Increased expression of long-isoform thymic stromal lymphopoietin is associated with rheumatoid arthritis and fosters inflammatory responses

Thymic stromal lymphopoietin (TSLP) is a pleiotropic cytokine that is involved in the pathogenesis of inflammatory diseases and asthma, but the expression and biological implications of the existence of two isoforms, long TSLP (lTSLP) and short TSLP (sTSLP), in RA have yet to be elucidated. Here we report that lTSLP is the predominant TSLP isoform in RA and active RA, whereas sTSLP is the major TSLP isoform in inactive RA and healthy controls. lTSLP expression is associated with disease activity, including 28-joint Disease Activity Score (DAS28) and erythrocyte sedimentation rate (ESR), as well as proinflammatory cytokine expression, irrespective of other laboratory parameters. Importantly, lTSLP alone or combined with LPS promotes the expression of proinflammatory cytokines IL-1β, IL-6, and IL-8 in PBMCs of RA, but restrains anti-inflammatory cytokine IL-10 expression in PBMCs of RA. Furthermore, we found that STAT5 signaling is involved in lTSLP-induced inflammatory accumulation in PBMCs of RA. Therefore, these results highlight the clinical significance of lTSLP in RA pathology and inflammatory response in acute-phase disease, which may provide a therapeutic target for RA

Giant magnetocaloric effect in magnets down to the monolayer limit

Two-dimensional magnets could potentially revolutionize information technology, but their potential application to cooling technology and magnetocaloric effect (MCE) in a material down to the monolayer limit remain unexplored. Herein, we reveal through multiscale calculations the existence of giant MCE and its strain tunability in monolayer magnets such as CrX$_3$ (X=F, Cl, Br, I), CrAX (A=O, S, Se; X=F, Cl, Br, I), and Fe$_3$GeTe$_2$. The maximum adiabatic temperature change ($\Delta T_\text{ad}^\text{max}$), maximum isothermal magnetic entropy change, and specific cooling power in monolayer CrF$_3$ are found as high as 11 K, 35 $\mu$Jm$^{-2}$K$^{-1}$, and 3.5 nWcm$^{-2}$ under a magnetic field of 5 T, respectively. A 2% biaxial and 5% $a$-axis uniaxial compressive strain can remarkably increase $\Delta T_\text{ad}^\text{max}$ of CrCl$_3$ and CrOF by 230% and 37% (up to 15.3 and 6.0 K), respectively. It is found that large net magnetic moment per unit area favors improved MCE. These findings advocate the giant-MCE monolayer magnets, opening new opportunities for magnetic cooling at nanoscale

Computational identification of rare codons of Escherichia coli based on codon pairs preference

<p>Abstract</p> <p>Background</p> <p>Codon bias is believed to play an important role in the control of gene expression. In <it>Escherichia coli</it>, some rare codons, which can limit the expression level of exogenous protein, have been defined by gene engineering operations. Previous studies have confirmed the existence of codon pair's preference in many genomes, but the underlying cause of this bias has not been well established. Here we focus on the patterns of rarely-used synonymous codons. A novel method was introduced to identify the rare codons merely by codon pair bias in <it>Escherichia coli</it>.</p> <p>Results</p> <p>In <it>Escherichia coli</it>, we defined the "rare codon pairs" by calculating the frequency of occurrence of all codon pairs in coding sequences. Rare codons which are disliked in genes could make great contributions to forming rare codon pairs. Meanwhile our investigation showed that many of these rare codon pairs contain termination codons and the recognized sites of restriction enzymes. Furthermore, a new index (F_rare) was developed. Through comparison with the classical indices we found a significant negative correlation between F_rareand the indices which depend on reference datasets.</p> <p>Conclusions</p> <p>Our approach suggests that we can identify rare codons by studying the context in which a codon lies. Also, the frequency of rare codons (F_rare) could be a useful index of codon bias regardless of the lack of expression abundance information.</p

Mild temperature photothermal assisted anti-bacterial and anti-inflammatory nanosystem for synergistic treatment of post-cataract surgery endophthalmitis

Rationale: Endophthalmitis, which is one of the severest complications of cataract surgeries, can seriously threaten vision and even lead to irreversible blindness owing to its complicated microenvironment, including both local bacterial infection and severe inflammation. It is urgent to develop a comprehensive treatment for both anti-bacterial and anti-inflammatory effects. Methods: Herein, we developed AuAgCu2O-bromfenac sodium nanoparticles (AuAgCu2O-BS NPs), which was designed to combine anti-bacterial and anti-inflammatory effects for integrated therapy of endophthalmitis after cataract surgery. The AuAgCu2O-BS NPs could eradicate methicillin-resistant Staphylococcus aureus (MRSA) bacterial strain relied on their photodynamic effects and the release of metal ions (Ag+ and Cu+) by the hollow AuAgCu2O nanostructures mediated mild photothermal effects. The anti-inflammatory drug, bromfenac sodium, released from the nanoparticles were able to significantly reduce the local inflammation of the endophthalmitis and promote tissue rehabilitation. In vivo bacterial elimination and anti-inflammation were confirmed by a postcataract endophthalmitis rabbit model. Results: Excellent antibacterial ability of AuAgCu2O-BS NPs was verified both in vitro and in vivo. Ophthalmological clinical observation and pathologic histology analysis showed prominent treatment of inflammatory reaction. Importantly, the mild temperature photothermal effect not only promoted the release of metal ions and bromfenac sodium but also avoided the thermal damage of the surrounding tissues, which was more suitable for the practical application of ophthalmology due to the complex structure of the eyeball. Moreover, superior biocompatibility was approved by the preliminary toxicity investigations, including low cytotoxicity, negligible damage to major organs, and stable intraocular pressure. Conclusions: Our studies of nanosystem provide a promising synergic therapeutic strategy for postcataract endophthalmitis treatment with favorable prognosis and promise in clinical translations.Peer reviewe

A novel parametric approach to mine gene regulatory relationship from microarray datasets

<p>Abstract</p> <p>Background</p> <p>Microarray has been widely used to measure the gene expression level on the genome scale in the current decade. Many algorithms have been developed to reconstruct gene regulatory networks based on microarray data. Unfortunately, most of these models and algorithms focus on global properties of the expression of genes in regulatory networks. And few of them are able to offer intuitive parameters. We wonder whether some simple but basic characteristics of microarray datasets can be found to identify the potential gene regulatory relationship.</p> <p>Results</p> <p>Based on expression correlation, expression level variation and vectors derived from microarray expression levels, we first introduced several novel parameters to measure the characters of regulating gene pairs. Subsequently, we used the naïve Bayesian network to integrate these features as well as the functional co-annotation between transcription factors and their target genes. Then, based on the character of time-delay from the expression profile, we were able to predict the existence and direction of the regulatory relationship respectively.</p> <p>Conclusions</p> <p>Several novel parameters have been proposed and integrated to identify the regulatory relationship. This new model is proved to be of higher efficacy than that of individual features. It is believed that our parametric approach can serve as a fast approach for regulatory relationship mining.</p

Using histogram analysis of the intrinsic brain activity mapping to identify essential tremor

BackgroundEssential tremor (ET) is one of the most common movement disorders. Histogram analysis based on brain intrinsic activity imaging is a promising way to identify ET patients from healthy controls (HCs) and further explore the spontaneous brain activity change mechanisms and build the potential diagnostic biomarker in ET patients.MethodsThe histogram features based on the Resting-state functional magnetic resonance imaging (Rs-fMRI) data were extracted from 133 ET patients and 135 well-matched HCs as the input features. Then, a two-sample t-test, the mutual information, and the least absolute shrinkage and selection operator methods were applied to reduce the feature dimensionality. Support vector machine (SVM), logistic regression (LR), random forest (RF), and k-nearest neighbor (KNN) were used to differentiate ET and HCs, and classification performance of the established models was evaluated by the mean area under the curve (AUC). Moreover, correlation analysis was carried out between the selected histogram features and clinical tremor characteristics.ResultsEach classifier achieved a good classification performance in training and testing sets. The mean accuracy and area under the curve (AUC) of SVM, LR, RF, and KNN in the testing set were 92.62%, 0.948; 92.01%, 0.942; 93.88%, 0.941; and 92.27%, 0.939, respectively. The most power-discriminative features were mainly located in the cerebello-thalamo-motor and non-motor cortical pathways. Correlation analysis showed that there were two histogram features negatively and one positively correlated with tremor severity.ConclusionOur findings demonstrated that the histogram analysis of the amplitude of low-frequency fluctuation (ALFF) images with multiple machine learning algorithms could identify ET patients from HCs and help to understand the spontaneous brain activity pathogenesis mechanisms in ET patients

Cortical Gyrification and Sulcal Spans in Early Stage Alzheimer's Disease

Alzheimer's disease (AD) is characterized by an insidious onset of progressive cerebral atrophy and cognitive decline. Previous research suggests that cortical folding and sulcal width are associated with cognitive function in elderly individuals, and the aim of the present study was to investigate these morphological measures in patients with AD. The sample contained 161 participants, comprising 80 normal controls, 57 patients with very mild AD, and 24 patients with mild AD. From 3D T1-weighted brain scans, automated methods were used to calculate an index of global cortex gyrification and the width of five individual sulci: superior frontal, intra-parietal, superior temporal, central, and Sylvian fissure. We found that global cortex gyrification decreased with increasing severity of AD, and that the width of all individual sulci investigated other than the intra-parietal sulcus was greater in patients with mild AD than in controls. We also found that cognitive functioning, as assessed by Mini-Mental State Examination (MMSE) scores, decreased as global cortex gyrification decreased. MMSE scores also decreased in association with a widening of all individual sulci investigated other than the intra-parietal sulcus. The results suggest that abnormalities of global cortex gyrification and regional sulcal span are characteristic of patients with even very mild AD, and could thus facilitate the early diagnosis of this condition

Analysis of the Spatial Distribution Characteristics of Residences and Workplaces under the Influence of Metro Transportation in Metropolises from the Perspectives of Accessibility and Travelers’ Industries: The Case of Guangzhou

The spatial separation between residences and workplaces of citizens is a challenge encountered by many, causing urban problems like long-distance commutes, traffic congestion, and environmental pollution due to the heavy usage of cars. As a result of this phenomenon, metro transportation has become an increasingly important means of transportation in metropolises. To further understand the spatial separation issues, we analyzed the spatial distribution characteristics of areas under the influence of metro transportation in metropolises, and this could provide new approaches to this challenge. This research used Guangzhou city as a case study to investigate the spatial distribution characteristics of residences and workplaces from two perspectives: accessibility, and the type of the travelers’ industries. The analysis was mainly based on (1) passengers’ travel data provided by Guangzhou Metro Group Co., Ltd. (Guangzhou, China); (2) the resident population, based on the sixth national census in China; and (3) the employed population, based on the third economic census of China. Our research resulted in three key findings. First, the spatial separation of residences and workplaces was generally noticeable in Guangzhou but was less noticeable in the area with metro stations. Second, workplaces were concentrated in the central ring while residences were concentrated in the inner suburban ring in Guangzhou. Third, there was a relative concentration of workplaces in the same service industry and the workplaces of each service industry were concentrated in separate, respective areas in Guangzhou. On the basis of these findings, we provided suggestions for policymakers to develop specific and effective actions to mitigate the negative impacts of spatial separation