Transcription modulated by the circadian clock is diverse across cell types, underlying circadian control of peripheral metabolism and its observed perturbation in human diseases. We report that ...knockout of the lineage-specifying Hnf4a gene in mouse liver causes associated reductions in the genome-wide distribution of core clock component BMAL1 and accessible chromatin marks (H3K4me1 and H3K27ac). Ectopically expressing HNF4A remodels chromatin landscape and nucleates distinct tissue-specific BMAL1 chromatin binding events, predominantly in enhancer regions. Circadian rhythms are disturbed in Hnf4a knockout liver and HNF4A-MODY diabetic model cells. Additionally, the epigenetic state and accessibility of the liver genome dynamically change throughout the day, synchronized with chromatin occupancy of HNF4A and clustered expression of circadian outputs. Lastly, Bmal1 knockout attenuates HNF4A genome-wide binding in the liver, likely due to downregulated Hnf4a transcription. Our results may provide a general mechanism for establishing circadian rhythm heterogeneity during development and disease progression, governed by chromatin structure.
The extensive application of plastic in human life brings about microplastic (MP) pollution in the environment. Identifying the potential sources of MPs is necessary to diminish its pollution. In ...this study, the occurrence, composition and distribution of MPs in the influents and effluents from 9 domestic wastewater treatment plants (WWTPs), 5 industrial WWTPs, wastewater of 10 industrial plants, 4 livestock farms and 4 fish ponds in China were investigated. Water samples were enzymatically treated followed by digestion with hydrogen peroxide and density separation. MPs were characterized using micro-Raman spectroscopy and were categorized by shape, size and color. Results showed that MP abundance in the influents and effluents of domestic WWTPs was 18–890 and 6–26 n·L−1, respectively, with the removal efficiency ranging from 35 to 98%. The effluents of industrial WWTPs contained 6–12 n·L−1 and the levels of MPs in the wastewater of industrial plants, livestock farms and fish ponds were in the range of 8–23, 8–40 and 13–27 n·L−1, respectively. No significant differences of MP abundance were demonstrated among effluents or wastewater of different sources, indicating they all constitute sources of MP pollution. Polyethylene (PE), polypropylene (PP) and polystyrene (PS) made up almost 83% of the total MPs. Fragment and film were the most abundant shapes and the majority of MPs were smaller than 500 μm. Polymer type and shape in different sources did not vary statistically, however, there were slight differences among different sources concerning size and color of MPs. This study could fill MP data gaps regarding different sources, guide future monitoring work and policy making.
Display omitted
•A wide campaign has been performed to reveal MPs in different wastewater sources.•Levels of MPs in the influents of domestic WWTPs varied from 18 to 890 n·L−1.•Abundance of MPs in effluents or wastewater from different sources was 6–40 n·L−1.•Type and shape of MPs from different wastewater did not significantly vary.•Size and color of MPs slightly differed among wastewater from different sources.
Display omitted
•Methamphetamine could be adsorbed by microplastics in water.•The toxicity of methamphetamine was aggravated significantly by microplastics.•Microplastics increase the filter-feeding ...fate of snail.•Microplastics increase the enrichment of R-methamphetamine in aquatic organism.•Showing the bio-effect of microplastics and methamphetamine through aquatic food chain.
The biological impacts of microplastics on many organisms have been well documented. However, the combined effects of microplastics and chiral chemicals on the aquatic food chain are less clear. In the present study, the enantioselective environmental behaviors of methamphetamine co-exposed with microplastics through an aquatic food chain (from Chlorella pyrenoidosa to Cipangopaludian cathayensis) have been investigated in a laboratory environment. It was found that the acute toxicity of methamphetamine against these two species was significantly increased in the presence of microplastics: Chlorella pyrenoidosa showed an EC50 shift from 0.77 to 0.32 mg L−1, while cipangopaludian cathayensis showed an LC50 shift from 4.15 to 1.48 mg L−1, upon the addition of microplastics as a co-contaminant with methamphetamine. Upon exposure to methamphetamine and microplastics, the oxidative damage of algae (19.9 to 36.8 nmol mgprot−1), apoptosis (increase about 2.17 times) and filtration rate (41.2 to 65.4 mL h−1) of snails were observably higher when compared to exposure to methamphetamine alone. After ingestion and accumulation of microplastics, the enantioselectivity, BCFs, BMFs, and distribution of methamphetamine were significantly altered. These results provide evidence that the co-occurrence of microplastics and the chiral drug methamphetamine may increase the burden on aquatic species, with potential further impacts throughout aquatic food chain.
Display omitted
•The ROS of venlafaxine and O-desmethylvenlafaxine were analyzed in liver tissue in the presence and absence of microplastic.•The enantiomeric bioaccumulation and metabolism of ...venlafaxine in the presence and absence of microplastic were studied.•R-venlafaxine and its metabolite R-O-desmethylvenlafaxine were biotransformed preferentially.•The distribution of venlafaxine and O-desmethylvenlafaxine in liver subcellular changed when co-exposure to microplastic.
In present study, we investigated the enantioselective behaviors of the chiral antidepressant venlafaxine and its metabolite O-desmethylvenlafaxine in loach Misgurnus anguillicaudatus (M. anguillicaudatus), as well as effects of microplastic on toxicity, distribution and metabolism through a 40-day co-exposure. The contents of SOD and MDA in loach liver elevated when the loach was exposed to venlafaxine and O-desmethylvenlafaxine. Moreover, co-exposure with microplastic might lead to more adverse effect against loach. The distribution of venlafaxine and O-desmethylvenlafaxine were both detected in loach tissues and liver subcellular. The concentrations of venlafaxine and O-desmethylvenlafaxine were lower in water in microplastic-present treatment. Whilst, more contaminants were accumulated in liver through the “vehicle” (microplastic). Enantioselective behavior of venlafaxine and O-desmethylvenlafaxine occurred with R-enantiomers being preferentially degraded. With microplastic present, the bioaccumulation factor (BAF) of venlafaxine and O-desmethylvenlafaxine in loach tissue amplified more than 10 times. In liver subcellular structure, microplastic may help to transport more compounds into subtle areas and postpone the contaminants metabolism in organisms. The present study for the first time gained an insight into the potential ecological effects and environmental behaviors of combined pollutions of chiral pharmaceuticals and microplastic, which could supply important information for environment risk assessment of concurrent organic pollutants and microplastic.
Plastic pollution has become a pressing issue due to its persistence in the environment. Smaller plastics are more easily ingested, potentially exerting greater influences on organisms. In this ...study, the effects of polystyrene nanoplastics (NP) on the toxic effects, bioaccumulation, biodegradation and enantioselectivity of ibuprofen (IBU) in algae Chlorella pyrenoidosa were explored. The influences on the growth rate, chlorophyll a, total antioxidant capacity (T-AOC), reactive oxygen species (ROS) and lipid peroxidation (MDA) were evaluated after 96 h of exposure to a combination of polystryene NP (1 mg L−1) and IBU (5–100 mg L−1). The results indicated that the inhibitory effect of IBU on C. pyrenoidosa growth was alleviated in the presence of NP. For instance, the 96 h-IC50 value for rac-IBU in the treatment lacking NP was 45.7 mg L−1, and the corresponding value in the treatment containing NP was 63.9 mg L−1. The co-exposure of NP led to a significant enhancement of T-AOC and slight reduction of ROS and MDA compared with the individual exposure (IBU) group, suggesting a decreased oxidative stress. In addition, treatment with NP led to a decreased bioaccumulation and accelerated biodegradation of IBU in C. pyrenoidosa and enhanced removal in the medium. The enantioselective toxicity, bioaccumulation and biodegradation of IBU were observed both in the absence and presence of NP. S-IBU exhibited a greater toxicity, and R-IBU was preferentially accumulated and degraded in C. pyrenoidosa. No interconversion of the two enantiomers occurred regardless of the presence of NP. This consequence implied that the influence of coexistent NP should be considered in the environmental risk assessment of pharmaceuticals and personal care products in aquatic environments.
Display omitted
•NP mitigated the inhibitory effect of ibuprofen on C. pyrenoidosa growth.•Co-exposure of NP significantly elevated antioxidative capability in C. pyrenoidosa.•IBU bioaccumulation in C. pyrenoidosa was reduced by the presence of NP.•Treatment with NP led to an accelerated biodegradation of IBU in C. pyrenoidosa.•IBU enantioselectivity was observed both in the absence and presence of NP.
This work indicated that co-exposure with NP could alleviate the inhibitory effect, decrease the bioaccumulation and accelerate the biodegradation of IBU in C. pyrenoidosa.
Abstract
Motivation
The large-scale multidimensional omics data in the Genomic Data Commons (GDC) provides opportunities to investigate the crosstalk among different RNA species and their regulatory ...mechanisms in cancers. Easy-to-use bioinformatics pipelines are needed to facilitate such studies.
Results
We have developed a user-friendly R/Bioconductor package, named GDCRNATools, for downloading, organizing and analyzing RNA data in GDC with an emphasis on deciphering the lncRNA-mRNA related competing endogenous RNAs regulatory network in cancers. Many widely used bioinformatics tools and databases are utilized in our package. Users can easily pack preferred downstream analysis pipelines or integrate their own pipelines into the workflow. Interactive shiny web apps built in GDCRNATools greatly improve visualization of results from the analysis.
Availability and implementation
GDCRNATools is an R/Bioconductor package that is freely available at Bioconductor (http://bioconductor.org/packages/devel/bioc/html/GDCRNATools.html). Detailed instructions, manual and example code are also available in Github (https://github.com/Jialab-UCR/GDCRNATools).
The gated structure of the long short‐term memory (LSTM) alleviates the defects of gradient disappearance and explosion in the recurrent neural network (RNN). It has received widespread attention in ...sequence learning such as text analysis. Although LSTM has good performance in handling remote dependencies, information loss often occurs in long‐distance transmission. We propose a new model called ELSTM based on the computational complexity and gradient dispersion in the traditional LSTM model. This model simplifies the input gate of LSTM, reduces some time complexity by reducing some components, and improves the output gate. By introducing the exponential linear unit activation layer, the problem of gradient dispersion is alleviated. Comparing the new model with multiple existing models, when predicting language sequences, the time used by the model has been greatly reduced, and the language confusion has been reduced, showing good performance.
•First study on enantiomeric occurrence of chiral drugs and metabolites in surface water in China.•NODDV and α-hydroxymetoprolol were for the first time confirmed in domestic water.•The ...transformation products contributed to 60% of the total load of 11 compounds.•TPs could be transported substantial distances along the river with limited attenuation.•R-venlafaxine was more readily biotransformed than the S-form.
The present work aimed to discuss the enantiomeric occurrence of chiral pharmaceuticals including 5 parent compounds (PCs) metoprolol, propranolol, atenolol, venlafaxine and fluoxetine as well as 6 of their transformation products (TPs) in surface water in Beijing. Among which, 9 out of 11 were detected during the two sampling campaigns with N-O-Didesmethylvenlafaxine (NODDV) and α-hydroxymetoprolol confirmed in the catchment for the first time. Metoprolol acid (MTPA) was the most abundant up to 1508 ng L−1, followed by metoprolol and O-desmethylvenlafaxine (ODV). Most compounds showed 100% detection frequency or nearly, while norfluoxetine (the main metabolite of fluoxetine) and 4-hydroxypropranololone (one TP of propranolol) were not detected. Metoprolol (MTP) and venlafaxine (VFX) did not vary significantly between two sampling periods with mean concentrations of 280.7 and 22.9 ng L−1, respectively. Enantiomeric enrichment was observed for venlafaxine, metoprolol and NODDV, where R-venlafaxine was preferentially biotransformed than the S-form through O-desmethylation. Risk assessment indicated that fluoxetine and atenolol could pose harmful effects to aquatic organisms. This work provides enantiospecific profiles of pharmaceutically active compounds (PhACs), and extended the concept of applying the ratio of TPs vs. parent compound plus their enantiomeric traits for quantitative assessment of in situ biodegradation. Due to the considerable contribution by TPs (64% in present study) as well as the unexpected impacts from enantiomeric existence, the stereoselectivity of chiral pollutants during environmental process should be taken into account in future study. To the best of the authors’ knowledge, it is the first comprehensive evaluation of chiral pharmaceuticals and transformation products at enantiomeric level in aquatic environment in China, which would facilitate better understanding of their environmental fate.
In this work, we propose a combinative strategy based on regression and clustering for solving point set matching problems under a Bayesian framework, in which the regression estimates the ...transformation from the model to the scene- and the clustering establishes the correspondence between two point sets. The point set matching model is illustrated by a hierarchical directed graph, and the matching uncertainties are approximated by a coarse-to-fine variational inference algorithm. Furthermore, two Gaussian mixtures are proposed for the estimation of heteroscedastic noise and spurious outliers, and an isotropic or anisotropic covariance can be imposed on each mixture in terms of the transformed model points. The experimental results show that the proposed approach achieves comparable performance to state-of-the-art matching or registration algorithms in terms of both robustness and accuracy.
A piezoelectric positioning platform by means of inchworm motion principle is developed, and it can achieve both linear and rotary motions. The designed positioning platform can provide large range ...motion with high resolution in a compact size. Eight piezoelectric stacks and several flexible hinges are used in the stator and the slider. The working principle of the proposed positioning platform is analyzed. Experiments of the prototype are carried out and the results show that the developed positioning platform has stable working characteristics under the certain working conditions. For the rotary motion of the positioning platform, the minimum stepping angle is 0.23 mu rad, the maximum rotary velocity is 3521.70 mu rad/s and the output torque is 0.294N m. When the platform works in the linear model, the minimum stepping displacement is 0.15 mu m, the maximum velocity is 105.31 mu m/s and the largest output load is 4.9 N. The designed positioning platform can be used in the fields of nanotechnology, precision machining. MEMS, bioscience and so on.
PDF
