Atrial fibrillation is one of the most common cardiac arrhythmias. Myocardial fibrosis is closely associated with atrial remodeling, which leads to heightened risk of atrial fibrillation. This study ...aimed to explore whether forkhead box protein O3 (FOXO3a) impacts myocardial fibrosis incidence by regulating mitophagy.
Cell viability was assessed by cell counting kit-8 (CCK-8) assays. The expression of vimentin and cytochrome C was detected by immunofluorescence assays. Quantitative real-time polymerase chain reaction (PCR) was used to analyze the relative mRNA level of FOXO3a. Expression of FOXO3a, phosphorylated FOXO3a, Collagen I, Collagen III, alpha-smooth muscle actin (α-SMA), matrix metalloprotease 9 (MMP9), light chain 3 (LC3), phosphatase and tensin homolog (PTEN)-induced kinase 1 (PINK1), Parkin, and sequestosome-1 (p62) proteins were determined by western blotting. 5-ethynyl-2'-deoxyuridine (EDU) incorporation was employed to measure cell proliferation. Changes in mitochondrial membrane potential were determined by 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl-imidacarbocyanine iodide (JC-1) staining. A wound healing assay was used to examine cell migration, and the levels of reactive oxygen species were determined by flow cytometry.
The expression of FOXO3a was upregulated in cardiac fibroblasts treated with angiotensin II (AngII), while the expression of phosphorylated FOXO3a was downregulated under these conditions. FOXO3a knockdown significantly inhibited the proliferation, migration and collagen secretion of cardiac fibroblasts treated with AngII. The ratio of LC3 II/I as well as expression of PINK1 and Parkin was increased, and the expression of p62 was decreased, in cardiac fibroblasts treated with AngII. Moreover, these effects were limited by FOXO3a knockdown. Finally, the mitophagy inducer everolimus (RAD001) attenuated the suppressive effect of FOXO3a knockdown on cardiac fibroblast activation.
FOXO3a promotes the progress of myocardial fibrosis by triggering mitophagy in cardiac fibroblasts.
Numerical simulation has been widely used in nuclear reactor safety analyses to gain insight into key phenomena. The Critical Heat Flux (CHF) is one of the limiting criteria in the design and ...operation of nuclear reactors. It is a two-phase flow phenomenon, which rapidly decreases the heat transfer performance at the rod surface. This paper presents a numerical simulation of a steady state flow in a vertical pipe to predict the CHF phenomena. The detailed Computational Fluid Dynamic (CFD) modeling methodology was developed using FLUENT. Eulerian two-phase flow model is used to model the flow and heat transfer phenomena. In order to gain the peak wall temperature accurately and stably, the effect of different turbulence models and wall functions are investigated based on different grids. Results show that O type grid should be used for the simulation of CHF phenomenon. Grids with Y+ larger than 70 are recommended for the CHF simulation because of the acceptable results of all the turbulence models while Grids with Y+ lower than 50 should be avoided. To predict the dry-out position accurately in a fine grid, Realizable k-ε model with standard wall function is recommended. These conclusions have some reference significance to better predict the CHF phenomena of vertical pipe. It can also be expanded to rod bundle of Boiling Water Reactor (BWR) by using same pressure condition.
Wearable electronics have showed their profound impact in military, sports, medical and other fields, but their large-scale applications are still limited due to high manufacturing costs. As an ...advanced micro-fabrication process, laser processing technology has the advantages of high speed, high flexibility, strong controllability, environmental protection and non-contact in preparing micro-nano structures of wearable electronics. In this paper, a 355 nm ultraviolet laser was used to pattern the copper foil pasted on the flexible substrate, and the interconnection electrodes and wires were constructed. A processing method of multi-parallel line laser cutting and high-speed laser scanning is proposed to separate and assist in peeling off excess copper foil. The process parameters are optimized. A stretchable 3 × 3 light-emitting diode (LED) array was prepared and its performance was tested. The results showed that the LED array can work normally under the conditions of folding, bending and stretching, and the stretch rate can reach more than 50%. A stretchable temperature measurement circuit that can be attached to a curved surface was further fabricated, which proves the feasibility of this process in the fabrication of small-scale flexible wearable electronic devices. Requiring no wet etching or masking process, the proposed process is an efficient, simple and low-cost method for the fabrication of stretchable circuits.
We describe herein dual-modality imaging of intraperitoneal colon tumor using an avidin/biotin pretargeting system. A novel dual-modality probe, (99m)Tc-HYNIC-lys(Cy5.5)-PEG4-biotin, was designed, ...synthesized and characterized. Single-photon emission computed tomography/ computed tomography (SPECT/CT) imaging and near infrared fluorescence (NIRF) imaging were developed using intraperitoneal LS180 human colon adenocarcinoma xenografts. Following avidin preinjection for 4 hours, (99m)Tc-HYNIC-lys(Cy5.5)-PEG4-biotin could successfully detect colon tumors of different sizes inside the abdominal region using both modalities, and the imaging results showed no differences. Biodistribution studies demonstrated that the tumors had a very high uptake of the probe (99m)Tc-HYNIC-lys(Cy5.5)-PEG4-biotin (12.74 ± 1.89% ID/g at 2 h p.i.), and the clearance from blood and other normal tissues occured very fast. The low tumor uptake in the non-pretargeted mice (1.63 ± 0.50% ID/g at 2 h p.i.) and tumor cell staining results showed excellent tumor binding specificity of the pretargeting system. The ability of the novel probe to show excellent imaging quality with high tumor-to-background contrast, a high degree of binding specificity with tumors and excellent in vivo biodistribution pharmacokinetics should prove that the avidin/biotin based dual-modality pretargeting probe is a promising imaging tool during the entire period of tumor diagnosis and treatment.
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Salt, promoting oxidative stress, contributes to insulin resistance, whereas K, inhibiting oxidative stress, improves insulin sensitivity. Oxidative stress activation of NLRP3 inflammasome is a ...central player in the induction of insulin resistance. Therefore, we hypothesised that NLRP3 inflammasome may mediate the effects of salt and K on insulin resistance. In all, fifty normotensive subjects were recruited from a rural community of Northern China. The protocol included a low-salt diet for 7 d, then a high-salt diet for 7 d and a high-salt diet with K supplementation for another 7 d. In addition, THP-1 cells were cultured in different levels of Na with and without K. The results showed that salt loading elevated fasting blood glucose, insulin and C-peptide levels, as well as insulin resistance, whereas K supplementation reversed them. Meanwhile, additional K reversed the active effects of high salt on NLRP3 inflammasome in both the subjects and THP-1 cells, and the change of insulin resistance index notably related with the alteration of plasma IL-1β, the index of NLRP3 inflammasome activation, during intervention in the subjects. Additional K ameliorated oxidative stress induced by high salt in both the subjects and cultured THP-1 cells, and the change of oxidative stress related with the alteration of plasma IL-1β during intervention in the subjects. In vitro, antioxidant N-acetyl-l-cysteine significantly prevented the active effects of high Na or oxidant Rosup on NLRP3 inflammasome, so did K. Our study indicates that oxidative stress modulation of NLRP3 inflammasome may be involved in the impacts of Na and K on insulin resistance.
The aim of the present study was to evaluate whether the ratio of the absolute number of platelets to the number of lymphocytes (PLR) correlates with the severity of coronary artery disease (CAD) and ...major adverse cardiovascular disease (CVD) events in Chinese patients with CAD. PLR was calculated as follows: PLR=platelet count/lymphocyte count, using the complete blood counts of 854 Chinese Han subjects. CAD severity was determined using angiographic evidence by cardiologists unaware of the study aims. The association between PLR and CAD severity was analyzed by logistic regression. Clinical endpoints were evaluated during a median follow-up period of 42 months. The association between PLR and CVD events was assessed using Cox regression models. Patients with PLR>171 exhibited more severe coronary artery stenosis odds ratio, 2.393; 95% confidence intervals (CI), 1.394-4.108; P=0.002 and worse prognoses, with a higher rate of major adverse CVD events during five years of follow-up (hazard ratio, 1.982; 95% CI, 1.329-2.957; P=0.001). A Kaplan-Meier curve demonstrated that the CVD event rate of 34.27% in patients with PLR>171 was significantly higher than that in patients with PLR<100 (P<0.001). These findings suggest that PLR is independently associated with CAD severity and long-term major adverse CVD events; therefore, high PLR may predict poor prognosis of CAD in the Chinese Han population.
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High dietary salt intake contributes to the development of autoimmune/inflammatory diseases including metabolic syndrome (MetS) which potassium supplementation can potentially reverse. T helper (Th) ...17 cells as well as its production interleukin (IL)-17A are involved in the pathogenesis of MetS. The polarization of Th17 cells and enhanced IL-17A production induced by high salt might increase the risk of autoimmune/inflammatory diseases.
45 normotensive subjects (aged 29 to 65 years) were enrolled from a rural community of Northern China at random. All of the participants were maintained on a low-salt (3 g/day) diet for 7 days, a high-salt (18 g/day) diet for 7 days, and then a high-salt diet with potassium supplementation (4.5 g/day, KCl) for another 7 days. Insulin resistance (IR) was determined based on the homeostasis model assessment index (HOMA-IR).
Participants exhibited increased plasma insulin level, as well as progressed HOMA-IR, during a high-salt diet intervention, which potassium supplementation reversed. Moreover, after salt loading, the plasma IL-17A concentrations increased significantly (4.2±2.1 pg/mL to 9.7±5.1 pg/mL;
<0.01), whereas dropped considerably when dietary potassium was supplemented (9.7±5.1 pg/mL to 2.0±0.9 pg/mL;
<0.001). Statistically significant correlations were found between changes in HOMA-IR and changes in plasma IL-17A concentrations during the interventions (low- to high-salt: r=0.642,
<0.01; high-salt to potassium supplementation: r=0.703,
<0.01). Based on multivariate regression analysis, plasma IL-17A showed as an independent predictor of IR.
The amelioration of salt-loading-induced IR by potassium supplementation in participants may be related to the reduction in plasma IL-17A concentration.
is an important zoonotic pathogen from sick and recessive carrier pigs that poses a serious threat to animal husbandry production and public health. It usually causes horizontal transmission among ...pigs. The morbidity and mortality of this disease are very high. Human infection is caused through direct or indirect contact with sick pigs. The two large-scale outbreaks in China were due to the outbreak of
on pig farms, which spread to human infection; thus, detecting
in pig herds is crucial. At present, the commercial
ELISA type 2 kits on the market can only detect single serotypes, high probabilities of interaction reactions, and biosafety risks when using inactivated
as an antigen. Phosphate-3-glyceraldehyde dehydrogenase (GAPDH), muramidase-released protein (MRP), and dihydrolipoamide dehydrogenase (DLDH) are important
type 2,
type 7, and
type 9 protective antigens. This study purified the GMD protein (B-cell-dominant epitopes of GAPDH, MRP, and DLDH antigens) and used a diverse combination of dominant epitopes of the multiple different antigens as coated antigens, improving the sensitivity and safety of the indirect ELISA experiments. An indirect ELISA method (GMD-ELISA) was developed for detecting
antibodies. The antigen-antibody response was optimized using checkerboard titration. The results of testing using ELISA for
(
),
(
),
(
), and
(
) were all negative, indicating that this method had strong specificity. The results were still positive when the dilution ratio of
-positive serum reached 1:6, 400, thus indicating that the method had high sensitivity. The results of the reproducibility assay for indirect ELISA showed that the intra-assay coefficient of variation and the inter-assay coefficient of variation were less than 10%, indicating that the method had good repeatability. We investigated the seroprevalence of
in 167 serum samples collected in East China, and 33.5% of the samples were positive for antibodies against
, indicating that the prevalence of
is high in pig farms in Eastern China. The novel GMD-ELISA is a convenient, sensitive, and specific diagnostic method that provides technical support for rapid diagnosis and epidemiological investigation.
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In digital cameras, we find a major limitation: the image and video form inherited from a film camera obstructs it from capturing the rapidly changing photonic world. Here, we present vform, a bit ...sequence array where each bit represents whether the accumulation of photons has reached a threshold, to record and reconstruct the scene radiance at any moment. By employing only consumer-level complementary metal–oxide semiconductor (CMOS) sensors and integrated circuits, we have developed a spike camera that is 1000× faster than conventional cameras. By treating vform as spike trains in biological vision, we have further developed a spiking neural network (SNN)-based machine vision system that combines the speed of the machine and the mechanism of biological vision, achieving high-speed object detection and tracking 1000× faster than human vision. We demonstrate the utility of the spike camera and the super vision system in an assistant referee and target pointing system. Our study is expected to fundamentally revolutionize the image and video concepts and related industries, including photography, movies, and visual media, and to unseal a new SNN-enabled speed-free machine vision era.
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Causal inference in cue combination is to decide whether the cues have a single cause or multiple causes. Although the Bayesian causal inference model explains the problem of causal inference in cue ...combination successfully, how causal inference in cue combination could be implemented by neural circuits, is unclear. The existing method based on calculating log posterior ratio with variable elimination has the problem of being unrealistic and task-specific. In this paper, we take advantages of the special structure of the Bayesian causal inference model and propose a hierarchical inference algorithm based on importance sampling. A simple neural circuit is designed to implement the proposed inference algorithm. Theoretical analyses and experimental results demonstrate that our algorithm converges to the accurate value as the sample size goes to infinite. Moreover, the neural circuit we design can be easily generalized to implement inference for other problems, such as the multi-stimuli cause inference and the same-different judgment.
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