We analysed the peripheral blood lymphocyte subsets of human immunodeficiency virus (HIV)-negative patients infected with pneumocystis pneumonia (PCP) to determine the relationships between the ...levels of different types of lymphocytes and the prognosis of patients.
We retrospectively reviewed HIV-negative patients with PCP diagnosed in our department. All the eligible patients underwent lymphocyte subset analysis on admission.
A total of 88 HIV-negative PCP patients were enrolled in the study. In univariate analyses, low CD4+ T cell count, low CD8+ T cell count, and low natural killer cell (NK cell) count were associated with higher in-hospital mortality. CD8+ T cell count ≤300/μL was found to be an independent risk factor for poor prognosis in multivariate logistical regression analysis (p = 0.015, OR = 11.526, 95% CI = 1.597-83.158). Although low CD4+ T cell and NK cell counts were not independent risk factors, the mortality rates of PCP patients decreased as the CD4+ T cell and NK cell counts increased.
The immune process of Pneumocystis jirovecii infection is complex but important. We propose that lymphocyte subsets could give clinicians a better understanding of patient immune status, helping with the early identification of potentially lethal infections and treatment decision making, such as adjusting the immunosuppressive regimen and choosing an appropriate patient monitoring level.
By relating the charge multiplicity distribution and the temperature of a de-exciting nucleus through a deep neural network, we propose that the charge multiplicity distribution can be used as a ...thermometer of heavy-ion collisions. Based on an isospin-dependent quantum molecular dynamics model, we study the caloric curve of reaction Pd103 + Be9 with the apparent temperature determined through the charge multiplicity distribution. The caloric curve shows a characteristic signature of nuclear liquid-gas phase transition around the apparent temperature Tap = 6.4MeV, which is consistent with that through a traditional heavy-ion collision thermometer, and indicates the viability of determining the temperature in heavy-ion collisions with multiplicity distribution.
Ammonia, one of the major limiting environment factors in aquaculture, may pose a threat to the shrimp growth, reproduction and survival. In this study, to understand molecular differences of ...transcriptomic and metabolomic responses and investigate the tolerance mechanisms underlying ammonia stress in Litopenaeus vannamei, ammonia-tolerant family (LV-AT) and ammonia-sensitive family (LV-AS) of these two extreme families were exposed to high-concentration (NH4Cl, 46 mg/L) ammonia for 24 h. The comparative transcriptome analysis between ammonia-treated and control (LV-C) groups revealed involvement of immune defense, cytoskeleton remodeling, antioxidative system and metabolic pathway in ammonia-stress response of L. vannamei. Likewise, metabolomics analysis showed that ammonia exposure could disturb amino acid metabolism, nucleotide metabolism and lipid metabolism, with metabolism related-genes changed according to RNA-seq analysis. The comparison of metabolite and transcript profiles between LV-AT and LV-AS indicated that LV-AT used the enhanced glycolysis and tricarboxylic acid (TCA) cycle strategies for energy supply and ammonia excretion to adapt high-concentration ammonia. Furthermore, some of genes involved in the detoxification and ammonia excretion were highly expressed in LV-AT. We speculate that the higher ability of ammonia excretion and detoxification and the accelerated energy metabolism for energy supplies might be the adaptive strategies for LV-AT relative to LV-AS after ammonia stress. Collectively, the combination of transcriptomics and metabolomics results will greatly contribute to incrementally understand the stress responses on ammonia exposure to L. vannamei and supply molecular level support for evaluating the environmental effects of ammonia on aquatic organisms. The results further constitute new sights on the potential molecular mechanisms of ammonia adaptive strategies in shrimps at the transcriptomics and metabolomics levels.
•Transcriptomic and metabolomic responses to high-concentration of ammonia were studied in L. vannamei.•Ammonia exposure influences immune defense, cytoskeleton remodeling, antioxidative system and metabolic pathway.•Ammonia exposure disturbs the amino acid metabolism, lipid metabolism and nucleotide metabolism.•Higher ability of excretion and detoxification and accelerated energy metabolism might be related to ammonia tolerance.
In this article, a robot skills learning framework is developed, which considers both motion modeling and execution. In order to enable the robot to learn skills from demonstrations, a learning ...method called dynamic movement primitives (DMPs) is introduced to model motion. A staged teaching strategy is integrated into DMPs frameworks to enhance the generality such that the complicated tasks can be also performed for multi-joint manipulators. The DMP connection method is used to make an accurate and smooth transition in position and velocity space to connect complex motion sequences. In addition, motions are categorized into different goals and durations. It is worth mentioning that an adaptive neural networks (NNs) control method is proposed to achieve highly accurate trajectory tracking and to ensure the performance of action execution, which is beneficial to the improvement of reliability of the skills learning system. The experiment test on the Baxter robot verifies the effectiveness of the proposed method.
Background Accumulating evidence showed that regulating tumor microenvironment plays a vital role in improving antitumor efficiency. Programmed Death Ligand 1 (PD-L1) is expressed in many cancer cell ...types, while its binding partner Programmed Death 1 (PD1) is expressed in activated T cells and antigen-presenting cells. Whereas, its dysregulation in the microenvironment is poorly understood. In the present study, we confirmed that evodiamine downregulates MUC1-C, resulting in modulating PD-L1 expression in non-small cell lung cancer (NSCLC). Methods Cell viability was measured by MTT assays. Apoptosis, cell cycle and surface PD-L1 expression on NSCLC cells were analyzed by flow cytometry. The expression of MUC1-C and PD-L1 mRNA was measured by real time RT-PCR methods. Protein expression was examined in evodiamine-treated NSCLC cells using immunoblotting or immunofluorescence assays. The effects of evodiamine treatment on NSCLC sensitivity towards T cells were investigated using human peripheral blood mononuclear cells and Jurkat, apoptosis and IL-2 secretion assays. Female H1975 xenograft nude mice were used to assess the effect of evodiamine on tumorigenesis in vivo. Lewis lung carcinoma model was used to investigate the therapeutic effects of combination evodiamine and anti-PD-1 treatment. Results We showed that evodiamine significantly inhibited growth, induced apoptosis and cell cycle arrest at G2 phase of NSCLC cells. Evodiamine suppressed IFN-gamma-induced PD-L1 expression in H1975 and H1650. MUC1-C mRNA and protein expression were decreased by evodiamine in NSCLC cells as well. Evodiamine could downregulate the PD-L1 expression and diminish the apoptosis of T cells. It inhibited MUC1-C expression and potentiated CD8.sup.+ T cell effector function. Meanwhile, evodiamine showed good anti-tumor activity in H1975 tumor xenograft, which reduced tumor size. Evodiamine exhibited anti-tumor activity by elevation of CD8.sup.+ T cells in vivo in Lewis lung carcinoma model. Combination evodiamine and anti-PD-1 mAb treatment enhanced tumor growth control and survival of mice. Conclusions Evodiamine can suppress NSCLC by elevating of CD8.sup.+ T cells and downregulating of the MUC1-C/PD-L1 axis. Our findings uncover a novel mechanism of action of evodiamine and indicate that evodiamine represents a potential targeted agent suitable to be combined with immunotherapeutic approaches to treat NSCLC cancer patients. MUC1-C overexpression is common in female, non-smoker, patients with advanced-stage adenocarcinoma. Keywords: Evodiamine, PD-L1, MUC1-C, NSCLC, Immune microenvironment
Columnar jointed structures are often observed in basalt rock masses and play an important role in controlling the mechanical behaviors. In this paper, a homogenization-based modeling method is ...proposed to study the effects of columnar jointed structure on the mechanical properties of rock masses. Firstly, a modified constrained centroid Voronoi tessellation (CCVT) algorithm is developed to generate realistic columnar jointed structures. Secondly, a numerical homogenization study is conducted with the models to estimate their mechanical parameters. Comparisons with in-situ testing results indicate that the homogenization-based modeling method using a periodic boundary condition gives satisfactory estimations of the mechanical properties. A parametric study shows that the elastic parameters of columnar jointed rock mass are closely dependent on the characteristics of the columnar joints: joint density, thickness, coefficient of variation, and infilled material property. The findings in this study are useful for understanding the mechanical properties of columnar jointed rock masses as well as crystalline rocks.
•A modified constrained centroid Voronoi tessellation method for columnar jointed structure modeling is proposed.•Homogenization-based mechanical parameters estimation of columnar jointed rock mass is implemented and validated.•The effects of columnar jointed structure on mechanical properties of rock masses are analyzed and discussed.
•myod and myf5 were predominant in skeletal muscle with the highest expression in white muscle.•myod and myf5 mRNAs were the highest at 10 dph and the segmentation period, respectively.•LPS affected ...the expression of muscle related genes, and activated satellite cells.
Myod and Myf5 are muscle-specific basic helix-loop-helix (bHLH) transcription factors that play essential roles in regulating skeletal muscle development and growth. In order to investigate potential function of myod and myf5 of Megalobrama amblycephala, an economically important freshwater fish species, in the present study, we characterized the sequences and expression profiles of M. amblycephala myod and myf5. The open reading frame (ORF) sequences of myod and myf5 encoded 275 and 240 amino acids, respectively, possessing analogous structure with the highly conserved domains, bHLH and C-terminal helix III domains. Spatio-temporal expression patterns revealed that myod and myf5 were predominant in skeletal muscle with the highest expression in white muscle, and the highest at 10 days post-hatching (dph) and the segmentation period, respectively. Furthermore, we evaluated the effects of lipopolysaccharide (LPS) on the expression of muscle-related genes in white and red muscle, and proliferation and differentiation of satellite cells. The myod, myf5 and pax-7 expression generally increased and then decreased with increase of LPS concentration and treatment time in red muscle, while these genes showed inconsistent expression patterns in white muscle. In addition, LPS administration caused the frequency increase of satellite cells in red and white muscle especially at 3 and 7 days after LPS-injection.
•We present a digital image processing-based method for numerical model generation of heterogeneous material with FEM and DEM;•Both 2D bitmap and 3D volumetric images are supported;•Microstructure of ...heterogeneous material with complex connected region can be extracted;•A ready-to-use open source Matlab code and user manual are provided in this study.
An open source software package to generate numerical model for finite element method (FEM) and discrete element method (DEM) based on digital image is proposed. Both 2D bitmap and 3D volumetric images are supported. This package includes geometrical and analytical routines for vectorizing bitmap image, computing geometric information statistics, and generating numerical models. The ability of handling complex connected region enables the modeling of heterogeneous materials with complex microstructure. Four examples have indicated that the code is robust, efficient, and user-friendly. As an open source and ready-to-use Matlab package, it has broad application prospect in mechanical behavior analysis for heterogeneous materials.
Clear cell renal cell carcinoma (ccRCC) is one of the most common malignant carcinomas and its molecular mechanisms remain unclear. Long noncoding RNA (lncRNA) could bind sites of miRNA which affect ...the expression of mRNA according to the competing endogenous (ceRNA) theory. The aim of the present study was to construct a ceRNA network and to identify key lncRNA to predict survival prognosis. We identified differentially expressed mRNA, lncRNA and miRNA between tumor tissues and normal tissues from The Cancer Genome Atlas database. Then, using bioinformatics tools, we explored the connection of 89 lncRNA, 10 miRNA and 22 mRNA, and we constructed the ceRNA network. Furthermore, we analyzed the functions and pathways of 22 differentially expressed mRNA. Then, univariate and multivariate Cox regression analyses of these 89 lncRNA and overall survival were explored. Nine lncRNA were finally screened out in the training group. The patients were divided into high‐risk and low‐risk groups according to the 9 lncRNA and low‐risk scores having better clinical overall survival (P < .01). Furthermore, the receiver operating characteristic curve demonstrates the predicted role of the 9 lncRNA. The 9‐lncRNA signature was successfully proved in the testing group and the entire group. Finally, multivariate Cox regression analysis and stratification analysis further proved that the 9‐lncRNA signature was an independent factor to predict survival. In summary, the present study provides a deeper understanding of the lncRNA‐related ceRNA network in ccRCC and suggests that the 9‐lncRNA signature could serve as an independent biomarker to predict survival in ccRCC patients.
The lncRNA‐miRNA‐mRNA ceRNA network.
PDF
