As a common air pollutant, formaldehyde is widely present in nature, industrial production and consumer products. Endogenous formaldehyde is mainly produced through the oxidative deamination of ...methylamine catalysed by semicarbazide‐sensitive amine oxidase (SSAO) and is ubiquitous in human body fluids, tissues and cells. Vascular endothelial cells and smooth muscle cells are rich in this formaldehyde‐producing enzyme and are easily damaged owing to consequent cytotoxicity. Consistent with this, increasing evidence suggests that the cardiovascular system and stages of heart development are also susceptible to the harmful effects of formaldehyde. Exposure to formaldehyde from different sources can induce heart disease such as arrhythmia, myocardial infarction (MI), heart failure (HF) and atherosclerosis (AS). In particular, long‐term exposure to high concentrations of formaldehyde in pregnant women is more likely to affect embryonic development and cause heart malformations than long‐term exposure to low concentrations of formaldehyde. Specifically, the ability of mouse embryos to effect formaldehyde clearance is far lower than that of the rat embryos, more readily allowing its accumulation. Formaldehyde may also exert toxic effects on heart development by inducing oxidative stress and cardiomyocyte apoptosis. This review focuses on the current progress in understanding the influence and underlying mechanisms of formaldehyde on cardiovascular disease and heart development.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
In this paper, we first construct ontology and entity learning to construct a knowledge graph by matching the knowledge to the schema layer. Then, we obtain users’ learning styles, extract interest ...keywords from user behavioral data, map them into the vector space encoded based on the KgTransH algorithm, and compare them with the original algorithm on multiple datasets. Then, the business English learning path is planned based on learning path length, learning time and achievement ranking. Finally, the effect of the knowledge graph-based business English learning path planning method is analyzed through comparative experiments. Through 50 iterations, the satisfaction of the knowledge graph method, GA method and ACO method are between 4.3-4.8, 4-4.7 and 4.05-4.7, respectively, which indicates that the method of this paper is better than the other methods. This study is important for improving the learning effect of Business English.
This article discusses the relationship between language and society, introduces the definition and scope of sociolinguistics, demonstrates the social variation of language, regional variation, as ...well as the relationship between language and ethnicity and culture, and ultimately proposes how to apply sociolinguistic theories to college English teaching activities.
Doxorubicin (DOX) is a kind of representative anthracyclines. It has greatly prolonged lifespan of cancer patients. However, a long course of DOX chemotherapy could induce various forms of deaths of ...cardiomyocytes, such as apoptosis, pyroptosis and ferroptosis, contributing to varieties of cardiac complications called cardiotoxicity. It has become a major concern considering the large number of cancer patients' worldwide and increased survival rates after chemotherapy. Exosomes, a subgroup of extracellular vesicles (EVs), are secreted by nearly all cells and consist of lipid bilayers, nucleic acids and proteins. They can serve as mediators between intercellular communication via the transfer of bioactive molecules from secretory to recipient cells, modulating multiple pathophysiological processes. It has been proven that exosomes in body fluids can serve as biomarkers for doxorubicin-induced cardiotoxicity (DIC). Moreover, exosomes have attracted considerable attention because of their capacity as carriers of certain proteins, genetic materials (miRNA and lncRNA), and chemotherapeutic drugs to decrease the dosage of DOX and alleviate cardiotoxicity. This review briefly describes the characteristics of exosomes and highlights their clinical application potential as diagnostic biomarkers and drug delivery vehicles for DIC, thus providing a strategy for addressing it based on exosomes.
Background and Purpose
Curcumin, a natural antioxidant isolated from Curcuma longa, has been reported to exert neuroprotective effect in animal models of ischemic stroke. However, the underlying ...mechanism is still not fully understood. The purpose of this study was to investigate the effect of curcumin treatment on neuronal apoptosis in the periinfarct cortex after cerebral ischemia/reperfusion (I/R) injury and in mouse N2a cells after oxygen‐glucose deprivation/reoxygenation (OGD/R) injury and its underlying mechanism.
Methods
The cerebral I/R injury was established by 1‐hr middle cerebral artery occlusion (MCAO) and reperfusion in mice. Infarct volume was determined by TTC staining, and neurological score was evaluated by mNSS. Cell morphology in the ischemic boundary zone were detected by HE staining. The number and apoptotic rate of neurons in ischemic boundary zone were assayed by immunohistochemistry and TUNEL, respectively. Mouse neuroblastoma N2a cells were subjected to OGD/R. Cell viability was assessed with CCK‐8. The mitochondrial membrane potential was measured using JC‐1 staining. The expression of Bax, Bcl‐2, and caspase‐3 was detected using Western blotting. Besides, cellular distribution of Bax was determined by immunofluorescence assays.
Results
Curcumin treatment reduced infarct volume, improved neurological function, alleviated the morphological damage of neurons, and increased neuronal survival rate after I/R injury in vivo. Moreover, curcumin treatment improved cell viability, reduced cell apoptosis, increased Bcl‐2 protein levels while decreased Bax and caspase‐3 expressions in mouse N2a cells after OGD/R injury. Besides, curcumin treatment inhibited Bax activation and maintained mitochondrial membrane integrity.
Conclusion
Curcumin promotes neuron survival in vivo and in vitro to exert neuroprotective effects against ischemia injury. Moreover, our results for the first time demonstrated curcumin inhibited ischemia‐induced mitochondrial apoptosis via restricting Bax activation, which may be one of the possible mechanisms underlying the neuroprotective effects of curcumin.
Curcumin promotes neuron survival in vivo and in vitro to exert neuroprotective effects against ischemia injury. Moreover, our results for the first time demonstrated curcumin inhibited ischemia‐induced mitochondrial apoptosis via restricting Bax activation, which may be one of the possible mechanisms underlying the neuroprotective effects of curcumin.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
How cooperation emerges and is stabilized has been a puzzling problem to biologists and sociologists since Darwin. One of the possible answers to this problem lies in the mobility patterns. These ...mobility patterns in previous works are either random-like or driven by payoff-related properties such as fitness, aspiration, or expectation. Here we address another force which drives us to move from place to place: reputation. To this end, we propose a reputation-based model to explore the effect of migration on cooperation in the contest of the prisoner's dilemma. In this model, individuals earn their reputation scores through previous cooperative behaviors. An individual tends to migrate to a new place if he has a neighborhood of low reputation. We show that cooperation is promoted for relatively large population density and not very large temptation to defect. A higher mobility sensitivity to reputation is always better for cooperation. A longer reputation memory favors cooperation, provided that the corresponding mobility sensitivity to reputation is strong enough. The microscopic perception of the effect of this mechanism is also given. Our results may shed some light on the role played by migration in the emergence and persistence of cooperation.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary
Osteoblast apoptosis contributes to age‐related bone loss. Advanced oxidation protein products (AOPPs) are recognized as the markers of oxidative stress and potent inducers of apoptosis. We ...have demonstrated that AOPP accumulation was correlated with age‐related bone loss. However, the effect of AOPPs on the osteoblast apoptosis still remains unknown. Exposure of osteoblastic MC3T3‐E1 cells to AOPPs caused the excessive generation of reactive oxygen species (ROS) by activating nicotinamide adenine dinucleotide phosphate (NADPH) oxidases. Increased ROS induced phosphorylation of mitogen‐activated protein kinases (MAPKs), which subsequently triggered intrinsic apoptosis pathway by inducing mitochondrial dysfunction, endoplasmic reticulum stress, and Ca2+ overload and eventually leads to apoptosis. Chronic AOPP loading in aged Sprague‐Dawley rats induced osteoblast apoptosis and activated NADPH oxidase signaling cascade, in combination with accelerated bone loss and deteriorated bone microstructure. Our study suggests that AOPPs induce osteoblast apoptosis by the NADPH oxidase‐dependent, MAPK‐mediated intrinsic apoptosis pathway.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Interleukin (IL)-1β and tumor necrosis factor (TNF)-α, in particular, control the degeneration of articular cartilage, making them prime targets for osteoarthritis (OA) therapeutic strategies. ...Advanced oxidation protein products (AOPPs) are prevalent in numerous diseases. Our previous work demonstrates that intra-articular injections of AOPPs accelerate regression of cartilage in OA models. Whether AOPPs exist in the course of OA and their effects on TNF-α and IL-1β expression in chondrocytes are still unclear. This study confirmed that AOPPs levels in human synovial fluid were positively associated with severity of OA. We also found AOPPs deposition in articular cartilage in anterior cruciate ligament transection (ACLT) induced rodent OA models. AOPPs increased expression of TNF-α and IL-1β in chondrocytes in vitro, which was inhibited by pre-treatment with SB202190 (p38-MAPK inhibitor) or apocynin (NADPH oxidase inhibitor) or NOX4 knockdown by siRNAs. Subsequently, we further verified in vivo that exogenous injection of AOPPs in OA mice up-regulated expression of TNF-α and IL-1β in cartilage, which was blocked by treatment with apocynin. In parallel, apocynin attenuated articular cartilage degeneration resulting in substantially lower OARSI scores. Specifically, apocynin reduced NOX4, p-P38, TNF-α and IL-1β and increased collagen II and glycosaminoglycan (GAG). This study demonstrated that AOPPs increased expression of TNF-α and IL-1β in chondrocytes via the NADPH oxidase4-dependent and p38-MAPK mediated pathway, and accelerated cartilage degeneration in OA progression. These findings suggest an endogenous pathogenic role of AOPPs in OA progression. Targeting AOPPs-triggered cellular mechanisms might be a promising therapeutic option for patients with OA.
•AOPPs present in OA joint.•AOPPs increased TNF-α and IL-1β expression in chondrocytes and accelerates progression of OA.•NADPH oxidase inhibitor decreased TNF-α and IL-1β expression and attenuates progression of OA.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•Analytical solution is developed for deeply tunnelling in viscoelastic-plastic geomaterials, considering actual loading path.•The solutions are compared with the previous ones without considering ...stress path, and the difference is identified.•The influence of supporting time etc. on the time-dependent responses of surrounding rock is investigated.
The rock rheology and time process of tunnel construction make the mechanical responses of rock a function of time and are closely related to the loading path, however, these factors are not properly or correctly considered in analytical studies. The analytical study for deep tunnels in rheological rock is performed in this study, strictly taking into account the viscoelastic‒plastic characteristic of surrounding rocks and the actual loading path during excavation and supporting stages.
The plane-strain problem of a circular tunnel in infinite plane under hydraulic far-field stress is simplified, with the time-dependent supporting pressure exerted at a specific time to consider the effect of delay installation of yielding support. The solving procedure as well as the time-dependent analytical solution of displacement, stress, and plastic radius in the excavation and supporting stages are presented in detail when the rocks satisfy the Unified strength theory and perfect plasticity. The analytical solutions agree very well with the numerical results, where the time procedure of tunnel excavation and support is simulated in the numerical model. Furthermore, the proposed solution can predict well the long-term deformation of the Shangxinzhai tunnel, which validates its applicability in real engineering. It is found that the tunnel deformation is underestimated if the unloading stage is not correctly considered. Based on the analytical solution, the influence of the supporting time, start time of the yielding stage and viscosity coefficient on the time dependence of tunnel convergence and stresses is investigated.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Phosphoglycerate kinase 1 (PGK1), a critical component of the glycolytic pathway, relates to the development of various cancers. However, the mechanisms of PGK1 inhibition and physiological ...significance of PGK1 inhibitors in cancer cells are unclear. Long non-coding RNAs (lncRNAs) play a vital role in tumor growth and progression. Here, we identify a lncRNA LINC00926 that negatively regulates PGK1 expression and predicts good clinical outcome of breast cancer. LINC00926 downregulates PGK1 expression through the enhancement of PGK1 ubiquitination mediated by E3 ligase STUB1. Moreover, hypoxia inhibits LINC00926 expression and activates PGK1 expression largely through FOXO3A. FOXO3A/LINC00926/PGK1 axis regulates breast cancer glycolysis, tumor growth, and lung metastasis both in vitro and in vivo. In breast cancer patients, LINC00926 expression is negatively correlated with PGK1 and positively correlated with FOXO3A expression. Our work established FOXO3A/LINC00926/PGK1 as a critical axis to regulate breast cancer growth and progression. Targeting PGK1 or supplement of LINC00926 or FOXO3A could be potential therapeutic strategies in breast cancer.
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Chu et al. established FOXO3A/LINC00926/PGK1 as a critical axis to regulate BC growth and progression. LINC00926 is a novel negative regulator of PGK1, which enhances the ubiquitination of PGK1 mediated by E3 ligase STUB1 and predicts good clinical outcome of breast cancer. In addition, hypoxia inhibits LINC00926 expression and activates PGK1 expression largely through FOXO3A. Targeting PGK1 or supplement of LINC00926 or FOXO3A could be potential therapeutic strategies in breast cancer.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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