Receptor interacting protein 3 (RIP3) is a protein kinase essential for TNF-induced necroptosis. Phosphorylation on Ser-227 in human RIP3 (hRIP3) is required for its interaction with human mixed ...lineage kinase domain-like (MLKL) in the necrosome, a signaling complex induced by TNF stimulation. RIP1 and RIP3 mediate necrosome aggregation leading to the formation of amyloid-like signaling complexes. We found that TNF induces Thr-231 and Ser-232 phosphorylation in mouse RIP3 (mRIP3) and this phosphorylation is required for mRIP3 to interact with mMLKL. Ser-232 in mRIP3 corresponds to Ser-227 in hRIP3, whereas Thr-231 is not conserved in hRIP3. Although the RIP3-MLKL interaction is required for necroptosis in both human and mouse cells, hRIP3 does not interact with mMLKL and mRIP3 cannot bind to hMLKL. The species specificity of the RIP3-MLKL interaction is primarily determined by the sequence differences in the phosphorylation sites and the flanking sequence around the phosphorylation sites in hRIP3 and mRIP3. It appears that the RIP3-MLKL interaction has been selected as an evolutionarily conserved mechanism in mediating necroptosis signaling despite that differing structural and mechanistic bases for this interaction emerged simultaneously in different organisms. In addition, we further revealed that the interaction of RIP3 with MLKL prevented massive abnormal RIP3 aggregation, and therefore should be crucial for formation of the amyloid signaling complex of necrosomes. We also found that the interaction between RIP3 and MLKL is required for the translocation of necrosomes to mitochondria-associated membranes. Our data demonstrate the importance of the RIP3-MLKL interaction in the formation of functional necrosomes and suggest that translocation of necrosomes to mitochondria-associated membranes is essential for necroptosis signaling.
Background: Receptor interacting protein 3 (RIP3)-mixed lineage kinase domain-like (MLKL) interaction is essential for necroptosis.
Results: Murine RIP3 does not interact with human MLKL and vice versa due to sequence differences in and around the RIP3 phosphorylation sites.
Conclusion: Different sequences in human and mouse RIP3 control the functionally conserved RIP3-MLKL interaction.
Significance: This study provided new insights into the function of RIP3-MLKL interaction in necroptosis.
This study validated the school psychological capital (PsyCap) scale in the Chinese context and examined the predictive effect of PsyCap resources on academic engagement and achievement emotions. ...Self-report data for PsyCap resources, student engagement, enjoyment, anxiety, and boredom toward English learning were collected from 1,000 sophomores. Item-level analyses and confirmatory factor analysis were used to verify the validity of the school PsyCap scale, and structural equation modeling was applied to reveal the predictive effect of school PsyCap resources on academic engagement and achievement emotions. Results showed that the school PsyCap scale retained superior psychometric properties. Besides, PsyCap resources were demonstrated to have a positive relationship to academic engagement and enjoyment, and a negative relationship to anxiety and boredom. The effectiveness of the school PsyCap scale was verified among Chinese college students, and besides the traditional predictors, school PsyCap is also critically important for students’ academic engagement and achievement emotions. Limitations and implications are discussed.
Display omitted
•PAH induced by MCT is a progressive disease with persistent inflammation.•The inflammation in MCT-PAH model includes acute (the first 6 days after MCT injection) and chronic stages ...(after acute inflammation stage).•Acute inflammation stage may be the time window of anti-inflammatory treatment in PAH induced by MCT.
A growing evidence demonstrates that inflammation is a major contributor to the pathogenesis of pulmonary arterial hypertension (PAH). However, blocking inflammation has only been shown to be of minor clinical benefit due to a lack of understanding of the precise inflammation present in PAH. Thus, the present study aimed to investigate characteristics of inflammatory process in PAH induced by monocrotaline (MCT) in rats.
Adult male Sprague-Dawley rats received a single dose of MCT (50 mg/kg, ip), and the occurrence of PAH and inflammation biomarkers were measured at 3, 6, 9, 12, 15, 18, 21, 24, 27 and 30 days after MCT injection.
From the 6th day after the injection of MCT, the mean pulmonary artery pressure gradually increased and doubled on the 30th day, accompanied by right ventricular hypertrophy and pulmonary arterial remodeling in a time-dependent manner. In the first 6 days after MCT treatment, only pro-inflammatory cytokines TNF-α, IL-1β increased, which was defined as acute inflammatory phase, after that, both pro-inflammatory factors TNF-α, IL-1β, IL-6, IL-12 and anti-inflammatory factors Arg1, IL-10, TGF-β increased, which was defined as chronic inflammatory phase. The M1/M2 macrophage ratios in lung and alveolar lavage fluid were elevated on the 6th and 30th day, moreover, which were higher on the 6th than 30th day, and the PI3K/Akt signaling pathway increased along with the progression of PAH and correlated with pro-inflammatory proteins, which revealed also to some extent the characteristics of inflammation of PAH induced by MCT.
The course of PAH induced by MCT injection is progressive with persistent inflammation, which is defined as acute inflammatory phase within 6 days after MCT treatment, after that, is defined as chronic inflammatory phase.
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality among all types of diseases in the world, affecting many millions of individuals every year. CVD includes hypertension, ...atherosclerosis, pulmonary hypertension, heart failure, cardiomyopathy, coronary heart disease, etc., which are involved in complex etiology, pathogenesis and many risk factors. Modern pharmacological studies have revealed that Epimedium possesses a variety of beneficial effects in regulating cardiovascular inflammation and other biological activities, which provides a therapeutic value for the prevention and treatment of these cardiovascular diseases. In this review, we discuss the cardiovascular protective effects of icariin, an active component from Epimedium, and its metabolites. We summarize a range of studies showing that the modes of action of icariin on CVD relate to its inhibition of myocardial apoptosis and prevention of inflammation on endothelial cell injury, emphasizing the multiple effects of icariin and its metabolites in the repair of common heart failure and myocardial infarction, as well as the formation of neointima. In particular, an emphasis is placed on the discussion of the action mechanism of icariin in combination with new advances in the understanding of the pathology of CVD with potential application of icariin in the treatment of this human disorder.
Osthole (Ost) is a coumarin that exhibits wide pharmacological effects in the cardiovascular system. However, whether Ost can inhibit apoptosis and inflammation in right ventricle (RV) cardiomyocytes ...and prevent RV remodeling is not clear. This study was designed to investigate the effect of Ost on RV remodeling and the underlying mechanism. By applying a monocrotaline (MCT)-induced rat model, the effect of Ost on RV remodeling was investigated. Rats were given a single dose of MCT (50mg/kg) subcutaneously (s.c.) to establish the RV remodeling model, followed by treatment with 10 or 20mg/kg Ost via daily gavage for 28 days. The RV pressure was measured, and a histological analysis was performed. The results suggested that Ost remarkably decreased RV pressure and improved myocardial hypertrophy and mitochondrial swelling, vacuolization, and sarcoplasmic reticulum enlargement when compared with the model group. To further investigate the roles of apoptosis and inflammation in the effects of Ost on MCT-induced RV remodeling, apoptosis-related factors and inflammatory-associated factors were examined by western blot. Ost was found to inhibit myocardial apoptosis and inflammation in the RV. Overall, the present results indicate that Ost suppresses the RV remodeling process induced by MCT in rats, which may be at least partially mediated through the reduction of myocardial apoptosis and inflammation.
Solution processed organic near-infrared (NIR) photodetectors (PDs) based on a porphyrin small molecule as a donor material and (6,6)-phenyl-C61-butyric acid methyl ester (PC sub(61)BM) as an ...acceptor material are reported. Operating at room temperature, these PDs show a low dark current density of 3.44 nA cm super(-2), a broad spectral response from 380 to 960 nm with high external quantum efficiencies around 20% in the NIR region at a bias of 0 V. Detectivities over 10 super(12) cm H super(1/2) W super(-1) in the whole range from 380 to 930 nm are achieved, which rank as one of the best performances among previously reported NIR PDs.
Due to the demand for temporary rapid grid connection in renewable energy power plants, the topology structure of T-connected power lines has been widely used in the power grid. In this ...three-terminal system, fault localization is difficult because of traditional impedance-based or traveling wave-based fault localization methods; the three-terminal data should be synchronized and communicated. Since different terminal assets belong to different enterprises, it is actually difficult to maintain good synchronization between them. Therefore, in practical applications, the fault location of T-connected power lines often fails. This article proposes a single terminal fault location method for a T-connection power line to address this issue. It is based on the fact that the local topology of the T-connected power line in the healthy phase remains unchanged during the fault-clearing process. It utilizes the sequential current and voltage data changes generated by the sequential tripping ping emitted by the circuit breaker from different terminals to describe the constant topology of the healthy phase as an equation and calculates the accurate fault location after solving the equation. The Levenberg–Marquardt algorithm was used to calculate fault distance and transition resistance, and the effectiveness of this method was verified through simulation.
The primary control goals of a wind turbine (WT) are structural load shedding, maximum wind energy capture in the underpowered situation, and consistent power production in the full power condition. ...A crucial component of the control problem for wind turbines with varying speeds is maximum power tracking control. Conventional maximum power tracking control tracks the ideal blade tip speed ratio to provide the most wind power at the specified wind speeds. However, because of the wind turbine’s great nonlinearity and the significant external disturbances it encounters, it is difficult to react quickly to variations in wind speed, and the tracking speed is sluggish, which lowers the amount of electricity produced annually. In light of this, this work develops a novel preset performance controller for a wind power system maximum power tracking control. With this technique, the convergence rate and tracking precision may be set. In particular, based on the concept of time-varying feedback, a time-varying function, known as the preset performance function, is first created to allow the convergence speed and accuracy to be predetermined; then this time-varying function is used to transform the actual specified time problem of the original system into a bounded time problem of the new system; finally, a direct robust controller design strategy with pre-defined performance is suggested based on the design concept of the backstepping technique. The plan may maximize the rotor power coefficient by altering the wind turbine speed, track the ideal blade tip speed ratio for a given tracking accuracy and speed, and get the most wind power to produce the most power with the strongest robustness. The simulation results show that the recommended control technique works.
Circuit breakers on the filter bank branches in converter stations are vulnerable to contact wear and mechanical deterioration caused by frequent operations, which can lead to circuit breaker ...breakdowns and explosions. It is imperative to conduct research on the early detection of abnormal states in circuit breakers. Existing electrical quantity-based detection methods are constrained by a priori assumptions, and their measurement methods are susceptible to interference, leading to misjudgments. To address this issue, this paper examines the influence of changes in critical breakdown field strength and contact spacing on circuit breaker operation states. It also proposes a technical scheme that employs breakdown current values to comprehensively characterize circuit breaker operation states, replacing the use of critical breakdown field strength and contact spacing. An early detection method for abnormal circuit breaker states based on a sequence of breakdown current ratios at different times is proposed, and its effectiveness is verified through simulation and field recording data.
Calcium-sensing receptor (CaSR) is a G protein-coupled receptor, widely distributed in various tissues, including vascular endothelial cells and smooth muscle cells, which plays an important role in ...the migration and homing of stem/progenitor cells and the proliferation of tissue cells. Restenosis after Percutaneous coronary intervention (PCI) seriously affects its prognosis and application. Our previous research has found that ginsenoside Rg1 (GS-Rg1) can inhibit the occurrence of restenosis after balloon injury of the common carotid artery in rats, but the mechanism is still unclear. In this study, it was found that GS-Rg1 (4, 8, 16 mg/kg) inhibited vascular restenosis caused by balloon injury, and mobilize endothelial progenitor cells (EPCs) to promote reendothelialization and inhibit intimal hyperplasia, which significantly reduced after administration of CaSR antagonist NPS 2143. Interestingly, CaSR and its downstream JNK, P38 were highly expressed in the proliferative intima and participated in the abnormal proliferation of vascular smooth muscle cells mediated by smooth muscle progenitor cells (SMPCs). GS-Rg1 inhibited intimal hyperplasia, while it decreased the expression of CaSR, JNK, and P38. This might relate to the distribution of CaSR and the facilitation of GS-Rg1 on the vascular endothelial repair. It is concluded that CaSR plays a key role in GS-Rg1 promoting reendothelialization to inhibit intimal hyperplasia after balloon Injury.
Display omitted
•GS-Rg1 mobilizes EPCs to promote reendothelialization after balloon injury.•CaSR inhibitor reduces the effects of Rg1.•The expression of CaSR is decreased in hyperplastic intimal after GS-Rg1 treatment.•Contradiction of CaSR involves its distribution and endothelial repair effect of Rg1.
PDF
