Phase II metabolic enzymes are a battery of critical proteins that detoxify xenobiotics by increasing their hydrophilicity and enhancing their disposal. These enzymes have long been studied for their ...preventative and protective effects against mutagens and carcinogens and for their regulation via the Keap1 (Kelch-like ECH associated protein 1)/Nrf2 (Nuclear factor erythroid 2 related factor 2)/ARE (antioxidant response elements) pathway. Recently, a series of studies have reported the altered expression of phase II genes in postmortem tissue of patients with various neurological diseases. These observations hint at a role for phase II enzymes in the evolution of such conditions. Furthermore, promising findings reveal that overexpression of phase II genes, either by genetic or chemical approaches, confers neuroprotection in vitro and in vivo. Therefore, there is a need to summarize the current literature on phase II genes in the central nervous system (CNS). This should help guide future studies on phase II genes as therapeutic targets in neurological diseases. In this review, we first briefly introduce the concept of phase I, II and III enzymes, with a special focus on phase II enzymes. We then discuss their expression regulation, their inducers and executors. Following this background, we expand our discussion to the neuroprotective effects of phase II enzymes and the potential application of Nrf2 inducers to the treatment of neurological diseases.
•Silicon application enhanced plant resistance to salt-induced osmotic stress.•Silicon enhanced plant root hydraulic conductance and water uptake ability.•Silicon increased plant root hydraulic ...conductance by regulating aquaporin activity.•Silicon enhanced aquaporin transcript levels and inhibited H2O2 production.
It has been widely reported that silicon (Si) improves the resistance of plants to salt stress. Most of the previous studies have examined how silicon prevents Na+ uptake, but the performance and underlying mechanism through which silicon alleviates salt-induced osmotic stress has been largely ignored. In the present study, the mechanism through which Si alleviates salt-induced osmotic stress was investigated using sorghum in a hydroponic system. Si had no effect on seedling growth under normal conditions. Under salt stress, the photosynthesis and transpiration rate were decreased, but these decreases were alleviated by Si application. In addition, the leaf water content and leaf elongation rate were maintained at higher levels with Si than without Si. The root hydraulic conductance (Lp) of the seedlings were inhibited by salt, but Si application alleviated this inhibition. Under salt stress, the transpiration rates of the seedlings both with and without Si were decreased to the same level by HgCl2 treatment and partially rescued by β-mercaptoethanol treatment, suggesting that aquaporin was responsible for the alleviation of the decrease in Lp. Moreover, transcript levels of several aquaporin genes were upregulated by Si. Under salt stress, Si inhibited the increase in the root H2O2 levels and enhanced the activities of antioxidant enzymes. Moreover, similar to Si, pre-treatment with catalase alleviated the decrease in the transpiration rate, indicating that Si enhanced aquaporin activity by reducing H2O2 accumulation. These results indicate that under short-term salt stress, Si application can alleviate the decrease in Lp by mediating aquaporin activity, leading to increased water uptake and resistance to salt-induced osmotic stress.
Gastric mucosal ulcer caused by drug overdose is very rare in clinical practice, and here is a case of gastric antral ulcer caused by drug overdose.
A 35-year-old housewife from a mountainous region ...in China took 48 Ibuprofen Sustained-Release capsules (300 mg/capsule) orally at 1 time. Because of severe tingling in the upper abdomen accompanied by a sharp increase in blood pressure, she came to the doctor 48 hours later.
Gastric antral ulcer (multiple stage A1), duodenococcitis, chronic nonatrophic gastritis, Helicobacter pylori infection, moderate depression, and cognitive impairment.
Acid suppression, antihypertensive and a series of symptomatic treatments.
All somatic symptoms disappeared after a follow-up visit 2 months later.
This case provides valuable information to the clinic, through the compilation of literature and case analysis, the author found that paying attention to mental health, to women in poor areas and to women from families of low education level are indispensable in medical diagnosis and treatment.
Microglia are the resident immune cells of the central nervous system that exert diverse roles in the pathogenesis of ischemic stroke. During the past decades, microglial polarization and chemotactic ...properties have been well-studied, whereas less attention has been paid to phagocytic phenotypes of microglia in stroke. Generally, whether phagocytosis mediated by microglia plays a beneficial or detrimental role in stroke remains controversial, which calls for further investigations. Most researchers are in favor of the former proposal currently since efficient clearance of tissue debris promotes tissue reconstruction and neuronal network reorganization in part. Other scholars propose that excessively activated microglia engulf live or stressed neuronal cells, which results in neurological deficits and brain atrophy. Upon ischemia challenge, the microglia infiltrate injured brain tissue and engulf live/dead neurons, myelin debris, apoptotic cell debris, endothelial cells, and leukocytes. Cell phagocytosis is provoked by the exposure of "eat-me" signals or the loss of "don
t eat-me" signals. We supposed that microglial phagocytosis could be initiated by the specific "eat-me" signal and its corresponding receptor on the specific cell type under pathological circumstances. In this review, we will summarize phagocytic characterizations of microglia after stroke and the potential receptors responsible for this programmed biological progress. Understanding these questions precisely may help to develop appropriate phagocytic regulatory molecules, which are promoting self-limiting inflammation without damaging functional cells.
Proper finite element modelling of elastoplastic behavior under cyclic and multiaxial loading requires the consideration of nonlinear kinematic hardening. Popular models available for nonlinear ...kinematic hardening are based on multiple additive backstresses, whose evolution include a dynamic recovery term and follow the Armstrong-Frederick proposal; among them, the Ohno-Wang models. Whereas the small strain theory and its numerical implementation are satisfying, large strain extensions are more controversial, specially regarding the mathematical treatment of flow kinematics and the numerical implementation. In this work we present a new approach for modelling nonlinear kinematic hardening at large strains, reproducing the Ohno-Wang model at small strains without explicitly employing the backstress concept. The formulation uses only the classical Kröner-Lee multiplicative decomposition. It avoids the Lion decomposition and it is fully hyperelastic, employing only elastic variables both in the elastic and hardening parts, as well as in the flow equations. The theory has no restriction on the form of stored energies or in the amount of elastic strains so it can be used in soft materials, and it is weak-invariant and volume-preserving by construction. Furthermore, it has the same additive structure of classical small strain algorithms. Geometrical mapping tensors are systematically employed to account for large strain kinematics whereas the iterative algorithmic part is identical to the small strains model, which is recovered bypassing the geometrical mappings. The modelling of visco-hyperelastoplasticity is also straightforward by combining the present theory with finite nonlinear viscoelasticity formulations based on the same framework previously developed by our group.
•Alternative formulation for large-strain cyclic hyperelastoplasticity that substitutes the Armstrong-Frederick formulation.•The formulation recovers the Ohno-Wang model at small strains.•The model does not use the Lion decomposition, but classical Kröner-Lee decompositions.•The formulation is volume-preserving, weak-invariant and allow for any stored energy functions.•Iterative algorithm as a small strain formulation: nonlinear kinematics reduce to noniterative pre- and post-processors.
Lipid peroxide‐derived reactive carbonyl species (RCS), generated downstream of reactive oxygen species (ROS), are critical damage‐inducing species in plant aluminum (Al) toxicity. In mammals, RCS ...are scavenged primarily by glutathione (reduced form of glutathione, GSH), but in plant Al stress, contribution of GSH to RCS detoxification has not been evaluated. In this study, Arabidopsis plants overexpressing the gene AtGR1 (accession code At3g24170), encoding glutathione reductase (GR), were generated, and their performance under Al stress was examined. These transgenic plants (GR‐OE plants) showed higher GSH levels and GSH/GSSG (oxidized form of GSH) ratio, and an improved Al tolerance as they suffered less inhibition of root growth than wild‐type under Al stress. Exogenous application of 4‐hydroxy‐2‐nonenal, an RCS responsible for Al toxicity in roots, markedly inhibited root growth in wild‐type plants. GR‐OE plants suffered significantly smaller inhibition, indicating that the enhanced GSH level increased the capacity of RCS detoxification. The generation of H2O2 due to Al stress in GR‐OE plants was lower by 26% than in wild‐type. Levels of various RCS, such as malondialdehyde, butyraldehyde, phenylacetaldehyde, (E)‐2‐heptenal and n‐octanal, were suppressed by more than 50%. These results indicate that high levels of GSH and GSH/GSSG ratio by GR overexpression contributed to the suppression of not only ROS, but also RCS. Thus, the maintenance of GSH level by overexpressing GR reinforces dual detoxification functions in plants and is an efficient approach to enhance Al tolerance.
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D-Limonene (D-Lim), a volatile oil extracted from citrus fruits, has therapeutic effects on lung inflammation and cancer, whilst the deep delivery of D-Lim was challenging due to its ...physical instability for a long period of time. To prevent the volatilization of D-Lim and achieve efficient pulmonary delivery, herein, D-Lim was loaded into biodegradable γ-cyclodextrin metal-organic framework (γ-CD-MOF) with optimal loading efficiency achieving 13.79 ± 0.01% (molar ratio of D-Lim and γ-CD-MOF was 1.6:1), which possessed cubic shape with controllable particle size (1–5 μm). The experimental results indicated that γ-CD-MOF could improve the stability of D-Lim. A series of characterizations and molecular docking were used to reveal the interaction between D-Lim and γ-CD-MOF. The solidification of D-Lim by γ-CD-MOF played a crucial role in the exploitation of its inhalable dosage form, dry powder inhaler (DPI). Specifically, the aerosolization of D-Lim@γ-CD-MOF for inhalation was satisfactory with a fine particle fraction (FPF) of 33.12 ± 1.50% at 65 L/min of flow rate. Furthermore, in vivo study had shown a 2.23-fold increase in bioavailability of D-Lim solidified by γ-CD-MOF for inhalation compared to D-Lim for oral administration. Therefore, it is considered that γ-CD-MOF could be an excellent carrier for pulmonary drug delivery to realize solidification and lung therapeutic effects of volatile oils.
Ischemic stroke is a debilitating clinical disorder that affects millions of people, yet lacks effective neuroprotective treatments. Fish oil is known to exert beneficial effects against cerebral ...ischemia. However, the underlying protective mechanisms are not fully understood. The present study tests the hypothesis that omega-3 polyunsaturated fatty acids (n-3 PUFAs) attenuate ischemic neuronal injury by activating nuclear factor E2-related factor 2 (Nrf2) and upregulating heme oxygenase-1 (HO-1) in both in vitro and in vivo models. We observed that pretreatment of rat primary neurons with docosahexaenoic acid (DHA) significantly reduced neuronal death following oxygen-glucose deprivation. This protection was associated with increased Nrf2 activation and HO-1 upregulation. Inhibition of HO-1 activity with tin protoporphyrin IX attenuated the protective effects of DHA. Further studies showed that 4-hydroxy-2E-hexenal (4-HHE), an end-product of peroxidation of n-3 PUFAs, was a more potent Nrf2 inducer than 4-hydroxy-2E-nonenal derived from n-6 PUFAs. In an in vivo setting, transgenic mice overexpressing fatty acid metabolism-1, an enzyme that converts n-6 PUFAs to n-3 PUFAs, were remarkably resistant to focal cerebral ischemia compared with their wild-type littermates. Regular mice fed with a fish oil-enhanced diet also demonstrated significant resistance to ischemia compared with mice fed with a regular diet. As expected, the protection was associated with HO-1 upregulation, Nrf2 activation, and 4-HHE generation. Together, our data demonstrate that n-3 PUFAs are highly effective in protecting the brain, and that the protective mechanisms involve Nrf2 activation and HO-1 upregulation by 4-HHE. Further investigation of n-3 PUFA neuroprotective mechanisms may accelerate the development of stroke therapies.
With the rapid development of information media, senior counselors face many new opportunities and challenges in ideological and political education discourse. This study divides the counselor ...discourse modal system into linguistic and visual image modal. Adopting the advanced Transformer architecture and combining the BERT and RoBERTa algorithms, this paper profoundly analyzes the syntactic structure in the discourse. It extracts the emotional features in the text using the bert word vector model. Meanwhile, the dynamic features in the audio information of the discourse are extracted by MFCC technique. After completing the preprocessing of discourse features, we used Bayesian classifier for classification and recognition to further refine the annotation of discourse information. The study results showed that the overall sentiment of the discourse of tutor number 1 tended to be harmful during the 30 minutes, with six segments having an emotional pleasantness of more than -2. In addition, the density of positive discourse sentiment of tutor number 3 was 0.0811 higher than that of tutor number 4. In contrast, the number of discourse labeling of tutor number 5 was reduced by 74 times. Through in-depth analysis and understanding of these discourse modalities and affective features, tutors can better adapt to the information media environment and effectively carry out ideological and political education work.
The purpose of continuum plasticity models is to efficiently predict the behavior of structures beyond their elastic limits. The purpose of multiscale materials science models, among them crystal ...plasticity models, is to understand the material behavior and design the material for a given target. The current successful continuum hyperelastoplastic models are based in the multiplicative decomposition from crystal plasticity, but significant differences in the computational frameworks of both approaches remain, making comparisons not straightforward.
In previous works we have presented a theory for multiplicative continuum elastoplasticity which solved many long-standing issues, preserving the appealing structure of additive infinitesimal Wilkins algorithms. In this work we extend the theory to crystal plasticity. We show that the new formulation for crystal plasticity is parallel and comparable in structure to continuum plasticity, preserving the attractive aspects of the framework: (1) simplicity of the kinematics resulting in additive strain updates as in the infinitesimal framework; (2) possibility of very large elastic strains and unrestricted type of hyperelastic behavior; (3) immediate plain backward-Euler algorithmic implementation of the continuum theory avoiding algorithmically motivated exponential mappings, yet preserving isochoric flow; (4) absence of Mandel-type stresses in the formulation; (5) objectiveness and weak-invariance by construction due to the use of flow rules in terms of elastic corrector rates. We compare the results of our crystal plasticity formulation with the classical formulation from Kalidindi, Bronkhorst and Anand based on quadratic strains and an exponential mapping update of the plastic deformation gradient.
•New crystal plasticity formulation based on elastic corrector rates.•Comparable formulation to the continuum plasticity formulation using the same framework.•Additive structure parallel to infinitesimal plasticity.•Plain backward-Euler integration algorithm without exponential mapping.•Mandel stress plays no role.•Comparison with the classical Kalidindi-Bronkhorst-Anand formulation.
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