We investigated the bioaccumulation of antibiotics in bile, plasma, liver and muscle tissues of wild fish from four rivers in the Pearl River Delta region. In total, 12 antibiotics were present in at ...least one type of fish tissues from nine wild fish species in the four rivers. The mean values of log bioaccumulation factors (log BAFs) for the detected antibiotics in fish bile, plasma, liver, and muscle tissues were at the range of 2.06–4.08, 1.85–3.47, 1.41–3.51, and 0.48–2.70, respectively. As the digestion tissues, fish bile, plasma, and liver showed strong bioaccumulation ability for some antibiotics, indicating a different bioaccumulation pattern from hydrophobic organic contaminants. Human health risk assessment based on potential fish consumption indicates that these antibiotics do not appear to pose an appreciable risk to human health. To the best of our knowledge, this is first report of bioaccumulation patterns of antibiotics in wild fish bile and plasma.
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•We investigated the bioaccumulation of antibiotics in wild fish from the Pearl River Delta region.•Twelve antibiotics were found in fish bile, plasma, liver and muscle tissues.•High log bioaccumulation factors suggested strong bioaccumulation ability for some antibiotics in wild fish tissues.•The presence of antibiotics in fish bile and plasma tissues indicates a novel bioaccumulation pattern.•Potential adverse effects are possibly caused by the high internal antibiotic concentrations in tissues.
Fish bile and plasma displayed strong bioaccumulation ability for some antibiotics, indicating a novel bioaccumulation pattern for antibiotics in the contaminated environment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Steroids are excreted from humans and animals and discharged with wastewaters into the environment, resulting in potential adverse effects on organisms. Based on the excretion rates from different ...groups of humans and animals, the emissions of seven steroids (estrone (E1), 17β-estradiol (E2), estriol (E3), testosterone (T), androsterone (A), progesterone (P), and cortisol (C)) were comprehensively estimated in 58 river basins of whole China, and their multimedia fate was simulated by using a level III fugacity multimedia model. The results showed that higher emission densities for the steroids were found in the river basins of east China than in west China. This distribution was found to be generally similar to the distribution of Gross Domestic Product (GDP) across China. E3, A, and P displayed higher emission densities than the other steroids in most of the river basins. The total excretion of steroids by humans and animals in China was estimated to be 3069 t/yr. The excretion of steroids from animals was two times larger than that from humans. After various treatments, the total emission of steroids was reduced to 2486 t/yr, of which more than 80% was discharged into the water compartment. The predicted concentrations in water were within an order of magnitude of the measured concentrations available in the literature. Owing to wastewater irrigation, more steroid mass loadings in agricultural soil were found in the basins of Haihe River and Huaihe River in comparison with the other river basins. To the best of our knowledge, this is the first report on the emissions and multimedia fate of seven steroids in the river basins of China.
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IJS, KILJ, NUK, PNG, UL, UM
Herein, a palladium-catalyzed general synthetic strategy to access an attractive and decorated set of chiral spiro derivatives of benzoxazine compounds is unveiled utilizing vinyl benzoxazinanones ...reacted with pyrazolone 4,5-diones, which extends the application of vinyl benzoxazinanones with ketones. This asymmetric catalytic 4+2 cycloaddition reaction demonstrates a broad substrate scope with functional group tolerance in yields of up to 76% and up to 96% ee. A facile scale-up and straightforward conversion to diversely substituted products verify the synthetic utility of this method.
A palladium-catalyzed general synthetic strategy to access an attractive and decorated set of spirooxazinane skeletons was successfully achieved using vinyl benzoxazinanone derivatives and ketones.
Background and purpose
Recent genetic progress has shown many causative/risk genes linked to Parkinson's disease (PD), mainly in patients of European ancestry. The study aimed to investigate the ...PD‐related genes and determine the mutational spectrum of early‐onset PD in ethnic Chinese.
Methods
In this study, whole‐exome sequencing and/or gene dosage analysis were performed in 704 early‐onset PD (EOPD) patients (onset age ≤45 years) and 1866 controls. Twenty‐six PD‐related genes and 20 other genes linked to neurodegenerative and lysosome diseases were analysed.
Results
Eighty‐two (11.6%, 82/704) EOPD patients carrying rare pathogenic/likely pathogenic variants in PD‐related genes were identified. The mutation frequency in autosomal recessive inheritance EOPD (42.9%, 27/63) was much higher than that in autosomal dominant inheritance EOPD (0.9%, 12/110) or sporadic EOPD (8.1%, 43/531). Bi‐allelic mutations in PRKN were the most frequent, accounting for 5.1% of EOPD cases. Three common pathogenic variants, p.A53V in SNCA, p.G284R in PRKN and p.P53Afs*38 in CHCHD2, occur exclusively in Asians. The putative damaging variants from GBA, PRKN, DJ1, PLA2G6 and GCH1 contributed to the collective risk for EOPD. Notably, the protein‐truncating variants in CHCHD2 were enriched in EOPD, especially for p.P53Afs*38, which was also found in three patients from an independent cohort of patients with late‐onset PD (n = 1300). Functional experiments confirmed that truncated CHCHD2 variants cause loss of function and are linked to mitochondrial dysfunction.
Conclusions
Our study reveals that the genetic spectrum of EOPD in Chinese, which may help develop genetic scanning strategies, provided more evidence supporting CHCHD2 in PD.
Three common pathogenic variants, p.A53V in SNCA, p.G284R in PRKN and p.P53Afs*38 in CHCHD2, occur exclusively in Asians. The putative damaging variants from GBA, PRKN, DJ1 and PLA2G6 contributed the collective risk for early‐onset Parkinson’s disease (PD). The protein‐truncating variants in CHCHD2 were significantly enriched in early‐onset PD, especially for p.P53Afs*38, which was confirmed in an independent cohort of patients with late‐onset PD and functional experiments.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Qishen Yiqi Pills (QSYQ) is a classical herbal formula for treating heart failure (HF) and has potential efficacy in improving cognitive function. The latter is one of the most common complications ...in patients with HF. However, there is no study on treating HF-related cognitive dysfunction by QSYQ.
The study aims to investigate the effect and mechanism of QSYQ on treating post-HF cognitive dysfunction based on network pharmacology and experimental validation.
Network pharmacology analysis and molecular docking was used to explore endogenous targets of QSYQ in treating cognitive impairment. Ligation of the anterior descending branch of the left coronary artery and sleep deprivation (SD) were used to induce HF-related cognitive dysfunction in rats. The efficacy and potential signal targets of QSYQ were then verified by functional evaluation, pathological staining, and molecular biology experiments.
384 common targets were identified by intersecting QSYQ ‘compound targets’ and ‘cognitive dysfunction’ disease targets. KEGG analysis showed these targets were enriched to the cAMP signal, and four marks responsible for regulating the cAMP signal were successfully docked with core compounds of QSYQ. Animal experiments demonstrated that QSYQ significantly ameliorated cardiac function and cognitive function in rats suffering from HF and SD, inhibited the reduction of cAMP and BDNF content, reversed the upregulation of PDE4 and downregulation of CREB, suppressed the loss of neurons, and restored the expression of synaptic protein PSD95 in the hippocampus.
This study clarified that QSYQ could improve HF-related cognitive dysfunction by modulating cAMP-CREB-BDNF signals. It provides a rich basis for the potential mechanism of QSYQ in the treatment of heart failure with cognitive dysfunction.
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•QSYQ ameliorated cognitive dysfunction caused by HF combined with SD.•cAMP signal contributed to HF-related cognitive dysfunction through the regulation of synaptic plasticity.•cAMP-CREB-BDNF was involved in the efficacy of QSYQ against cognitive dysfunction caused by HF and SD.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
One of the challenges surrounding nonalcoholic fatty liver disease (NAFLD) is to discover the mechanisms that underlie the initiation of it. The aim of the present study was to elucidate the effects ...of Toll‐like receptor 4 (TLR4) signaling in liver parenchymal cells during the early stage of NAFLD. Male TLR4‐wildtype, TLR4‐knockout, TLR2‐knockout, MyD88‐knockout, and TRIF‐knockout mice were fed a normal diet or high‐fat diet (HFD). Liver steatosis, alanine aminotransferase levels, nuclear translocation of nuclear factor kappa B (NF‐κB) (p65), macrophage accumulation, and neutrophil infiltration were assessed. Using Kupffer cell depletion or bone marrow transplantation, we examined the potential role of Kupffer cells and myeloid infiltrating cells during the initiation of NAFLD. Immunohistochemistry and western blotting were implemented to determine the release of high‐mobility group box1 (HMGB1). The neutral‐antibody against HMGB1 was used to block the activity of free HMGB1. Here we report that the activation of TLR4 signaling in hepatocytes, accompanied with the relocation of P65 in nucleus, was proven to play an important role during the initiation of NAFLD. Importantly, HMGB1 releasing from hepatocytes in response to free fatty acid (FFA) infusion was first reported as the key molecule for the TLR4/MyD88 activation and cytokines expression in vitro and in vivo. Treatment with neutralizing antibody to HMGB1 protects against FFA‐induced tumor necrosis factor alpha and interleukin‐6 production. Conclusion: Our study supports the notion that TLR4/MyD88 signaling in liver parenchymal cells plays a pivotal role during the early progression of HFD‐induced NAFLD, in which free HMGB1 served as a positive component mediating TLR4 activation. (HEPATOLOGY 2011;)
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
A social force model is developed in this paper to study the crowd evacuation when a terrorist attack occurs in the public place. The persons in the model are divided into two groups—terrorists and ...pedestrians. On one hand, each terrorist chooses the nearest pedestrian as the target. Once the distance between him and his target is small enough, the terrorist will launch attacks on his target and the target will be killed with a certain probability. On the other hand, each pedestrian tries to avoid the terrorists and reach the exits. An emergency exit choice strategy which emphasizes the security risk factor is developed for pedestrians. The main simulation results are summarized as follows. First, the number of deaths in the terrorist attack increases with the number of terrorists and with the density of pedestrians. If the number of exits decreases, the death toll will become more sensitive to the change of the density of pedestrians. Second, adding the number of exits can significantly reduce casualties. Third, more pedestrians will be killed and the evacuation speed will be reduced if terrorists start the attack from the positions of the exits. Fourth, the emergency exit choice strategy has an advantage over the ordinary exit choice strategy in daily life for reducing casualties. The more unbalanced the terrorists’ initial distribution around the exits is, the more noticeable this advantage will be. Fifth, the number of deaths will decrease obviously if at least half of the exits are available and safe. Our study is valuable for developing an effective evacuation scheme to reduce casualties in a terrorist attack.
•A new social force model for the pedestrian evacuation in a terrorist attack.•The interaction between terrorists’ attack and pedestrians’ evacuation is studied.•An emergency exit choice strategy is developed for pedestrians.•More people will be killed if terrorists start the attack from the exits.•Many people will be saved if at least half of the exits are available and safe.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Nineteen biocides were investigated in the Yangtze River to understand their spatiotemporal distribution, mass loads and ecological risks. Fourteen biocides were detected, with the highest ...concentrations up to 166 ng/L for DEET in surface water, and 54.3 ng/g dry weight (dw) for triclocarban in sediment. The dominant biocides were DEET and methylparaben, with their detection frequencies of 100% in both phases. An estimate of 152 t/y of 14 biocides was carried by the Yangtze River to the East China Sea. The distribution of biocides in the aquatic environments was significantly correlated to Gross Domestic Product (GDP), total phosphorus (TP) and total nitrogen (TN), suggesting dominant input sources from domestic wastewater of the cities along the river. Risk assessment showed high ecological risks posed by carbendazim in both phases and by triclosan in sediment. Therefore, proper measures should be taken to reduce the input of biocides into the river systems.
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•Biocides were ubiquitous in the surface water and sediment of the Yangtze River.•The dominant biocides in the Yangtze River were DEET and methylparaben.•Annual flux of biocides was 152 tons from the Yangtze River to the East China Sea.•Domestic wastewater was the main source of the biocides.•Carbendazim and triclosan posed high ecological risks.
Biocides showed wide presence in the Yangtze River and some of them could pose high ecological risks to aquatic organisms.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Chromatin dynamics regulated by epigenetic modification is crucial in genome stability and gene expression. Various epigenetic mechanisms have been identified in the pathogenesis of human diseases. ...Here, we examined the effects of ten epigenetic agents on pseudorabies virus (PRV) infection by using GFP-reporter assays. Inhibitors of bromodomain protein 4 (BRD4), which receives much more attention in cancer than viral infection, was found to exhibit substantial anti-viral activity against PRV as well as a range of DNA and RNA viruses. We further demonstrated that BRD4 inhibition boosted a robust innate immune response. BRD4 inhibition also de-compacted chromatin structure and induced the DNA damage response, thereby triggering the activation of cGAS-mediated innate immunity and increasing host resistance to viral infection both in vitro and in vivo. Mechanistically, the inhibitory effect of BRD4 inhibition on viral infection was mainly attributed to the attenuation of viral attachment. Our findings reveal a unique mechanism through which BRD4 inhibition restrains viral infection and points to its potent therapeutic value for viral infectious diseases.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Although isolated distal deep vein thrombosis (IDDVT) is a clinical complication for acute ischemic stroke (AIS) patients, very few clinicians value it and few methods can predict early IDDVT. This ...study aimed to establish and validate an individualized predictive nomogram for the risk of early IDDVT in AIS patients.
This study enrolled 647 consecutive AIS patients who were randomly divided into a training cohort (n = 431) and a validation cohort (n = 216). Based on logistic analyses in training cohort, a nomogram was constructed to predict early IDDVT. The nomogram was then validated using area under the receiver operating characteristic curve (AUROC) and calibration plots.
The multivariate logistic regression analysis revealed that age, gender, lower limb paralysis, current pneumonia, atrial fibrillation and malignant tumor were independent risk factors of early IDDVT; these variables were integrated to construct the nomogram. Calibration plots revealed acceptable agreement between the predicted and actual IDDVT probabilities in both the training and validation cohorts. The nomogram had AUROC values of 0.767 (95% CI: 0.742-0.806) and 0.820 (95% CI: 0.762-0.869) in the training and validation cohorts, respectively. Additionally, in the validation cohort, the AUROC of the nomogram was higher than those of the other scores for predicting IDDVT.
The present nomogram provides clinicians with a novel and easy-to-use tool for the prediction of the individualized risk of IDDVT in the early stages of AIS, which would be helpful to initiate imaging examination and interventions timely.
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