Alterations of NURR1 and Cytokines in the Peripheral Blood Mononuclear Cells: Combined Biomarkers for Parkinson’s Disease

Nuclear receptor related 1 protein (NURR1), a transcription factor as key player for maintaining dopamine neuron functions and regulating neuroinflammation in the central nerves system, is a potential susceptibility gene for Parkinson’s disease (PD). To ascertain whether the expression levels of NURR1 gene and inflammatory cytokines are altered in patients with PD, we measured their mRNA levels in the peripheral blood mononuclear cells (PBMCs) in 312 PD patients, 318 healthy controls (HC), and 332 non-PD neurological disease controls (NDCs) by quantitative real-time PCR. Our data showed that NURR1 gene expression was significantly decreased in the PBMCs of PD as compared with that of HC and NDC (p < 0.01). Since NURR1 was reported to have regulating effects on neuroinflammation, we assessed the expression levels of cytokines (TNF-α, IL-1β, IL-4, IL-6, and IL-10) in the PBMCs of PD and controls (HC and NDC). Our results showed that the expression levels of those cytokines were significantly higher than those of controls. Statistical analysis revealed that NURR1 expression presented a negative correlation with the expression of TNF-α, IL-1β, IL-6, and IL-10, and collectively the measurements of NURR1 plus those cytokines significantly improve the diagnostic accuracy. All these findings suggested that NURR1 is likely to be involved in the process of PD by mediating the neuroinflammation, and the combination of NURR1 and cytokines assessment in the PBMCs can be potential biomarkers for PD diagnosis

Potential biomarkers of Parkinson’s disease revealed by plasma metabolic profiling

The plasma of Parkinson's disease (PD) patients may contain various altered metabolites associated with the risk or progression of the disease. Characterization of the abnormal metabolic pattern in PD plasma is therefore critical for the search for potential PD biomarkers. We collected blood plasma samples from PD patients and used an LC-MS based metabolomics approach to identify 17 metabolites with significantly altered levels. Metabolic network analysis was performed to place the metabolites linked to different pathways. The metabolic pathways involved were associated with tyrosine biosynthesis, glycerol phospholipid metabolism, carnitine metabolism and bile acid biosynthesis, within which carnitine and bile acid metabolites as potential biomarkers are first time reported. These abnormal metabolic changes in the plasma of patients with PD were mainly related to lipid metabolism and mitochondrial function

Challenge Analysis and Schemes Design for the CFD Simulation of PWR

CFD simulation for a PWR is an important part for the development of Numerical Virtual Reactor (NVR) in Harbin Engineering University of China. CFD simulation can provide the detailed information of the flow and heat transfer process in a PWR. However, a large number of narrow flow channels with numerous complex structures (mixing vanes, dimples, springs, etc.) are located in a typical PWR. To obtain a better CFD simulation, the challenges created by these structural features were analyzed and some quantitative regularity and estimation were given in this paper. It was found that both computing resources and time are in great need for the CFD simulation of a whole reactor. These challenges have to be resolved, so two schemes were designed to assist/realize the reduction of the simulation burden on resources and time. One scheme is used to predict the combined efficiency of the simulation conditions (configuration of computing resources and application of simulation schemes), so it can assist the better choice/decision of the combination of the simulation conditions. The other scheme is based on the suitable simplification and modification, and it can directly reduce great computing burden

Elevated Plasma microRNA-105-5p Level in Patients With Idiopathic Parkinson’s Disease: A Potential Disease Biomarker

Parkinson’s disease (PD) is the second most common neurodegenerative disease, which still lacks a biomarker to aid in diagnosis and to differentiate diagnosis at the early stage of the disease. microRNAs (miRNAs) are small and evolutionary conserved non-coding RNAs that are involved in post-transcriptional gene regulation. Several miRNAs have been proposed as potential biomarkers in several diseases. In the present study, we screened miRNAs using a network vulnerability analysis, to evaluate their potential as PD biomarkers. We first extracted miRNAs that were differentially expressed between PD and healthy controls (HC) samples. Then we constructed the PD-specific miRNA-mRNA network and screened miRNA biomarkers using a new bioinformatics model. With this model, we identified miR-105-5p as a putative biomarker for PD. Moreover, we measured miR-105-5p levels in the plasma of patients with idiopathic PD (IPD) (n = 319), neurological disease controls (NDC, n = 305) and HC (n = 273) using reverse transcription real-time quantitative PCR (RT-qPCR). Our data clearly demonstrated that the plasma miR-105-5p level in IPD patients was significantly higher than those of HC (251%, p < 0.001) and NDC (347%, p < 0.001). There was no significant difference in miR-105-5p expression between IPD patients with or without anti-PD medications. Interestingly, we found that the plasma miR-105-5p expression level may be able to differentiate IPD from parkinsonian syndrome, essential tremor and other neurodegenerative diseases. We believe that a change in the plasma miR-105-5p level is a potential biomarker for IPD

Multi-omic analysis reveals that Bacillus licheniformis enhances pekin ducks growth performance via lipid metabolism regulation

Introduction:Bacillus licheniformis (B.licheniformis) was widely used in poultry feeds. However, it is still unclear about how B.licheniformis regulates the growth and development of Pekin ducks.Methods: The experiment was designed to clarify the effect and molecular mechanism of B. licheniformis on the lipid metabolism and developmental growth of Pekin ducks through multiomics analysis, including transcriptomic and metabolomic analyses.Results: The results showed that compared with the control group, the addition of 400 mg/kg B. licheniformis could significantly increase the body weight of Pekin ducks and the content of triglyceride (p < 0.05), at the same time, the addition of B. licheniformis could affect the lipid metabolism of liver in Pekin ducks, and the addition of 400 mg/kg B. licheniformis could significantly increase the content of lipoprotein lipase in liver of Pekin ducks. Transcriptomic analysis revealed that the addition of B. licheniformis primarily impacted fatty acid and glutathione, amino acid metabolism, fatty acid degradation, as well as biosynthesis and elongation of unsaturated fatty acids. Metabolomic analysis indicated that B. licheniformis primarily affected the regulation of glycerol phospholipids, fatty acids, and glycerol metabolites. Multiomics analysis demonstrated that the addition of B. licheniformis to the diet of Pekin ducks enhanced the regulation of enzymes involved in fat synthesis via the PPAR signaling pathway, actively participating in fat synthesis and fatty acid transport.Discussion: We found that B. licheniformis effectively influences fat content and lipid metabolism by modulating lipid metabolism-associated enzymes in the liver. Ultimately, this study contributes to our understanding of how B. licheniformis can improve the growth performance of Pekin ducks, particularly in terms of fat deposition, thereby providing a theoretical foundation for its practical application.Conclusion:B. licheniformis can increase the regulation of enzymes related to fat synthesis through PPAR signal pathway, and actively participate in liver fat synthesis and fatty acid transport, thus changing the lipid metabolism of Pekin ducks, mainly in the regulation of glycerol phospholipids, fatty acids and glycerol lipid metabolites

SpikingJelly: An open-source machine learning infrastructure platform for spike-based intelligence

Spiking neural networks (SNNs) aim to realize brain-inspired intelligence on neuromorphic chips with high energy efficiency by introducing neural dynamics and spike properties. As the emerging spiking deep learning paradigm attracts increasing interest, traditional programming frameworks cannot meet the demands of the automatic differentiation, parallel computation acceleration, and high integration of processing neuromorphic datasets and deployment. In this work, we present the SpikingJelly framework to address the aforementioned dilemma. We contribute a full-stack toolkit for pre-processing neuromorphic datasets, building deep SNNs, optimizing their parameters, and deploying SNNs on neuromorphic chips. Compared to existing methods, the training of deep SNNs can be accelerated $11\times$, and the superior extensibility and flexibility of SpikingJelly enable users to accelerate custom models at low costs through multilevel inheritance and semiautomatic code generation. SpikingJelly paves the way for synthesizing truly energy-efficient SNN-based machine intelligence systems, which will enrich the ecology of neuromorphic computing.Comment: Accepted in Science Advances (https://www.science.org/doi/10.1126/sciadv.adi1480

Effects of silybin supplementation on growth performance, serum indexes and liver transcriptome of Peking ducks

As an emerging feed additive extracted from the traditional herb milk thistle, silybin has few applications and studies in Peking ducks. The aim of this study was to explore the practical significance of silymarin application in Peking ducks and to provide more theoretical support for the application of silymarin in livestock and poultry production. A total of 156 1-day-old healthy Peking ducks were randomly divided into four groups and supplemented with 0 mg/kg (control group), 400 mg/kg (S400), 800 mg/kg (S800) and 1,600 mg/kg (S1600) of silybin in the diets at day 14, to investigate the effects of silymarin on the growth, serum indexes and liver transcriptome of Peking ducks. The whole experiment lasted until day 42, and the sample collection was scheduled to take place in the morning. A substantial inprovement in average daily gain (ADG) and a decrease in feed conversion ratio (FCR) occurred in the S1600 group on days 14–28 compared to the control group (p < 0.05). The FCRs of other additive groups in the same period showed the same results. Supplementation of diets with silybin significantly increased serum IgA levels and when 1,600 mg/kg of silybin was given, levels of TNF-α and IL-6 were also significantly decreased (p < 0.05). In addition, we observed that the S1600 group had a significantly lower (p < 0.05) glutamine transaminase and an increased (p < 0.05) T-SOD level in the S400 group (p < 0.05). Liver transcriptome sequencing showed that 71 and 258 differentially expressed genes (DEGs) were identified in the S400 and S1600 groups, respectively, compared with the control group. DEGs related to cell composition and function, antigen processing and presentation were up-regulated, while DEGs related to insulin resistance and JAK–STAT were down-regulated. Conclusively, silybin can be used as a feed additive to improve the growth performance and health status of Peking ducks

CBX4 Promotes Antitumor Immunity by Suppressing Pdcd1 Expression in T Cells

E3 SUMO-protein ligase CBX4 (CBX4), a key component of polycomb-repressive complexes 1 (PRC1), has been reported to regulate a variety of genes implicated in tumor growth, metastasis, and angiogenesis. However, its role in T-cell-mediated antitumor immunity remains elusive. To shed light on this issue, we generated mice with T-cell-specific deletion of Cbx4. Tumor growth was increased in the knockout mice. Additionally, their tumor-infiltrating lymphocytes exhibited impaired tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) production, with an elevated programmed cell death protein 1 (PD-1) level. In fact, dysregulated Pdcd1 expression was observed in all major subsets of peripheral T cells from the knockout mice, which was accompanied by a functional defect in response to T-cell receptor (TCR) stimulation. In support of a direct link between CBX4 and PD-1, Cbx4 overexpression resulted in the downregulation of Pdcd1 expression. Epigenetic analyses indicated that Cbx4 deficiency leads to diminished accumulation of inhibitory histone modifications at conserved region (CR)-C and CR-B sites of the Pdcd1 promoter, namely mono-ubiquitinated histone H2A at lysine 119 (H2AK119ub1) and trimethylated histone H3 at lysine 27 (H3K27me3). Moreover, inhibition of either the E3 ligase activity of polycomb-repressive complexes 1 (PRC1) or the methyltransferase activity of polycomb-repressive complexes 2 (PRC2) restores Pdcd1 expression in Cbx4-transfected cells. Cumulatively, this study reveals a novel function of CBX4 in the regulation of T-cell function and expands our understanding of the epigenetic control of Pdcd1 expression

Goose STING mediates IFN signaling activation against RNA viruses

Stimulator of the interferon gene (STING) is involved in mammalian antiviral innate immunity as an interferon (IFN) activator. However, there is still a lack of clarity regarding the molecular characterization of goose STING (GoSTING) and its role in the innate immune response. In the present study, we cloned GoSTING and performed a series of bioinformatics analyses. GoSTING was grouped into avian clades and showed the highest sequence similarity to duck STING. The in vitro experiments showed that the mRNA levels of GoSTING, IFNs, IFN-stimulated genes (ISGs), and proinflammatory cytokines were significantly upregulated in goose embryo fibroblast cells (GEFs) infected with Newcastle disease virus (NDV). Overexpression of GoSTING in DF-1 cells and GEFs strongly activated the IFN-β promoter as detected by a dual-luciferase reporter assay. Furthermore, overexpression of GoSTING induced the expression of other types of IFN, ISGs, and proinflammatory cytokines and inhibited green fluorescent protein (GFP)-tagged NDV (NDV-GFP) and GFP-tagged vesicular stomatitis virus (VSV) (VSV-GFP) replication in vitro. In conclusion, these data suggest that GoSTING is an important regulator of the type I IFN pathway and is critical in geese’s innate immune host defense against RNA viruses