data. The proposed method is verified by means of the telemetry data of the weak anomaly speed of a satellite reaction wheel. The simulation results demonstrate that the proposed method can effectively identify the anomaly of the spacecraft and has obvious advantage in recognition speed.

The molecular mechanisms of transcription factor 21 (TCF21) in regulating chicken adipogenesis remain unclear. Thus, the current study was designed to investigate the signaling pathway mediating the effect of TCF21 on chicken adipogenesis. Immortalized chicken preadipocytes cell line (ICP), a preadipocyte cell line stably overexpressing TCF21 (LV-TCF21) and a control preadipocyte cell line (LV-control) were used in the current study. We found that the phosphorylation of c-Jun N-terminal kinases (JNK) was significantly elevated in LV-TCF21 compared to LV-control. After treating ICP cells with a JNK inhibitor SP600125, the differentiation of ICP was inhibited, as evidenced by decreased accumulation of lipid droplets and reduced expression of peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer binding protein α (C/EBPα), adipocyte fatty acid binding protein (A-FABP), and lipoprotein lipase (LPL). Moreover, we found that the inhibition of JNK by SP600125 remarkably impaired the ability of TCF21 to drive adipogenesis. Taken together, our results suggest that TCF21 promotes the differentiation of adipocytes at least in part via activating MAPK/JNK pathway.

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by symmetric polyarthritis with swelling and pain at synovial joints. In RA patients, delayed neutrophil apoptosis amplifies the inflammatory response and massively released neutrophil extracellular traps (NETs) induce tissue damage and provide self-antigens. Andrographolide (AD) is the major active labdane diterpenoid derived from Andrographis paniculata, which has multiple pharmacological effects, including hepatoprotection, anti-angiogenesis, anti-thrombosis, and anti-inflammation. In the present study, we investigated the effect of AD on an adjuvant-induced arthritis (AA) murine model of RA and found that AD alleviated murine arthritis by reducing neutrophil infiltration and NETosis in the ankle joints and relieved the systematic inflammation. In vitro experiments showed that AD accelerated the apoptosis of lipopolysaccharide-activated neutrophils and inhibited autophagy-dependent extracellular traps formation of neutrophils. These findings suggest that AD has considerable potential for RA therapy.

Rheumatoid arthritis (RA) is a prototypical autoimmune disorder mainly characterized by joint inflammation and cartilage destruction. Neutrophils actively take part in the initiation and progression of RA. Neutrophils express inflammatory mediators, including cytokines and chemokines. Aberrant formation of neutrophil extracellular traps (NETs) has been demonstrated in the pathogenesis of RA. Thus, neutrophils are regarded as important therapeutic targets in RA treatment. Quercetin is one of the major flavonoids found in fruits and vegetables. Previous studies have demonstrated that quercetin is a potential agent for the treatment of RA. However, the underlying antiarthritic mechanism of quercetin has not been investigated clearly. In this study, we analyzed the therapeutic mechanism of quercetin for RA. Our results showed that quercetin ameliorates inflammation in RA mice by inhibiting neutrophil activities. Quercetin inhibited neutrophil infiltration and reduced the plasma levels of inflammatory cytokines. Quercetin promoted the apoptosis of activated neutrophils. In addition, quercetin inhibited NET formation by suppressing autophagy. These findings suggest that quercetin may be an alternative agent for the treatment of RA by inhibiting neutrophil activities.

The grey model GM(1,1) is widely applied in prediction problems, but the applicable range and the prediction precision of classical GM(1,1) is limited by the background value. In order to improve the applicability of this model, a modified unbiased grey prediction model GM(1,1), which is based on ensemble empirical mode decomposition (EEMD) is put forward. The original data is decomposed into a finite number of intrinsic mode functions (IMFs) by EEMD, and a conversion formula is used to improve the exponential smoothing of every IMF, then using each processed IMF components as input data of Unbiased GM(1,1), we accumulate all results and get the final predict result of the original data. An example is shown that the modified Unbiased GM(1,1) prediction model based on EEMD solved the predicting singular points problem of classical GM(1,1) model and improved the prediction precision.