Highly Stable Lanthanide Metal-Organic Framework as an Internal Calibrated Luminescent Sensor for Glutamic Acid, a Neuropathy Biomarker.

Glutamic acid (Glu) is the most abundant excitatory neurotransmitter in the central nervous system, and an elevated level of Glu may indicate some neuropathological diseases. Herein, three isomorphic microporous lanthanide metal-organic frameworks (MOFs) [(CH3)2NH2]2[Ln6(µ3-OH)8(BDC-OH)6(H2O)6]·(solv)x (ZJU-168; ZJU = Zhejiang University, H2BDC-OH = 2-hydroxyterephthalic acid, Ln = Eu, Tb, Gd) were designed for the detection of Glu. ZJU-168(Eu) and ZJU-168(Tb) suspensions simultaneously produce the characteristic emission bands of both lanthanide ions and ligands. When ZJU-168(Eu) and ZJU-168(Tb) suspensions exposed to Glu, the fluorescence intensity of ligands increases while the emission of lanthanide ions is almost unchanged. By utilizing the emission of ligands as the detected signal and the emission of lanthanide ions as the internal reference, an internal calibrated fluorescence sensor for Glu was obtained. There is a good linear relationship between fluorescence intensity ratio and Glu concentration in a wide range with the detection limit of 3.6 µM for ZJU-168(Tb) and 4.3 µM for ZJU-168(Eu). Major compounds present in blood plasma have no interference for the detection of Glu. Furthermore, a convenient analytical device based on a one-to-two logic gate was constructed for monitoring Glu. These establish ZJU-168(Tb) as a potential turn-on, ratiometric, and colorimetric fluorescent sensor for practical detection of Glu.

A novel label-free terbium(iii)-aptamer based aptasensor for ultrasensitive and highly specific detection of acute lymphoma leukemia cells.

Acute leukemia is a malignant clonal disease of hematopoietic stem cells with a high prevalence and mortality rate. However, there are no efficient tools to facilitate early diagnosis and treatment of leukemia. Therefore, development of new methods for the early diagnosis and prevention of leukemia, especially non-invasive diagnosis at the cellular level, is imperative. Here, a label-free signal-on fluorescence aptasensor based on terbium(iii)-aptamer (Tb3+-apt) was applied for the detection of leukemia. The aptamer sensitizes the fluorescence of Tb3+ and forms the strong fluorescent Tb3+-apt probe. The target cells, the T-cell acute lymphoblastic leukemia cell line (CCRF-CEM) combined with the Tb3+-apt probe to form the Tb3+-apt-CEM complex, were removed by centrifugation, and the supernatant containing a small amount of the Tb3+-apt probe was detected using a fluorescence spectrophotometer. The logarithm of cell concentration showed a good linear relationship (R2 = 0.9881) with the fluorescence signal. The linear range for CCRF-CEM detection was 5-5 × 106 cells per ml, while the detection limit was 5 cells per ml of the binding buffer. Clinical samples were collected from 100 cases, and the specificity and positive rates detected by this method were up to 94% and 90%, respectively. Therefore, a single-stranded DNA-sensitized terbium(iii) luminescence method diagnostic was developed which is rapid, sensitive, and economical and can be used for diagnosis of various types of leukemia at the early stage.

Toxic effects of environmental rare earth elements on delayed outward potassium channels and their mechanisms from a microscopic perspective.

The wide applications cause a large amount of rare earth elements (REEs) to be released into the environment, and ultimately into the human body through food chain. Toxic effects of REEs on humans have been extensively studied, but their toxic effects and binding targets in cells are not understood. Delayed outward potassium channels (K+ channels) are good targets for exogenous substances or clinical drugs. To evaluate cellular toxicities of REEs and clarify toxic mechanisms, the toxicities of REEs on the K+ channel and their structural basis were investigated. The results showed that delayed outward potassium channels on the plasma membrane are the targets of REEs acting on living organisms, and the changes in the thermodynamic and kinetic characteristics of the K+ channel are the reasons of diseases induced by REEs. Two types of REEs, a light REE La3+ and a heavy REE Tb3+, displayed different intensity of toxicities on the K+ channel, in which the toxicity of Tb3+ was stronger than that of La3+. More interestingly, in comparison with that of heavy metal Cd2+, the cytotoxicities of the light and heavy REEs showed discriminative differences, and the cytotoxicity of Tb3+ was higher than that of Cd2+, while the cytotoxicity of La3+ was lower than that of Cd2+. These different cytotoxicities of La3+, Tb3+ and Cd2+ on human resulted from the varying binding abilities of the metals to this channel protein.

Toxic effects of heavy metal terbium ion on the composition and functions of cell membrane in horseradish roots.

The environmental safety of rare earth elements (REEs), especially the toxic effect of REEs on plants, has attracted increasing attention. However, the cellular mechanism of this toxic effect remains largely unknown. Here, the toxic effects of heavy REE terbium ion [Tb(III)] on the cell membrane of horseradish roots were investigated by using electron microscope autoradiography (EMARG) and histochemical methods. The results indicated that Tb(III) was distributed in the extracellular and intracellular spaces of the roots after horseradish was treated with Tb(III). Moreover, the percentage contents of the unsaturated fatty acids in the membrane lipids, the current of the outward K(+) channel and the average diameter of membrane proteins in the roots of horseradish treated with Tb(III) were decreased; on the contrary, the percentage contents of the saturated fatty acids and malondialdehyde in the roots of horseradish treated with Tb(III) were increased. Furthermore, the contents of intracellular N, P, Mg and Fe in the roots of horseradish treated with Tb(III) were decreased, while the contents of intracellular K and Ca in the roots of horseradish treated with Tb(III) were increased. Finally, the effects of Tb(III) on horseradish roots were increased with increasing concentration or duration of Tb(III) treatment. In conclusion, after horseradish was treated with Tb(III), Tb(III) could enter the cells of horseradish roots and lead to the toxic effects on horseradish, which caused the oxidation of the unsaturated fatty acids in the membrane lipids, the changes in the membrane proteins (including the outward K(+) channel), the decrease in the membrane fluidity, and then the inhibition of the intracellular/extracellular-ion exchange in horseradish roots.

Cytotoxicity and cell imaging potentials of submicron color-tunable yttria particles.

Increased demand of environment protection encouraged scientists to design products and processes that minimize the use and generation of hazardous substances. This work presents comprehensive result of large-scale fabrication and investigation of red-to-green tunable submicron spherical yttria particles codoped with low concentrations of Eu(+3) and Tb(+3). The color emission of synthesized particles can be precisely tuned from red to green by simple variation of Tb/Eu ratio and excitation wavelength. The Tb/Eu-codoped Y(2)O(3) particles did not adversely affect the viability of L-929 fibroblastic cells at concentrations less than 62.5 ppm. Through internalization and wide distribution inside the cells, Tb/Eu codoped Y(2)O(3) particles with intense bright green or red fluorescence rendered cell imaging to be possible. The high brightness, excellent stability, low-toxicity, and imaging capability along with fine color-tunability of synthesized particles enable to find promising application in various areas.

Toxic effect of terbium ion on horseradish cell.

The toxic effect of terbium (III) ion on the horseradish cell was investigated by scanning electron microscopy, gas chromatography, and standard biochemical methods. It was found that the activity of horseradish peroxidase in the horseradish treated with 0.2 mM terbium (III) ion decreased and led to the excessive accumulation of free radicals compared with that in the control horseradish. The excessive free radicals could oxidize unsaturated fatty acids in the horseradish cell and then increase the cell membrane lipid peroxidation of horseradish. The increase in the lipid peroxidation could lead to the destruction of the structure and function of the cell membrane and then damage of the horseradish cell. We propose that this is a possible mechanism for the toxic action of terbium in the biological systems.

Preparation of luminescent and mesoporous Eu3+/Tb3+ doped calcium silicate microspheres as drug carriers via a template route.

Luminescent and mesoporous Eu(3+)/Tb(3+) doped calcium silicate microspheres (LMCS) were synthesized by using mesoporous silica spheres as the templates. The LMCS and drug-loaded samples were characterized by means of X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), N(2) adsorption/desorption, and photoluminescence (PL) spectra. The results reveal that the LMCS have uniform spherical morphology with a diameter around 400 nm and the mesopore size of 6 nm. The prepared samples exhibit little cytotoxicity at concentrations below 5 mg mL(-1) via MTT assay. In addition, drug storage/release properties of the LMCS were demonstrated for ibuprofen (IBU). The obtained LMCS can be used to encapsulate drugs and release them. Under excitation by UV light, the IBU-loaded samples still show the characteristic (5)D(0)-(7)F(1-3) emission lines of Eu(3+) and the characteristic (5)D(4)-(7)F(3-6) emission lines of Tb(3+). The PL intensity of Eu(3+) in the drug carrier system increases with the cumulative released amount of IBU, making the drug release able to be tracked or monitored by the change of luminescence of Eu(3+). The LMCS reported here with mesoporous structure, good biocompatibility and luminescent property can be a promising drug delivery carrier.

Effects of heavy metal terbium on contents of cytosolic nutrient elements in horseradish cell.

The wide application of rare earth elements (REEs) has led to the accumulation of REEs in soil and plant. Thereby, the effect of Tb(3+) on the contents of cytosolic nutrient elements in horseradish was investigated with the synchronous detection technique of scanning electron microscope and energy dispersive X-ray spectrometry. It was found for the first time that the foliar spraying treatment of Tb(3+) destroyed the structure of horseradish mesophyll cells, and then changed the contents of the cytosolic nutrient elements in horseradish, especially Ca. The effect of Tb(3+) was increased with increasing the concentration of Tb(3+). The hydroponical treatment of Tb(3+) could not obviously change the structure of protoplast and the contents of the cytosolic nutrient elements in horseradish leaves. The results indicated that the accumulation of Tb(3+) in soil and plant leaves displayed the different toxic effect on plant leaves.

Toxic effect of heavy metal terbium ion on cell membrane in horseradish.

In order to understand the toxic mechanism of terbium ion (Tb(III)) on plants, the subcellular distribution of Tb(III) in horseradish, the effect of Tb(III) on the composition of the fatty acids in the cell membrane, the peroxidation of membrane lipid, the morphological character of protoplast, the cellular ultrastructure in horseradish were investigated using transmission electron microscopic autoradiography, molecular dynamics simulation, gas chromatography, scanning electron microscopy and transmission electron microscopy. The results show that Tb(III) could not enter the horseradish cell in the presence of 5 mgL(-1) Tb(III) and it was distributed on the cell wall and plasma membrane. The behavior caused the decrease in the contents of unsaturated fatty acids and then the increase in the peroxidation of membrane lipid. Thereby the structure of horseradish cell was damaged. The effects of Tb(III) mentioned above were aggravated in horseradish treated with 60 mgL(-1) Tb(III) because Tb(III) could enter the horseradish cell. It was a possible cytotoxic mechanism of Tb(III) on horseradish.

Photosynthetic responses to heavy metal terbium stress in horseradish leaves.

In order to understand the toxic effect of terbium (Tb(III)) on the plant photosynthesis, we investigated the photosynthesis, the ultrastructural structure of chloroplast, the subcellular distribution of horseradish peroxidase (HRP), the activity of HRP, and the content of malondialdehyde in horseradish by a portable gas exchange system, transmission electron microscopy and the other biochemical technologies. The results indicated that after horseradish treated with 5 mg L(-1) Tb(III), the subcellular distribution of HRP was not obviously changed. However, the activities of guaiacol and ascorbate HRP were decreased comparing with that of horseradish treated without Tb(III). It could cause the peroxidation of membrane lipid, the damage of chloroplast ultrastructure and the decrease in the photosynthesis and the content of chlorophyll. Moreover, after horseradish treated with 60 mg L(-1) of Tb(III), the distribution of HRP on the plasma membrane and tonoplast was decreased, while the distribution of HRP on the cell wall was increased comparing with that of horseradish treated without Tb(III). The change in the subcellular distribution of HRP could induce the excess accumulation of the reactive oxygen, leading to the damage of the chloroplast ultrastructure and then the decrease in the photosynthesis. Furthermore, the effects of Tb(III) on the indexes mentioned above were increased with prolonging the treating time of Tb(III). These results demonstrated that the function of HRP in horseradish treated with Tb(III) was decreased, leading to the damage of chloroplast ultrastructure and then the inhibition of photosynthesis. It was a possible toxic effect of Tb(III) on the plant photosynthesis.

Subcellular location of horseradish peroxidase in horseradish leaves treated with La(III), Ce(III) and Tb(III).

The agricultural application of rare-earth elements (REEs) would promote REEs inevitably to enter in the environment and then to threaten the environmental safety and human health. Therefore, the distribution of the REEs ion, (141)Ce(III) and effects of La(III), Ce(III) and Tb(III) on the distribution of horseradish peroxidase (HRP) in horseradish mesophyll cells were investigated with electron microscopic radioautography and transmission electron microscopic cytochemistry. It was found for the first time that REEs ions can enter into the mesophyll cells, deposit in both extra and intra-cellular. Compared to the normal condition, after the horseradish leaves treated with La(III) or Tb(III), HRP located on the tonoplast is decreased and HRP is mainly located on the cell wall, while HRP is mainly located on the plasma membrane after the horseradish leaves were treated with Ce(III). This also indicated that REEs ions may regulate the plant growth through changing the distribution of enzymes.

Distribution of terbium and increase of calcium concentration in the organs of mice i.v.-administered with terbium chloride.

To investigate the biological effects of terbium (Tb), male mice were intravenously administered with TbCl3 at 10, 25, or 50 mg Tb/kg. Time-course and dose-related changes in organ distributions of Tb were determined. More than 95% of the Tb in blood was in plasma, and the concentrations decreased rapidly. Contrary to normal pharmacokinetics, Tb concentrations in plasma were higher in the 10 mg/kg group than in the 50 mg/kg group. The concentrations after injection of 25 mg/kg were between 10 and 50 mg/kg injections. Tb was incorporated mainly in liver, lung, and spleen. In all groups more than 80% of Tb administered were found in these three organs. Disappearance of Tb in these organs was very slow. Tb was also found in kidney, heart and other organs. Coincidentally, it was found that the Ca concentration was increased in organs in which Tb was incorporated. After administration of Tb (50 mg/kg) the Ca concentration, compared to the controls, was 70-fold in spleen, 20-fold in lung, and 6-fold in liver. There were highly positive correlations between Tb and Ca concentrations in organs. Excretion of Tb in urine was 0.15-0.3% and that in feces was 1.7-12.5% for up to 7 days. These results indicate that liver, lung, and spleen are the main target organs of Tb administered intravenously, and that the increase in Ca concentrations is one of the important biological effects of Tb in target organs.

Pulmonary toxicity of systemic terbium chloride in mice.

Terbium (Tb) is a rare earth metal that finds use in several emerging technologies. However, little is known about the biological effects of Tb. Thus, in this study the pulmonary toxicity of systemic Tb in mice was investigated. Mice were treated intravenously with a single dose of 20 or 200 mumol Tb/kg, as TbCly and killed at 3, 6, 12, 24, 48, or 72 h later. Administration of Tb at a dose of 200 mumol/kg increased pulmonary weight, lipid peroxidation, and protein content but decreased pulmonary glutathione content. Pulmonary gamma-glutamyl transpeptidase (gamma-GTP) activity was increased after Tb administration at a dose of 200 mumol/kg. Pulmonary alkaline phosphatase (ALP) activity was also increased after Tb administration at a dose of 200 mumol/kg. Investigation of the defense system against oxidative damage in the lung showed that superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities were all decreased after Tb administration at the higher dose. The concentrations of Tb, Ca, and P in lung was increased by the dose of 200 mumol/kg. These results suggest that pulmonary lipid peroxidation may be an early and sensitive consequence of Tb exposure and that SOD, CAT, and GSH-Px might be considered as potential modulators of Tb-induced lipid peroxidation. The mechanisms involved in Tb-induced pulmonary lipid peroxidation deserve further study.

[Hygienic regulation of yttrium, terbium, ytterbium and lutetium fluorides in the air of the workplace]. / K voprosu o gigienicheskoi reglamentatsii soderzhaniia ftoridov ittriia, terbiia. itterbiia i liutetsiia v vozdukhe rabochei zony.

The study (experiments on animals and on culture of rats' peritoneal macrophages) covered fluorides of rare-earth metals (REM) assigned to yttrium group--yttrium, terbium, ytterbium, lutetium. Fluorides of REM have low toxicity and cumulativity, induce no local irritation of skin and eyes. Fluorides of yttrium, terbium and lutetium, if administered into stomach, result in specific intoxication (fluorosis). Fluoride of ytterbium did not cause such intoxication. According to short-term tests of cytotoxicity, the foreseeable fibrogenic danger for ytterbium fluoride is moderate, for fluorides of yttrium, terbium and lutetium is mild. The authors recommend to control the level of yttrium, terbium and lutetium fluorides in the air of workplace through the MACs for the fluorides at 2.5 mg/cu m (maximal single concentration) and 0.5 mg/cu m (average shift concentration), the level of ytterbium fluoride as moderate fibrogenic dust at 6 mg/cu m.

Studies of nutritional safety of some heavy metals in mice.

Heavy metals have been proposed as nutrient markers to allow the accurate determination of the time of passage, nutrient intake, or apparent utilization of multiple nutrients. In order to evaluate possible toxic effects of scandium, chromium, lanthanum, samarium, europium, dysprosium, terbium, thulium, and ytterbium oxides, and barium sulfate upon growth, general development, reproduction, and lactation, mice were fed different levels of these compounds for three generations. The amount of elements fed were 0,110, 100, and 1000 times the use amount. The use amounts were (in ppm2.) : Sc, 0.12; Cr, 0.02; La.0.40;; Sm. 0.80; Eu, 0.036:TB, 1.20; Dy, 1.20; Tm. 0.08; Tb, 0.12; and Ba, 0.008. The use amount was one-fifth of the concentration required for activation analysis. Mortality and morbidity were negligible. No consistent growth rate changes were observed; however, different groups showed different growth rates during different generations. The number of mice born showed no significant differences amoung treatment groups. Survival, growth rate, hematology, morphological development, maturation, reproduction, and lactational performance were comparable in mice fed the different levels of 10 heavy metal oxides to those mice fed the basal diet.