Enhanced phytoremediation of uranium contaminated soil by artificially constructed plant community plots.

In order to develop an artificially constructed plant community plot for the enhanced phytoremediation of uranium contaminated soils, three uranium accumulators including Bamboo-willow (Salix sp.), Paspalum scrobiculatum linn and Macleaya cordata were used to construct four artificial plant community plots, and greenhouse experiments were conducted to investigate the bioaccumulation of uranium by the plants and the organic acid content, enzyme activity, and the change of microbial community structure in their rhizosphere soils. The transfer factor (TF) and the total bioaccumulation amount (TBA) of uranium were used to describe remediation efficiencies in this paper. It was found that their remediation efficiencies were in the order Bamboo-willow (Salix sp.)-Paspalum scrobiculatum linn-Macleaya cordata > Bamboo-willow (Salix sp.)-Macleaya cordata > Paspalum scrobiculatum linn-Macleaya cordata > Bamboo-willow (Salix sp.)-Paspalum scrobiculatum linn. The bioaccumulation amount of uranium by each plant in the Bamboo-willow (Salix sp.)-Paspalum scrobiculatum linn-Macleaya cordata community plot was significantly (P < 0.05) higher than that by its single population, the bioaccumulation amounts of uranium by Bamboo-willow (Salix sp.), Paspalum scrobiculatum linn and Macleaya cordata were 0.29, 0.32 and 2.19 mg/plant, respectively, and they were increased by 31.82%, 77.78% and 146.07%, respectively, and the transfer efficiencies by the plants were increased by 150%, 110% and 52.17%, respectively. The interaction between the plants' roots and the microorganisms in the rhizosphere soil of the Bamboo-willow (Salix sp.)-Paspalum scrobiculatum linn-Macleaya cordata community plot resulted in the high content of organic acids such as oxalic acid in the rhizosphere soil of the plant community plot, which was significantly (P < 0.05) higher than that of its single population. The chelation of the organic acids with uranium led to an increase in the proportion of exchangeable uranium in soil solution. In addition, Burkholderia, which is an iron-producing carrier bacterium and can increase the uptake and accumulation of uranium by plants, and Leptolyngbya, which is a plant growth promoting rhizobacteria and can increase the biomass of plants, emerged in the rhizosphere soil of the plant community plot. These may be the mechanisms by which the phytoremediation of the uranium contaminated soils was enhanced by the plant community plot.

Hypoxia-induced upregulation of BMX kinase mediates therapeutic resistance in acute myeloid leukemia.

Oncogenic addiction to the Fms-like tyrosine kinase 3 (FLT3) is a hallmark of acute myeloid leukemia (AML) that harbors the FLT3-internal tandem duplication (FLT3-ITD) mutation. While FLT3 inhibitors like sorafenib show initial therapeutic efficacy, resistance rapidly develops through mechanisms that are incompletely understood. Here, we used RNA-Seq-based analysis of patient leukemic cells and found that upregulation of the Tec family kinase BMX occurs during sorafenib resistance. This upregulation was recapitulated in an in vivo murine FLT3-ITD-positive (FLT3-ITD+) model of sorafenib resistance. Mechanistically, the antiangiogenic effects of sorafenib led to increased bone marrow hypoxia, which contributed to HIF-dependent BMX upregulation. In in vitro experiments, hypoxia-dependent BMX upregulation was observed in both AML and non-AML cell lines. Functional studies in human FLT3-ITD+ cell lines showed that BMX is part of a compensatory signaling mechanism that promotes AML cell survival during FLT3 inhibition. Taken together, our results demonstrate that hypoxia-dependent upregulation of BMX contributes to therapeutic resistance through a compensatory prosurvival signaling mechanism. These results also reveal the role of off-target drug effects on tumor microenvironment and development of acquired drug resistance. We propose that the bone marrow niche can be altered by anticancer therapeutics, resulting in drug resistance through cell-nonautonomous microenvironment-dependent effects.

Construction of the Syngonium podophyllum-Pseudomonas sp. XNN8 Symbiotic Purification System and Investigation of Its Capability of Remediating Uranium Wastewater.

The endophyte Pseudomonas sp. XNN8 was separated from Typha orientalis which can secrete indole-3-acetic acid and 1-aminocyclopropane-1-carboxylate deaminase and siderophores and has strong resistance to uranium it was then colonized in the Syngonium podophyllum; and the S. podophyllum-Pseudomonas sp. XNN8 symbiotic purification system (SPPSPS) for uranium-containing wastewater was constructed. Afterwards, the hydroponic experiments to remove uranium from uranium-containing wastewater by the SPPSPS were conducted. After 24 days of treatment, the uranium concentrations of the wastewater samples with uranium concentrations between 0.5 and 5.0 mg/L were lowered to below 0.05 mg/L. Furthermore, the uranium in the plants was assayed using Fourier transform infrared spectroscopy (FTIR) and extended X-ray absorption fine structure (EXAFS) spectroscopy. The Pseudomonas sp. XNN8 was found to generate substantial organic groups in the roots of the Syngonium podophyllum, which could improve the complexing capability of S. podophyllum for uranium. The uranium in the roots of S. podophyllum was found to be the uranyl phosphate (47.4 %) and uranyl acetate (52.6 %).

Thalamic miR-338-3p mediates auditory thalamocortical disruption and its late onset in models of 22q11.2 microdeletion.

Although 22q11.2 deletion syndrome (22q11DS) is associated with early-life behavioral abnormalities, affected individuals are also at high risk for the development of schizophrenia symptoms, including psychosis, later in life. Auditory thalamocortical (TC) projections recently emerged as a neural circuit that is specifically disrupted in mouse models of 22q11DS (hereafter referred to as 22q11DS mice), in which haploinsufficiency of the microRNA (miRNA)-processing-factor-encoding gene Dgcr8 results in the elevation of the dopamine receptor Drd2 in the auditory thalamus, an abnormal sensitivity of thalamocortical projections to antipsychotics, and an abnormal acoustic-startle response. Here we show that these auditory TC phenotypes have a delayed onset in 22q11DS mice and are associated with an age-dependent reduction of miR-338-3p, a miRNA that targets Drd2 and is enriched in the thalamus of both humans and mice. Replenishing depleted miR-338-3p in mature 22q11DS mice rescued the TC abnormalities, and deletion of Mir338 (which encodes miR-338-3p) or reduction of miR-338-3p expression mimicked the TC and behavioral deficits and eliminated the age dependence of these deficits. Therefore, miR-338-3p depletion is necessary and sufficient to disrupt auditory TC signaling in 22q11DS mice, and it may mediate the pathogenic mechanism of 22q11DS-related psychosis and control its late onset.

Bioreduction of U(VI) and stability of immobilized uranium under suboxic conditions.

In order to study the bioreduction of U(VI) and stability of immobilized uranium under suboxic conditions, microcosm were amended with ethanol, lactate and glucose, and incubated under suboxic conditions. During the incubation, total dissolved U in amended microcosms decreased from 0.95 mg/L to 0.03 mg/L. Pyrosequencing results showed that, the proportion of anaerobic microorganisms capable of reducing U(VI) under suboxic conditions was small compared with that under anoxic conditions; the proportion of aerobic and facultative anaerobic microorganisms capable of consuming the dissolved oxygen was large; and some of the facultative anaerobic microorganisms could reduce U(VI). These results indicated that different microbial communities were responsible for the bioreduction of U(VI) under suboxic and anoxic conditions. After the electron donors were exhausted, total dissolved U in the amended microcosms remained unchanged, while the U(VI)/U(IV) ratio in the solid phase of sediments increased obviously. This implied that the performance of bioreduction of the U(VI) can be maintained under suboxic condition.

An artificially constructed Syngonium podophyllum-Aspergillus niger combinate system for removal of uranium from wastewater.

Aspergillus niger was inoculated to the roots of five plants, and the Syngonium podophyllum-A. niger combinate system (SPANCS) was found to be the most effective in removing uranium from hydroponic liquid with initial uranium concentration of 5 mg L(-1). Furthermore, the hydroponic experiments on the removal of uranium from the hydroponic liquids with initial uranium concentrations of 0.5, 1.0, and 3.0 mg L(-1) by the SPANCS were conducted, the inhibitory effect of A. niger on the growth of S. podophyllum in the SPANCS was studied, the accumulation characteristics of uranium by S. podophyllum in the SPANCS were analyzed, and the Fourier transform infrared (FT-IR) and extended X-ray absorption fine structure (EXAFS) spectra were measured. The results show that the removal of uranium by the SPANCS from the hydroponic liquids with initial uranium concentrations of 0.5, 1.0, and 3.0 mg L(-1) reached 98.20, 97.90, and 98.50%, respectively, after 37 days of accumulation of uranium; that the uranium concentrations in the hydroponic liquids decreased to 0.009, 0.021, and 0.045 mg L(-1), respectively, which are lower than the stipulated concentration for discharge of 0.050 mg L(-1) by the People's Republic of China; that A. niger helped to generate more groups in the root of S. podophyllum which can improve the complexing capability of S. podophyllum for uranium; and that the uranium accumulated in the root of S. podophyllum was in the form of phosphate uranyl and carboxylic uranyl.

Bioreduction of U(VI) in groundwater under anoxic conditions from a decommissioned in situ leaching uranium mine.

To determine whether the U(VI) in groundwater under anoxic conditions at a decommissioned in situ leaching (ISL) uranium mine could be bioreduced, groundwater samples containing suspended sediments were taken from the mine, experimental setup was fabricated, and the jar containing the groundwater in the setup was amended with ethanol and incubated under anoxic conditions. The variations of pH, chemical oxygen demand, nitrate, sulfate, U(VI), and dissolved oxygen (DO) concentrations were monitored during the incubation. U(VI) concentration dropped to 0.043 mg/L when the stimulated microorganisms were active, and it then increased to 0.835 mg/L within 10 days after the metabolism of the stimulated microorganisms was inhibited. The DO variation was observed in the amended jar during the incubation, and the metabolism of the stimulated microorganisms was found to affect the DO concentration. Firmicutes were found to be dominant in the sediments in the amended jar through the 16S rRNA pyrosequencing. The results indicate that it is possible to bioreduce U(VI) in the groundwater under anoxic conditions at the decommissioned ISL uranium mine by adding carbon source into it without removing the oxygen from it.

Phytoextraction of uranium from contaminated soil by Macleaya cordata before and after application of EDDS and CA.

This is the first report on using Macleaya cordata for phytoextraction of uranium from the uranium contaminated soil in the greenhouse. Macleaya M. cordata was found to increase uranium concentration in the soil solution by increasing the dissolved organic carbon (DOC). The amendment experiments with citric acid (CA) and [S,S]-ethylenediamine disuccinic acid (EDDS) at the rates of 1.0, 2.5, 5.0, and 10.0 mmol kg(-1) dry weight (DW) soil showed that EDDS was more efficient to increase uranium concentration in the shoot than CA when they were applied at the same rate. The applications of 5.0 mmol kg(-1) EDDS and 10.0 mmol kg(-1) CA were most appropriate for increasing uranium concentrations in the shoot of M. cordata. CA was more efficient to increase the solubility of uranium at the same application rates except for 2.5 mmol kg(-1) application rate. There was a linear correlation between the uranium concentration in the shoot and the average uranium concentration of one planted pot during 14 days in soil solution after the application of different rates of EDDS and CA, respectively (r(2) = 0.972, P < 0.01; r (2) = 0.948, P < 0.01), indicating that uranium uptake was dependent on the soluble uranium concentration. The Fe-U-DOC and Mn-U-DOC complexes were probably formed after the application of CA. Soil solution pH and Fe, Mn, Ca, and DOC concentrations in soil solution were found to be changed by the chelates.

Emergence of polyclonal FLT3 tyrosine kinase domain mutations during sequential therapy with sorafenib and sunitinib in FLT3-ITD-positive acute myeloid leukemia.

PURPOSE: To evaluate the clinical activity of sequential therapy with sorafenib and sunitinib in FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD)-positive acute myelogenous leukemia (AML) and monitor the emergence of secondary FLT3 tyrosine kinase domain (TKD) mutations during treatment. EXPERIMENTAL DESIGN: Six children with relapsed/refractory AML were treated with sorafenib in combination with clofarabine and cytarabine, followed by single-agent sorafenib if not a candidate for transplantation. Sunitinib was initiated after sorafenib relapse. Bone marrow samples were obtained for assessment of FLT3 TKD mutations by deep amplicon sequencing. The phase of secondary mutations with ITD alleles was assessed by cloning and sequencing of FLT3 exons 14 through 20. Identified mutations were modeled in Ba/F3 cells, and the effect of kinase inhibitors on FLT3 signaling and cell viability was assessed. RESULTS: Four patients achieved complete remission, but 3 receiving maintenance therapy with sorafenib relapsed after 14 to 37 weeks. Sunitinib reduced circulating blasts in two patients and marrow blasts in one. Two patients did not respond to sorafenib combination therapy or sunitinib. FLT3 mutations at residues D835 and F691 were observed in sorafenib resistance samples on both ITD-positive and -negative alleles. Deep sequencing revealed low-level mutations and their evolution during sorafenib treatment. Sunitinib suppressed leukemic clones with D835H and F691L mutations, but not D835Y. Cells expressing sorafenib-resistant FLT3 mutations were sensitive to sunitinib in vitro. CONCLUSIONS: Sunitinib has activity in patients that are resistant to sorafenib and harbor secondary FLT3 TKD mutations. The use of sensitive methods to monitor FLT3 mutations during therapy may allow individualized treatment with the currently available kinase inhibitors.

Removal and recovery of uranium (VI) from aqueous solutions by immobilized Aspergillus niger powder beads.

The immobilized Aspergillus niger powder beads were obtained by entrapping nonviable A. niger powder into Ca-alginate gel. The effects of pH, contact time, initial uranium (VI) concentration and biomass dosage on the biosorption of uranium (VI) onto the beads from aqueous solutions were investigated in a batch system. Biosorption equilibrium data were agreeable with Langmuir isotherm model and the maximum biosorption capacity of the beads for uranium (VI) was estimated to be 649.4 mg/g at 30 °C. The biosorption kinetics followed the pseudo-second-order model and intraparticle diffusion equation. The variations in enthalpy (26.45 kJ/mol), entropy (0.167 kJ/mol K) and Gibbs free energy were calculated from the experimental data. SEM and EDS analysis indicated that the beads have strong adsorption capability for uranium (VI). The adsorbed uranium (VI) on the beads could be released with HNO(3) or HCl. The results showed that the immobilized A. niger powder beads had great potential for removing and recovering uranium (VI) from aqueous solutions.

Screening of plant species for phytoremediation of uranium, thorium, barium, nickel, strontium and lead contaminated soils from a uranium mill tailings repository in South China.

The concentrations of uranium, thorium, barium, nickel, strontium and lead in the samples of the tailings and plant species collected from a uranium mill tailings repository in South China were analyzed. Then, the removal capability of a plant for a target element was assessed. It was found that Phragmites australis had the greatest removal capabilities for uranium (820 µg), thorium (103 µg) and lead (1,870 µg). Miscanthus floridulus had the greatest removal capabilities for barium (3,730 µg) and nickel (667 µg), and Parthenocissus quinquefolia had the greatest removal capability for strontium (3,920 µg). In this study, a novel coefficient, termed as phytoremediation factor (PF), was proposed, for the first time, to assess the potential of a plant to be used in phytoremediation of a target element contaminated soil. Phragmites australis has the highest PFs for uranium (16.6), thorium (8.68), barium (10.0) and lead (10.5). Miscanthus floridulus has the highest PF for Ni (25.0). Broussonetia papyrifera and Parthenocissus quinquefolia have the relatively high PFs for strontium (28.1 and 25.4, respectively). On the basis of the definition for a hyperaccumulator, only Cyperus iria and Parthenocissus quinquefolia satisfied the criteria for hyperaccumulator of uranium (36.4 µg/g) and strontium (190 µg/g), and could be the candidates for phytoremediation of uranium and strontium contaminated soils. The results show that the PF has advantage over the hyperaccumulator in reflecting the removal capabilities of a plant for a target element, and is more adequate for assessing the potential of a plant to be used in phytoremediation than conventional method.