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This paper aimed to investigate the role of adenosine triphosphate-binding cassette (ABC) transporters on the efflux and the toxicity of nanoparticles in liver and kidney cells. In this study, we synthesized CdTe quantum dots (QDs) that were monodispersed and emitted green fluorescence (maximum peak at 530 nm). Such QDs tended to accumulate in human hepatocellular carcinoma cells (HepG2), human kidney cells 2 (HK-2), and Madin-Darby canine kidney (MDCK) cells, and cause significant toxicity in all the three cell lines. Using specific inhibitors and inducers of P-glycoprotein (Pgp) and multidrug resistance associated proteins (Mrps), the cellular accumulation and subsequent toxicity of QDs in HepG2 and HK-2 cells were significantly affected, while only slight changes appeared in MDCK cells, corresponding well with the functional expressions of ABC transporters in cells. Moreover, treatment of QDs caused concentration- and time- dependent induction of ABC transporters in HepG2 and HK-2 cells, but such phenomenon was barely found in MDCK cells. Furthermore, the effects of CdTe QDs on ABC transporters were found to be greater than those of CdCl 2 at equivalent concentrations of cadmium, indicating that the effects of QDs should be a combination of free Cd 2 + and specific properties of QDs. Overall, these results indicated a strong dependence between the functional expressions of ABC transporters and the efflux of QDs, which could be an important reason for the modulation of QDs toxicity by ABC transporters. [ABSTRACT FROM AUTHOR]

Nowadays, trace detection of thiram is in urgent demand due to its widespread application in agriculture and significant harmful effects on public health. In this work, a three-dimensional (3D) sea cucumber-like flexible porous surface-enhanced Raman scattering (SERS) substrate composed of a poly(vinylidene fluoride) (PVDF) membrane, ZnO nanorods, gold films, and Ag nanoparticles (Ag/Au/ZnO/P) has been established for the highly sensitive detection of thiram. The substrate takes advantage of the 3D morphology of the Ag/Au/ZnO system on a flexible porous PVDF membrane to produce abundant plasmonic hot spots. Meanwhile, the employment of an AgNPs/Au shell system combined the benefits of both gold and silver metals, thus guaranteeing stable and sensitive detection. With 4-mercaptobenzoic acid (4-MBA) as a probe molecule, the Ag/Au/ZnO/P substrate exhibited excellent linear detection in the range of 10−11–10−5 M, with a correlation coefficient (R2) of 0.99 and an enhancement cofactor of 7.09 × 107. The substrate exhibited excellent uniformity with a related standard deviation (RSD) value of 3.82% and demonstrated high stability during a 15 d-storage test. In addition, the substrate could detect thiram in an aqueous solution at concentrations as low as 10−10 M with excellent selectivity. Meanwhile, thiram on the surface of apple peel could be easily detected by the Ag/Au/ZnO/P substrate with the "paste-and-peel" method in less than 10 s, and the detection limit could be as low as 0.48 ng cm−2. Overall, the remarkable performance of the Ag/Au/ZnO/P SERS substrate demonstrated its great potential for the environmental monitoring of thiram. [ABSTRACT FROM AUTHOR]

Anti-fungal blue light (ABL) therapies have been widely studied to treat various microbial infections in the literature. The blue light with wavelengths ranging from 400 to 470 nm has been reported to be effective to inhibit various kinds of bacteria and fungi. The existing studies usually report the viability rates of the pathogens under the irradiation of the blue light with different dosage parameters. However, to the best of our knowledge, there is still no work especially focusing on studying the effect of ABL therapies on treating candida vaginitis, where it is important to study the viability of both the Candida albicans (C. albicans) and the human vaginal epithelial cells. It is the purpose of this work to conduct ABL experiments on both of these two cells, analyze the effects, and determine the best ABL wavelength out of three candidates, i.e., 405-nm, 415-nm, and 450-nm wavelength. The viability rates of the C. albicans and the human vaginal epithelial cells irradiated by the three blue LED light sources were measured, whose irradiance (power density) were all set to 50 mW/cm2. The dynamic viability models of the C. albicans and the epithelial cells were built based on the experimental data. Moreover, in this work, we also built a functional relationship between the viability of these two types of cells, by which we further compared the effects of the blue light irradiation on both the C. albicans and vaginal epithelial cells. The experimental data showed that when an approximately 80% inhibiting rate of the C. albicans was achieved, the survival rates of the epithelial cells were 0.6700, 0.7748, and 0.6027, respectively for the treatment by the 405-nm, 415-nm, and 450-nm wavelength light. On the other hand, by simulating the functional relationship between the viability of the two types of cells, the survival rates of the epithelial cells became 0.5783, 0.6898, and 0.1918 respectively using the 405-nm, 415-nm and 450-nm wavelength light, when the C. albicans was completely inhibited. Therefore, both the experimental data and the model simulation results have demonstrated that the 415-nm light has a more effective anti-fungal result with less damage to the epithelial cells than the 405-nm and 450-nm light. [ABSTRACT FROM AUTHOR]

A novel method is reported to discriminate human and animal blood by Raman spectroscopy without complex sample preparation. A partial least squares discriminant analysis model was constructed from a calibration set of Raman spectra from three species of animal blood using 785-nm laser excitation. The discrimination between human and nonhuman blood was calculated by three sigma. Various performance measures, including a blind test and external validation, confirmed the discriminatory performance of the chemometric model. The model provided 100% accuracy in its differentiation between human and nonhuman blood. These results demonstrate that Raman spectroscopy is a promising tool for the discrimination of animal and human blood. [ABSTRACT FROM PUBLISHER]

The increasingly serious environmental pollution worldwide has posed a great threat to the ecosystem and human health, and yet the development of portable in situ monitoring techniques that are sensitive to gaseous and water pollutants remains incomplete. Herein, we report a highly active surface-enhanced Raman spectroscopy (SERS) substrate fabricated by immobilizing gold nanoparticles (AuNPs) onto a polyvinylidene fluoride (PVDF) membrane for continuous in situ SERS detection of pollutants in water and atmosphere. 4-Mercaptobenzoic acid (4-MBA) was adopted as a probe molecule to evaluate the performance of the substrate, and the results indicate that the polymer-based flexible substrate features high sensitivity, uniformity, and repeatability. The fabricated PVDF/SERS substrate was integrated with a portable Raman spectrometer operating under both passing-by and passing-through modes. The integrated system accomplishes quantitative detection and real-time online monitoring of pH in a liquid environment with a response speed of less than 10 s and the rapid SERS response to gas molecules at a low concentration within 30 s. We also demonstrated the highly sensitive detection for mainstream smoke (MS) and sidestream (SS) of cigarette smoke and verified their differences in the main constituent which contributes to the harmful secondhand smoke in public. The developed portable Raman system has excellent application prospects in online liquid and gas environmental detection. [ABSTRACT FROM AUTHOR]

Although colorectal cancer (CRC) is common, there is a paucity of information regarding its molecular pathogenesis. Studies have shown that miRNAs play pivotal roles in the development and progression of CRC. There is a need to further investigate the biological functions of miRNAs in CRC. In particular, it has been reported that miR-942-5p exhibits tumor-suppressive properties. Thus, we analyzed the functional significance of miR-942-5p in CRC and the underlying molecular mechanisms. We found that miR-942-5p was downregulated in CRC tissues and cells. Cell Counting Kit-8, EdU, and colony formation assays revealed that the overexpression of miR-942-5p by mimics inhibited the proliferation of CRC cells. Use of the miR-942-5p inhibitor effectively enhanced the proliferative potential of CRC cells. Further, in vivo xenograft experiments confirmed these results. Increased expression of miR-942-5p suppressed the invasion, migration, and epithelial-mesenchymal transition of CRC cell lines, while decreased miR-942-5p expression had the opposite effect. CCBE1, a secretory molecule for lymphangiogenesis, was established as a downstream target of miR-942-5p, and its expression was inversely correlated with the expression of miR-942-5p in CRC cells. Additionally, cotransfection of the miR-942-5p inhibitor with si-CCBE1 into CRC cells reversed the effects induced by miR-942-5p overexpression. In conclusion, we confirmed that miR-942-5p exerts oncogenic actions in CRC by targeting CCBE1 and identified miR-942-5p as a potential clinical biomarker for CRC diagnosis and therapy. [ABSTRACT FROM AUTHOR]

Fragile X syndrome (FXS) is a heritable mental retardation disease caused by unstable trinucleotide repeat sequences in FMR1. FXS is characterized by delayed development, hyperactivity, and autism behavior. Zebrafish is an excellent model to study FXS and the underlying function of fmr1. However, at present, fmr1 function is mainly studied via morpholinos or generated mutants using targeting induced local lesions in genomes. However, both of these methods generate off-target effects, making them suboptimal techniques for studying FXS. In this study, CRISPR/Cas9 technology was used to generate two zebrafish fmr1 mutant lines. High-throughput behavior analysis, qRT-PCR, and alcian blue staining experiments were employed to investigate fmr1 function. The fmr1 mutant line showed abnormal behavior, learning memory defects, and impaired craniofacial cartilage development. These features are similar to the human FXS phenotype, indicating that the fmr1 mutant generated in this study can be used as a new model for studying the molecular pathology of FXS. It also provides a suitable model for high-throughput screening of small molecule drugs for FXS therapeutics. [ABSTRACT FROM AUTHOR]

Due to its important role in tumor development and treatment, hyaluronidase (HAase) has been widely investigated in vitro and in vivo. However, such investigation was limited by the absence of sensitive and in situ detection methods. Herein, a hyaluronic acid (HA) hydrogel based on the fluorescence resonance energy transfer (FRET) effect was constructed for the detection of HAase. FITC and AuNPs were covalently coupled with two HA derivatives respectively to form a fluorescent donor-acceptor pair. In the presence of HAase, the hydrogel established by cross-linking of HA derivatives was hydrolyzed specifically. The FRET effect in the hydrogel disappeared and the fluorescence intensity increased proportionally with the changes in the concentration of the HAase. Experiments proved that the HAase sensing system had a wide response range (0.5–100 U/mL), good anti-interference, and excellent biocompatibility. When the hydrogel was used for 3D culture of lung cancer cells, in situ fluorescent response could be achieved. [ABSTRACT FROM AUTHOR]

This work aimed to establish a fast and accurate method to detect glioma by combining surface‐enhanced Raman scattering (SERS) and mathematical analysis. At first, 785‐nm laser was selected as the optimum laser to acquire Raman spectra of human brain tissue. Second, it was verified that Raman data in the range of 1,200–1,600 cm−1 could improve the performance of classifier. Based on the analytical results of 1,200–1,600 cm−1 data, the sensitivity and specificity of partial least square (PLS) analysis and back‐propagation neural network (BPNN) were as high as 100%, whereas the sensitivity and specificity of support vector machine (SVM) were 96% and 100%, respectively. Among them, PLS was more potential in the detection of glioma, because of its lower computational cost compared with SVM and BPNN. Moreover, the correlation between observed Raman peaks and 2‐hydroxyglutarate (2HG; 512, 790, 1,204, 1,302, and 1,463 cm−1) was observed, suggesting 2HG as a potential marker of glioma using its Raman spectroscopic signatures. After all, SERS combining with mathematical analysis could be a promising tool for the accurate detection of glioma. [ABSTRACT FROM AUTHOR]

Here, we utilized the ultrasonic emulsification technique to generate hyaluronic acid microspheres incorporating a fluorescence-based glucose biosensor. We synthesized a novel lanthanide ion luminophore based on Eu3+. Eu sulfosuccinimidyl dextran (Eu-dextran) and Alexa Fluor 647 sulfosuccinimidyl-ConA (Alexa Fluor 647-ConA) were encapsulated in hyaluronic acid hydrogel to generate microspheres. Glucose sensing was carried out using a fluorescence resonance energy transfer (FRET)-based assay principle. A proportional fluorescence intensity increase was found within a 0.5-10-mM glucose concentration range. The glucose-sensing strategy showed an excellent tolerance for potential interferents. Meanwhile, the fluorescent signal of hyaluronic acid microspheres was very stable after testing for 72 h in glucose solution. Overall, hyaluronic acid microspheres encapsulating sensing biomolecules offer a stable and biocompatible biosensor for a variety of applications including cell culture systems, tissue engineering, detection of blood glucose, etc.We report an ingenious biosensor encapsulated in hyaluronic acid microspheres for monitoring of glucose. Glucose sensing is carried out using a fluorescence resonance energy transfer-based assay principle with a novel lanthanide ions luminophore. The glucose detection system has excellent biocompatibility and stability for monitoring of glucose [ABSTRACT FROM AUTHOR]

Previous studies in our lab have revealed that both P-glycoprotein (Pgp) and multi-resistance associated protein (Mrp) 1 played important roles in the detoxification of heavy metals and polycyclic aromatic hydrocarbon (PAH) in zebrafish embryos. This paper aims to extend this research by using mrp1 -deficient model to illustrate the individual function of Mrp1. In this respect, CRISPR/Cas9 system was employed to generate a frameshift mutation in zebrafish mrp1 causing premature translational stops in Mrp1. Significant reduction on the efflux function of Mrps was found in mutant zebrafish embryos, which correlated well with the significantly enhanced accumulation and toxicity of cadmium chloride (CdCl 2 ) and benzo[a]pyrene (BαP), indicating the protective role of the corresponding protein. The different alteration on the accumulation and toxicity of Cd 2+ and BαP could be attributed to the fact that Cd 2+ and its metabolites were mainly excreted by Mrp1, while BαP was primarily pumped out by Pgp. More importantly, the compensation mechanism for the absence of Mrp1, including elevated glutathione (GSH) level and up-regulated expression of pgp and mrp2 were also found. Thus, mrp1 -deficient zebrafish embryo could be a useful tool in the investigation of Mrp1 functions in the early life stages of aquatic organisms. However, compensation mechanism should be taken into consideration in the interpretation of results obtained with mrp1 -deficient fish. [ABSTRACT FROM AUTHOR]

[Display omitted] • Efflux of n-TiO 2 and AuNPs were not mediated by ABC transporters. • N-TiO 2 and AuNPs induced the expressions of PGP and MRP1 after significant cell death. • PGP and MRP1 detoxified nanoparticles by reducing the oxidative stress. • Excessive oxidative stress could be an important reason for the up-regulation of ABC transporters. • Both PXR and NRF2 modulated the up-regulation of pgp and mrp1. This paper aimed to systemically investigate the role of adenosine triphosphate-binding cassette (ABC transporters) in the detoxification of non-substrate nanoparticles including titanium dioxide (n-TiO 2 , 5−10 nm) and gold (AuNPs, 3 nm, 15 nm, and 80 nm, named as Au-3, Au-15 and Au-80) in human lung cancer (A549) and human cervical cancer (HeLa) cells. All these nanoparticles were of larger hydrophilic diameters than the channel sizes of ABC transporters, thus should not be the substrates of membrane proteins. After 24-h treatment, they induced significant cytotoxicity as reflected by the reduction in cell viability and glutathione (GSH) contents, as well as the increase in reactive oxygen species (ROS) level. At median-lethal concentrations (10 mg/L n-TiO 2 , 2 mg/L Au-3, 5 mg/L Au-15, and 10 mg/L Au-80 for A549 cells; 20 mg/L n-TiO 2 , 2 mg/L Au-3, 5 mg/L Au-15, and 10 mg/L Au-80 for Hela cells), all the nanoparticles significantly induced the gene expressions and activities of ABC transporters including P-glycoprotein (PGP) and multidrug resistance associated protein 1 (MRP1). Addition of transporter inhibitors enhanced the ROS levels produced by nanoparticles, but didn't alter their death-inducing effects and intracellular accumulations. With specific suppressors, transcription factors like nuclear factor-erythroid 2-related factor-2 (NRF2) and pregnane X receptor (PXR) were proved to be important in the induction of ABC transporters by nanoparticles. After all, this paper revealed a damage-dependent modulation of ABC transporters by non-substrate nanoparticles. The up-regulated ABC transporters could help in reducing the oxidative stress produced by nanoparticles. Such information should be useful in assessing the environmental risk of nanoparticles, as well as their interactions with other chemical toxicants or drugs. [ABSTRACT FROM AUTHOR]

• Parental exposure CdCL 2 reduce behaviour activity in F1 offspring; • Parental exposure CdCL 2 reduce dopamine, serotonin, acetylcholine in F1 offspring; • Disrupted neuronal development and neurotransmitter metabolism genes in F1 offspring. As an important environmental pollutant, the heavy metal cadmium has a significant negative impact on the stability of the ecological environment and on organismal health. Previous studies have shown that cadmium chloride can damage the nervous, skeletal, endocrine, and reproductive systems, but to our knowledge, the effects of cadmium on the behavior, neurotransmitter levels, and neuronal development in the offspring of exposed animals have not been reported. In the present study, sexually-mature zebrafish were exposed to cadmium chloride at different concentrations for 60 days, and in this background, behavior, neurotransmitters level, neuro-development and neurotransmitter metabolism was investigated in the F1 offspring. The results showed that exposure of the parental zebrafish to cadmium chloride resulted swimming speed and distance of F1 offspring significantly reduced; the levels of neurotransmitters, such as dopamine, serotonin, and acetylcholine is disrupted. neuro-development and neurotransmitter metabolism related genes expression pattern was altered, which cause zebrafish F1 offspring developmental neurotoxicity. These findings provide further insights into the harm posed by cadmium chloride to the aquatic ecosystems. [ABSTRACT FROM AUTHOR]