Tasmanian devils face extinction owing to the emergence of a contagious cancer. Devil facial tumour disease (DFTD) is a clonal cancer spread owing to a lack of major histocompatibility complex (MHC) ...barriers in Tasmanian devil populations. We present a comprehensive screen of MHC diversity in devils and identify 25 MHC types and 53 novel sequences, but conclude that overall levels of MHC diversity at the sequence level are low. The majority of MHC Class I variation can be explained by allelic copy number variation with two to seven sequence variants identified per individual. MHC sequences are divided into two distinct groups based on sequence similarity. DFTD cells and most devils have sequences from both groups. Twenty per cent of individuals have a restricted MHC repertoire and contain only group I or only group II sequences. Counterintuitively, we postulate that the immune system of individuals with a restricted MHC repertoire may recognize foreign MHC antigens on the surface of the DFTD cell. The implication of these results for management of DFTD and this endangered species are discussed.
β2 adrenergic receptor (β2AR) is a G-protein-coupled receptor involved in cardiac protection. In chronic heart failure (CHF), persistent sympathetic nervous system activation occurs, resulting in ...prolonged β2AR activation and subsequent receptor desensitization and downregulation. Notoginsenoside R1 (NGR1) has the functions of enhancing myocardial energy metabolism and mitigating myocardial fibrosis. The mechanisms of NGR1 against ischemic heart failure are unclear. A left anterior descending (LAD) artery ligation procedure was performed on C57BL/6 J mice for four weeks. From the 4th week onwards, they were treated with various doses (3, 10, 30 mg/kg/day) of NGR1. Subsequently, the impacts of NGR1 on ischemic heart failure were evaluated by assessing cardiac function, morphological changes in cardiac tissue, and the expression of atrial natriuretic peptide (ANP) and beta-myosin heavy chain (β-MHC). H9c2 cells were protected by NGR1 when exposed to OGD/R conditions. H9c2 cells were likewise protected from OGD/R damage by NGR1. Furthermore, NGR1 increased β2AR levels and decreased β2AR ubiquitination. Mechanistic studies revealed that NGR1 enhanced MDM2 protein stability and increased the expression of MDM2 and β-arrestin2 while inhibiting their interaction. Additionally, under conditions produced by OGD/R, the protective benefits of NGR1 on H9c2 cells were attenuated upon administration of the MDM2 inhibitor SP141. According to these findings, NGR1 impedes the interplay between β-arrestin2 and MDM2, thereby preventing the ubiquitination and degradation of β2AR to improve CHF.
•Notoginsenoside R1 improved cardiac function and remodeling in chronic heart failure mice.•Notoginsenoside R1 increased β2AR levels and decreased β2AR ubiquitination.•β2AR ubiquitanation was inhibited by Notoginsenoside R1 via regulation of the MDM2/β-arrestin2.
A stable Ni–Al
4
Ni
3
–Al
2
O
3
superhydrophobic surface (SHS) was fabricated on aluminum (Al) substrate via etching, subsequent replacement deposition and then annealing. The water contact angle of ...the SHS could reach to 155°, and the water sliding angle was less than 2°. The morphology and chemical composition of the samples were characterized using scanning electron microscopy, X-ray diffraction pattern, energy-dispersive spectroscopy and X-ray photoelectron spectroscopy. Anti-corrosion behaviors of the samples were investigated via Tafel extrapolation and electrochemical impedance, and the SHS showed a better corrosion resistance than that of pure Al. In addition, when the water drops impinged on the SHS, the drops could fully bounce, exhibiting exquisite self-cleaning property. The catalytic property of the samples was evaluated by the reduction of 4-nitrophenol (4-NP) at room temperature, in which the SHS served as the hydrogen generator as well as a catalyst. The degradation rate of 4-NP at the existence of the superhydrophobic samples in NaOH aqueous solution was 97%. And the reaction rate constant of 4-NP at the existence of the superhydrophobic samples was 9.51
×
10
−2
s
−1
, which was about twice as large as that at the existence of pure Al. This work offers an effective strategy to fabricate SHSs and expands industrial applications for Al and its alloys.
This study aimed to clarify the efficacy and safety of Xinbao pill (XBP) as an adjunctive treatment for chronic heart failure (CHF).
Randomized controlled trials (RCTs) on the efficacy and safety of ...XBP in the treatment of CHF were searched from the six databases. The risk of bias assessment tool recommended by Cochrane Handbook 5.1 were used to assess the methodological quality of the included studies. RevMan 5.3 software was used for meta-analysis. The subgroup and sensitivity analyses were also performed. The grading recommendations assessment, development, and evaluation (GRADE) technique were used to assess the evidence's certainty.
Nine RCTs with a total of 882 patients were identified in this study. The meta-analysis demonstrated that XBP as adjunctive therapy was superior to conventional medicine alone for the treatment of CHF in improving the left ventricular ejection fraction (LVEF; MD = 5.34; 95% CI 4.68 to 5.99;
< 0.001), the total effective rate (RR = 1.21; 95% CI, 1.14 to 1.29;
< 0.001), the cardiac output (MD = 0.56; 95% CI 0.42 to 0.70;
< 0.001), the stroke volume (MD = 3.42; 95% CI 2.03 to 4.81;
< 0.001) and the 6-min walking distance (6-MWD; MD = 31.95; 95% CI 21.83 to 42.06;
< 0.001), meanwhile reducing the left ventricular end-diastolic diameter (LVEDD; MD = -3.22; 95% CI -4.03 to -2.42;
< 0.001) and left ventricular end-systolic dimension (LVESD; MD = -2.93; 95% CI -3.80 to -2.06;
< 0.001). Regarding safety, a total of 2.4% (11/456) adverse reactions occurred in the XBP groups while 3.9% (18/456) in the control group. The outcomes' evidentiary quality ranged from "very low" to "moderate".
This study indicated that XBP as adjunctive therapy combined with conventional medicine seemed to be safe and more effective than conventional medicine alone in treating CHF. However, due to the poor methodological quality of the included RCTs, further well-designed RCTs are required to confirm the efficacy and safety of XBP.
Environmental regulation can facilitate the economy's green transformation through two channels: green technology innovation and industrial structure upgrading. However, the roles of economic ...development levels play on the effects of environmental regulation are usually ignored. In view of this, we estimate the heterogeneous impacts of environmental regulation on green technology innovation and industrial structure in 105 Chinese environmental monitoring cities through the partially linear functional-coefficient panel models. The new methodological framework can allow the variable, environmental regulation, to enter the model with coefficients being functions of economic development levels. Our results show that when the economic development levels are low, environmental regulation will restrain the development of green technology innovation but have insignificant impacts on the upgrading of industrial structure. With the growth of economic development levels, environmental regulation will show relatively weak impacts on green technology innovation and industrial structure. And when the economic development levels tend to be high, environmental regulation will significantly promote green technology innovation and industrial structure upgrading. Furthermore, we identify the mixed impacts of environmental regulation in different Chinese cities and put forward relevant policy recommendations for green transformation in China.
•We study the impacts of ER on green technology innovation and industrial structure.•The partially linear functional-coefficient panel models are used to do analysis.•The impacts of ER are mixed in regions with different economic development levels.
A multicolor immunochromatographic assay platform based on quantum dot nanobeads (QBs) for the rapid and simultaneous detection of nitrofuran metabolites in different aquatic products is documented. ...These metabolites include 3-amino-2-oxazolidinone (AOZ), 1-aminohydantoin (AHD), semicarbazide (SEM), and 3-amino-5-morpholino-methyl-1,3-oxazolidinone (AMOZ). QBs with emission colors of red, yellow, green, and orange were employed and functionalized with the corresponding antibodies to each analyte to develop a multicolor channel. The visual detection limits (cutoff values) of our method for AOZ, AHD, SEM, and AMOZ reached up to 50 ng/mL, which were 2, 20, 20, and 20 times lower than those of traditional colloidal gold test strips, respectively. The test strip is capable of detection within 10 min in real samples while still achieving good stability and specificity. These results demonstrate that the developed multicolor immunochromatographic assay platform is a promising technique for multiplex, highly sensitive, and on-site detection of nitrofuran metabolites.
Oxidative stress plays a significant role in exacerbation of asthma. The role of vitamin D in oxidative stress and asthma exacerbation remains unclear. We aimed to determine the relationship between ...vitamin D status and oxidative stress in asthma exacerbation. Severe asthma exacerbation patients with 25-hydroxyvitamin D3-deficiency (V-D deficiency) or 25-hydroxyvitamin D-sufficiency (V-D sufficiency) were enrolled. Severe asthma exacerbation with V-D-deficiency showed lower forced expiratory volume in one second (FEV1) compared to that with V-D-sufficiency. V-D-deficiency intensified ROS release and DNA damage and increased TNF-α, OGG1 and NFκB expression and NFκB phosphorylation in severe asthma exacerbation. Supplemental vitamin D3 significantly increased the rates of FEV1 change and decreased ROS and DNA damage in V-D-deficiency. Vitamin D3 inhibited LPS-induced ROS and DNA damage and were associated with a decline in TNF-α and NFκB in epithelial cells. H2O2 reduces nuclear translocation of glucocorticoid receptors in airway epithelial cell lines. V-D pretreatment enhanced the dexamethasone-induced nuclear translocation of glucocorticoid receptors in airway epithelial cell lines and monocytes from 25-hydroxyvitamin D3-deficiency asthma patients. These findings indicate that V-D deficiency aggravates oxidative stress and DNA damage, suggesting a possible mechanism for corticosteroid resistance in severe asthma exacerbation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Agrobacterium tumefaciens
is a specialized plant pathogen that causes crown gall disease and is commonly used for
Agrobacterium
-mediated transformation. As a pathogen,
Agrobacterium
triggers plant ...immunity, which affects transformation. However, the signaling components and pathways in plant immunity to
Agrobacterium
remain elusive. We demonstrate that two
Arabidopsis
mitogen-activated protein kinase kinases (MAPKKs) MKK4/MKK5 and their downstream mitogen-activated protein kinases (MAPKs) MPK3/MPK6 play major roles in both
Agrobacterium
-triggered immunity and
Agrobacterium
-mediated transformation. Agrobacteria induce MPK3/MPK6 activity and the expression of plant defense response genes at a very early stage. This process is dependent on the MKK4/MKK5 function. The loss of the function of
MKK4
and
MKK5
or their downstream
MPK3
and
MPK6
abolishes plant immunity to agrobacteria and increases transformation frequency, whereas the activation of MKK4 and MKK5 enhances plant immunity and represses transformation. Global transcriptome analysis indicates that agrobacteria induce various plant defense pathways, including reactive oxygen species (ROS) production, ethylene (ET), and salicylic acid- (SA-) mediated defense responses, and that MKK4/MKK5 is essential for the induction of these pathways. The activation of MKK4 and MKK5 promotes ROS production and cell death during agrobacteria infection. Based on these results, we propose that the MKK4/5-MPK3/6 cascade is an essential signaling pathway regulating
Agrobacterium
-mediated transformation through the modulation of
Agrobacterium-
triggered plant immunity.
Background:
Myocardial infarction (MI), characterized by reduced blood flow to the heart, is a coronary artery disorder with the highest morbidity and mortality among cardiovascular diseases. ...Consequently, there is an urgent need to identify effective drugs to treat MI.
Rhizoma Corydalis
(RC) is the dry tuber of
Corydalis yanhusuo
W.T. Wang, and is extensively applied in treating MI clinically in China. Its underlying pharmacological mechanism remains unknown. This study aims to clarify the molecular mechanism of RC on MI by utilizing network pharmacology and experimental verification.
Methods:
Based on network pharmacology, the potential targets of the RC ingredients and MI-related targets were collected from the databases. Furthermore, core targets of RC on MI were identified by the protein-protein interaction (PPI) network and analyzed with Gene Ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Molecular docking was used to validate the binding affinity between the core targets and the bioactive components. Oxygen-glucose deprivation (OGD) was performed on H9c2 cells to mimic MI
in vitro
. A Cell Counting Kit-8 assay was used to assess the cardioprotective effect of the active ingredient against OGD. Western blot analysis and RT-qPCR were used to measure the cell apoptosis and inflammation level of H9c2 cells.
Results:
The network pharmacology obtained 60 bioactive components of RC, 431 potential targets, and 1131 MI-related targets. In total, 126 core targets were screened according to topological analysis. KEGG results showed that RC was closely related to the phosphatidylinositol 3-kinase (PI3K)/Protein kinase B (PKB, also called Akt) signaling pathway. The experimental validation data showed that tetrahydropalmatine (THP) pretreatment preserved cell viability after OGD exposure. THP suppressed cardiomyocyte apoptosis and inflammation induced by OGD, while LY294002 blocked the inhibition effect of THP on OGD-induced H9c2 cell injury. Moreover, the molecular docking results indicated that THP had the strongest binding affinity with Akt over berberine, coptisine, palmatine, and quercetin.
Conclusion:
THP, the active ingredient of RC, can suppress OGD-induced H9c2 cell injury by activating the PI3K/Akt pathway, which in turn provides a scientific basis for a novel strategy for MI therapy and RC application.
Parkinson's disease (PD) is a prevalent brain disorder, and PD diagnosis is crucial for treatment. Existing methods for PD diagnosis are mainly focused on behavior analysis, while the functional ...neurodegeneration of PD has not been well investigated. This paper proposes a method to signify functional neurodegeneration of PD with dynamic functional connectivity analysis. A functional near-infrared spectroscopy (fNIRS)-based experimental paradigm was designed to capture brain activation from 50 PD patients and 41 age-matched healthy controls in clinical walking tests. Dynamic functional connectivity was constructed with sliding-window correlation analysis, and k-means clustering was applied to generate the key brain connectivity states. Dynamic state features including state occurrence probability, state transition percentage and state statistical features were extracted to quantify the variations of brain functional networks. A support vector machine was trained to classify PD patients and healthy controls. Statistical analysis was conducted to investigate the difference between PD patients and healthy controls as well as the relationship between dynamic state features and the MDS-UPDRS sub-score of gait. The results showed that PD patients had a higher probability of transiting to brain connectivity states with high levels of information transmission compared with healthy controls. The MDS-UPDRS sub-score of gait and the dynamics state features showed a significant correlation. Moreover, the proposed method had better classification performances than the available fNIRS-based methods in terms of accuracy and F1 score. Thus, the proposed method well signified functional neurodegeneration of PD, and the dynamic state features may serve as promising functional biomarkers for PD diagnosis.
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