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Introduction Endothelial cells act as a physical barrier for the vessel intima, and produce various factors, including nitric oxide ([NO.sup.*]) and interleukin-8 (IL-8) that regulate vascular tone, blood flow, and [...], Oxidized low density lipoprotein (oxLDL) induced injury of endothelial cells is considered to be the first step in the pathogenesis of atherosclerosis. This study aimed to investigate some of the effects and mechanisms of puerarin on oxLDL-induced endothelial injuries. We measured cell viability, and the release of lactate dehydrogenase (LDH), nitric oxide (NO), and interleukin-8 (IL-8) to evaluate the protective effects of puerarin. Intracellular reactive oxygen species (ROS) were detected using 2',7'-dichlorofluorescein diacetate (DCFH-DA). The expression of lectin-like low-density lipoprotein receptor-1 (LOX-1), endothelial nitric oxide synthase (eNOS), cyclooxygenase 2 (COX-2), p38MAPK, and protein kinase B (PKB) phosphorylation, nuclear factor-κB (NF-κB) nuclear translocation, and inhibitor of κB(IκB) degradation were detected using quantitative real-time PCR or Western blot. The results showed that oxLDL significantly decreased cell viability, increased LDH and IL-8 release, inhibited NO production, and induced COX-2 expression. Pretreatment with puerarin led to a strong inhibition of these effects. OxLDL stimulated the expression of LOX-1, the overproduction of ROS, the phosphorylation of p38MAPK, the dephosphorylation of PKB, activation of NF-κB, and the degradation of IκB. These oxLDL-induced effects were suppressed after puerarin pretreatment. These results suggest that puerarin inhibits oxLDL-induced endothelial cell injuries, at least in part, via inhibition of the LOX-1mediated p38MAPK-NF-κB inflammatory and the PKB-eNOS signaling pathways. Key words: puerarin, endothelial cells, atherosclerosis, lectin-like low-density lipoprotein receptor-1, eNOS. On considere que les dommages endotheliaux induits par les lipoproteines de faible densite oxydees (oxLDL) constituent la premiere etape de la pathogenese de l'atherosclerose. La presente etude vise a examiner certains effets et les mecanismes d'action de la puerarine sur les dommages endotheliaux induits par les oxLDL. La viabilite cellulaire ainsi que la liberation de lactate deshydrogenase (LDH), d'oxyde nitrique (NO) et d'interleukine-8 (IL-8) ont ete mesures afin d'evaluer les effets protecteurs de la puerarine. Les especes reactives d'oxygene intracellulaires (ERO) ont ete detectees a l'aide de di-acetate de 2'-7'-dichlorofluoresceine (DCFH-DA). L'expression du recepteur LOX-1 (lectin-like low-density lipoprotein receptor-1), de la synthase d'oxyde nitrique endotheliale (eNOS) et de la cyclooxygenase 2 (COX-2), ainsi que la phosphorylation de la p38 MAPK et de la proteine kinase B (PKB), la translocation du NF-κB et la degradation de IκB ont ete detectees par QPCR ou par buvardage Western. Les resultats ont montre que le traitement aux oxLDL diminuait significativement la viabilite cellulaire, accroissait la liberation de LDH et d'IL-8, inhibait la production de NO et induisait l'expression de COX-2. Un pretraitement a la puerarine inhibait de facon importante ces effets induits par les oxLDL. Les oxLDL stimulaient l'expression de LOX-1, la surproduction d'ERO, la phosphorylation de p38 MAPK, la dephosphorylation de PKB, l'activation de NF-κB et la degradation de IκB. Ces effets induits par les oxLDL etaient abolis par le pretraitement a la puerarine. Ces resultats suggerent que la puerarine inhibe les dommages endotheliaux induits par les oxLDL, du moins en partie, par l'inhibition de la voie inflammatoire p38 MAPK-NF-κB et de la voie de signalisation PKB-eNOS dependantes de LOX-1. [Traduit par la Redaction] Mots-cles: puerarine, cellules endotheliales, atherosclerose, recepteur LOX-1, eNOS.

To improve the accuracy of the financial early warning of the company, aiming at defects of slow learning speed, trapped in local solution and inaccurate operating result of the traditional BP neural network with random initial weights and thresholds, a parallel ensemble learning algorithm based on improved harmony search algorithm using good point set (GIHS) optimize the BP_Adaboost is proposed. Firstly, the good-point set is used to construct a more high quality initial harmony library, and it adjusts the parameters dynamically during the search process and generates several solutions in each iteration so as to make full use of information of harmony memory to improve the global search ability and convergence speed of algorithm. Secondly, ten financial indicators are chosen as the inputs of BP neural network value, and GIHS algorithm and BP neural network are combined to construct the parallel ensemble learning algorithm to optimize BP neural network initial weights value and output threshold value. Finally, many of these weak classifier is composed as strong classifier through the AdaBoost algorithm. The improved algorithm is validated in the company's financial early warning. Simulation results show that the performance of GIHS algorithm is better than the basic HS and IHS algorithm, and the GIHS-BP_AdaBoost classifier has higher classification and prediction accuracy.

Background: Tracheobronchopathia osteochondroplastica (TO) is a rare idiopathic disease with a stable course that involves the mucous membrane of the tracheobronchial tree. Most cases present no specific symptoms, and there are currently no established guidelines for diagnosis and treatment. In this report, we discuss a single case of a patient with TO who was diagnosed based on clinical imaging and histopathology. Case Summary: A patient with a history of smoking and alcohol consumption, but no specific clinical symptoms, was diagnosed with TO after undergoing fiber-optic bronchoscopy. Nodular processes with smooth surface mucosa and detached bronchial mucosa were observed. The presence of TO was confirmed by pathological examination. Conclusion: The diagnosis of TO is difficult, and early fiber-optic bronchoscopy and pathological examination should be performed to facilitate the diagnosis. [ABSTRACT FROM AUTHOR]

The main proteases (Mpro), also termed 3‐chymotrypsin‐like proteases (3CLpro), are a class of highly conserved cysteine hydrolases in β‐coronaviruses. Increasing evidence has demonstrated that 3CLpros play an indispensable role in viral replication and have been recognized as key targets for preventing and treating coronavirus‐caused infectious diseases, including COVID‐19. This review is focused on the structural features and biological function of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) main protease Mpro (also known as 3CLpro), as well as recent advances in discovering and developing SARS‐CoV‐2 3CLpro inhibitors. To better understand the characteristics of SARS‐CoV‐2 3CLpro inhibitors, the inhibition activities, inhibitory mechanisms, and key structural features of various 3CLpro inhibitors (including marketed drugs, peptidomimetic, and non‐peptidomimetic synthetic compounds, as well as natural compounds and their derivatives) are summarized comprehensively. Meanwhile, the challenges in this field are highlighted, while future directions for designing and developing efficacious 3CLpro inhibitors as novel anti‐coronavirus therapies are also proposed. Collectively, all information and knowledge presented here are very helpful for understanding the structural features and inhibitory mechanisms of SARS‐CoV‐2 3CLpro inhibitors, which offers new insights or inspiration to medicinal chemists for designing and developing more efficacious 3CLpro inhibitors as novel anti‐coronavirus agents. [ABSTRACT FROM AUTHOR]

Abstract Background Systematic research on fish immunogenetics is indispensable in understanding the origin and evolution of immune systems. This has long been a challenging task because of the limited number of deep sequencing technologies and genome backgrounds of non-model fish available. The newly developed Solexa/Illumina RNA-seq and Digital gene expression (DGE) are high-throughput sequencing approaches and are powerful tools for genomic studies at the transcriptome level. This study reports the transcriptome profiling analysis of bacteria-challenged Lateolabrax japonicus using RNA-seq and DGE in an attempt to gain insights into the immunogenetics of marine fish. Results RNA-seq analysis generated 169,950 non-redundant consensus sequences, among which 48,987 functional transcripts with complete or various length encoding regions were identified. More than 52% of these transcripts are possibly involved in approximately 219 known metabolic or signalling pathways, while 2,673 transcripts were associated with immune-relevant genes. In addition, approximately 8% of the transcripts appeared to be fish-specific genes that have never been described before. DGE analysis revealed that the host transcriptome profile of Vibrio harveyi-challenged L. japonicus is considerably altered, as indicated by the significant up- or down-regulation of 1,224 strong infection-responsive transcripts. Results indicated an overall conservation of the components and transcriptome alterations underlying innate and adaptive immunity in fish and other vertebrate models. Analysis suggested the acquisition of numerous fish-specific immune system components during early vertebrate evolution. Conclusion This study provided a global survey of host defence gene activities against bacterial challenge in a non-model marine fish. Results can contribute to the in-depth study of candidate genes in marine fish immunity, and help improve current understanding of host-pathogen interactions and evolutionary history of immunogenetics from fish to mammals.

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Mobile edge computing is a new paradigm which provides cloud computing capabilities at the edge of pervasive radio access networks in close proximity to users. The problem of edge server selection in mobile edge environment in terms of user's overhead is investigated in this paper. Due to the limited resources of edge server, we firstly study the task completion probability of edge servers. Secondly, we formally model the problem of edge server selection in terms of time latency and energy consumption. More especially, the computation overhead method for completing the task in cases of both service migration and non-migration is investigated. Then, a new optimized edge server selection algorithm, called combined Genetic algorithm and simulated Annealing algorithm for edge Server Selection (GASS) is designed. Finally, a series of experiments on a real-word data-trace are conducted to evaluate the performance of GASS. The results show that GASS can effectively minimize the overhead of the user and outperform traditional heuristic algorithms. [ABSTRACT FROM AUTHOR]

A functional association is uncovered between the ribosome-associated trigger factor (TF) chaperone and the ClpXP degradation complex. Bioinformatic analyses demonstrate conservation of the close proximity of tig, the gene coding for TF, and genes coding for ClpXP, suggesting a functional interaction. The effect of TF on ClpXP-dependent degradation varies based on the nature of substrate. While degradation of some substrates are slowed down or are unaffected by TF, surprisingly, TF increases the degradation rate of a third class of substrates. These include λ phage replication protein λO, master regulator of stationary phase RpoS, and SsrA-tagged proteins. Globally, TF acts to enhance the degradation of about 2% of newly synthesized proteins. TF is found to interact through multiple sites with ClpX in a highly dynamic fashion to promote protein degradation. This chaperone–protease cooperation constitutes a unique and likely ancestral aspect of cellular protein homeostasis in which TF acts as an adaptor for ClpXP. ClpXP is the main ATP-dependent proteolytic complex in bacteria, is essential for maintaining cellular protein homeostasis and is also critical for bacterial pathogenesis. Here, the authors establish a functional link between ClpXP and trigger actor, a chaperone involved in the early stages of protein folding. [ABSTRACT FROM AUTHOR]

Background: Surgical treatment is indicated for unstable acromioclavicular (AC) joint dislocation. The hook plate (HP) technique is a commonly used treatment method, but the use of the suture button (SB) technique is increasing. Purpose: To conduct a meta-analysis of clinical studies evaluating patient outcomes between the SB and HP techniques for acute unstable AC joint dislocation. Study Design: Meta-analysis. Methods: A literature search of the Embase, PubMed, and Cochrane Library databases was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Cohort studies and case-control studies comparing the SB and HP procedures for acute unstable AC joint dislocation were included. Statistical analysis was performed with RevMan (v 5.3.5). Results: Eight clinical studies that met the inclusion criteria were identified and included a total of 204 patients treated with the SB technique and 195 patients with the HP technique. Patients treated with the SB technique had a higher Constant score (mean difference [MD], 3.95; 95% CI, 1.20-6.70; P =.005) and a lower visual analog scale pain score (MD, –0.75; 95% CI, –1.12 to 0.37; P <.0001) when compared with the HP technique. No significant differences in operation time (MD, –0.38; 95% CI, –7.14 to 6.37; P =.91), coracoclavicular distance (MD, –0.07; 95% CI, –0.49 to 0.35; P =.75), complications (odds ratio, 0.59; 95% CI, 0.22-1.54; P =.28), and loss of reduction (odds ratio, 2.55; 95% CI, 0.66-9.83; P =.17) were found between the SB and HP techniques. The subgroup analysis showed that the arthroscopic SB technique resulted in a higher Constant score (MD, 6.75; 95% CI, 4.21-9.29; P <.00001) as compared with the HP technique, but no differences were observed between the open SB and HP techniques (MD, 0.69; 95% CI, –0.82 to 2.20; P =.37). Conclusion: This meta-analysis demonstrated that the SB technique resulted in better functional outcomes and a reduced visual analog scale pain score when compared with the HP technique. However, for operation time, coracoclavicular distance, complications, and loss of reduction, there were no statistically significant differences between the techniques. Compared with the open procedure, arthroscopic SB may be superior for better functional outcomes. [ABSTRACT FROM AUTHOR]