Mucosal-associated invariant T (MAIT) cells, a novel population of innate-like lymphocytes, have been involved in various inflammatory and autoimmune diseases. However, their role in the development ...of nonalcoholic fatty liver disease (NAFLD) remains unclear. In this study, we investigated the alterations of phenotype and immunological function of MAIT cells in NAFLD. Analysis of PBMCs in 60 patients with NAFLD and 48 healthy controls (HC) revealed that circulating MAIT cell frequency decreased in NAFLD, especially in the patients with higher serum levels of γ-glutamyl transferase or total triglyceride. Functional alterations of circulating MAIT cells were also detected in NAFLD patients, such as the increased production of IL-4 whereas the decreased production of IFN-γ and TNF-α. Furthermore, elevated expression of CXCR6 was observed in circulating MAIT cells of patients. Meanwhile, we found an increased number of MAIT cells in the livers of NAFLD, and the number was even greater in patients with higher NAFLD activity score. Moreover, activated MAIT cells induced monocytes/macrophages differentiation into M2 phenotype
. Additionally, MAIT cells were enriched and displayed Th2 type cytokines profile in livers of wild type mice fed with methionine and choline deficient diet (MCD). Notably, mice deficient of MAIT cells exhibited more severe hepatic steatosis and inflammation upon MCD, accompanied with more CD11c
proinflammatory macrophages (M1) and less CD206
anti-inflammatory macrophages (M2) in livers. Our results indicate that MAIT cells protect against inflammation in NAFLD through producing regulatory cytokines and inducing anti-inflammatory macrophage polarization, which may provide novel therapeutic strategies for NAFLD.
Parkinson disease associated with farming and exposure to agricultural chemicals has been reported in numerous studies; little is known about Parkinson disease risk factors for those living in urban ...areas. The authors investigated the relation between copper, lead, or manganese emissions and Parkinson disease incidence in the urban United States, studying 29 million Medicare beneficiaries in the year 2003. Parkinson disease incidence was determined by using beneficiaries who had not changed residence since 1995. Over 35,000 nonmobile incident Parkinson disease cases, diagnosed by a neurologist, were identified for analysis. Age-, race-, and sex-standardized Parkinson disease incidence was compared between counties with high cumulative industrial release of copper, manganese, or lead (as reported to the Environmental Protection Agency) and counties with no/low reported release of all 3 metals. Parkinson disease incidence (per 100,000) in counties with no/low copper/lead/manganese release was 274.0 (95% confidence interval (CI): 226.8, 353.5). Incidence was greater in counties with high manganese release: 489.4 (95% CI: 368.3, 689.5) (relative risk = 1.78, 95% CI: 1.54, 2.07) and counties with high copper release: 304.2 (95% CI: 276.0, 336.8) (relative risk = 1.1, 95% CI: 0.94, 1.31). Urban Parkinson disease incidence is greater in counties with high reported industrial release of copper or manganese. Environmental exposure to metals may be a risk factor for Parkinson disease in urban areas.
Small-particle interlayers (lenticles) show some characteristic hydraulic properties and can affect the movement of unsaturated water. In this study, we developed a novel online ...capillary-water-absorption monitoring device and conducted three groups of comparison tests to simulate lenticle positions and thicknesses with respect to the capillary rise. The results show that the characteristic wetting front exhibits a fast rise in the early stage, a slow rise in the middle stage, and stability in the later stage. The motion of the capillary water in the lenticle is mainly transversal, with the upward curve being “flat,” and the longer is “flat,” the longer is the time needed for the water to move. The interlayer can form a capillary stagnation zone with moisture content close to saturation. The high interlayer may form a discontinuous corrugated capillary zone. Thus, when the wetting front reaches the “coarse-grain (lower)-fine-grain (upper)” interface, the “anti-capillary barrier effect” results in more moisture in the upper layer. Thus, when the wetting front of the capillary water reaches the “fine-grain (upper)-coarse-grain (lower)” interface, the “capillary barrier effect” causes the moisture content of the upper tailings to decreases sharply because of the horizontal movement of the water in the fine medium. It is clear that the presence of lenticles can retard the rise of capillary water by storing water.
This paper has designed an anchor point lever beam coupled tuning fork micro-gyroscope and tested its output performance. The tuning fork micro-gyro is designed to eliminate the output error caused ...by orthogonal coupling and in-phase-inverting coupling by structural decoupling and electrical decoupling, and can improve the anti-vibration performance and the modal optimization ability. It has derived the dynamic response working model of the non-ideal tuning fork micro-gyroscope, and optimized the structural parameters of the micro-gyroscope by simulation analysis. The microstructure processing has been realized by the SOI-MEMS process, sealed the processed structural prototype, and tested the performance through the established experimental system. According to the test results, the designed micro-gyroscope driving direction has greatly reduced the in-phase-inverting coupling through the anchor coupling lever beam, and the detection direction effectively suppressed the in-phase-inverting coupling through the stiffness matching electrode. While closed-loop detecting, the measured Aallan variance zero-bias stability is 1.779°/h, and the 1σ zero-bias stability is 8.3°/h. While applying a stiffness matching voltage, the measured vibration sensitivity is 23.9°/h/g.
Nitrogen is an important nutrient element that limits plant growth and yield formation, but excessive nitrogen has negative effects on plants and the environment. It is important to reveal the ...molecular mechanism of high NUE (nitrogen use efficiency) for breeding peach rootstock and variety with high NUE. In this study, two peach rootstocks, Shannong–1 (S) and Maotao (M), with different NUE were used as materials and treated with 0.1 mM KNO3 for transcriptome sequencing together with the control group. From the results of comparison between groups, we found that the two rootstocks had different responses to KNO3, and 2151 (KCL_S vs. KCL_M), 327 (KNO3_S vs. KCL_S), 2200 (KNO3_S vs. KNO3_M) and 146 (KNO3_M vs. KCL_M) differentially expressed genes (DEGs) were identified, respectively, which included multiple transcription factor families. These DEGs were enriched in many biological processes and signal transduction pathways, including nitrogen metabolism and plant hormone signal transduction. The function of PpNRT2.1, which showed up-regulated expression under KNO3 treatment, was verified by heterologous expression in Arabidopsis. The plant height, SPAD (soil and plant analyzer development) of leaf and primary root length of the transgenic plants were increased compared with those of WT, indicating the roles of PpNRT2.1 in nitrogen metabolism. The study uncovered for the first time the different molecular regulatory pathways involved in nitrogen metabolism between two peach rootstocks and provided gene reserve for studying the molecular mechanism of nitrogen metabolism and theoretical basis for screening peach rootstock or variety with high NUE.
Over the past two decades, magnetic resonance imaging (MRI) has been widely used for diagnosis in gestational women. Though it has several advantages, animal and human studies on the safety of MRI ...for the fetus remain inconclusive. Epigenetic modifications, which are crucial for cellular functioning, are prone to being affected by environmental changes. Therefore, we hypothesized that MRI during gestation may cause epigenetic modification alterations. Here, we investigated DNA methylation patterns of leptin promoter in the placenta and cord blood of women exposed to MRI during gestation. Results showed that average methylation levels of leptin in the placenta and cord blood were not affected by MRI. We also found that the methylation levels in the placenta and cord blood were not affected by different magnetic fields (1.5T and 3.0T MRI). However, if pregnant women were exposed to MRI at 15 to 20 weeks of gestation, the methylation level of leptin in cord blood was visibly lower than that of pregnant women exposed to MRI after 20-weeks of gestation (P = 0.037). mRNA expression level of leptin in cord blood was also altered, though mRNA expression of leptin in the placenta was not significantly affected. Therefore, we concluded that gestational MRI may not have major effects on the methylation level of leptin in cord blood and the placenta except for MRI applied before 20 weeks of gestation.
This paper researches the electro hydraulic control system of two-column shield hydraulic supports, takes the hydraulic support base advancing loop as the position servo control system, and studies ...its dynamic characteristics. It establishes the power amplifier, position sensor, hydraulic cylinder and loading mathematical model of the position servo control system, determines the model parameters of the advancing control system according to the shield hydraulic support used in the 1315 working face of GuoTun coal mine, and derives the opening loop transfer function of the valve controlled advancing cylinder. This paper also analyzes the stability of the control system of the advancing loop with the modern design method, and verifies the stability of the electro-hydraulic control system loop according to the simulation curve and the stability. By comparing with the valve core displacement and system flow curve while the system opening or closing, this paper explains the application effect of servo control system. It provides a new research idea and method for the study of the overall stability and effectively reduces the failure rate of electro-hydraulic control system of the hydraulic support. It also plays practical significance and value to improve the mining efficiency of the coal mining face.
Genome-wide association studies have identified 19p13.3 locus associated with primary biliary cholangitis (PBC). Here we aim to identify causative variant(s) and initiate efforts to define the ...mechanism by which the 19p13.3 locus variant(s) contributes to the pathogenesis of PBC. A genome-wide meta-analysis of 1931 PBC subjects and 7852 controls in two Han Chinese cohorts confirms the strong association between 19p13.3 locus and PBC. By integrating functional annotations, luciferase reporter assay and allele-specific chromatin immunoprecipitation, we prioritize rs2238574, an AT-Rich Interaction Domain 3A (ARID3A) intronic variant, as a potential causal variant at 19p13.3 locus. The risk allele of rs2238574 shows higher binding affinity of transcription factors, leading to an increased enhancer activity in myeloid cells. Genome-editing demonstrates the regulatory effect of rs2238574 on ARID3A expression through allele-specific enhancer activity. Furthermore, knock-down of ARID3A inhibits myeloid differentiation and activation pathway, and overexpression of the gene has the opposite effect. Finally, we find ARID3A expression and rs2238574 genotypes linked to disease severity in PBC. Our work provides several lines of evidence that a non-coding variant regulates ARID3A expression, presenting a mechanistic basis for association of 19p13.3 locus with the susceptibility to PBC.
Dental pulp stem cells (DPSCs) were the most widely used seed cells in the field of neural regeneration and bone tissue engineering, due to their easily isolation, lack of ethical controversy, low ...immunogenicity and low rates of transplantation rejection. The purpose of this study was to investigate the role of basic fibroblast growth factor (bFGF) and nerve growth factor (NGF) on neural differentiation of DPSCs in vitro. DPSCs were cultured in neural differentiation medium containing NGF and bFGF alone or combination for 7 days. Then neural genes and protein markers were analyzed using western blot and RT-PCR. Our study revealed that bFGF and NGF increased neural differentiation of DPSCs synergistically, compared with bFGF and NGF alone. The levels of Nestin, MAP-2, βIII-tubulin and GFAP were the most highest in the DPSCs + bFGF + NGF group. Our results suggested that bFGF and NGF signifiantly up-regulated the levels of Sirt1. After treatment with Sirt1 inhibitor, western blot, RT-PCR and immunofluorescence staining showed that neural genes and protein markers had markedly decreased. Additionally, the ERK and AKT signaling pathway played a key role in the neural differentiation of DPSCs stimulated with bFGF + NGF. These results suggested that manipulation of the ERK and AKT signaling pathway may be associated with the differentiation of bFGF and NGF treated DPSCs. Our date provided theoretical basis for DPSCs to treat neurological diseases and repair neuronal damage.
MicroRNAs (miRNAs) play a key role in regulating cell differentiation. In the present study, we aimed to explore the role of miR-140-5p in odontoblastic differentiation of dental pulp stem cells ...(DPSCs).
DPSCs from normal human impacted third molars were isolated and cultured. After overexpression or silencing of miR-140-5p in DPSCs, activity, proliferation, and odontoblastic differentiation of DPSCs were evaluated. The possible target gene of miR-140-5p was verified by luciferase reporter gene assay. Using gene transfection technology, RT-CPR, and Western blot to confirm miR-140-5p regulates the odontoblastic differentiation of DPSCs through Wnt1/β-catenin signaling.
We found the expression of miR-140-5p decreased in the differentiated DPSCs for odontoblastic cells, and at the same time, the expressions of Wnt1 and β-catenin increased. Wnt1 was the target gene of miR-140-5p which was confirmed by luciferase reporter gene system. miR-140-5p overexpression suppressed the expression of Wnt1. miR-140-5p inhibitor could promote the odontoblastic differentiation of DPSCs. miR-140-5p mimic could weaken the odontoblastic differentiation of DPSCs, which could be reversed by the overexpression of Wnt1.
Our data demonstrated that miR-140-5p regulates the odontoblastic differentiation of DPSCs via targeting Wnt1/β-catenin signaling. Therefore, miR-140-5p might be a molecular target to regulate the odontoblastic differentiation for the therapeutic agents in dental medicine.
PDF
