46 research outputs found

    Analysis of the Interactive Strategy of Microblog for Snack Food Enterprises

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    With the development of economic conditions and consumption patterns, snack foods have become the first choice in people\u27s daily diet and consumption, while the market scale is rising, snack foods have also gained high public opinion attention. The existing research results show that the micro-blog interaction effect will positively affect the sales performance, but there are few characterization studies on the effective micro-blog interaction strategy of the snack food enterprises. In this paper, the typical snack food enterprises as an example, mainly through the network crawler to collect micro-blog interactive contents, text analysis, and finally through ANOVA analysis to study the effect of different interaction strategies. The research finds that the strategy of micro-blog interaction of snack food enterprises is better. The characteristic research results of this paper possibly provide reference and enlightenment for the future research of micro-blog interaction strategy of snack food enterprises

    Spatial distribution and diversity of the heterotrophic flagellates in the Cosmonaut Sea, Antarctic

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    As predators of bacteria and viruses and as food sources for microzooplankton, heterotrophic flagellates (HFs) play an important role in the marine micro-food web. Based on the global climate change’s impact on marine ecosystems, particularly sea ice melting, we analyzed the community composition and diversity of heterotrophic flagellates, focusing on the Antarctic Cosmonaut Sea. During the 36th China Antarctic research expedition (2019-2020), we collected seawater samples, subsequently analyzing HFs through IlluminaMiSeq2000 sequencing to assess community composition and diversity. Notable variations in HFs abundance were observed between the western and eastern sectors of the Cosmonaut Sea, with a distinct concentration at a 100-meter water depth. Different zones exhibited diverse indicators and dominants taxa influenced by local ocean currents. Both the northern Antarctic Peninsula and the western Cosmonaut Sea, where the Weddell Eddy and Antarctic Land Slope Current intersect, showcased marine stramenopiles as dominant HFs species. Our findings offer insights into dominant taxa, spatial distribution patterns among heterotrophic flagellates, correlations between taxa distribution and environmental factors, and the exploration of potential indicator taxa

    Analysis of loss to follow-up in 4099 multidrug-resistant pulmonary tuberculosis patients

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    Loss to follow-up (LFU) of 2 consecutive months contributes to the poor levels of treatment success in multidrug-resistant tuberculosis (MDR-TB) reported by TB programmes. We explored the timing of when LFU occurs by month of MDR-TB treatment and identified patient-level risk factors associated with LFU. We analysed a dataset of individual MDR-TB patient data (4099 patients from 22 countries). We used Kaplan–Meier survival curves to plot time to LFU and a Cox proportional hazards model to explore the association of potential risk factors with LFU. Around one-sixth (n=702) of patients were recorded as LFU. Median (interquartile range) time to LFU was 7 (3–11) months. The majority of LFU occurred in the initial phase of treatment (75% in the first 11 months). Major risk factors associated with LFU were: age 36–50 years (HR 1.3, 95% CI 1.0–1.6; p=0.04) compared with age 0–25 years, being HIV positive (HR 1.8, 95% CI 1.2–2.7; p<0.01) compared with HIV negative, on an individualised treatment regimen (HR 0.7, 95% CI 0.6–1.0; p=0.03) compared with a standardised regimen and a recorded serious adverse event (HR 0.5, 95% CI 0.4–0.6; p<0.01) compared with no serious adverse event. Both patient- and regimen-related factors were associated with LFU, which may guide interventions to improve treatment adherence, particularly in the first 11 months

    Discovery of a novel, liver-targeted thyroid hormone receptor-β agonist, CS271011, in the treatment of lipid metabolism disorders

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    IntroductionThyroid hormone receptor β (THR-β) plays a critical role in metabolism regulation and has become an attractive target for treating lipid metabolism disorders in recent years. Thus, in this study, we discovered CS271011, a novel THR-β agonist, and assessed the safety and efficiency of CS271011 compared to MGL-3196 in vitro and in vivo. MethodsWe conducted luciferase reporter gene assays to assess the activation of THR-β and α in vitro. C57BL/6J mice were fed a high-fat diet for 12 weeks, CS271011 was administered by gavage at the dose of 1 mg/kg and 3 mg/kg, and MGL-3196 was administered at the dose of 3 mg/kg for 10 weeks. Body weight, food intake, serum and hepatic parameters, histological analysis, pharmacokinetic studies, RNA sequencing of the liver and heart, and expression of hepatic lipid-metabolic genes were determined to evaluate the safety and efficiency of CS271011. ResultsCompared with MGL-3196, CS271011 showed higher THR-β activation in vitro. In the diet-induced obesity mice model, CS271011 demonstrated favourable pharmacokinetic properties in mice and was enriched in the liver. Finally, CS271011 improved dyslipidaemia and reduced liver steatosis in the diet-induced obesity murine model. Mechanistically, CS271011 and MGL-3196 showed potent regulation of lipid metabolism-related genes. ConclusionsCS271011 is a potent and liver-targeted THR-β agonist for treating lipid metabolism disorders

    Understanding the relation between Zika virus infection during pregnancy and adverse fetal, infant and child outcomes: a protocol for a systematic review and individual participant data meta-analysis of longitudinal studies of pregnant women and their infants and children

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    IntroductionZika virus (ZIKV) infection during pregnancy is a known cause of microcephaly and other congenital and developmental anomalies. In the absence of a ZIKV vaccine or prophylactics, principal investigators (PIs) and international leaders in ZIKV research have formed the ZIKV Individual Participant Data (IPD) Consortium to identify, collect and synthesise IPD from longitudinal studies of pregnant women that measure ZIKV infection during pregnancy and fetal, infant or child outcomes.Methods and analysisWe will identify eligible studies through the ZIKV IPD Consortium membership and a systematic review and invite study PIs to participate in the IPD meta-analysis (IPD-MA). We will use the combined dataset to estimate the relative and absolute risk of congenital Zika syndrome (CZS), including microcephaly and late symptomatic congenital infections; identify and explore sources of heterogeneity in those estimates and develop and validate a risk prediction model to identify the pregnancies at the highest risk of CZS or adverse developmental outcomes. The variable accuracy of diagnostic assays and differences in exposure and outcome definitions means that included studies will have a higher level of systematic variability, a component of measurement error, than an IPD-MA of studies of an established pathogen. We will use expert testimony, existing internal and external diagnostic accuracy validation studies and laboratory external quality assessments to inform the distribution of measurement error in our models. We will apply both Bayesian and frequentist methods to directly account for these and other sources of uncertainty.Ethics and disseminationThe IPD-MA was deemed exempt from ethical review. We will convene a group of patient advocates to evaluate the ethical implications and utility of the risk stratification tool. Findings from these analyses will be shared via national and international conferences and through publication in open access, peer-reviewed journals.Trial registration numberPROSPERO International prospective register of systematic reviews (CRD42017068915).</jats:sec

    Drug-induced adverse events in the treatment of multidrug-resistant tuberculosis and quantification of between-study heterogeneity: an individual participant data meta-analysis of observational studies

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    Multidrug-resistant tuberculosis (MDR-TB), defined as tuberculosis (TB) that is resistant to at least isoniazid and rifampin, has become a major threat to global TB control. MDR-TB treatment requires prolonged usage of multiple second-line TB drugs, which are generally less effective and more toxic than first-line TB drugs. Since the majority of the published studies of MDR-TB treatment have observational designs, individual participant data meta-analysis (IPD-MA) is a useful tool to assess the drug efficacy and toxicity in MDR-TB therapy. In 2016, we assembled a database of 50 studies with 12,030 patients which contains detailed individual level data of patient characteristics, treatment regimens, adverse events (AEs) and outcomes.In the first study of this thesis, we analyzed drug-induced AEs that resulted in permanent discontinuation of anti-tuberculosis medications. Meta-analysis for proportions and arm-based network meta-analysis were conducted to estimate the incidence of AEs for each TB drug. A ranking-based non-parametric approach was used to assess the relative toxicity among different drugs. 30 studies with 8970 patients were included in the analyses. Using meta-analysis of proportions, low risks of AE occurrence were estimated for levofloxacin (1.1%, 95% confidence interval 0.2-5.7), moxifloxacin (2.8%, 1.5-5.1), bedaquiline 1.5% (0.6-4.1) and clofazimine (1.8%, 0.5-6.3). Relatively high toxicity was seen in all three second-line injectable drugs (amikacin: 7.4%, 4.6-11.6; kanamycin: 7.5%, 4.6-11.9; capreomycin: 7.7%, 5.7-10.2), as well as with PAS (9.8%, 6.2-15.2) and linezolid (13.7%, 9.2-19.8). Similar findings were observed in the arm-based network meta-analysis and the ranking-based approach. Although the analyses were limited by the observational design and the between-study differences in the definitions, diagnosis and management of AEs, all three analytic approaches demonstrated that fluoroquinolones, clofazimine, and bedaquiline were the safest drugs, while second-line injectable drugs, PAS and linezolid were the most toxic drugs.In the second study of this thesis, we quantified and evaluated four commonly used heterogeneity metrics in a one-stage IPD-MA using random effects multivariable logistic regression to estimate the association of use of individual TB drugs and treatment success. Unadjusted and four sets of adjusted analyses were performed. τ2, R and 95% prediction interval were derived from the model, and I2 was estimated using a simulation-based approach based on its similarity with the intraclass correlation coefficient. All measures indicated the presence of between-study variation in the one-stage IPD-MA. However, the simulation-based I2 showed a consistent trend to decrease with greater adjustment for confounding, but no such trend was observed for the τ2, R and 95% prediction interval. Compared to the I2 estimated in the two-stage approach, the I2 estimated in the one-stage approach correlated with the forest plots but was consistently higher. Although future validations are necessary, we believe that the I2 may be a useful metric in quantifying heterogeneity in one-stage IPD-MA.Tuberculose multirésistante (TB-MR), est défini comme le tuberculose (TB) qui est résistante au moins aux médicaments d'isoniazide et rifampine, est le TB-MR est devenu une menace pour le control du TB mondiale. TB-MR demande l'utilisation prolongé des médicaments antituberculeux de deuxième intention qui sont normalement moins efficace et plus toxique que des antituberculeux de première intention. Car la plupart des études du TB-MR qui ont étaient publiés sont du design observationnel un méta-analyse des données des participants individuelle (IPD-MA) est utile pour évaluer l'efficacité et toxicité des thérapies du TB-MR. En 2016 nous avons assemblés une base des données de 50 études y compris des détails pour des caractéristiques, traitements, des événements indésirables et des résultats de chaqu'un des 12,030 patients.Dans la première étude qui fait partie de cette thèse, nous avons analyser des résultats des événements indésirables qui sont résulter dans l'arrêt permanent des médicaments antituberculeux. Un méta-analyse des proportions et un méta-analyse des branches du réseau ont étaient faites pour estimer l'incidence des événements indésirables pour chaque médicament antituberculeux. Un système basé sur le rang qui est non-paramétrique était utiliser pour estimer la toxicité parmi des médicaments différents. Trente études avec 8970 patients ont étaient inclus dans l'analyse. En utilisant le méta-analyse des proportions, des faibles risques de l'occurrence des événements indésirables ont été estimer pour lévofloxacine (1.1%, 95% intervalle de confiance 0.2-5.7), moxifloxacine (2.8%, 1.5-5.1), bedaquiline 1.5% (0.6-4.1) et clofazimine (1.8%, 0.5-6.3). Une toxicité élevée était vue en tous les trois médicaments antituberculeux injectable de deuxième intention (amikacine: 7.4%, 4.6-11.6; kanamycine: 7.5%, 4.6-11.9; capréomycine: 7.7%, 5.7-10.2), et aussi avec PAS (9.8%, 6.2-15.2) et linézolide (13.7%, 9.2-19.8). Conclusions similaires ont été observer dans le méta-analyse des branches du réseau et le système basé sur le rang. Bien que les analyses étaient limitées par le design observationnel et l'entre- étude différence dans les définitions, le diagnostic et la gestion des événements indésirables, les trois approches analytiques ont démontré que les fluoroquinolones, clofazimine, and bedaquiline sont les médicaments le plus sûr tandis que les médicaments antituberculeux injectable de deuxième intention, PAS et linezolid sont les médicaments le plus toxique. Dans la deuxième étude qui fait partie de cette thèse, nous avons quantifié et évalué quatre métriques d'hétérogénéité couramment utilisées dans un méta-analyse des données des participants individuelle en utilisant un régression logistique multivariée à effets aléatoires pour estimer l'association avec l'utilisation des médicaments antituberculeux individuels et le succès du traitement. Des analyses non ajustées et quatre séries d'ajustées ont été fait. τ2, R et le 95% intervalle de prédiction ont été dérivés parmi le model, et I2 était estimer par une approche basée sur la simulation fondé sur la similarité avec le coefficient de corrélation intraclasse. Toutes les mesures ont indiqué la présence de variations inter-études dans l'IPD-MA d'une étape. Néanmoins l'I2 basée sur la simulation ont démontré une tendance constante à diminuer avec un ajustement plus important pour les facteurs de confounding il n'y avait pas la même tendance pour le τ2, R et le 95% intervalle de prédiction. Par rapport à l'estimation I2 dans l'approche en deux étapes, l'estimation I2 d'une étape était corrélé avec des « forest plots » mais était régulièrement plus haut. Bien que des validations dans l'avenir sont nécessaire, nous croyons que l'I2 peut être une mesure utile pour quantifier l'hétérogénéité dans IPD-MA d'une étape

    The role of DELLA proteins in plant-insect interactions

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    Jasmonates (JAs) play a major role in plant defense against herbivores while some caterpillar species use effectors in their labial saliva to suppress the induction of JA-mediated defense responses. On the other hand, activation of plant defense is associated with slowed plant growth which is controlled by gibberellins (GA) and growth repressor DELLA proteins. Recent studies have shown that DELLA proteins play an important role in plant stress response and are involved in the crosstalk between JA and GA pathways. However, the role of DELLA proteins in plant-insect interactions remains unclear. In this study, wild-type Arabidopsis, wild-type sprayed with GA and a quadruple-della Arabidopsis mutant (quad-della) were subject to herbivory by beet armyworm Spodoptera exigua caterpillars with either intact or impaired labial salivary secretions. Wild-type Arabidopsis, Arabidopsis + GA and the quad-della mutant showed a JA burst in response to herbivory. This was reflected in increased transcript levels of the JA-dependent gene markers, such as AtPDF1.2, AtLOX2 and AtVSP2. A caterpillar saliva-specific pattern of JA hormone levels (JA, JA-isoleucine, OPDA) were observed in the wild-type background but not in the quad-della mutant, suggesting that DELLAs are involved in plant response to caterpillar saliva, probably by mediating the crosstalk between JA- and salicylic acid (SA)-dependent pathways. Additionally, high constitutive expression of the SA pathway marker gene AtPR1 was observed in the quad-della mutant but not in wild-type Arabidopsis, which indicates that DELLAs play a role in maintaining the homeostasis of SA signalling by repressing its constitutive induction.Les Jasmonates (JAs) font une partie importante dans la défense des plantes contre les herbivores. Certaines espèces de chenilles utilisent des effecteurs dans leur salive labiale pour supprimer l'induction de réponses de défense induites par les JAs. En revanche, l'activation de défense de la plante est associée au ralentissement de la croissance des plantes. La croissance des plantes est contrôlée par les gibbérellines (GA) et les répresseurs de la croissance, les protéines DELLA. Des études récentes ont montré que les protéines DELLA font partie de la réponse des plantes au stress et participent à la diaphonie entre les voies métaboliques du JA et GA. Cependant, le rôle des protéines DELLA reste incertain. Dans cette étude, Arabidopsis type sauvage, Arabidopsis type sauvage traités avec une pulvérisation du GA, et le mutant quadruple-della (quad-della) souffert des attaques par le herbivore Spodoptera exigua. Les chenilles sont normales ou avec les facultés affaiblies dans les glandes salivaires. Les trois groupes des plantes ont montré une explosion du JA en réponse aux herbivores. Cette réponse a été reflétée dans les niveaux de transcription des gènes dépendant de JA, comme AtPDF1.2, AtLOX2 et AtVSP2. Un motif spécifique à la salive des niveaux des hormones JA (JA, JA-isoleucine, OPDA) a été observé dans le type sauvage mais pas dans les mutants. Ce résultat suggère que DELLAs sont impliquées dans la réponse de la plante à la salive probablement par la médiation de la diaphonie entre les voies métaboliques du JA et du acide salicylique (SA). Ailleurs, une forte expression du gène AtPR1, qui est partie de la voie d'SA, a été observé dans le mutant quad-della. Ce résultat suggère que DELLAs sont impliquées dans l'homéostasie de la signalisation de SA en réprimant son expression constitutive

    A Computationally Efficient Model for FDSOI MOSFETs and Its Application for Delay Variability Analysis

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    This paper proposes a compact, physics-based current model for fully depleted silicon-on-insulator (FDSOI) MOSFETs and applies it to delay variability analysis. An analytical method is applied to avoid the numerical iterations required in the evaluation of surface potential, which directly improves the computational efficiency. The accuracy of the explicit surface potential approximation is 190.3 nV, which allows for fast convergence. Surface potential and current calculations achieve 1.8&times; and 1.4&times; acceleration compared with BSIM-IMG, respectively. To establish the relationship between delay and underlying process parameters, we introduce the effective current and propose a process variation-aware delay prediction model. Higher-order derivatives are calculated to compensate the nonlinearity of delay variations with respect to process parameters. Experiments show a significant improvement in the prediction accuracy with higher-order derivatives, which are proved to be able to handle nonlinearity under process variations. The front gate work function contributes the most to the nonlinearity of the delay variation and the accuracy of the third-order prediction is 4.07%. Under the variation in the channel length and width, front and back gate oxide thickness and body thickness, delay variations have similar characteristics and the second-order prediction is found to be sufficient to model the nonlinearity with a maximum relative error of 1.22%. The delay prediction model only requires a single-point HSPICE DC or transient simulation and is universal for different voltages and different cells. Compared with the Monte Carlo (MC) simulation, the accuracy of the first-order prediction in the above-threshold region (0.8 V) is 0.94%. In the sub-threshold region (0.3 V), a prediction accuracy of 2.01% can be obtained while achieving a 21&times; reduction in computational time

    DELLA proteins modulate Arabidopsis defences induced in response to caterpillar herbivory

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    Upon insect herbivory, many plant species change the direction of metabolic flux from growth into defence. Two key pathways modulating these processes are the gibberellin (GA)/DELLA pathway and the jasmonate pathway. In this study, the effect of caterpillar herbivory on plant-induced responses was compared between wild-type Arabidopsis thaliana (L.) Heynh. and quad-della mutants that have constitutively elevated GA responses. [...] Early expression of the salicylic acid (SA)-marker gene, AtPR1, was not affected by herbivory which also reflected SA hormone levels; however, this gene showed LS-dependent expression in the quad-della mutant. DELLA proteins may positively regulate glucosinolate levels and suppress laccase-like multicopper oxidase activity in response to herbivory. The present results show a link between DELLA proteins and early, induced plant defences in response to insect herbivory; in particular, these proteins are necessary for caterpillar LS-associated attenuation of defence hormones

    Effects of Simulated In Vitro Digestion on the Structural Characteristics, Inhibitory Activity on α-Glucosidase, and Fermentation Behaviours of a Polysaccharide from <i>Anemarrhena asphodeloides</i> Bunge

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    The purpose of this study is to investigate the effects of the simulated saliva–gastrointestinal digestion of AABP-2B on its structural features, inhibitory α-glucosidase activity, and human gut microbiota. The salivary–gastrointestinal digestion results show that there is no significant change in the molecular weight of AABP-2B, and no free monosaccharides are released. This indicates that, under a simulated digestive condition, AABP-2B is not degraded and can be further utilized by gut microbiota. AABP-2B still possessed good inhibitory activity on α-glucosidase after salivary–gastrointestinal digestion, which may be attributed to the largely unchanged structural characteristics of AABP-2B after simulated digestion. Furthermore, in vitro fecal fermentation with AABP-2B after salivary–gastrointestinal digestion showed that AABP-2B modulated the gut microbiota structure and increased the relative proportions of Prevotella, Faecalibacterium, and Megasphaera. AABP-2B can also modify the intestinal flora composition by inhibiting pathogen growth. Moreover, the AABP-2B group resulted in a significant increase in short-chain fatty acid (SCFAs) content during fermentation. These findings demonstrate that AABP-2B can be used as a prebiotic or functional food to promote gut health
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