An electrochemical molecularly imprinted microfluidic paper-based chip for detection of inflammatory biomarkers IL-6 and PCT.

Based on surface biomolecular imprinting technology, a rotary microfluidic electrochemical paper-based chip (MIP-ePADs) was proposed for sensitive and selective detection of human interleukin 6 (IL-6) and procalcitonin (PCT). Compared with the traditional method, the sample can be added directly on the MIP-ePAD by rotating the working electrode, which avoids the loss of the liquid to be tested and greatly simplifies the process of electropolymerization imprinting and template elution. Our experimental results show that linear concentration ranges of IL-6 and PCT in the electrochemical molecularly imprinted microfluidic paper-based chip ranged from 0.01 to 5 ng mL-1, with their detection limits being 3.5 and 2.1 pg mL-1, respectively. For the detection of actual serum samples, there was no significant difference between the results of MIP-ePADs and the traditional electrochemiluminescence method used in hospitals, indicating that the paper-based chip can be used for stable and accurate analysis and detection. The chip greatly reduces the cost of clinical trials due to its advantages of easy preparation and low cost. The chip can be used for the analysis of non-antibody inflammation markers and can be widely used in home and hospital treatment detection. This method will not only play an important role in rapid detection, but also provide new ideas for the improvement of rapid detection technology.

Occurrence, Distribution, and Trophic Transfer of Pharmaceuticals and Personal Care Products in the Bohai Sea.

The ubiquitous presence of pharmaceuticals and personal care products (PPCPs) in environments has aroused global concerns; however, minimal information is available regarding their multimedia distribution, bioaccumulation, and trophic transfer in marine environments. Herein, we analyzed 77 representative PPCPs in samples of surface and bottom seawater, surface sediments, and benthic biota from the Bohai Sea. PPCPs were pervasively detected in seawater, sediments, and benthic biota, with antioxidants being the most abundant PPCPs. PPCP concentrations positively correlated between the surface and bottom water with a decreasing trend from the coast to the central oceans. Higher PPCP concentrations in sediment were found in the Yellow River estuary, and the variations in the physicochemical properties of PPCPs and sediment produced a different distribution pattern of PPCPs in sediment from seawater. The log Dow, but not log Kow, showed a linear and positive relationship with bioaccumulation and trophic magnification factors and a parabolic relationship with biota-sediment accumulation factors. The trophodynamics of miconazole and acetophenone are reported for the first time. This study provides novel insights into the multimedia distribution and biomagnification potential of PPCPs and suggests that log Dow is a better indicator of their bioaccumulation and trophic magnification.

Three dimensionally printed nitrocellulose-based microfluidic platform for investigating the effect of oxygen gradient on cells.

In this article, we present a novel nitrocellulose-based microfluidic chip with 3-dimensional (3D) printing technology to study the effect of oxygen gradient on cells. Compared with conventional polydimethylsiloxane (PDMS) chips of oxygen gradient for cell cultures that can only rely on fluorescence microscope analysis, this hybrid nitrocellulose-based microfluidic platform can provide a variety of analysis methods for cells, including flow cytometry, western blot and RT-PCR, because the nitrocellulose-based chips with cells can be taken out from the growth chambers of 3D printed microfluidic chip and then used for cell collection or lysis. These advantages allow researchers to acquire more information and data on the basic biochemical and physiological processes of cell life. The effect of oxygen gradient on the zebrafish cells (ZF4) was used as a model to show the performance and application of our platform. Hypoxia caused the increase of intercellular reactive oxygen species (ROS) and accumulation of hypoxia-inducible factor 1α (HIF-1α). Hypoxia stimulated the transcription of hypoxia-responsive genes vascular endothelial growth factor (VEGF) and induced cell cycle arrest of ZF4 cells. The established platform is able to obtain more information from cells in response to different oxygen concentration, which has potential for analyzing the cells under a variety of pathological conditions.

Dietary gossypol suppressed postprandial TOR signaling and elevated ER stress pathways in turbot (Scophthalmus maximus L.).

Gossypol is known to be a polyphenolic compound toxic to animals. However, its molecular targets are far from fully characterized. To evaluate the physiological and molecular effects of gossypol, we chose turbot (Scophthalmus maximus L.), a carnivorous fish, as our model species. Juvenile turbots (7.83 ± 0.02 g) were fed diets containing gradient levels of gossypol at 0 (G0), 600 (G1), and 1,200 (G2) mg/kg diets for 11 wk. After the feeding trial, fish growth, body protein, and fat contents were significantly reduced in the G2 group compared with those of the G0 group (P < 0.05). Gossypol had little impact on digestive enzyme activities and intestine morphology. However, gossypol caused liver fibrosis and stimulated chemokine and proinflammatory cytokine secretions. More importantly, gossypol suppressed target of rapamycin (TOR) signaling and induced endoplasmic reticulum (ER) stress pathway in both the feeding experiment and cell cultures. Our results demonstrated that gossypol inhibited TOR signaling and elevated ER stress pathways both in vivo and in vitro, thus providing new mechanism of action of gossypol in nutritional physiology.

Aging increases the particulate- and leachate-induced toxicity of tire wear particles to microalgae.

The toxic effects of tire wear particles (TWPs) on organisms have attracted widespread concerns over the past decade. However, the underlying toxicity mechanism of TWPs, especially aged TWPs to marine microalgae remains poorly understood. This study investigated the physiological and metabolic responses of Phaeodactylum tricornutum to different concentrations of TWPs (Experiment 1), virgin and differently aged TWPs (Experiment 2) as well as their leachates and leached particles (Experiment 3). Results demonstrated that TWPs promoted the growth of microalgae at low concentrations (0.6 and 3 mg L-1) and inhibited their growth at high concentrations (15 and 75 mg L-1). Moreover, aged TWPs induced more profound physiological effects on microalgae than virgin TWPs, including inhibiting microalgae growth, decreasing the content of Chla, promoting photosynthetic efficiency, and causing oxidative damage to algal cells. Untargeted metabolomics analysis confirmed that aged TWPs induced more pronounced metabolic changes than virgin TWPs. This study represented the first to demonstrate that both particulate- and leachate-induced toxicity of TWPs was increased after aging processes, which was confirmed by the changes in the surface morphology of TWPs and enhanced release of additives. Through the significant correlations between the additives and the microalgal metabolites, key additives responsible for the shift of microalgal metabolites were identified. These results broaden the understanding of the toxicity mechanism of aged TWPs to microalgae at the physiological and metabolic levels and appeal for considering the effects of long-term aging on TWP toxicity in risk assessment of TWPs.

Development and application of diffusive gradients in thin-films for in-situ monitoring of 6PPD-Quinone in urban waters.

The occurrence and risk of N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone (6PPD-Q), derived from the oxidation of the tire antidegradant 6PPD, has raised significant concern since it was found to cause acute mortality in coho salmon when exposed to urban runoff. Given the short half-life period and low solubility of 6PPD-Q, reliable in situ measurement techniques are required to accurately understand its occurrence and behaviour in aquatic environments. Here, using the diffusive gradients in thin-films (DGT) method with HLB as a binding agent, we developed a new methodology to measure 6PPD-Q in urban waters. 6PPD-Q was rapidly and strongly adsorbed on the HLB-binding gel and was efficiently extracted using organic solvents. The HLB-DGT accumulated 6PPD-Q linearly for >7 d and its performance was not significantly affected by pH (6.5-8.5), ionic strength (0.0001-0.5 M) or dissolved organic matter (0-20 mg L-1). Field evaluation of the DGT method demonstrated its effectiveness in urban runoff, detecting 6PPD-Q levels of 15.8-39.5 ng L-1 in rivers. In snowmelt, DGT detected 6PPD-Q levels of 210 ng L-1 which is two times higher than the value obtained by grab sampling. 6PPD-Q levels were much higher in snowmelt than those in rivers. This indicates that snowfall constitutes an important transport pathway for 6PPD-Q and that DGT effectively captured the fraction continuously released from dust particles in the snow samples. 6PPD-Q posed a substantial risk to migratory fish in urban waters, and its release from tire wear particles requires further investigation. This study is the first to develop a DGT-based method for 6PPD-Q determination in urban waters, and the method can ensure an accurate measurement of the release of 6PPD-Q to the environment, particularly in rainfall or snowmelt, important pathways for its entry into the aquatic environment.

Dissolved oxygen gradient on three dimensionally printed microfluidic platform for studying its effect on fish at three levels: cell, embryo, and larva.

A simple and low-cost dissolved oxygen gradient platform of three dimensionally (3D) printed microfluidic chip was developed for cultivating cells, embryos, and larvae of fish. "Christmas tree" structure channel networks generated a dissolved oxygen gradient out of two fluids fed to the device. Polydimethylsiloxane (PDMS) membrane with high biocompatibility was used as the substrate for cell culture in the 3D-printed microfluidic chip, which made the cell analysis easy. The embryos and larvae of fish could be cultured directly in the chip, and their development can be observed in real time with a microscope. Using zebrafish as a model, we assessed the effect of different dissolved oxygen on its cells, embryos, and larvae. Hypoxia induced production of reactive oxygen species (ROS) in zebrafish cells, embryos, and larvae, eventually leading to cell apoptosis and developmental impairment. Hypoxia also increased nitric oxide content in zebrafish cells, which might be a defensive strategy to overcome the adverse effect of hypoxia in fish cells. This is the first platform that could comprehensively investigate the effects of different dissolved oxygen on fish at the cell, embryo, and larva levels, which has great potential in studying the responses of aquatic organisms under different oxygen concentrations.

Profiling of the spatiotemporal distribution, risks, and prioritization of pharmaceuticals and personal care products in coastal waters of the northern Yellow Sea, China.

Pharmaceuticals and personal care products (PPCPs) have aroused global concerns due to their ubiquitous occurrence and detrimental effects. The spatiotemporal distributions of 64 PPCPs and their synergetic ecological risks were comprehensively investigated in the seawater of Yantai Bay, and 1 H-benzotriazole (BT), ethenzamide, phenazone, propyphenazone, 4-hydroxybenzophenone and N, N'-diphenylurea were first determined in the seawater of China. Fifty-six PPCPs were detected and their concentrations were 27.5-182 ng/L, with BT contributing around 58.0%. Higher PPCP concentrations were observed in winter and spring, with the concentrations of antioxidants, analgesic/anti-inflammatory drugs and human-used antibiotics significantly higher in winter, while those of aquaculture-used antibiotics and UV filters significantly higher in summer, which was closely related with their usage patterns. Positive correlations were observed for PPCP concentrations between surface and bottom water, except summer, during which time the weak vertical exchange and varied environmental behaviors among different PPCPs resulted in the distinct compositions and concentrations. Terrestrial inputs and mariculture resulted in higher PPCP concentrations in the area located adjacent to the coast and aquaculture bases. The PPCP mixtures posed medium to high risk to crustaceans, and bisphenol A was identified as a high-risk pollutant that needs special attention.

Surface-enhanced Raman scattering labeled nanoplastic models for reliable bio-nano interaction investigations.

Nanoplastics (NPs) have attracted great attention as an emerging pollution. To date, their interaction with biological systems has been studied mostly by using fluorescent-labeled NPs, which suffered from serious drawbacks such as biological autofluorescence interference and false-positive results. Reliable optically labeled NP models are eagerly desired until now. Herein, a novel near-infrared (NIR) surface-enhanced Raman scattering (SERS) labeled NP model was proposed, which gained single-particle ultra-sensitivity, deep tissue detection, multiplex labeling ability, and anti-interference property. More importantly, the NP demonstrated satisfactory in vivo signal stability which completely prevented the positive-false problems. The advantages of the NPs enabled direct, dynamic in vivo behavior imaging study in living zebrafish embryo, adult zebrafish and green vegetable Brassica rapa. It was found for the first time that NPs entered blood circulation system of zebrafish larva via dermal uptake route, which only occurred in a short 48 h-window post-hatch. NPs widely distributed in roots, shoots and leaves of Brassica rapa seedlings germinating and growing in the NP-containing hydroponic culture. Different depths of one root showed varied adsorption capabilities towards NPs with fulvic acid, lipid and sodium dodecyl sulfate eco-coronas. This work provided an ideal tool for reliable bio-NP interaction study for a variety of organisms, which could promote the research of NPs.

Hybrid Three Dimensionally Printed Paper-Based Microfluidic Platform for Investigating a Cell's Apoptosis and Intracellular Cross-Talk.

In this paper, we first proposed a novel hybrid three-dimensional (3D) printed and paper-based microfluidic platform and applied it for investigating the cell's apoptosis and intracellular cross-talk. The fabrication of a 3D-printed microfluidic chip is much easier than polydimethylsiloxane (PDMS) chip and can be applied in many common labs without soft lithogrophy fabrication equipment. Moreover, 3D printing can be perfectly combined with paper-based chips that can provide 3D scaffold for cell culture and analysis. In addition, these paper chips are disposable after use, greatly reducing the experimental cost. We integrated "Christmas Tree" structure with the top layer of the 3D-printed microfluidic chip to generate a continuous concentration gradient, and the bottom layer contained paper-based chips as cell culture area. The two-layer structure allows the concentration gradient forming layer to be separated from the cell culture layer, which can simplify the planting of cells in the microfluidic chip and make sure the cells stay in the culture chambers and don't clog the microfluidic channels. Applying this hybrid platform, we examined the effect of H2S on cancer cells. Continuous exposure to a low concentration of H2S inhibited cancer cell SMMC-7721 proliferation by inducing cell apoptosis. We also found that two gaseous molecules H2S and NO have cross-talk in cancer cells; they formed bioactive intermediate polysulfides in cancer cells. It is expected that this novel hybrid 3D-printed and paper-based microfluidic platform will have widespread application prospects in cell investigation.