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Chronic pain patients often have anxiety disorders, and some of them suffer from anxiety even after analgesic administration. In this study, we investigated the role of AMPAR-mediated synaptic transmission in the ventromedial prefrontal cortex (vmPFC) in chronic pain-induced persistent anxiety in mice and explored potential drug targets. Chronic inflammatory pain was induced in mice by bilateral injection of complete Freund's adjuvant (CFA) into the planta of the hind paws; anxiety-like behaviours were assessed with behavioural tests; S-nitrosylation and AMPAR-mediated synaptic transmission were examined using biochemical assays and electrophysiological recordings, respectively. We found that CFA induced persistent upregulation of AMPAR membrane expression and function in the vmPFC of anxious mice but not in the vmPFC of non-anxious mice. The anxious mice exhibited higher S-nitrosylation of stargazin (an AMPAR-interacting protein) in the vmPFC. Inhibition of S-nitrosylation by bilaterally infusing an exogenous stargazin (C302S) mutant into the vmPFC rescued the surface expression of GluA1 and AMPAR-mediated synaptic transmission as well as the anxiety-like behaviours in CFA-injected mice, even after ibuprofen treatment. Moreover, administration of ZL006, a small molecular inhibitor disrupting the interaction of nNOS and PSD-95 (20 mg·kg-1·d-1, for 5 days, i.p.), significantly reduced nitric oxide production and S-nitrosylation of AMPAR-interacting proteins in the vmPFC, resulting in anxiolytic-like effects in anxious mice after ibuprofen treatment. We conclude that S-nitrosylation is necessary for AMPAR trafficking and function in the vmPFC under chronic inflammatory pain-induced persistent anxiety conditions, and nNOS-PSD-95 inhibitors could be potential anxiolytics specific for chronic inflammatory pain-induced persistent anxiety after analgesic treatment.
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Ansiedade , Dor Crônica , Córtex Pré-Frontal , Receptores de Glutamato , Animais , Camundongos , Ansiedade/etiologia , Ansiedade/metabolismo , Transtornos de Ansiedade , Dor Crônica/complicações , Dor Crônica/metabolismo , Ibuprofeno , Córtex Pré-Frontal/metabolismo , Transmissão Sináptica , Receptores de Glutamato/química , Receptores de Glutamato/metabolismo , Inflamação/complicações , Inflamação/metabolismoRESUMO
Due to its advantages of low latency, low power consumption, and high flexibility, FPGA-based acceleration technology has been more and more widely studied and applied in the field of computer vision in recent years. An FPGA-based feature extraction and tracking accelerator for real-time visual odometry (VO) and visual simultaneous localization and mapping (V-SLAM) is proposed, which can realize the complete acceleration processing capability of the image front-end. For the first time, we implement a hardware solution that combines features from accelerated segment test (FAST) feature points with Gunnar Farneback (GF) dense optical flow to achieve better feature tracking performance and provide more flexible technical route selection. In order to solve the scale invariance and rotation invariance lacking problems of FAST features, an efficient pyramid module with a five-layer thumbnail structure was designed and implemented. The accelerator was implemented on a modern Xilinx Zynq FPGA. The evaluation results showed that the accelerator could achieve stable tracking of features of violently shaking images and were consistent with the results from MATLAB code running on PCs. Compared to PC CPUs, which require seconds of processing time, the processing latency was greatly reduced to the order of milliseconds, making GF dense optical flow an efficient and practical technical solution on the edge side.
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Historical residual of persistent organic pollutants (POPs) in flood sediment from a karst cave were investigated. Fifteen vertical sediment samples were collected from a 6 m-deep flood sediment profile in the Longwang Cave, and the concentrations of organochlorine pesticides (OCPs), polycyclic aromatic hydrocarbons (PAHs) and particle size distribution in the sediments were analysed. The concentrations of OCPs and PAHs varied from 0.85 ng g-1 to 63.1 ng g-1 (mean 8.11 ng g-1) and 5.05 ng g-1 to 82.6 ng g-1 (mean 13.9 ng g-1), respectively; major PAHs in the profile were 2- and 3-ringed PAHs and a few were 5- or 6- ringed PAHs, which indicated less influence from industry but a high impact from the local combustion of coal and biomass; HCHs and DDTs in the profile were historically residual in this region, and HCHs mainly originated from the application of Lindane, while DDTs originated from the application of dicofol and technical DDTs; no significant correlation between the concentrations of OCPs and PAHs and the sedimental particle size in the sediments was found.
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Hidrocarbonetos Clorados/história , Resíduos de Praguicidas/história , Hidrocarbonetos Policíclicos Aromáticos/história , Poluentes Químicos da Água/história , Cavernas , China , Inundações , Sedimentos Geológicos/química , História do Século XX , Hidrocarbonetos Clorados/análise , Resíduos de Praguicidas/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Poluentes Químicos da Água/análiseRESUMO
The rising incidence of fibrosis poses a major threat to global public health, and the continuous exploration of natural products for the effective treatment of fibrotic diseases is crucial. Berberine (BBR), an isoquinoline alkaloid, is widely used clinically for its anti-inflammatory, anti-tumor and anti-fibrotic pharmacological effects. Until now, researchers have worked to explore the mechanisms of BBR for the treatment of fibrosis, and multiple studies have found that BBR attenuates fibrosis through different pathways such as TGF-ß/Smad, AMPK, Nrf2, PPAR-γ, NF-κB, and Notch/snail axis. This review describes the anti-fibrotic mechanism of BBR and its derivatives, and the safety evaluation and toxicity studies of BBR. This provides important therapeutic clues and strategies for exploring new drugs for the treatment of fibrosis. Nevertheless, more studies, especially clinical studies, are still needed. We believe that with the continuous implementation of high-quality studies, significant progress will be made in the treatment of fibrosis.
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The incidence of liver disease continues to rise, encompassing a spectrum from simple steatosis or non-alcoholic fatty liver disease (NAFLD) to non-alcoholic steatohepatitis (NASH), cirrhosis and liver cancer. Dietary habits in individuals with liver disease may significantly impact the treatment and prevention of these conditions. This article examines the role of chili peppers, a common dietary component, in this context, focusing on capsaicin, the active ingredient in chili peppers. Capsaicin is an agonist of the transient receptor potential vanilloid subfamily 1 (TRPV1) and has been shown to exert protective effects on liver diseases, including liver injury, NAFLD, liver fibrosis and liver cancer. These protective effects are attributed to capsaicin's anti-oxidant, anti-inflammatory, anti-steatosis and anti-fibrosis effects. This article reviewed the different molecular mechanisms of the protective effect of capsaicin on liver diseases.
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Many efforts have been made to understand excitotoxicity and develop neuroprotectants for the therapy of ischemic stroke. The narrow treatment time window is still to be solved. Given that the ischemic core expanded over days, treatment with an extended time window is anticipated. Bestrophin 1 (BEST1) belongs to a bestrophin family of calcium-activated chloride channels. We revealed an increase in neuronal BEST1 expression and function within the peri-infarct from 8 to 48 h after ischemic stroke in mice. Interfering the protein expression or inhibiting the channel function of BEST1 by genetic manipulation displayed neuroprotective effects and improved motor functional deficits. Using electrophysiological recordings, we demonstrated that extrasynaptic glutamate release through BEST1 channel resulted in delayed excitotoxicity. Finally, we confirmed the therapeutic efficacy of pharmacological inhibition of BEST1 during 6-72 h post-ischemia in rodents. This delayed treatment prevented the expansion of infarct volume and the exacerbation of neurological functions. Our study identifies the glutamate-releasing BEST1 channel as a potential therapeutic target against ischemic stroke with a wide time window.
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Background and aim: Ulcerative colitis is a chronic inflammatory bowel disease, and intestinal flora plays an important role in ulcerative colitis. In this study, we conducted a bibliometric analysis of publications in the field of intestinal flora and ulcerative colitis research in the past 10 years to summarize the current status of the field and analyze the trends in the field. Methods: On July 15, 2022, we chose the Web of Science Core Collection database as the study's data source. CiteSpace.5.8.R3 and VOSviewer 1.6.17 were used to examine publications of research on intestinal flora and ulcerative colitis that were published between 2012 and 2021. We looked through the papers for journals, organizations, nations and regions, authors, and key terms. Results: This analysis covered a total of 2,763 papers on studies into intestinal flora and ulcerative colitis. There were 13,913 authors, 93 nations, 3,069 organizations, and 759 journals in all of the articles. In the USA, 767 publications were the most. The university with the most publications was Harvard Medical School. The author with the most articles was Antonio Gasbarrini. Conclusion: This study summarizes the global research trends in intestinal flora and ulcerative colitis. Publications in this field have increased year by year in the last decade and the field of research on intestinal flora and ulcerative colitis has good prospects for growth.
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Irritable bowel syndrome (IBS) is a gastrointestinal disorder with no structural damage, and its pathogenesis remains unclear. Studies have shown that the brain-gut axis is closely related to the occurrence of IBS. However, studies of IBS related to the brain-gut axis have not been systematically analyzed by bibliometrics and visual analysis. This study is based on 631 publications in the Web of Science Core Collection (WoSCC) to analyze hot spots and trends in this field. The collaborations between different authors, institutions, countries, and keywords were bibliometrically analyzed by CiteSpace software. Meanwhile, VOSviewer analyzed the references. The results show that since 2012, the number of publications has been growing rapidly. According to the collaborative network analysis, the United States, the National University of Ireland, Cork, and J.F. Cryan are the countries, institutions, and authors contributing the most, respectively. Through keywords and literature analysis, mechanisms and therapy associated with IBS and the brain-gut axis have still been a research focus in recent years. Furthermore, the physiological and pathological mechanisms of the brain-gut axis influencing IBS (related to gastrointestinal dysfunction, vagus nerve, visceral pain, intestinal flora, serotonin, tryptophan metabolism, stress, brain-derived neurotrophic factor (BDNF), and malonyldialdehyde) are the future research trends, especially the mechanisms related to intestinal flora. This is the first bibliometric and visualization analysis of IBS and brain-gut axis-related literature to explore research hotspots and trends.
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Unconfined compressive strength (UCS) is the most significant mechanical index for cemented backfill, and it is mainly determined by traditional mechanical tests. This study optimized the extreme gradient boosting (XGBoost) model by utilizing the whale optimization algorithm (WOA) to construct a hybrid model for the UCS prediction of cemented backfill. The PT proportion, the OPC proportion, the FA proportion, the solid concentration, and the curing age were selected as input variables, and the UCS of the cemented PT backfill was selected as the output variable. The original XGBoost model, the XGBoost model optimized by particle swarm optimization (PSO-XGBoost), and the decision tree (DT) model were also constructed for comparison with the WOA-XGBoost model. The results showed that the values of the root mean square error (RMSE), coefficient of determination (R2), and mean absolute error (MAE) obtained from the WOA-XGBoost model, XGBoost model, PSO-XGBoost model, and DT model were equal to (0.241, 0.967, 0.184), (0.426, 0.917, 0.336), (0.316, 0.943, 0.258), and (0.464, 0.852, 0.357), respectively. The results show that the proposed WOA-XGBoost has better prediction accuracy than the other machine learning models, confirming the ability of the WOA to enhance XGBoost in cemented PT backfill strength prediction. The WOA-XGBoost model could be a fast and accurate method for the UCS prediction of cemented PT backfill.
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Background and objectives: Diabetes mellitus is a serious metabolic disease that causes a serious economic burden worldwide. Gut flora is a major component of diabetes research, and the aim of this study was to understand the trends and major components of research related to diabetes and gut flora in the last 11 years. Methods: We searched the Web of Science Core Collection database for articles on diabetes and gut flora related research from 2011-2021 on July 2, 2022. The literature data were analyzed for country, institution, author, steward, journal, and highly cited literature using Citespace.5.8.R3 and Vosviewer1.6.17. Results: Finally 4834 articles that met the requirements were included. The overall trend of articles published in the last 11 years is increasing, and the trend of articles published after 2019 is increasing significantly. In total, 109 countries, 4820 institutions, and 23365 authors were involved in the field of research. The highest number of publications was 1262 articles from the United States, the institution with the most publications was the University of Copenhagen with 134 articles, and the author with the most publications was PATRICE D CANI with 52 articles. Conclusion: The number of studies related to diabetes and intestinal flora is increasing and more and more researchers are involved in this field. Intestinal flora provides a key research direction for the treatment of diabetes. In the future, gut flora will remain the focus of the diabetes field.
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Diabetes Mellitus , Microbioma Gastrointestinal , Humanos , Bibliometria , Publicações , Diabetes Mellitus/epidemiologia , Bases de Dados FactuaisRESUMO
Inflammatory bowel disease (IBD) is a chronic non-specific inflammatory disease of intestinal tract and a common digestive system disease. Current studies have shown that IBD significantly increases the incidence of colorectal cancer (CRC), and is positively correlated with the degree and extent of inflammation of IBD. The relationship between IBD and CRC has attracted extensive attention. However, the relationship between IBD and CRC has not been systematically studied by bibliometrics and visual analysis. This study conducted bibliometric analysis based on 3528 publications from the Core Collection of Web of Science to determine the research status, research hotspots and frontiers of this field. The results show that the number of publications has increased significantly over the past 10 years. The cooperative network analysis shows that the United States, Mayo Clin and Bo Shen are the country, institution and author with the most publications respectively. Belgium, Icahn Sch Med Mt Sinai and Erik Mooiweer are the most collaborative country, institution and author respectively. Analysis of keywords and references showed that inflammation, intestinal flora, and obesity were hot topics in this field. Analysis of keyword outbreaks shows that the gut microbiome and metabolism will be an emerging new research area and a potential hot spot for future research. This study is the first to visually examine the association between IBD and CRC using bibliometrics and visual analysis, and to predict potential future research trends.
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Karst groundwater is an important water resource but it is vulnerable to contaminants, due to the distinctive geological features of abundant transmissive fractures and conduits in the karst area which connect the surface to the underground systems. Anthropogenic activity-derived polycyclic aromatic hydrocarbons (PAHs) on the surface environment could enter groundwater easily and rapidly and threaten water security in karst areas. Samples in the multimedia environment from 10 specific karst spring systems from Western Hubei of Central China were collected to analyze 16 priority PAHs and to investigate their transport in these karst spring systems. The total concentrations of PAHs in the soil, river water, river sediments, spring water, and spring sediments ranged between 6.04 and 67.7 ng g-1, 4.56 and 11.4 ng L-1, 29.9 and 1041 ng g-1, 4.09 and 222 ng L-1, and 5.88 and 83.0 ng g-1, respectively. Levels of PAHs in this area were relatively low when compared to other karst areas. Proportions of low-molecular-weight (LMW)-PAHs in the water, sediments and soil (average 58.2-78.8%) were much higher than those of high-molecular-weight (HMW)-PAHs. The proportion of LMW-PAHs in the sediments (especially in river sediments) was higher than that in the soil. Characteristic ratio analysis and principal component analysis showed that PAHs were from high-temperature combustion of the mixture of coal and biomass, and vehicle emission, where coal and biomass combustion were the dominant sources. Significant correlations of PAH compositions in different media of karst spring systems were observed, especially in the Yuquangdong (YQD)-Migongquan (MGQ), Jiuzhenziquan (JZZQ), Xianyudong (XYD) and Fengdong (FD) karst spring systems, indicating the rapid PAH transport from the recharge area soil to the discharge area of spring water and sediments.
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Hidrocarbonetos Policíclicos Aromáticos , Poluentes Químicos da Água , China , Carvão Mineral/análise , Monitoramento Ambiental , Sedimentos Geológicos , Hidrocarbonetos Policíclicos Aromáticos/análise , Rios , Solo , Água/análise , Poluentes Químicos da Água/análiseRESUMO
Karst groundwater is crucial, but particularly vulnerable to contaminants. Anthropologically derived pollutants on the surface-environment in karst areas could easily and rapidly enter groundwater through highly developed transmissible structures and threaten water safety. To investigate such transport, we analyzed 24 organochlorine pesticides (OCPs) in the multimedia environment from the Zigui karst area of China, where agriculture is the predominant human activity. OCPs were frequently detected with the total OCP concentrations ranged from 228 to 7970 pg/g, 300 to 32,200 pg/L, 318 to 2250 pg/L, 149 to 2760 pg/g, and 752 to 12,000 pg/g in the soil, spring water, river water, spring sediment, and river sediment, respectively. HCB and p,p'-DDT were the most dominant OCP species. Isomeric and metabolic ratios indicated fresh inputs of Lindane, technical DDT, and Aldrin, although they have been banned in China. The spatial distributions, correlation analysis, and regression analysis suggested rapid OCP transport from the soil to the spring water, and from the soil and spring water to river water. OCPs in the soil and springs explained 92.3% and 89.0% of those in the spring water and river water, respectively. The solid transport with the fast-moving water was predominant for OCPs in sediments. Highly dynamic water systems and rapid OCP transport in the intro- and inter-medium suggested by our results substantiate the groundwater's vulnerability in karst areas. More studies on levels and transport of organic contaminants in karst systems and policy for protecting the karst groundwater are urgently required to control contaminant sources and ensure groundwater sustainability, since the karst water resources may suffer a potentially bleak future consisted of the decreased groundwater quantity and low water quality.