Elevated expression of AhR and NLRP3 link polycyclic aromatic hydrocarbon exposure to cytokine storm in preschool children

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs), as a group of persistent organic pollutants, are linked to impaired immune function and low-grade inflammation in adults and children. However, the potential of PAHs to lead to a cytokine storm associated with AhR (aryl hydrocarbon receptor) and NLRP3 (NLR family pyrin domain containing 3) in humans has been poorly studied. OBJECTIVES: We aimed to investigate the associations between PAH exposure, AhR and NLRP3 expression, and cytokines associated with a cytokine storm in healthy preschoolers. METHODS: Basic demographic surveys and physical examinations were conducted on 248 preschoolers from an electronic waste (e-waste) recycling area (Guiyu, n = 121) and a reference area (Haojiang, n = 127). Ten urinary PAH metabolite (OH-PAH) concentrations were measured. We also measured the expression levels of AhR and NLRP3 and seventeen serum cytokine levels. RESULTS: The concentrations of multiple OH-PAHs were significantly higher in the exposed group than those in the reference group, especially 1-hydroxynaphthalene (1-OH-Nap) and 2-hydroxynaphthalene (2-OH-Nap). PAH exposure was closely related to a child's living environment and hygiene habits. Expression levels of AhR and NLRP3 were significantly higher in the exposed group than in the reference group. Similarly, serum IL-1β, IL-4, IL-5, IL-10, IL-12p70, IL-13, IL-17A, IL-18, IL-22, IL-23, and IFN-γ levels were notably higher in the e-waste-exposed children than in the reference children. After adjusting for age, gender, BMI, family income, parental education level, and second-hand smoke exposure, we found that increased PAH exposure was associated with higher AhR and NLRP3 expression and elevated IL-4, IL-10, IL-12p70, IL-18, IL-22, IL-23, TNF-α, and IFN-γ levels. The associations between PAH exposure and IL-1β, IL-18, IFN-γ, and TNF-β were mediated by NLRP3 expression, and the relationships between PAH exposure and IL-4, IL-10, IL-12p70, IL-22, IL-23, and TNF-α were mediated by AhR expression. CONCLUSIONS: Our findings suggest that the association between PAH exposure and a cytokine storm may be mediated by AhR and NLRP3 expression among preschoolers

Downregulation of hypoxia-inducible factor-1α by RNA interference alleviates the development of collagen-induced arthritis in rats

Rheumatoid arthritis (RA) is the most common type of autoimmune arthritis. Hypoxia-inducible factor-1α (HIF-1α) as a transcription factor in response to hypoxia suggests that it could be a potential therapeutic target for the treatment of RA. In this study, we assessed whether the HIF pathway blockade attenuates the manifestations of RA in the collagen-induced arthritis (CIA) rat model. We constructed a short hairpin RNA (shRNA) lentiviral expression vector targeting HIF-1α (pLVX-shRNA-HIF-1α) and to achieve HIF-1α RNA interference. Quantitative RT-PCR, immunofluorescence staining, and western blot were used to detect the expressions of HIF-1α, vascular endothelial growth factor (VEGF), phsopho (p)-p65, and p-IКBɑ mRNA and protein, respectively. Micro-computed tomography was used to investigate joint morphology at different time points after CIA induction. Moreover, enzyme-linked immunosorbent assay (ELISA) was used to monitor the expression of inflammatory cytokines. In vitro analyses revealed that pLVX-shRNA-HIF-1α effectively inhibited the expression of HIF-1α and VEGF and led to the activation of p-65 and p-IКBɑ, as well as decreased proinflammatory cytokine expression in cell culture. Inhibition of HIF-1α in rats decreased signs of a systemic inflammatory condition, together with decreased pathological changes of RA. Moreover, downregulation of HIF-1α expression markedly reduced the synovitis and angiogenesis. In conclusion, we have shown that pharmacological inhibition of HIF-1 may improve the clinical manifestations of RA

Multidelay multiparametric arterial spin labeling perfusion MRI and mild cognitive impairment in early stage Parkinson's disease.

Mild cognitive impairment (MCI), a well-defined nonmotor manifestation of Parkinson's disease (PD), greatly impairs functioning and quality of life. However, the contribution of cerebral perfusion, quantified by arterial spin labeling (ASL), to MCI in PD remains poorly understood. The selection of an optimal delay time is difficult for single-delay ASL, a problem which is avoided by multidelay ASL. This study uses a multidelay multiparametric ASL to investigate cerebral perfusion including cerebral blood flow (CBF) and arterial transit time (ATT) in early stage PD patients exhibiting MCI using a voxel-based brain analysis. Magnetic resonance imaging data were acquired on a 3.0 T system at rest in 39 early stage PD patients either with MCI (PD-MCI, N = 22) or with normal cognition (PD-N, N = 17), and 36 age- and gender-matched healthy controls (HCs). CBF and ATT were compared among the three groups with SPM using analysis of variance followed by post hoc analyses to define regional differences and examine their relationship to clinical data. PD-MCI showed prolonged ATT in right thalamus compared to both PD-N and HC, and in right supramarginal gyrus compared to HC. PD-N showed shorter ATT in left superior frontal cortex compared to HC. Prolonged ATT in right thalamus was negatively correlated with the category fluency test (p = .027, r = -0.495) in the PD-MCI group. This study shows that ATT may be a more sensitive marker than CBF for the MCI, and highlights the potential role of thalamus and inferior parietal region for MCI in early stage PD

Genome-Wide Association Study for Adult-Plant Resistance to Stripe Rust in Chinese Wheat Landraces (Triticum aestivum L.) From the Yellow and Huai River Valleys

Stripe rust (also known as yellow rust), caused by the pathogen Puccinia striiformis f. sp. tritici (Pst), is a common and serious fungal disease of wheat (Triticum aestivum L.) worldwide. To identify effective stripe rust resistance loci, a genome-wide association study was performed using 152 wheat landraces from the Yellow and Huai River Valleys in China based on Diversity Arrays Technology and simple sequence repeat markers. Phenotypic evaluation of the degree of resistance to stripe rust at the adult-plant stage under field conditions was carried out in five environments. In total, 19 accessions displayed stable, high degrees of resistance to stripe rust development when exposed to mixed races of Pst at the adult-plant stage in multi-environment field assessments. A marker–trait association analysis indicated that 51 loci were significantly associated with adult-plant resistance to stripe rust. These loci included 40 quantitative trait loci (QTL) regions for adult-plant resistance. Twenty identified resistance QTL were linked closely to previously reported yellow rust resistance genes or QTL regions, which were distributed across chromosomes 1B, 1D, 2A, 2B, 3A, 3B, 4A, 4B, 5B, 6B, 7A, 7B, and 7D. Six multi-trait QTL were detected on chromosomes 1B, 1D, 2B, 3A, 3B, and 7D. Twenty QTL were mapped to chromosomes 1D, 2A, 2D, 4B, 5B, 6A, 6B, 6D, 7A, 7B, and 7D, distant from previously identified yellow rust resistance genes. Consequently, these QTL are potentially novel loci for stripe rust resistance. Among the 20 potentially novel QTL, five (QDS.sicau-2A, QIT.sicau-4B, QDS.sicau-4B.2, QDS.sicau-6A.3, and QYr.sicau-7D) were associated with field responses at the adult-plant stage in at least two environments, and may have large effects on stripe rust resistance. The novel effective QTL for adult-plant resistance to stripe rust will improve understanding of the genetic mechanisms that control the spread of stripe rust, and will aid in the molecular marker-assisted selection-based breeding of wheat for stripe rust resistance

Haploinsufficiency of CYP8B1 associates with increased insulin sensitivity in humans

10.1172/JCI152961The Journal of clinical investigation13221e152961

Erratum: Sequence data and association statistics from 12,940 type 2 diabetes cases and controls.

This corrects the article DOI: 10.1038/sdata.2017.179

A 3D study on the amplification of regional haze and particle growth by local emissions

The role of new particle formation (NPF) events and their contribution to haze formation through subsequent growth in polluted megacities is still controversial. To improve the understanding of the sources, meteorological conditions, and chemistry behind air pollution, we performed simultaneous measurements of aerosol composition and particle number size distributions at ground level and at 260 m in central Beijing, China, during a total of 4 months in 2015-2017. Our measurements show a pronounced decoupling of gas-to-particle conversion between the two heights, leading to different haze processes in terms of particle size distributions and chemical compositions. The development of haze was initiated by the growth of freshly formed particles at both heights, whereas the more severe haze at ground level was connected directly to local primary particles and gaseous precursors leading to higher particle growth rates. The particle growth creates a feedback loop, in which a further development of haze increases the atmospheric stability, which in turn strengthens the persisting apparent decoupling between the two heights and increases the severity of haze at ground level. Moreover, we complemented our field observations with model analyses, which suggest that the growth of NPF-originated particles accounted up to similar to 60% of the accumulation mode particles in the Beijing-Tianjin-Hebei area during haze conditions. The results suggest that a reduction in anthropogenic gaseous precursors, suppressing particle growth, is a critical step for alleviating haze although the number concentration of freshly formed particles (3-40 nm) via NPF does not reduce after emission controls.Peer reviewe