Zebrafish Behavioral Phenomics Links Artificial Sweetener Aspartame to Behavioral Toxicity and Neurotransmitter Homeostasis.

Artificial sweeteners (ASs) are extensively used as food additives in drinks and beverages to lower calorie intake and prevent lifestyle diseases such as obesity. Although clinical and epidemiological data revealed the link between the chronic overconsumption of ASs and adverse health effects, there still exist controversies over the potential adverse neural toxic effect of ASs such as aspartame (APM), with acceptable daily intake (ADI) for a long time, on human health. In addition, whether APM and its metabolites are neurotoxic remains debatable due to a lack of data from an animal experiment or clinical investigation. Herein, to fully describe the potential neurological effect of APM, adult zebrafish served as the animal model to assess neurophysiological alteration induced by APM exposure within the range of the ADI (1, 10, and 100 mg/L) for 2 months. A cohort of standardized neurobehavioral phenotyping assays was conducted, including light/dark preference tests (LDP), novel tank diving tests, novel object recognition tests, social interaction tests, and color preference tests. For instance, in the LDP test, saccharin remarkably decreased the swimming time of zebrafish in the DARK part from 111 ± 10.8 (control group) to 72.2 ± 11.4 (100 mg/L groups). Besides, brain chemistry involved in the alteration of total neurotransmitters was determined by LC-MS/MS to confirm the behavioral results. Overall, current research studies revealed that APM within the range of the ADI altered the total behavioral profiles of zebrafish and disturbed the homeostasis of neurotransmitters in the brain. The present study has established a set of experimental paradigms, revealing the standardized procedure of using adult zebrafish to determine the neural activity or toxicity of AS molecules phenotypically. Zebrafish behavioral phenotyping methods, which were characterized by a cohort of behavioral fingerprints, can link the phenotypical alteration to changes in neurotransmitters in the brain, so as to provide a predictive reference for the further exploration of the molecular mechanism of phenotypic changes induced by ASs.

Phenotyping Aquatic Neurotoxicity Induced by the Artificial Sweetener Saccharin at Sublethal Concentration Levels.

Artificial sweeteners (ASs) have generally been applied as food additives to improve the taste of sweetness. Thus, their potential toxic effects have received extensive attention. Saccharin (SAC), discovered more than a century ago, has been used as the first noncaloric AS in foods and beverages for over 100 years. Although the toxicological effects such as carcinogenicity of SAC have been controversial for a long time, there is a paucity of knowledge covering its potential behavioral toxicity and neurotoxicity. Methodologically, in current research, adult zebrafish neurobehavioral phenotypic screening approaches were introduced to systematically delineate the potential behavioral and neural toxicity of SAC by phenotyping the comprehensive neuro-behavioral profiles of adult zebrafish, which were chronically (2 months) subject to SAC (0, 1, 10, and 50 mg/L) exposure. Subsequently, a cohort of standard neurobehavioral tests including the light/dark preference (LDP) test, novel tank diving (NTD) test, novel object recognition (NOR) test, social interaction test (SIT), color-associated learning and memory test, and conditional place preference test were applied to delineate the general adverse effect of SAC. Specifically, in a concentration-dependent manner, SAC significantly increased the preference toward the dark side in the LDP test, inhibited exploratory behavior to the top arena in the NTD test, dampened the motivation to explore the novel object in the NOR test, weakened social preference in the SIT, and interfered in the color-based associative learning and memory ability. For example, in the LDP test, SAC remarkably increased the swimming distance of zebrafish in the dark part from 222 ± 34.6 (control group) to 675 ± 35.0 (50 mg/L group). Finally, the quantity of certain key neurotransmitters was further measured to determine the alteration induced by SAC on the brain chemistry. In total, the current research would provide a versatile neurobehavioral phenomics-based strategy to phenotypically screen the neurotoxicity of food additives at the overall animal level and provide a reference for further neurotoxicity exploration at the tissue and molecular level.

Discovery of Nonpeptide, Environmentally Sensitive Fluorescent Probes for Imaging p53-MDM2 Interactions in Living Cell Lines and Tissue Slice.

Based on structural optimization work, probes 9-11 with practical activity and selectivity in tissue as well as living cell lines are well designed and synthesized. All the probes showed potent inhibitory and acceptable cell toxicity compared with the commercially available p53-MDM2 inhibitor Nutlin-3, and can increase the protein expression level of p53 and MDM2 in the A549 cell line; in particular, probes 10 and 11 can increase the protein expression level of p53 better than Nutlin-3. Moreover, their application in imaging and detecting wild-type p53-MDM2 protein-protein interactions have been well demonstrated in at the cell and tissue levels. Overall, these environmentally sensitive fluorescent turn-on probes are affordable and rapid for imaging, which is expected for applications in target drug screening as well as in pathologic diagnosis.

Zebrafish neuro-behavioral profiles altered by acesulfame (ACE) within the range of "no observed effect concentrations (NOECs)".

Recently, artificial sweeteners have received widespread attention as the emerging environmental pollutants, among which, acesulfame (ACE) is ubiquitously present and extremely persistent in the ecosystem. Although the environmental behavior of ACE has already been well studied, its chronic eco-toxicological effects on aquatic organisms are rarely reported. Thus, more researches should be performed to determine the concentration which exerted the observable toxicological effect. Herein, we examined neuro-behavioral effects of ACE at 1, 10 and 100 mg/L on adult zebrafish via performing the behavioral test batteries including light/dark preference test, novel tank diving test, novel object exploration test, social preference test and colour-enhanced CPP test. In addition, in order to fully phenotype the behavioral alteration induced by ACE, we applied the techniques deriving from behavioral phenomics to analyze and interpret the big data from a large number of behavioral variables. Furthermore, the alterations of neurotransmitter in brain were also assayed to confirm the behavioral results. We found that ACE within the concentration range of No Observed Effect Concentrations (NOECs) had remarkably altered the neuro-behavioral profiles: altered the preference for light/dark, reduced the exploration ability of zebrafish in the novel tank and novel object exploration test, affected the group preference of zebrafish, changed the colour preference, learning and memory ability of zebrafish and disturbed the quantitative patterns of neurotransmitter in brain. As a result, this research can offer a reference for readjusting the NOECs of ACE and assessing neurotoxicity of artificial sweeteners.

Novel photoactivatable substrates for Renilla luciferase imaging in vitro and in vivo.

To develop a photoactivatable bioluminescence imaging technique, a set of high and efficient photoactivatable substrates for Renilla luciferase has been well designed and synthesized. Surprisingly, all of them could release the free luciferin that presented robust bioluminescent signals ex vivo and in living animals after UV irradiation at 365 nm.

Novel caged luciferin derivatives can prolong bioluminescence imaging in vitro and in vivo.

Based on N-cyclobutylaminoluciferin (cybLuc), a set of high and efficient caged bioluminescent derivatives (Clucs) as firefly luciferase pro-substrates has been developed herein. After careful examination, these molecules exhibited low cytotoxicity and prolonged bioluminescence imaging up to 6 h in vitro and in vivo. Importantly, these caged luciferin derivatives have the potential to serve as long-term tracking tools to explore some biological process by using bioluminescent imaging.

Mixed shell mesoporous silica nanoparticles for controlled drug encapsulation and delivery.

AIM: Smart mesoporous silica nanoparticles (MSNs) with mixed polymeric shell (MS-MSNs) were prepared to realize controlled encapsulation and responsive delivery of anticancer drugs. MATERIALS & METHODS: Two kinds of polymers, including nonthermoresponsive poly(ethylene glycol) and thermoresponsive poly(N-isopropyl acrylamide), were grafted onto the outlets of the MSNs through acidic liable Schiff base bonds. RESULTS: Poly(N-isopropyl acrylamide) chains could control the release rate of drugs through phase transition, while poly(ethylene glycol) chains could maintain the colloid stability of MSNs. Drugs can be released through the gradual hydrolysis of Schiff base bonds in tumor acidic environment. CONCLUSION: The MS-MSNs gave consideration to both the responsiveness and stability of carriers, and could realize the release of drugs as much as possible in tumor tissues.

Magnetic field assisted photocatalytic degradation of organic dyes in the presence of Ag/TiO(2) coated composite.

Ag/TiO(2) coated composite was prepared via sol-gel method in order to elucidate its application in magnetic field assisted photocatalytic degradation of dyes. Through the degradation of organic dyes, the key influences such as Ag amount, heat-treated temperature and time on the photocatalytic activity of Ag/TiO(2), as well as UV irradiation time, rotational speed, dye concentration and magnetic sheet number on the photocatalytic degradation were studied. Results showed that the Ag/TiO(2) with 25 wt% Ag content heat-treated at 550 °C for 60 min has the best photocatalytic activity. With the increase of UV light irradiation time, rotational speed and magnetic sheet number, the degradation rate is improved. Different dye degradation proved that the method could universally be used.

A new approach for rhenium(VII) recovery by using modified brown algae Laminaria japonica adsorbent.

Brown algae Laminaria japonica was chemically modified with sulfuric acid to obtain a crosslinked brown algae gel (CAS). The CAS gel showed a high affinity for Re(VII) comparing with other biomass gels, and the maximum adsorption capacity was evaluated as 37.20 mg g(-1) in case of pH 6, which could be explained by their different adsorption mechanisms. The adsorption equilibrium, kinetics and thermodynamic study for Re(VII) on the CAS gel was discussed in detail by the several models, such as Langmuir, Freundlich, Temkin and Dubinin-Radushkevich model for kinetics analysis, the pseudo first, the second-order, the Elovich and intraparticle diffusion equation for equilibrium analysis. Reutilization of the CAS gel was confirmed up to three adsorption-elution cycles in column-mode operation with no damage of gel, packed in the column. The result also provides a new approach for the recovery of Re(VII) from Re-containing wastewater by using the modified brown algae gel.

Spectroscopic analyses on sonocatalytic damage to bovine serum albumin (BSA) induced by ZnO/hydroxylapatite (ZnO/HA) composite under ultrasonic irradiation.

ZnO/hydroxylapatite (ZnO/HA) composite with HA molar content of 6.0% was prepared by the method of precipitation and heat-treated at 500°C for 40min and was characterized by powder X-ray diffraction (XRD). The sonocatalytic activities of ZnO/HA composite was carried out through the damage of bovine serum albumin (BSA) in aqueous solution. Furthermore, the effects of several factors on the damage of BSA molecules were evaluated by means of UV-vis and fluorescence spectra. Experimental results indicated that the damage degree of BSA aggravated with the increase of ultrasonic irradiation time, irradiation power and ZnO/HA addition amount, but weakened with the increase of solution acidity and ionic strength. In addition, the damage site to BSA was also studied by synchronous fluorescence technology and the damage site was mainly at tryptophan (Trp) residue. This paper provides a valuable reference for driving sonocatalytic method to treat tumor in clinic application.

Sonocatalytic degradation of organic dyes and comparison of catalytic activities of CeO2/TiO2, SnO2/TiO2 and ZrO2/TiO2 composites under ultrasonic irradiation.

The CeO(2)/TiO(2), SnO(2)/TiO(2) and ZrO(2)/TiO(2) composites were prepared by dispersing various nano-sized oxides (CeO(2), SnO(2), ZrO(2) and TiO(2)) with ultrasound and mixing TiO(2) with CeO(2), SnO(2) and ZrO(2), respectively, in boiling water in a molar ratio of 4:1, followed by calcining temperature 500 degrees C for 60 min. Then a series of sonocatalytic degradation experiments were carried out under ultrasonic irradiation in the presence of CeO(2)/TiO(2), SnO(2)/TiO(2) and ZrO(2)/TiO(2) composites and nano-sized TiO(2) powder. Also, the influences of heat-treatment temperature and heat-treatment time on the sonocatalytic activities of CeO(2)/TiO(2), SnO(2)/TiO(2) and ZrO(2)/TiO(2) composites, and of irradiation time and solution acidity on the sonocatalytic degradation of Acid Red B were investigated by UV-vis spectra. It was found that the sonocatalytic degradation of Acid Red B shows significant variation in rate and ratio that decreases in order: CeO(2)/TiO(2)>SnO(2)/TiO(2)>TiO(2)>ZrO(2)/TiO(2)>SnO(2)>CeO(2)>ZrO(2), and the corresponding ratios of Acid Red B in aqueous solution are 91.32%, 67.41%, 65.26%, 41.67%, 28.34%, 26.75% and 23.33%, respectively. And that the degradation ratio is only 16.67% under onefold ultrasonic irradiation. Because of the good degradation efficiency, this method may be an advisable choice for the treatment of non- or low-transparent wastewaters in the future.

Investigation on solar photocatalytic degradation of various dyes in the presence of Er(3+):YAlO(3)/ZnO-TiO(2) composite.

In this work, Er(3+):YAlO(3)/ZnO-TiO(2) and ZnO-TiO(2) composites were prepared by the ultrasonic dispersion and liquid boiling method. In succession, they were then characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM). Acid red B as a model dye compound was degraded under solar light irradiation to evaluate the photocatalytic activities of the Er(3+):YAlO(3)/ZnO-TiO(2) and ZnO-TiO(2) composites. We found that the photocatalytic activity of ZnO-TiO(2) composite can be enhanced by adding an appropriate amount of Er(3+):YAlO(3). We reviewed influencing factors, such as Er(3+):YAlO(3) content, heat-treated temperature and heat-treated time on the photocatalytic activity of the Er(3+):YAlO(3)/ZnO-TiO(2) composites. In addition, the effects of solar light irradiation time, dye initial concentration, Er(3+):YAlO(3)/ZnO-TiO(2) amount and solution acidity on the photocatalytic degradation of acid red B dye in aqueous solution were investigated in detail. Simultaneously, the degradation and comparison of other dyes such as methyl orange (MO), rhodamine B (RM-B), azo fuchsine (AF), congo red (CG-R) and methyl blue (MB) were also reviewed. In addition, we attempted to explore both the principle of possible excitation of Er(3+):YAlO(3)/ZnO-TiO(2) under solar light irradiation and the mechanism of photocatalytic degradation.

Assisted sonodynamic damage of bovine serum albumin by metronidazole under ultrasonic irradiation combined with photosensitive antitumor drug-Amsacrine.

By research, it was found that the Amsacrine (AMSA) can interact with bovine serum albumin (BSA). In this work, the AMSA was adopted as a sonosensitizer and the Metronidazole (MET) was used as a sensitizer to further damage BSA molecules under ultrasonic irradiation. It could be concluded that the damage degree of BSA molecules in the presence of AMSA and MET was more serious than in the presence of pure AMSA. That is, MET could aggravate the damage to BSA molecules under ultrasonic irradiation combined with AMSA. Meanwhile, the damage degree of BSA molecules was also influenced by some factors, such as ultrasonic irradiation time, MET concentration and solution acidity. In addition, the damage site of BSA molecules was estimated by synchronous fluorescence spectra. It was found that the tyrosine (Tyr) and tryptophan (Typ) residues were damaged almost averagely. Perhaps, these research results are of great significance for driving sonodynamic method to treat tumor in clinic application.

Two 3D chiral coordination polymers with 4-connected 6(6) topological net: synthesis, structure and magnetic properties.

The hydrothermal reaction of Co(II)/Cu(II), 5-hydroxyisophthalic acid and dipyridophenazine leads to the generation of two 3D chiral coordination polymers, [M(hip)(DPPZ)](n) (M = Co(), Cu(), H(2)hip = 5-hydroxyisophthalic acid, DPPZ = dipyridophenazine), which contain M-hip-M helical chains (M = Co, Cu) and possess a new four-connected 6(6) topological net. The resulting crystals were not a racemic mixture but an enantiomeric excess, which was confirmed by the measurement of optical rotation of the bulk samples using solid state vibrational circular dichroism (VCD) and solid circular dichroism (CD) based on the large crystals from one crystallization. The magnetic properties of 1 and 2 have been investigated by variable-temperature magnetic susceptibility and magnetization measurements, and the results reveal that antiferromagnetic interactions exist in 1 and 2.

Preparation of nano-sized mixed crystal TiO2-coated Er3+:YAlO3 by sol-gel method for photocatalytic degradation of organic dyes under visible light irradiation.

In this work, an upconversion luminescence agent, crystallized Er(3 + ):YAlO(3), was synthesized and then coated by the nano-sized TiO(2) film through sol-gel technique. A novel TiO(2) photocatalyst, Er(3 + ):YAlO(3)/TiO(2), with high activity in visible light was subsequently prepared. The Er(3 + ):YAlO(3) and Er(3 + ):YAlO(3)/TiO(2) were characterized by X-ray diffraction (XRD) and transmission electron microscope (TEM). The photocatalytic activity of Er(3 + ):YAlO(3)/TiO(2) photocatalyst was tested by the degradation of acid red B in aqueous solution as the primary model compound under visible light irradiation. The experimental results proved that the prepared TiO(2)-coated crystallized Er(3 + ):YAlO(3) was able to decompose the acid red B efficiently, and it is promising to use the idea to develop new TiO(2) photocatalyst with high activity for photocatalytic degradation under visible light.

[Determination of aluminum in sediments by atomic absorption spectrophotometer without FIA spectrophotometric analysis].

To search for a new method of determining, we developed a new flow injection analyzer, applied to the atomic absorption spectrophotometer, relying on it without flame in place of visible spectrophotometer, and studied the appropriate condition for the determination of aluminum in sediments, thus built up a kind of new analytical test technique. Three peak and two valley absorption values (A1, A2, A3, A4 and A5) can be continuously obtained simultaneously that all can be used for quantitative analysis, then we discussed its theory and experiment technique. Based on the additivity of absorbance (A = A1+A2+A3+A4+ A5), the sensitivity of FIA is enhanced, and its precision and linear relation are also good, raising the efficiency of AAS. The simple method has been applied to determining Al in sediments, and the results are satisfactory.

Poly[[diaqua-µ(4)-tartrato-µ(2)-tartrato-dimanganese(II)] dihydrate].

In the title compound, {[Mn(C(4)H(4)O(6))(H(2)O)]·H(2)O}(n), the Mn(2+) ion is connected to three different tartrate anions and a water mol-ecule, resulting in a distorted MnO(6) octa-hedral geometry. There are two tartrate half-anions in the asymmetric unit, both of which are completed by crystallographic twofold rotation symmetry. The tartrate dianions bridge the Mn(2+) ions to form a wave-like infinite layer. A series of O-H⋯O hydrogen bonds link the layers into a three-dimensional network.