GM1 Ameliorates Neuronal Injury in Rats after Cerebral Ischemia and Reperfusion: Potential Contribution of Effects on SPTBN1-mediated Signaling.

Monosialoganglioside GM1 (GM1) has long been used as a therapeutic agent for neurological diseases in the clinical treatment of ischemic stroke. However, the mechanism underlying the neuroprotective function of GM1 is still obscure until now. In this study, we investigated the effects of GM1 in ischemia and reperfusion (I/R) brain injury models. Middle cerebral artery occlusion and reperfusion (MCAO/R) rats were treated with GM1 (60 mg·kg-1·d-1, tail vein injection) for 2 weeks. The results showed that GM1 substantially attenuated the MCAO/R-induced neurological dysfunction and inhibited the inflammatory responses and cell apoptosis in ischemic parietal cortex. We further revealed that GM1 inhibited the activation of NFκB/MAPK signaling pathway induced by MCAO/R injury. To explore its underlying mechanism of the neuroprotective effect, transcriptome sequencing was introduced to screen the differentially expressed genes (DEGs). By function enrichment and PPI network analyses, Sptbn1 was identified as a node gene in the network regulated by GM1 treatment. In the MCAO/R model of rats and oxygen-glucose deprivation and reperfusion (OGD/R) model of primary culture of rat cortical neurons, we first found that SPTBN1 was involved in the attenuation of I/R induced neuronal injury after GM1 administration. In SPTBN1-knockdown SH-SY5Y cells, the treatment with GM1 (20 µM) significantly increased SPTBN1 level. Moreover, OGD/R decreased SPTBN1 level in SPTBN1-overexpressed SH-SY5Y cells. These results indicated that GM1 might achieve its potent neuroprotective effects by regulating inflammatory response, cell apoptosis, and cytomembrane and cytoskeleton signals through SPTBN1. Therefore, SPTBN1 may be a potential target for the treatment of ischemic stroke.

1-Methylcyclopropene Alleviates Postharvest Chilling Injury of Snap Beans by Enhancing Antioxidant Defense System.

Research background: Chilling injury is a major disorder affecting the quality of tropical and subtropical vegetables during low temperature storage. Snap bean (Phaseolus vulgaris L.) is sensitive to chilling injury. The main purpose of the present study is to investigate the alleviating effects of 1-methylcyclopropene (1-MCP) on chilling injury of snap bean. In addition, the related mechanisms were also detected from the perspective of the changes of antioxidant defense system. Experimental approach: Snap beans were exposed to different volume fractions of 1-MCP. After 24 h of treatment, snap beans were stored at 4 °C for up to 14 days. Chilling injury index, electrolyte leakage, titratable acidity and total soluble solids were determined. Contents of chlorophyll, ascorbic acid and malondialdehyde were assessed. The total antioxidant capacity, Fe(II) ion chelating capacity, scavenging capacities on free radicals and activities of antioxidant enzymes were detected. Total phenol content and activities of related metabolic enzymes were also determined. Results and conclusions: 1-MCP treatment reduced chilling injury index, electrolyte leakage rate and malondialdehyde content of snap beans. The amounts of total soluble solids, titratable acid, ascorbic acid and total chlorophyll in 1-MCP-treated snap beans were significantly higher than those of control. The snap beans treated with 1-MCP showed stronger total antioxidant capacity and metal chelating activity. The 1-MCP treatment enhanced scavenging effects of snap beans on superoxide, hydroxyl and 1,1-diphenyl-2-trinitrophenylhydrazine radicals. The activities of peroxidase, ascorbate peroxidase, superoxide dismutase and catalase in 1-MCP-treated group were higher than of control. The treatment also enhanced the accumulation of phenolic compounds in snap beans by regulating the activities of phenol-metabolizing enzymes such as shikimate dehydrogenase, phenylalanine ammonia lyase enzyme, cinnamic acid 4-hydroxylase and polyphenol oxidase. In conclusion, with the mechanism that involves the activation of enzymatic and non-enzymatic antioxidant systems, 1-MCP has the ability to avoid chilling injury of snap bean. Novelty and scientific contribution: This study gives insights into whether 1-MCP can regulate postharvest cold resistance in vegetables by enhancing the enzymatic antioxidant system and inducing the accumulation of non-enzymatic antioxidants. Considering the results, 1-MCP treatment could be an effective method to alleviate postharvest chilling injury of snap beans during low temperature storage.

Toxic vascular effects of polystyrene microplastic exposure.

Polystyrene microplastics (PSMPs) are some of the most common microplastic components, and the resulting pollution has become a global problem. Extensive studies have been conducted on the toxic effects of PSMPs on the heart, lungs, liver, kidneys, nerves, intestines and other tissues. However, the impact of PSMPs on vascular toxicity is poorly understood at present. The aim of this study was to reveal the vascular toxicity of microplastics (MPs). Patients were assigned to a calcification group (25 patients) or a non-calcification group (22 patients) based on the presence or absence of calcification in the thoracic aorta wall. We detected 7 polymer types in human feces. Patients with vascular calcification (VC) had higher levels of total MPs, polypropylene (PP) and polystyrene (PS) in feces than patients without VC. The thoracic aortic calcification score was significantly positively correlated with the total MP abundance (Spearman r = 0.8109, p < 0.0001), PP (Spearman r = 0.7211, p = 0.0160) and PS (Spearman r = 0.6523, p = 0.0471) in feces. We then explored the effects of PSMP exposure on normal and vitamin D3 + nicotine (VDN)-treated rats. PSMP exposure induced mild VC in normal rats and aggravated VC in VDN-treated rats. PSMP exposure disturbed the gut microbiota, causing Proteobacteria and Escherichia_Shigella to be the dominant phylum and genus, respectively. It also induced intestinal inflammatory responses in normal rats, aggravated intestinal inflammation in VDN-treated rats, impaired the intestinal mucosal barrier, and increased intestinal permeability. This study provides a theoretical basis for the risk assessment of MP-induced cardiovascular disease.

LINC00299 polymorphisms rs891058, rs13395467, and rs13398375 reduce the risk of allergic rhinitis among the Chinese Han population.

BACKGROUND: A few studies have reported that allergic rhinitis (AR) pathogenesis is related to genetic factors. And the most important genetic factor is single nucleotide polymorphism (SNP). The study aimed to investigate the effects of LINC00299 SNPs (rs891058, rs13395467 and rs13398375) on AR risk in the Chinese Han population. METHODS: Independent sample t-test was carried out for statistical analyses of the distribution of age and BMI in AR cases and healthy controls, and χ2 test was used for statistical analyses of gender and different regions. The Agena MassARRAY platform was applied for LINC00299 SNP genotyping. Further, the association between SNPs and AR risk was evaluated by odds ratios (ORs) as well as 95% confidence intervals (CIs). RESULTS: Our study found that LINC00299 rs891058, rs13395467, and rs13398375 were associated with a decreased risk of AR in the Chinese Han population. More precisely, rs891058 and rs13398375 were associated with a reduced risk of AR in subjects aged ≤ 43 years. In males, subjects with BMI ≤ 24 kg/m2, and from loess hills region, rs891058, rs13395467, and rs13398375 played a protective role against AR. The study on SNP-SNP interactions suggested that rs891058, rs13395467 and rs13398375 were related. CONCLUSIONS: LINC00299 polymorphisms rs891058, rs13395467, and rs13398375 are associated with a reduced risk of AR in the Chinese Han population, and these SNPs can be used as potential targets to assess AR risk.

Clinical manifestation score and characterization of cytokines and lymphocytes of dimethylacetamide-induced toxic hepatitis in spandex workers.

Occupational exposure to dimethylacetamide (DMAc) has been reported to cause toxic hepatitis. Sixty spandex workers were included in this study to research the clinical manifestations and expression of cytokines and lymphocytes in DMAc-induced toxic hepatitis. Chinese drugs (reduced glutathione and Hugan tablets) were used to treat them. The manifestations including jaundice, asthenia, appetite, nausea, emesis, abdominal distension, yellow urine, and dizziness were scored. The percentages of patients rated as 0-3, 4-6, 7-9, and 10-12 points were 33.3%, 43.3%, 21.7%, and 1.7%, respectively, before treatment, and all patients showed 0-3 points after the treatment. The ultrasonic and CT imaging revealed diffuse intrahepatic hypodensity, intrahepatic calcification, signs of liver injury, and splenomegaly, which improved after therapy. Blood analysis showed that ALT, AST, TBIL, IL-6, IL-10, TNF-α, IFN-γ, CD3+%, and CD4+/CD8+ statistically decreased after drug treatment. Correlation analysis demonstrated positive linear correlations between ALT and TBIL, AST and TBIL, IL-10 and ATL, IL-10 and AST, IL-10 and TBIL, IFN-γ and IL-6, IFN-γ and TNF-α, and CD3+% and ALT. Pro-inflammatory cytokines and lymphocytes in DMAc-induced toxic hepatitis reflected an active immune state that decreased after treatment. IL-10 may inhibit the immune response in this disease, as a protective mechanism.

Adenosine kinase promotes post-infarction cardiac repair by epigenetically maintaining reparative macrophage phenotype.

Pro-inflammatory and reparative macrophages are crucial in clearing necrotic myocardium and promoting cardiac repair after myocardial infarction (MI), respectively. Extracellular adenosine has been demonstrated to modulate macrophage polarization through adenosine receptors. However, the role of intracellular adenosine in macrophage polarization has not been explored and adenosine kinase (ADK) is a major enzyme regulating intracellular adenosine levels. Here, we aimed to elucidate the role of ADK in macrophage polarization and its subsequent impact on MI. We demonstrated that ADK was upregulated in bone marrow-derived macrophages (BMDMs) after IL-4 treatment and was highly expressed in the infarct area at day 7 post-MI, especially in macrophages. Compared with wild-type mice, myeloid-specific Adk knockout mice showed increased infarct size, limited myofibroblast differentiation, reduced collagen deposition and more severe cardiac dysfunction after MI, which was related to impaired reparative macrophage phenotype in MI tissue. We found that ADK deletion or inhibition significantly decreased the expression of reparative genes, such as Arg1, Ym1, Fizz1, and Cd206 in BMDMs after IL-4 treatment. The increased intracellular adenosine due to Adk deletion inhibited transmethylation reactions and decreased the trimethylation of H3K4 in BMDMs after IL-4 treatment. Mechanistically, we demonstrated that Adk deletion suppressed reparative macrophage phenotype through decreased IRF4 expression, which resulted from reduced levels of H3K4me3 on the Irf4 promotor. Together, our study reveals that ADK exerts a protective effect against MI by promoting reparative macrophage polarization through epigenetic mechanisms.

Chemokine-like receptor 1 deficiency impedes macrophage phenotypic transformation and cardiac repair after myocardial infarction.

BACKGROUND: Timely and appropriate transformation of macrophage phenotypes from proinflammatory to anti-inflammatory is essential for cardiac repair after myocardial infarction (MI). Chemokine-like receptor 1 (CMKLR1), which is expressed on macrophages, is regulated by proinflammatory and anti-inflammatory stimuli. However, the contribution of CMKLR1 to macrophage phenotypic transformation and the role it plays in modulating cardiac repair after MI remain unclear. METHODS: CMKLR1 knockout (CMKLR1-/-) mice were generated by CRISPR/Cas-mediated genome engineering. A model of murine MI was induced by permanent ligation along the left anterior descending artery. Cardiac function was evaluated by echocardiography. Infarct size and collagen deposition were detected by Masson's trichrome staining. Cardiac macrophages were obtained by fluorescence-activated cell sorting. The protein and mRNA expression of associated molecules was determined by Western blotting and qRT-PCR. RESULTS: We demonstrated that macrophages highly expressed CMKLR1 and accumulated in murine infarcted hearts during the anti-inflammatory reparative phase of MI. CMKLR1 deficiency impaired cardiac function, increased infarct size, induced maladaptive cardiac remodeling, and decreased long-term survival after MI. Furthermore, CMKLR1 deficiency impeded macrophage phenotypic transformation from M1 to M2 in vivo and in vitro. In addition, we demonstrated that CMKLR1 signaling through the PI3K/Akt/mTOR pathway stimulated C/EBPß activation while simultaneously limiting NF-κB activation, thereby promoting anti-inflammatory and prohibiting proinflammatory macrophage polarization. CONCLUSIONS: Our results reveal that CMKLR1 deficiency impedes macrophage phenotypic transformation and cardiac repair after MI involving the PI3K/AKT/mTOR pathway. CMKLR1 may thus represent a potential therapeutic target for MI.

Intensification of abdominal core skills in muscular strength training for sprinter athletes / Intensificação das habilidades do centro abdominal no treinamento de força muscular para atletas velocistas / Intensificación de las habilidades del núcleo abdominal en el entrenamiento de la fuerza muscular para atletas velocistas

ABSTRACT Introduction Running is a speed-based physical activity, and abdominal core strength training is a good technique for athletes. The method of abdominal core strength training consists of training the muscles of the central part of the human body, which also aims to improve the physical coordination of its practitioners. Objective Analyze the effects of abdominal core strength training on athletes' physical performance and performance in competitions. Methods Twenty sprinters were selected as volunteers and had their EMG signals and muscular endurance of the lower body muscles compared during the experiment. The athletes performed an abdominal core training cycle. The statistical method was used to perform an analysis of the obtained data. These experimental data were adjusted, and significant correlations were discovered. The research results of this paper provide a theoretical basis for formulating the athletes' training strategies. Results The maximum muscular endurance of male and female sprinters was statistically different (P<0.05). Fitness indicators improved in sprinters after abdominal core strength training. The studies were statistically different (P<0.05). Athletes' performance improved after abdominal core strength training. The data were statistically significant (P<0.05). Conclusion The physical performance and performance of sprinters are positively correlated with abdominal core strength training. Sprinters should focus on abdominal core strength training in their daily training. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução A corrida é uma atividade física baseada na velocidade e o treinamento da força do centro abdominal é uma técnica favorável aos seus atletas. O método de treinamento da força do centro abdominal consiste no treinamento dos músculos da parte central do corpo humano, que também tem como objetivo melhorar a coordenação física de seus praticantes. Objetivo Analisar os efeitos do treinamento de força do centro abdominal sobre o desempenho físico dos atletas e o desempenho em competições. Métodos Foram selecionados como voluntários 20 velocistas que tiveram seus sinais de EMG e a resistência muscular dos músculos da parte inferior do corpo comparados durante o experimento. Os atletas realizaram um ciclo de treinamento de centro abdominal. O método estatístico foi utilizado para realizar uma análise sobre os dados obtidos. Esses dados experimentais foram ajustados e descobriu-se correlações significativas. Os resultados da pesquisa deste trabalho fornecem base teórica para a formulação das estratégias de treinamento dos atletas. Resultados A resistência muscular máxima dos velocistas masculinos e femininos foi estatisticamente diferente (P<0,05). Os indicadores de aptidão física melhoraram nos velocistas após o treinamento de força do centro abdominal. Os estudos foram estatisticamente diferentes (P<0,05). O desempenho dos atletas melhorou após o treinamento de força do centro abdominal. Os dados foram estatisticamente significativos (P<0,05). Conclusão O desempenho físico e o desempenho dos velocistas estão positivamente correlacionados com o treinamento de força do centro abdominal. Os velocistas devem se concentrar no treinamento de força do centro abdominal em seu treinamento diário. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción La carrera a pie es una actividad física basada en la velocidad y el entrenamiento de la fuerza del núcleo abdominal es una técnica favorable a sus atletas. El método de entrenamiento de la fuerza del núcleo abdominal consiste en el entrenamiento de los músculos de la parte central del cuerpo humano, que también tiene como objetivo mejorar la coordinación física de sus practicantes. Objetivo Analizar los efectos del entrenamiento de la fuerza del núcleo abdominal en el rendimiento físico de los atletas y su desempeño en las competiciones. Métodos Se seleccionaron veinte velocistas como voluntarios, a los que se les compararon las señales EMG y la resistencia muscular de los músculos de la parte inferior del cuerpo durante el experimento. Los atletas realizaron un ciclo de entrenamiento del núcleo abdominal. Se utilizó el método estadístico para realizar un análisis de los datos obtenidos. Estos datos experimentales se ajustaron y se descubrieron correlaciones significativas. Los resultados de la investigación de este trabajo proporcionan una base teórica para formular las estrategias de entrenamiento de los atletas. Resultados La resistencia muscular máxima de los velocistas masculinos y femeninos fue estadísticamente diferente (P<0,05). Los indicadores de aptitud física mejoraron en los velocistas tras el entrenamiento de fuerza del núcleo abdominal. Los estudios fueron estadísticamente diferentes (P<0,05). El rendimiento de los atletas mejoró tras el entrenamiento de fuerza del núcleo abdominal. Los datos fueron estadísticamente significativos (P<0,05). Conclusión El rendimiento físico y el desempeño de los velocistas están positivamente correlacionados con el entrenamiento de la fuerza del núcleo abdominal. Los velocistas deben centrarse en el entrenamiento de la fuerza del núcleo abdominal en su entrenamiento diario. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Beneficial effect of the short-chain fatty acid propionate on vascular calcification through intestinal microbiota remodelling.

BACKGROUND: Vascular calcification is a major cause of the high morbidity and mortality of cardiovascular diseases and is closely associated with the intestinal microbiota. Short-chain fatty acids (SCFAs) are derived from the intestinal microbiota and can also regulate intestinal microbiota homeostasis. However, it remains unclear whether exogenous supplementation with propionate, a SCFA, can ameliorate vascular calcification by regulating the intestinal microbiota. This study was conducted to explore the roles of propionate and the intestinal microbiota in the process of vascular calcification. METHODS: In total, 92 patients were enrolled consecutively as the observational cohort to analyse the relationship between SCFAs and vascular calcification in both blood and faecal samples. A rat model of vascular calcification was induced by vitamin D3 and nicotine (VDN) to validate the effect of propionate. Differences in the intestinal microbiota were analysed by 16S ribosomal RNA gene sequencing. Faecal microbiota transplantation and Akkermansia muciniphila transplantation experiments were performed to evaluate the functions of the intestinal microbiota. RESULTS: The results of the observational cohort study revealed that the levels of SCFAs (particularly propionate) in both blood and faecal samples independently correlated negatively with calcification scores (P < 0.01). To verify the activities of propionate, it was provided to VDN-treated rats, and oral or rectal propionate delivery reshaped the intestinal microbiota, resulted in elevated SCFA production, improved intestinal barrier function and alleviated inflammation, ultimately ameliorating vascular calcification. Furthermore, we demonstrated that transplantation of the propionate-modulated intestinal microbiota induced beneficial outcomes similar to those with oral or rectal propionate administration. Interestingly, linear discriminant analysis (LDA) effect size (LEfSe) revealed that oral or rectal propionate administration and propionate-modulated intestinal microbiota transplantation both enriched primarily Akkermansia. Subsequently, we demonstrated that Akkermansia supplementation could ameliorate VDN-induced vascular calcification in rats. CONCLUSIONS: Propionate can significantly ameliorate vascular calcification in VDN-treated rats, and this effect is mediated by intestinal microbiota remodelling. The findings in our study indicate that the intestinal tract-vessel axis is a promising target for alleviating vascular calcification. Video Abstract.

Pd-Catalyzed γ-Acetoxylation of Alkylamides: Structural Influence of Directing Groups.

Although direct acetoxylation and cyclization of alkylamide have been extensively reported, investigation of the structural influence of directing groups on selectivity is limited. Pd-catalyzed 2-methoxyiminoacyl (MIA) assisted γ-acetoxylation of alkylamides has been developed. Further DFT studies have demonstrated that the directing groups have a significant influence on the reductive elimination step. The strong electron-donating effect of the OMe group in MIA leads to the preferential formation of a five-membered cyclopalladium (OAc-Pd-C) complex, which favors the acetoxylation pathway.

C5aR1 Mediates the Progression of Inflammatory Responses in the Brain of Rats in the Early Stage after Ischemia and Reperfusion.

C5a receptor 1 (C5aR1) can induce a strong inflammatory response to an injury. Targeting C5aR1 has emerged as a novel anti-inflammatory therapeutic method. However, the role of C5aR1 in cerebral ischemia and reperfusion (I/R) injury and the definitive mechanism have not been elucidated clearly. Here, we determined whether C5aR1 signaling was essential to the post-ischemic inflammation and brain injury and whether it is a valid target for therapeutic blockade by using soluble receptor antagonist PMX53 in the early stage after I/R injury. In an in vitro model (oxygen and glucose deprivation and reperfusion, OGD/R) and in vivo model (middle cerebral artery occlusion and reperfusion, MCAO/R) of I/R, the neuronal cells of rats showed significantly up-regulated gene expression of C5aR1, and a notable inflammatory response was demonstrated with elevated tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and IL-6. Inhibition of C5aR1 by PMX53 treatment significantly reduced cell injury and inflammation and promoted brain function recovery. Further mechanism studies showed that inhibiting C5aR1 by PMX53 protected the rats from MCAO/R injury, decreased cell inflammation, and apoptosis via inhibiting the TLR4 and NF-κB signaling pathway and reducing the production of TNF-α, IL-1ß, and IL-6 in MCAO/R rats. In addition, manipulation of the C5aR1 gene expression in vitro displayed that the inflammatory cascade signals including TLR4, TNF-α, IL-1ß, and IL-6 were coincidently regulated with the regulation of C5aR1 expression levels. Thus, our results demonstrated a pathogenic role for C5aR1 in the progression of brain injury and inflammation response following I/R injury. Our study clearly demonstrated that C5aR1 inhibition might be an effective treatment strategy for ischemic stroke.

Prediction Model for Coal Spontaneous Combustion Based on SA-SVM.

Accurate predictions of the coal temperature in coal spontaneous combustion (CSC) are important for ensuring coal mine safety. Gas coal (the Zhaolou coal mine in Shandong Province, China) was used in this paper. A large CSC experimental device was adopted to obtain its characteristic temperatures from the macroscopic characteristics of gas production. A simulated annealing-support vector machine (SA-SVM) prediction model was proposed to reflect the complex nonlinear mapping between characteristic gases and the coal temperature. The risk degree of CSC was estimated in the time domain, and the model was verified by using in situ data from an actual working face. Furthermore, back-propagation neural network (BPNN) and single SVM methods were adopted for comparison. The results showed that the BPNN could not adapt to the small-sample problem due to overfitting and the output of a single SVM was unstable due to its strong dependence on the setting of hyperparameters. Through the SA global optimization process, the optimal combination of hyperparameters was obtained. Therefore, SA-SVM had higher prediction accuracy, robustness, and error tolerance rate and better environmental adaptability. These findings have certain practical significances for eliminating the hidden danger of CSC in the gob and providing timely warnings about potential danger.

Isoquercetin Improves Inflammatory Response in Rats Following Ischemic Stroke.

Inflammatory response contributes to brain injury after ischemia and reperfusion (I/R). Our previous literature has shown isoquercetin plays an important role in protecting against cerebral I/R injury. The present study was conducted to further investigate the effect of isoquercetin on inflammation-induced neuronal injury in I/R rats with the involvement of cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) and inhibitor of NF-κB (I-κB)/nuclear factor-kappa B (NF-κB) signaling pathway mediated by Toll-like receptor 4 (TLR4) and C5a receptor 1 (C5aR1). In vivo middle cerebral artery occlusion and reperfusion (MCAO/R) rat model and in vitro oxygen-glucose deprivation and reperfusion (OGD/R) neuron model were used. MCAO/R induced neurological deficits, cell apoptosis, and release of cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 in ischemic brain in rats. Simultaneously, the expression of TLR4 and C5aR1 was significantly up-regulated in both MCAO/R rats and OGD/R neurons, accompanied with the inhibition of cAMP/PKA signaling and activation of I-κB/NF-κB signaling in the cortex of MCAO/R rats. Over-expression of C5aR1 in neurons induced decrease of cell viability, exerting similar effects with OGD/R injury. Isoquercetin acted as a neuroprotective agent against I/R brain injury to suppress inflammatory response and improve cell recovery by inhibiting TLR4 and C5aR1 expression, promoting cAMP/PKA activation, and inhibiting I-κB/NF-κB activation and Caspase 3 expression. TLR4 and C5aR1 contributed to inflammation and apoptosis via activating cAMP/PKA/I-κB/NF-κB signaling during cerebral I/R, suggesting that this signaling pathway may be a potent therapeutic target in ischemic stroke. Isoquercetin was identified as a neuroprotective agent, which maybe a promising therapeutic agent used for the treatment of ischemic stroke and related diseases.

Effects of Moisture and Associated Pyrite on the Microstructure of Anthracite Coal for Spontaneous Combustion.

To explore the micromechanism of the structural changes of anthracite due to heat accumulation by water and pyrite, during oxidation, anthracite with coal samples was selected in this work from Baijiao Coalmine, Sichuan, China. The samples were added with water of 1, 5, 10, 15, and 20 mass % and pyrite of 1, 2, 4, and 6 mass % and were conducted to experimented torts. As compared with the raw coal sample, the effects of water and pyrite on the microstructure of anthracite were studied. The results indicate that the oxygen-containing functional group of coal increases with the addition of water. The content of the aromatic structure in coal was thought to be due to water and pyrite synergistic effects. The synergistic effect of water and pyrite accelerates the oxidation process of seven types of active groups in coal samples. The water content was 10-15 mass %, and the associated pyrite content was 2-4 mass %; the contribution to the oxidation activity of the main active groups of coal was the largest under oxidizing conditions.

Schisandrin B improves cerebral ischemia and reduces reperfusion injury in rats through TLR4/NF-κB signaling pathway inhibition.

It has been established that poor outcomes in ischemic stroke patients are associated with the post-reperfusion inflammatory response and up-regulation of TLR4. Therefore, suppression of the TLR4 signaling pathway constitutes a potential neuroprotective therapeutic strategy. Schisandrin B, a compound extracted from Schisandra chinensis, has been shown to possess anti-inflammatory and neuroprotective properties. However, the mechanism remains unclear. In the present study, the therapeutic effect of schisandrin B was assessed following cerebral ischemia and reperfusion (I/R) injury in a model of middle cerebral artery occlusion and reperfusion (MCAO/R) in rats. The effects of schisandrin B were investigated with particular emphasis on TLR4 signal transduction and on the inflammatory response. Schisandrin B treatment conferred significant protection against MCAO/R injury, as evidenced by decreases in infarct volume, neurological score, and the number of apoptotic neurons and inflammatory signaling molecules. ABBREVIATIONS: I/R: schemia/reperfusion; IL: interleukin; MCAO/R: middle cerebral artery occlusion and reperfusion; NF-κB: nuclear; TLR4: Toll-like receptor 4; TNF-α: tumor necrosis factor-α.

Visualizing the Transport of Porcine Reproductive and Respiratory Syndrome Virus in Live Cells by Quantum Dots-Based Single Virus Tracking.

Quantum dots (QDs)-based single particle analysis technique enables real-time tracking of the viral infection in live cells with great sensitivity over a long period of time. The porcine reproductive and respiratory syndrome virus (PRRSV) is a small virus with the virion size of 40-60 nm which causes great economic losses to the swine industry worldwide. A clear understanding of the viral infection mechanism is essential for the development of effective antiviral strategies. In this study, we labeled the PRRSV with QDs using the streptavidin-biotin labeling system and monitored the viral infection process in live cells. Our results indicated that the labeling method had negligible effect on viral infectivity. We also observed that prior to the entry, PRRSV vibrated on the plasma membrane, and entered the cells via endosome mediated cell entry pathway. Viruses moved in a slow-fast-slow oscillatory movement pattern and finally accumulated in a perinuclear region of the cell. Our results also showed that once inside the cell, PRRSV moved along the microtubule, microfilament and vimentin cytoskeletal elements. During the transport process, virus particles also made contacts with non-muscle myosin heavy chain II-A (NMHC II-A), visualized as small spheres in cytoplasm. This study can facilitate the application of QDs in virus infection imaging, especially the smaller-sized viruses and provide some novel and important insights into PRRSV infection mechanism.

Achyranthes bidentata polypeptide k suppresses neuroinflammation in BV2 microglia through Nrf2-dependent mechanism.

BACKGROUND: Activated microglia play a critical role in regulating neuroinflammatory responses in central nervous system. Previous studies have shown that Achyranthes bidentata polypeptide k's (ABPPk's) neuroprotective effects are partly due to its anti-inflammatory effect, but the mechanism remains unknown. This study is aimed to investigate the anti-inflammatory effect of ABPPk on lipopolysaccharide (LPS)-activated neuroinflammation in BV2 microglia. METHODS: We pretreated BV2 microglia with different concentrations of ABPPk (0.04-5 µg/mL) for 30 minutes, and then stimulated microglia with LPS for 24 hours. Pro-inflammatory mediators including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), nitric oxide (NO) and prostaglandin E2 (PGE2) production were measured by enzyme-linked immunosorbent assay (ELISA) kits. Inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), phosphorylated nuclear factor kappa B (NF-κB), heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2) expression levels were detected by western blot. Glutathione (GSH) level was measured by GSH-Glo™ Glutathione assay. Immunofluorescent staining was used to detect the nuclear translocation of NF-κB and Nrf2. BV2 microglia transfected with Nrf2 siRNA were used to investigate the effect of Nrf2 on the anti-inflammatory activity of ABPPk. RESULTS: ABPPk (0.2-5 µg/mL) reduced the iNOS mediated NO and COX-2 mediated PGE2 production significantly in LPS-activated BV2 microglia. ABPPk (1 and 5 µg/mL) also suppressed the production of TNF-α and IL-6 significantly. NF-κB is phosphorylated and translocated into nuclear in LPS-activated BV2 microglia, but ABPPk is shown to inhibit the phosphorylation and translocation of NF-κB in a concentration-dependent way. ABPPk increased the protein expression levels of HO-1 and Nrf2, as well as the GSH content in BV2 microglia. Immunofluorescent staining showed that ABPPk also promoted nuclear translocation of Nrf2. After knocking down Nrf2 in BV2 cells with siRNA interference, ABPPk's inhibitory effect on pro-inflammatory mediators also disappeared. CONCLUSIONS: The present study suggests that ABPPk inhibits neuroinflammation in BV2 microglia through Nrf2-dependent mechanism. This provides some strong evidence for the potential of this neuroprotective natural compound to treat neurodegenerative diseases such as ischemic stroke and Parkinson's disease.

Archimedean spiral push-broom differential thermal imaging for gas leakage detection.

An uncooled infrared focal plane array (FPA) for a multiband optical imaging system monitoring small gas leakages is low in cost but limited by its frame rate and sensitivity. We propose the concept of Archimedean spiral push-broom filtering (ASPBF), where the trajectory of an Archimedean spiral over the FPA is approximated as a straight line. The ASPBF precisely matches the electronic pulse scanning of the uncooled infrared FPA row by row to improve the frame rate. We applied differential imaging to promote gas detection sensitivity. Prototype can detect 11 ml/min of ethylene gas at ΔT = 3 °C with frame rate of 8 fps.

Achyranthes bidentata polypeptide k improves long-term neurological outcomes through reducing downstream microvascular thrombosis in experimental ischemic stroke.

Achyranthes bidentata Bl. (A. bidentata) occupies an important position in traditional Chinese medicine owing to the property of promoting the circulation of blood and removing stasis. Achyranthes bidentata polypeptide k (ABPPk) is one of the active components isolated from A. bidentata. We previously demonstrated that ABPPk has potent neuroprotective effects against neuronal apoptosis both in vitro and in vivo, but the roles and mechanisms of ABPPk on long-term functional recovery after ischemic stroke remain unknown. In the current study, we investigated the neuroprotective effects of ABPPk on filament transient middle cerebral artery occlusion (tMCAO) rats and found that ABPPk reduced the infarct volume and maintained the neuronal integrity in the ischemic penumbra. Moreover, we found that ABPPk might reduce the formation of downstream microthrombus through preventing ischemic-induced oxidative damage of brain endothelial cells and activation of tissue factor (TF), plasminogen activator inhibitor-1 (PAI-1), and NF-κB. ABPPk also inhibited polymorphonuclear leukocytes (PMNs) infiltration and matrix metalloproteinase-2/-9 (MMP-2/-9) activation in the ischemic penumbra. Morris water maze, foot fault test, and modified neurological severity score were assessed for a period of 6 weeks following tMCAO. ABPPk improved long-term recognition abilities and neurological outcomes after stroke compared with saline-treated rats. Taken together, these results suggested that ABPPk is beneficial to the improvement of long-term outcomes after transient cerebral ischemia injury and can be used as a potential neuroprotective agent.