The size-fractionated characteristics of particulate polycyclic aromatic hydrocarbons (PAHs) were studied from January 2011 to October 2011 using a Micro-orifice Uniform Deposit Impactor (MOUDI) at ...the Yellow River Delta National Nature Reserve (YRDNNR), a background site located in the North China Plain. The average annual concentration of total PAHs in the YRDNNR (18.95±16.51ng/m3) was lower than that in the urban areas of China; however, it was much higher than that in other rural or remote sites in developed countries. The dominant PAHs, which were found in each season, were fluorene (5.93%–26.80%), phenanthrene (8.17%–26.52%), fluoranthene (15.23%–27.12%) and pyrene (9.23%–16.31%). A bimodal distribution was found for 3-ring PAHs with peaks at approximately 1.0–1.8μm and 3.2–5.6μm; however, 4–6 ring PAHs followed a nearly unimodal distribution, with the highest peak in the 1.0–1.8μm range. The mass median diameter (MMD) values for the total PAHs averaged 1.404, 1.467, 1.218 and 0.931μm in spring, summer, autumn and winter, respectively. The toxicity analysis indicated that the carcinogenic potency of particulate PAHs existed primarily in the <1.8μm size range. Diagnostic ratios and PCA analysis indicated that the PAHs in aerosol particles were mainly derived from coal combustion. In addition, back-trajectory calculations demonstrated that atmospheric PAHs were produced primarily by local anthropogenic sources.
•Size-resolved PAH characterizations were studied at a background site in the North China plain.•Toxicity analysis indicated that the carcinogenic potency of particulate PAHs exists primarily in the <1.8μm size ranges.•The sources of PAHs were investigated by diagnostic ratios and PCA.•Backward trajectory analysis showed that local anthropogenic emission dominated PAH levels.
Aim： There is a high incidence of the antiplatelet drug clopidogrel resistance （OR） in Asian populations. Because clopidogrel is a prodrug, polymorphisms of genes encoding the enzymes involved in its ...biotransformation may be the primary influential factors. The goal of this study was to investigate the associations of polymorphisms of CYP3A4, NRll2, CYP2C19 and P2RY12 genes with CR in Chinese patients with ischemic stroke. Methods： A total of 191 patients with ischemic stroke were enrolled. The patients were treated with clopidogrel for at least 5 days. Platelet function was measured by light transmission aggregometry. The SNPs NRll2 （rs13059232）, CYP3A4＊IG （rs2242480）, CYP2C19＊2 （rs4244285） and P2RY12 （rs2046934） were genotyped. Results： The CR rate in this population was 36%. The CYP2C19＊2 variant was a risk factor for CR （＊2/＊2＋wt/＊2 vs wt/wt, OR： 2.366 95% CI： 1.180-4.741, P=0.014）, whereas the CYP3A4＊IG variant had a protective effect on CR （＊1/＊1 vs ＊1G/＊IG＋＊1/＊IG, OR： 2.360, 95% CI： 1.247-4.468, P=0.008）. The NRll2 （rs13059232） polymorphism was moderately associated with CR （CC vs TT＋TC, OR： 0.533, 95% CI： 0.286-0.991, P=0.046）. The C allele in P2RY12 （rs2046934） was predicted to be a protective factor for CR （CC＋TC vs TT, OR： 0.407, 95% CI： 0.191-0.867, P=O.O18）. In addition, an association was found between hypertension and CR （P=0.022）. Conclusion： The individuals with both the CYP2C19＊2 allele and hypertension are at high risk of CR during anti-thrombosis therapy. The CYP3A4＊IG allele, P2RY12 （rs2046934） C allele and NRll2 （rs13059232） CC genotype may be protective factors for CR. The associated SNPs studied may be useful to predict clopidogrel resistance in Chinese patients with ischemic stroke.
Objectives. The variant rs3828903 within MICB, a nonclassical MHC class I chain-related gene, was detected to contribute to systemic lupus erythematosus (SLE) in a Caucasian population. This study ...aimed to investigate the association in a northern Han Chinese population. Methods. We recruited 1077 SLE patients and 793 controls for analysis. rs3828903 was genotyped by TaqMan allele discrimination assay. Using the public databases, its functional annotations and gene differential expression analysis of MICB were evaluated. Results. Significant association between the allele G of rs3828903 and risk susceptibility to SLE was observed after adjusting for sex and age ( P = 1.87 × 10 - 2 ). In silico analyses predicted a higher affinity to transcription factors for allele G (risk) and cis-expression quantitative trait loci (cis-eQTL) effects of rs3828903 in multiple tissues ( P ranging from 2.79 × 10 - 6 to 6.27 × 10 - 38 ). Furthermore, higher mRNA expressions of MICB were observed in B cells, monocytes, and renal biopsies from SLE patients compared to controls. Conclusion. An association between rs3828903 and susceptibility to SLE has been detected in a Chinese population. This together with the functional annotations of rs3828903 converts MICB into a main candidate in the pathogenesis of SLE.
The majority of TP53 missense mutations identified in cancer patients are in the DNA-binding domain and are characterized as either structural or contact mutations. These missense mutations exhibit ...inhibitory effects on wild-type p53 activity. More importantly, these mutations also demonstrate gain-of-function (GOF) activities characterized by increased metastasis, poor prognosis, and drug resistance. To better understand the activities by which TP53 mutations, identified in Li-Fraumeni syndrome, contribute to tumorigenesis, we generated mice harboring a novel germline Trp53R245W allele (contact mutation) and compared them with existing models with Trp53R172H (structural mutation) and Trp53R270H (contact mutation) alleles. Thymocytes from heterozygous mice showed that all three hotspot mutations exhibited similar inhibitory effects on wild-type p53 transcription in vivo, and tumors from these mice had similar levels of loss of heterozygosity. However, the overall survival of Trp53R245W/+ and Trp53R270H/+ mice, but not Trp53R172H/+ mice, was significantly shorter than that of Trp53+/- mice, providing strong evidence for p53-mutant-specific GOF contributions to tumor development. Furthermore, Trp53R245W/+ and Trp53R270H/+ mice had more osteosarcoma metastases than Trp53R172H/+ mice, suggesting that these two contact mutants have stronger GOF in driving osteosarcoma metastasis. Transcriptomic analyses using RNA sequencing data from Trp53R172H/+, Trp53R245W/+, and Trp53R270H/+ primary osteosarcomas in comparison with Trp53+/- indicated that GOF of the three mutants was mediated by distinct pathways. Thus, both the inhibitory effect of mutant over wild-type p53 and GOF activities of mutant p53 contributed to tumorigenesis in vivo. Targeting p53 mutant-specific pathways may be important for therapeutic outcomes in osteosarcoma.
p53 hotspot mutants inhibit wild-type p53 similarly but differ in their GOF activities, with stronger tumor-promoting activity in contact mutants and distinct protein partners of each mutant driving tumorigenesis and metastasis.
Liquid crystal monomers (LCMs) are potentially persistent, bioaccumulating, and toxic substances. However, limited data are available on the occurrence of LCMs in indoor and outdoor air particle ...matter (PM10) in residential areas. Herein, residential areas near an e-waste dismantling center (Guiyu Town, Shantou City), as well as areas away from the e-waste site (Jiedong District, Jieyang City) were selected as the sampling areas. PM10 was collected from the indoor environments of Guiyu (IGY) and Jieyang (IJY), as well as those from the outdoor environments (OGY and OJY) using the high-volume air samplers (TH-10000C). The levels of 57 LCMs in PM10 were analyzed, and the highest concentrations of LCMs were found in IGY (0.970–1080 pg/m3), followed by IJY (2.853–455 pg/m3), OGY (0.544–116 pg/m3) and OJY (0.258–35.8 pg/m3). No significant difference was observed for LCM levels in indoor PM10 between the two areas (p > 0.05), which were significantly higher than those in outdoors (p < 0.05), indicating that the release of electronic products in general indoor environments is a source of LCMs that cannot be ignored. The compositions of LCMs in outdoors were not consistent with those of indoors. The correlation analysis of individual LCMs suggested potential different sources to the LCMs in indoor and outdoor environments. The median daily intake values of Σ46LCMs via inhalation were estimated as 0.440, 1.46 × 10−2, 0.170 and 1.19 × 10−2 ng/kg BW/day for adults, and as 2.27, 2.60 × 10−2, 0.880 and 2.10 × 10−2 ng/kg BW/day for toddlers, respectively, indicating much higher exposure doses of LCMs indoors compared with the outdoors, and much higher doses for toddlers compared with adults (p < 0.05). These results reveal the potentially adverse effects of LCMs on vulnerable populations, such as toddlers, in indoor environments.
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•Indoor and outdoor PM10 LCMs in residential areas near and away from an e-waste area were analyzed.•LCMs in indoor PM10 were significantly higher than those in outdoors.•The release of various types of electronic products indoors is a non-negligible source of LCMs.•Higher exposure doses of LCMs were observed indoors compared with outdoors.•A low risk of exposure to LCMs via inhalation was found for adults and toddlers.
With the deepening of oil and gas exploration and development, the conventional seismic inversion technology has certain limitations for the fine research of complex reservoirs, and the actual ...production has high requirements for seismic resolution. The waveform indication technology is based on the waveform phase control mode, and uses the seismic waveform instead of the variogram. It can not only invert the wave impedance curve and realize high-precision prediction of the reservoir, but also simulate the characteristic curve reflecting the sensitivity of the reservoir to realize the reservoir under different parameters. characterization. Taking the second member of the Sangonghe Formation in the L block of the Manan slope in the Junggar Basin as an example, the sandstone changes rapidly laterally, has a small thickness, and has low conventional inversion resolution, making it unsuitable for predicting thin reservoirs. The waveform indication inversion was carried out to describe the distribution of the sandstone in the target layer, and the results were in line with geological understanding. After analyzing the relationship between the four properties of the reservoir, the oiliness of the sandstone in the target layer has a certain fitting relationship with the amplitude difference of the spontaneous potential curve. The reservoir indication simulation with the spontaneous potential curve as the characteristic curve was carried out. On the basis of the waveform indication inversion of the sandstone, further Oily sandstones were identified, and the simulation results were in good agreement with the drilling data.
Several studies have indicated metabolic function disruption effects of bisphenol analogues through peroxisome proliferator-activated receptor (PPAR) alpha and gamma pathways. In the present study, ...we found for the first time that PPARβ/δ might be a novel cellular target of bisphenol analogues. By using the fluorescence competitive binding assay, we found seven bisphenol analogues could bind to PPARβ/δ directly, among which tetrabromobisphenol A (TBBPA, 18.38-fold) and tetrachlorobisphenol A (TCBPA, 12.06-fold) exhibited stronger binding affinity than bisphenol A (BPA). In PPARβ/δ-mediated luciferase reporter gene assay, the seven bisphenol analogues showed transcriptional activity toward PPARβ/δ. Bisphenol AF (BPAF), bisphenol F (BPF) and bisphenol B (BPB) even showed higher transcriptional activity than BPA, while TBBPA and TCBPA showed comparable activity with BPA. Moreover, in human liver HL-7702 cells, the bisphenol analogues promoted the expression of two PPARβ/δ target genes PDK4 and ANGPTL4. Molecular docking simulation indicated the binding potency of bisphenol analogues to PPARβ/δ might depend on halogenation and hydrophobicity and the transcriptional activity might depend on their binding affinity and hydrogen bond interactions. Overall, the PPARβ/δ pathway may provide a new mechanism for the metabolic function disruption of bisphenol analogues, and TBBPA and TCBPA might exert higher metabolic disruption effects than BPA via PPARβ/δ pathway.
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•Bisphenol analogues directly bind to and activate PPARβ/δ receptor.•TBBPA and TCBPA exhibit stronger binding affinity with PPARβ/δ than BPA.•TBBPA and TCBPA exert higher PPARβ/δ disruption activity than BPA in HL-7702 cells.•Halogenation, hydrophobicity and hydrogen bond interactions play essential roles in binding and activity.
One of Android's main defense mechanisms against malicious apps is a risk communication mechanism which, before a user installs an app, warns the user about the permissions the app requires, trusting ...that the user will make the right decision. This approach has been shown to be ineffective as it presents the risk information of each app in a "tand-alone" ashion and in a way that requires too much technical knowledge and time to distill useful information.
We introduce the notion of risk scoring and risk ranking for Android apps, to improve risk communication for Android apps, and identify three desiderata for an effective risk scoring scheme. We propose to use probabilistic generative models for risk scoring schemes, and identify several such models, ranging from the simple Naive Bayes, to advanced hierarchical mixture models. Experimental results conducted using real-world datasets show that probabilistic general models significantly outperform existing approaches, and that Naive Bayes models give a promising risk scoring approach.
Deficiency of TOM5, a mitochondrial protein, causes organizing pneumonia (OP) in mice. The clinical significance and mechanisms of TOM5 in the pathogenesis of OP remain elusive. We demonstrated that ...TOM5 was significantly increased in the lung tissues of OP patients, which was positively correlated with the collagen deposition. In a bleomycin-induced murine model of chronic OP, increased TOM5 was in line with lung fibrosis. In vitro, TOM5 regulated the mitochondrial membrane potential in alveolar epithelial cells. TOM5 reduced the proportion of early apoptotic cells and promoted cell proliferation. Our study shed light on the roles of TOM5 in OP.
Dissociation of active H species over the catalytic sites with the carbon-supported Pt metals as the mainstream catalysts is crucial to facilitate hydrogen donation and accelerate the hydrogen ...addition process in catalytic hydrogenation systems to produce polymers, pharmaceuticals, agrochemicals, fragrances, and biofuels at million-ton scale. Much attention has been paid to the design of the more active catalytic site to effectively adsorb and activate reactants and H
2
molecules. At the same time, there is still a huge room to develop powerful strategies to accelerate the donation of acted H species to the reactants from the Pt surface further to boost the final catalytic efficiencies of Pt catalysts and depress the total Pt consumption. Herein, we present a new strategy for promoting the Pt-H bond dissociation by increasing surface hydrogen coverage on designed electron-deficient Pt nanoparticles. The electron deficiency of Pt nanoparticles has been successfully tuned by constructing a rectifying contact with an even “noble” boron-rich carbon support (Pt/BC). Theoretical and experimental results confirm the dominant role of the pronounced electron deficiencies of Pt nanoparticles in enhancing the H coverage for 2.3 times higher than that of neutral Pt nanoparticles, significantly boosting the Pt-H bond dissociation and thus the whole hydrogenation process as reflected by the extremely high turnover frequency (TOF) value of 388 h
−1
at 30 °C and 10 bar H
2
for phenol hydrogenation on the Pt/BC, outperforming the bench-marked catalysts by a factor of 9.
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