PM2.5 is becoming a worldwide environmental problem, which profoundly endangers public health, thus progressively capturing public attention this decade. As a fragile target of PM2.5, the underlying ...mechanisms of endothelial cell damage are still obscure. According to the previous microarray data and signaling pathway analysis, a new form of cell death termed ferroptosis in the current study is proposed following PM2.5 exposure. In order to verify the vital role of ferroptosis in PM2.5-induced endothelial lesion and further understand the potential mechanism involved, intracellular iron content, ROS release and lipid peroxidation, as well as biomarkers of ferroptosis were detected, respectively. As a result, uptake of particles increases cellular iron content and ROS production. Meanwhile, GSH depletion, and the decrease of GSH-Px and NADPH play significant roles in PM2.5-induced endothelial cell ferroptosis. Moreover, significantly changed expression of TFRC, FTL and FTH1 hinted that dysfunction of iron uptake and storage is a major inducer of ferroptosis. Importantly, index monitored above can be partially rescued by lipid peroxidation inhibitor ferrostatin-1 and iron chelator deferoxamine mesylate, which mediated antiferroptosis activity mainly depends on the restoration of antioxidant activity and iron metabolism. In conclusion, our data basically show that PM2.5 enhances ferroptosis sensitivity with increased ferroptotic events in endothelial cells, in which iron overload, lipid peroxidation and redox imbalance act pivotal roles.
PM2.5 could ignite endothelial cell ferroptosis through iron overload and redox imbalance.
Endothelial cells integrally form a crucial interface that maintains homeostasis of the cardiovascular system. As a vulnerable target of PM2.5, the underlying mechanisms of endothelial cell damage ...have yet to be fully elucidated. In the current study, two types of cell death, including autophagy and apoptosis, and an important organelle of the endoplasmic reticulum (ER) were focalized following PM2.5 exposure. As a result, the internalization of PM2.5 has the ability to induce excess ER stress, which is a crucial step for further autophagy and apoptosis in human endothelial cells, as confirmed by the pre-treatment with the inhibitor of ER stress (4-PBA) which effectively mitigates the apoptosis rate and LC3II expression. Intriguingly, crosstalk between ER stress and autophagy demonstrated that ER stress is probably involved in autophagic events, whereas autophagy has no significant effect on ER stress but confer a protective role against PM2.5-induced endothelial cell apoptosis. Moreover, PM2.5 results in blockage of autophagic flux (failed fusion between autophagosomes and lysosomes), which is detrimental to endothelial cell survival. In conclusion, our findings provide a valuable insight into the relation between autophagy and apoptosis under PM2.5-induced ER stress conditions, where the interplay between them ultimately determines cell fate.
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•ER stress induced by PM2.5 facilitates endothelial cell autophagy and apoptosis.•Autophagy confers a protective role in PM2.5-induced apoptosis.•Dysfunction of autophagic flux, or defective autophagy promotes cell apoptosis.•ER stress may lead to autophagic events in response to PM2.5, but not vice versa.
Owing to the increasing application of engineered nanoparticles (NPs), besides the workplace, human beings are also exposed to NPs from nanoproducts through the skin, respiratory tract, digestive ...tract and vein injection. This review states pathways of cellular uptake, subcellular distribution and excretion of NPs. The uptake pathways commonly include phagocytosis, micropinocytosis, clathrin‐ and caveolae‐mediated endocytosis, scavenger receptor‐related pathway, clathrin‐ or caveolae‐independent pathway, and direct penetration or insertion. Then the ability of NPs to decrease cell viability and metabolic activity, change cell morphology, and destroy cell membrane, cytoskeleton and cell function was presented. In addition, the lowest dose decreasing cell metabolic viability compared with the control or IC50 of silver, titanium dioxide, zinc oxide, carbon black, carbon nanotubes, silica, silicon NPs and cadmium telluride quantum dots to some cell lines was gathered. Next, this review attempts to increase our understanding of NP‐caused adverse effects on organelles, which have implications in mitochondrial dysfunction, endoplasmic reticulum stress and lysosomal rupture. In particular, the disturbance of mitochondrial biogenesis and mitochondrial dynamic fusion‐fission, mitophagy and cytochrome c‐dependent apoptosis are involved. In addition, prolonged endoplasmic reticulum stress will result in apoptosis. Rupture of the lysosomal membrane was associated with inflammation, and both induction of autophagy and blockade of autophagic flow can result in cytotoxicity. Finally, the network mechanism of the combined action of multiple organelle dysfunction, apoptosis, autophagy and oxidative stress was discussed.
This review attempted to summarize the uptake and excretion pathway of nanoparticles, nanoparticle‐induced cytotoxicity: decrease in cell viability and metabolic activity, morphological change, destruction of cell membrane, cytoskeleton and function, and disturbance of organelles. Furthermore, the mechanism of cytotoxicity, with respect to the crosstalk among mitochondrial dysfunction, endoplasmic reticulum stress, lysosomal rupture, autophagy, apoptosis, inflammation and increase of reactive oxygen species, has been discussed.
Internet has penetrated into people’s lives as the Internet education platform has faced many changes in the way vocal music is taught in the new situation. The teaching methods set up on the ...Internet have also undergone dramatic changes. A number of advanced music education concepts have emerged that require a careful review of the current state of music education in the world and in China. Current online learning environments are usually used only for formal or informal learning. The former overemphasizes the subjective role of the teacher and ignores the autonomy of the learner. Through a new modern network education method, this paper deeply analyzes the unique advantages and existing problems of a new voice education method based on the Internet and puts forward corresponding solutions. Its purpose is to encourage more ordinary vocal music teachers to better understand the new teaching methods, broaden their artistic horizons, consciously use modern teaching methods to support vocal music education in ordinary schools, and further expand the scope of music application. The experimental results show that for 4000 concurrent users, the response time of the system is less than 5 seconds, which can meet the time requirements of the system. For the service of querying some other data, the response time of the system is less than 9 seconds, so the response ability of the system to multiple users is impressive. Therefore, with the development of education, comprehensive network education platform is also the development direction of informatization in the future.
The structure of microvasculature cannot be resolved using standard clinical ultrasound (US) imaging frequencies due to the fundamental diffraction limit of US waves. In this work, we use a standard ...clinical US system to perform in vivo sub-diffraction imaging on a CD1, female mouse aged eight weeks by localizing isolated US signals from microbubbles flowing within the ear microvasculature, and compare our results to optical microscopy. Furthermore, we develop a new technique to map blood velocity at super-resolution by tracking individual bubbles through the vasculature. Resolution is improved from a measured lateral and axial resolution of 112 μm and 94 μm respectively in original US data, to super-resolved images of microvasculature where vessel features as fine as 19 μm are clearly visualized. Velocity maps clearly distinguish opposing flow direction and separated speed distributions in adjacent vessels, thereby enabling further differentiation between vessels otherwise not spatially separated in the image. This technique overcomes the diffraction limit to provide a noninvasive means of imaging the microvasculature at super-resolution, to depths of many centimeters. In the future, this method could noninvasively image pathological or therapeutic changes in the microvasculature at centimeter depths in vivo.
This paper examines the significance of physician agency in medical providers' prescription choices. Physician agency is considered as medical providers' responses to the price and markup percentage ...of prescription drugs. Their preferences are allowed to be heterogeneous using a random coefficient logit model. Using a sample of anti‐diabetic prescriptions with metformin from a population‐based database in Taiwan, empirical results reveal that physician owners, privately‐owned medical providers, small medical providers and the medical providers facing less competition are more likely to prescribe drugs with higher profit margins. The aggregate pharmaceutical demand is also found to increase with the markup, which is allowed to be endogenous in the estimation. Price elasticity estimates suggest medical providers are quite responsive to pharmaceutical price changes in Taiwan. Counterfactual analysis reveals the potential impact of physician agency is economically significant. Removing markups and lowering pharmaceutical prices are found to be more welfare enhancing than restricting physicians' dispensing services.
•Explore the immune effects of PM2.5 in respiratory tract.•Introduce the molecular mechanism of Th1/Th2 shift induced by PM2.5.•Four key obstacles encountered currently are indicated to enlighten the ...further research directions.
Airborne fine particulate matter (PM2.5) attracts more and more attention due to its environmental effects. The immune system appears to be a most sensitive target organ for the environmental pollutants. Inhaled PM2.5 can deposit in different compartments in the respiratory tract and interact with epithelial cells and resident immune cells. Exposed to PM2.5 can induce local or systematic inflammatory responses. This review focus on the effects of respiratory tract exposed to PM2.5. Firstly, we introduced the major emission sources, basic characteristics of PM2.5 and discussed its immunoadjuvant potential. Secondly, we elaborated the immune cells in the respiratory tract and the deposition of PM2.5 regarding the structural characteristics of the respiratory tract. Furthermore, we summarized the in vivo/vitro studies that revealed the immunotoxic effects of PM2.5 exposure to pulmonary cellular effectors and explored the contribution of PM2.5 exposure to the Th1/Th2 balance.
Despite the increasing number of neurotoxicological studies on metal-containing nanoparticles (NPs), the NP-induced neuroinflammation has not yet been well understood. This review provides a ...comprehensive understanding of inflammatory responses to two typical metal-containing NPs, namely silver NPs (Ag-NPs) and titanium dioxide NPs (TiO
-NPs). Ag-NPs and TiO
-NPs could translocate into the CNS through damaged blood-brain barrier, nerve afferent signaling and eye-to-brain ways, and even cell uptake. NPs could stimulate the activation of glial cells to release proinflammatory cytokines and generate reactive oxygen species and nitric oxide production, resulting in the neuroinflammation. The potential mechanisms of Ag-NPs and TiO
-NPs causing inflammation are complex, including several immune response relevant signaling pathways. Some parameters governing their ability to cause neuroinflammation are presented as well.
GrabCut in One Cut Meng Tang; Gorelick, Lena; Veksler, Olga ...
2013 IEEE International Conference on Computer Vision,
12/2013
Conference Proceeding, Journal Article
Among image segmentation algorithms there are two major groups: (a) methods assuming known appearance models and (b) methods estimating appearance models jointly with segmentation. Typically, the ...first group optimizes appearance log-likelihoods in combination with some spacial regularization. This problem is relatively simple and many methods guarantee globally optimal results. The second group treats model parameters as additional variables transforming simple segmentation energies into high-order NP-hard functionals (Zhu-Yuille, Chan-Vese, Grab Cut, etc). It is known that such methods indirectly minimize the appearance overlap between the segments. We propose a new energy term explicitly measuring L1 distance between the object and background appearance models that can be globally maximized in one graph cut. We show that in many applications our simple term makes NP-hard segmentation functionals unnecessary. Our one cut algorithm effectively replaces approximate iterative optimization techniques based on block coordinate descent.
In the medium access control layer (MAC) of WSN, the scheduling mechanism of nodes based on the periodical listen/sleep is an effective way of saving node energy consumption. In the case of data ...transmission which is not affected reduces the nodes’ proportions, we improve the protocols based on asynchronous MAC. This paper discusses a protocol which is a low duty cycle energy-efficient MAC protocol for WSN and can be adaptively updated based on the prediction nodes’ wake-up time. We call it AP-MAC protocol. In AP-MAC protocol, the nodes will not wake up or send data in the same period, and they will wake up in random time according to the algorithm that has been set. In this case, the network can avoid the problem of collision, cross-talk, etc. caused by all the nodes’ wake-up in the same time, and save more energy. To ensure the reliable transmission of network data, the node which sends data will predict the wake-up time of receiving nodes and ensure the receiving nodes wake up timely and establish a connection with sending note. At the same time, we join several adaptive update mechanisms in the network according to the dynamic changes of it. The experimental results show that the improved protocol not only can save the network energy consumption by effectively reducing the overall duty cycle of the network nodes and improving the reliable transmission of data but also can improve the adaptability of the network.
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