The NLRP3 inflammasome is a well-studied target for the treatment of multiple inflammatory diseases, but how to promote the current therapeutics remains a large challenge. CRISPR/Cas9, as a gene editing tool, allows for direct ablation of NLRP3 at the genomic level. In this study, we screen an optimized cationic lipid-assisted nanoparticle (CLAN) to deliver Cas9 mRNA (mCas9) and guide RNA (gRNA) into macrophages. By using CLAN encapsulating mCas9 and gRNA-targeting NLRP3 (gNLRP3) (CLANmCas9/gNLRP3), we disrupt NLRP3 of macrophages, inhibiting the activation of the NLRP3 inflammasome in response to diverse stimuli. After intravenous injection, CLANmCas9/gNLRP3 mitigates acute inflammation of LPS-induced septic shock and monosodium urate crystal (MSU)-induced peritonitis. In addition, CLANmCas9/gNLRP3 treatment improves insulin sensitivity and reduces adipose inflammation of high-fat-diet (HFD)-induced type 2 diabetes (T2D). Thus, our study provides a promising strategy for treating NLRP3-dependent inflammatory diseases and provides a carrier for delivering CRISPR/Cas9 into macrophages.

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The volume–volatility relationship during the dissemination stages of information flow is examined by analyzing various theories relating volume and volatility as complementary rather than competing models. The mixture of distributions hypothesis, sequential arrival of information hypothesis, the dispersion of beliefs hypothesis, and the noise trader hypothesis all add to the understanding of how volume and volatility interact for different types of futures traders. An integrated picture of the volume–volatility relationship is provided by investigating the dynamic linear and nonlinear associations between volatility and the volume of informed (institutional) and uninformed (the general public) traders. In particular, the trading behavior explanation for the persistence of futures volatility, the effect of the timing of private information arrival, and the response of institutional traders to excess noise trading risk is examined. © 2008 Wiley Periodicals, Inc. Jrl Fut Mark 28:963–992, 2008

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BackgroundRoutine non-therapeutic antimicrobial use and overcrowding in animal farming may facilitate the propagation of methicillin-resistant Staphylococcus aureus (MRSA). This study aimed to examine the carriage prevalence and phenotype–genotype characteristics of MRSA and methicillin-susceptible S. aureus isolated from pigs.MethodsNasal swabs were collected from 1,458 pigs in 9 pig farms and 3 slaughterhouses. All strains were tested for antimicrobial susceptibility, resistance genes, and virulence genes, and characterized by multilocus sequence typing. The correspondence analysis was conducted to explore the relationships between multiple phenotypic and molecular characteristics of S. aureus isolates.ResultsIn the 1,458 pigs, the carriage prevalence was 9.5% for S. aureus, 3.3% for MRSA, and 9.3% for multidrug-resistant S. aureus. Notably, 97.1% S. aureus isolates were multidrug resistant, and the predominant resistance pattern was non-susceptible to clindamycin, tetracycline, and erythromycin. The predominant genotype was CC9 (ST9) for S. aureus and MRSA isolates. Importantly, all S. aureus isolates were negative for the scn gene and resistant to tetracycline. Notably, all 9 linezolid-resistant isolates were classified as multidrug resistance, including 1 expressing the cfr gene and 6 expressing the optrA gene. The correspondence analysis showed a significant relationship between clonal complexes and resistance pattern or virulence genes. For example, CC9 was associated with extensive drug-resistance and co-carrying chp, sak, and hlb, and CC1 was associated with multidrug resistance and co-carrying sak and hlb.ConclusionThe significant correspondence relationship between multiple characteristics provides some implication for vaccine strategies and new ideas for monitoring new epidemiologic clones.

This article examines the characteristics of key measures of volatility for different types of futures contracts to provide a better foundation for modeling volatility behavior and derivative values. Particular attention is focused on analyzing how different measures of volatility affect volatility persistence relationships. Intraday realized measures of volatility are found to be more persistent than daily measures, the type of GARCH procedure used for conditional volatility analysis is critical, and realized volatility persistence is not coherent with conditional volatility persistence. Specifically, although there is a good fit between the realized and conditional volatilities, no coherence exists between their degrees of persistence, a counterintuitive finding that shows realized and conditional volatility measures are not a substitute for one another.

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Summary Background Group B streptococcus (GBS), which asymptomatically colonises the vaginal and rectal areas of women, is a leading cause of neonatal mortality and morbidity. This study aimed to determine the prevalence and factors associated with GBS colonisation among pregnant women in Shenzhen, China. Methods A hospital‐based cross‐sectional survey was conducted, using a multistage sampling method. Pregnant women at ≥28 weeks’ gestation completed a questionnaire and vaginal swabs were obtained for GBS analysis. Data were analysed by chi‐squared tests and logistic regression models. Results The colonisation rate of GBS among pregnant women was 4.9%. The influencing factors associated with GBS colonisation included body mass index before pregnancy (odds ratio [OR] = 3.79, 95% CI 1.28‐11.26), gestational age (OR = 5.81, 95% CI 1.20‐28.15), induced abortion (OR = 0.63, 95% CI 0.40‐0.98) and lotion use before pregnancy (OR = 1.59, 95% CI 1.04‐2.44). Conclusions Our findings suggest that obesity, gestational age, induced abortion and lotion use were significantly associated with GBS colonisation. Further longitudinal research is needed to establish the causal relationship and its biological mechanisms.