Uranium is a key resource for the development of the nuclear industry, and extracting uranium from the natural seawater is one of the most promising ways to address the shortage of uranium resources. ...Herein, a semiconducting covalent organic framework (named NDA‐TN‐AO) with excellent photocatalytic and photoelectric activities was synthesized. The excellent photocatalytic effect endowed NDA‐TN‐AO with a high anti‐biofouling activity by generating biotoxic reactive oxygen species and promoting photoelectrons to reduce the adsorbed UVI to insoluble UIV, thereby increasing the uranium extraction capacity. Owing to the photoinduced effect, the adsorption capacity of NDA‐TN‐AO to uranium in seawater reaches 6.07 mg g−1, which is 1.33 times of that in dark. The NDA‐TN‐AO with enhanced adsorption capacity is a promising material for extracting uranium from the natural seawater.
Photoelectric and photocatalytic effects endow the covalent organic framework NDA‐TN‐AO with good anti‐biofouling activity. This occurs by generating biotoxic reactive oxygen species and promoting photoelectrons to reduce the adsorbed UVI to insoluble UIV, thereby improving the uranium adsorption capacity.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Drug‐induced liver injury (DILI) is a leading cause of therapy failure in the clinic and also contributes much to acute liver failure cases. Investigations of predictive sensitivity in animal models ...have limitations due to interspecies differences. Previously reported in vitro models of liver injury based on primary human hepatocytes (PHHs) cannot meet the requirements of high physiological fidelity, low cost, simple operation, and high throughput with improved sensitivity. Herein, we developed an integrated biomimetic array chip (iBAC) for establishing extracellular matrix (ECM)‐based models. A collagen‐based 3D PHH model was constructed on the iBAC as a case for the prediction of clinical DILI at throughput. The iBAC has a three‐layer structure with a core component of 3D implanting holes. At an initial cell seeding numbers of 5000–10,000, the collagen‐based 3D PHH model was optimized with improved and stabilized liver functionality, including cell viability, albumin, and urea production. Moreover, basal activities of most metabolic enzymes on the iBAC were maintained for at least 12 days. Next, a small‐scale hepatotoxicity screening indicated that the 3D PHH model on the iBAC was more sensitive for predicting hepatotoxicity than the 2D PHH model on the plate. Finally, a large‐scale screening of liver toxicity using 122 clinical drugs further demonstrated that the collagen‐based 3D PHH model on the iBAC had superior predictive sensitivity compared to all previously reported in vitro models. These results indicated the importance of 3D collagen for liver physiological functionality and hepatotoxicity prediction. We anticipant it being a promising tool for risk assessment of drug‐induced hepatotoxicity with a widespread acceptance in drug industry.
A collagen‐based 3D primary human hepatocyte model on an integrated biomimetic array chip for the prediction of clinical drug‐induced liver injury was developed. Industrialized validation of liver toxicity using 122 clinical drugs demonstrated that this model had superior predictive sensitivity compared to all previously reported in vitro models. The improved sensitivity indicated the importance of the 3D collagen for liver physiological functionality and hepatotoxicity prediction.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Many important cell types in adult vertebrates have a mesenchymal origin, including fibroblasts and vascular mural cells. Although their biological importance is undisputed, the level of mesenchymal ...cell heterogeneity within and between organs, while appreciated, has not been analyzed in detail. Here, we compare single-cell transcriptional profiles of fibroblasts and vascular mural cells across four murine muscular organs: heart, skeletal muscle, intestine and bladder. We reveal gene expression signatures that demarcate fibroblasts from mural cells and provide molecular signatures for cell subtype identification. We observe striking inter- and intra-organ heterogeneity amongst the fibroblasts, primarily reflecting differences in the expression of extracellular matrix components. Fibroblast subtypes localize to discrete anatomical positions offering novel predictions about physiological function(s) and regulatory signaling circuits. Our data shed new light on the diversity of poorly defined classes of cells and provide a foundation for improved understanding of their roles in physiological and pathological processes.
Metal nanoclusters (NCs) are emerging as a new class of functional nanomaterials in the area of biological sensing, labelling, imaging and therapy due to their unique physical and chemical ...properties, such as ultrasmall size, HOMO-LUMO transition, strong luminescence together with good photostability and biocompatibility. A recent surge of interest in this field is the surface functionalization of these metal NCs through which one can tailor their physicochemical properties, such as stability in solution, and strong luminescence, as well as their biodistribution and toxicity in biological systems, which in turn can empower these functionalized NCs with desirable targeting, imaging, and therapeutic ability for biomedical applications. In this review, we first introduce the functionalization strategies for the metal NCs developed in the past few years, followed by highlighting some biomedical applications of these functionalized metal NCs. We then discuss the difference of
in vitro
and
in vivo
fate as well as toxicity between various functionalized metal NCs. Finally, we present a short discussion on the current challenges and provide an outlook of the future developments of these functional metal NCs.
Metal nanoclusters (NCs) are emerging as a new class of functional nanomaterials in the area of biological sensing, labelling, imaging and therapy due to their unique physical and chemical properties, such as ultrasmall size, HOMO-LUMO transition, strong luminescence together with good photostability and biocompatibility.
Abscisic acid (ABA) catabolism is one of the determinants of endogenous ABA levels affecting numerous aspects of plant growth and abiotic-stress responses. The major ABA catabolic pathway is ...triggered by ABA 8'-hydroxylation catalysed by ABA 8'-hydroxylase, the cytochrome P450 CYP707A family. In this study, the full-length cDNAs of AhCYP707A1 and AhCYP707A2 were cloned and characterized from peanut. Expression analyses showed that AhCYP707A1 and AhCYP707A2 were expressed ubiquitously in peanut roots, stems, and leaves with different transcript accumulation levels, including the higher expression of AhCYP707A1 in roots. The expression of AhCYP707A2 was significantly up-regulated by 20% PEG6000 or 250 mmol/L NaCl in peanut roots, stems, and leaves, whereas the up-regulation of AhCYP707A1 transcript level by PEG6000 or NaCl was observed only in roots instead of leaves and stems. Due to the osmotic and ionic stresses of high concentration of NaCl to plants simultaneously, low concentration of LiCl (30 mmol/L, at which concentration osmotic status of cells is not seriously affected, the toxicity of Li+ being higher than that of Na+) was used to examine whether the effect of NaCl might be related to osmotic or ionic stress. The results revealed visually the susceptibility to osmotic stress and the resistance to salt ions in peanut seedlings. The significant up-regulation of AhCYP707A1, AhCYP707A2 and AhNCED1 transcripts and endogenous ABA levels by PEG6000 or NaCl instead of LiCl, showed that the osmotic stress instead of ionic stress affected the expression of those genes and the biosynthesis of ABA in peanut. The functional expression of AhCYP707A1 cDNA in yeast showed that the microsomal fractions prepared from yeast cell expressing recombinant AhCYP707A1 protein exhibited the catalytic activity of ABA 8'-hydroxylase. These results demonstrate that the expressions of AhCYP707A1 and AhCYP707A2 play an important role in ABA catabolism in peanut, particularly in response to osmotic stress.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Chemical neurotransmission occurs at chemical synapses and endocrine glands, but up to now there was no means for direct monitoring of neurotransmitter exocytosis fluxes and their precise kinetics ...from inside an individual synapse. The fabrication of a novel finite conical nanoelectrode is reported perfectly suited in size and electrochemical properties for probing amperometrically inside what appears to be single synapses and monitoring individual vesicular exocytotic events in real time. This allowed obtaining direct and important physiological evidences which may yield important and new insights into the nature of synaptic communications.
Chemical neurotransmission occurs at chemical synapse, but up to now there was no means for direct monitoring of neurotransmitter exocytosis and its precise kinetics from inside individual infinitesimal synapse. A novel finite conical nanoelectrode is fabricated and used in a newly developed amperometric method (see picture) for probing inside what appears to be single synapses.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Various research tools have been used for in vitro detection of sperm chemotaxis. However, they are typically poor in maintenance of gradient stability, not to mention their low efficiency. ...Microfluidic device offers a new experimental platform for better control over chemical concentration gradient than traditional ones. In the present study, an easy-handle diffusion-based microfluidic chip was established. This device allowed for conduction of three parallel experiments on the same chip, and improved the performance of sperm chemotaxis research. In such a chip, there were six channels surrounding a hexagonal pool. The channels are connected to the hexagon by microchannels. Firstly, the fluid flow in the system was characterized; secondly, fluorescein solution was used to calibrate gradient profiles formed in the central hexagon; thirdly, sperm behavior was observed under two concentration gradients of progesterone (100 pM and 1 mM, respectively) as a validation of the device. Significant differences in chemotactic parameters were recognized between experimental and control groups (p < 0.05). Compared with control group, sperm motility was greatly enhanced in 1 mM group (p < 0.05), but no significant difference was found in 100 pM group. In conclusion, we proposed a microfluidic device for the study of sperm chemotaxis that was capable of generating multi-channel gradients on a chip and would help reduce experimental errors and save time in experiment.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The development of an
in vitro
model for predicting drug permeability through the human blood-brain barrier (BBB) will greatly accelerate the development of neural therapy. Previously reported ...platforms for BBB model construction cannot meet the requirements of constant-rate and high-throughput flow, as well as compatibility with the commercial meter for real-time transendothelial electrical resistance (TEER) measurement. Herein, a constant-rate perfused array chip (cPAC) was developed to establish a brain endothelium model for screening drug permeability. The cPAC consisted of 24 units with four layers. Three reservoirs on the top had a 0.5 mm center-to-center spacing, enabling real-time detection of the TEER with the commercial volt-ohm meter. With the optimized chip design, the constant-rate and high-throughput flow by gravity was achieved. Compared with the static culture of the Transwell, the brain endothelium model on the cPAC exhibited superior performance in barrier function, efflux functionality of the transporters, and reversible osmotic opening of the brain endothelium. More importantly, the permeability of model drugs on the cPAC matched the
in vivo
results with the correlation coefficient reaching 0.994. Finally, the brain endothelium model was cocultured with 3D tumor cells for simultaneous evaluation of drug permeability and brain tumor therapy. The drug efficacy at the target cells on the coculture model was also consistent with clinical findings. These results demonstrated that this platform provides a promising tool for brain endothelium model establishment to predict drug permeability and brain therapy. We anticipate the cPAC to be widely accepted for establishing various barrier models.
A constant-rate perfused array chip (cPAC) that enables constant-rate and high-throughput flow, as well as real-time transendothelial electrical resistance measurement was developed for screening drug permeability through brain endothelium.
Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to measure the expression of microRNA-155 in patients with temporal lobe epilepsy. Commercial kit and western blot ...analysis were used to measure gap-associated protein expression. The aim of the present study was to investigate the effect of microRNA-155 (miRNA-155) in the occurrence of epilepsy and the molecular mechanism involved. In patients with temporal lobe epilepsy, miRNA-155 expression was evidently higher than that in patients of the normal volunteers group. Overexpression of miRNA-155 resulted in decreased brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) protein expression, increased caspase-3 activity, tumor protein p53 (p53) and apoptosis regulator BAX (Bax) protein expression, and inhibited phosphoinositide 3-kinase (PI3K), phosphorylated (p-)protein kinase B (Akt) and p-mechanistic target of rapamycin (mTOR) protein expression in epilepsy cells. PI3K inhibitor accelerated the effect of miRNA-155 on the inhibition of BDNF and TrkB protein expression, the promotion of caspase-3 activity, p53 and Bax protein expression, and the inhibition of PI3K, p-Akt and p-mTOR protein expression in epilepsy cells. The present findings indicate that miRNA-155 contributes to the occurrence of epilepsy through the PI3K/Akt/mTOR signaling pathway.
Continuous blood pressure (BP) estimation using pulse transit time (PTT) is a promising method for unobtrusive BP measurement. However, the accuracy of this approach must be improved for it to be ...viable for a wide range of applications. This study proposes a novel continuous BP estimation approach that combines data mining techniques with a traditional mechanism-driven model. First, 14 features derived from simultaneous electrocardiogram and photoplethysmogram signals were extracted for beat-to-beat BP estimation. A genetic algorithm-based feature selection method was then used to select BP indicators for each subject. Multivariate linear regression and support vector regression were employed to develop the BP model. The accuracy and robustness of the proposed approach were validated for static, dynamic, and follow-up performance. Experimental results based on 73 subjects showed that the proposed approach exhibited excellent accuracy in static BP estimation, with a correlation coefficient and mean error of 0.852 and -0.001 ± 3.102 mmHg for systolic BP, and 0.790 and -0.004 ± 2.199 mmHg for diastolic BP. Similar performance was observed for dynamic BP estimation. The robustness results indicated that the estimation accuracy was lower by a certain degree one day after model construction but was relatively stable from one day to six months after construction. The proposed approach is superior to the state-of-the-art PTT-based model for an approximately 2-mmHg reduction in the standard derivation at different time intervals, thus providing potentially novel insights for cuffless BP estimation.
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