In vitro co-culture systems of hepatic and intestinal cells for cellular pharmacokinetic and pharmacodynamic studies of capecitabine against colorectal cancer.

BACKGROUND: As a prodrug of 5-fluorouracil (5-FU), orally administrated capecitabine (CAP) undergoes preliminary conversion into active metabolites in the liver and then releases 5-FU in the gut to exert the anti-tumor activity. Since metabolic changes of CAP play a key role in its activation, a single kind of intestinal or hepatic cell can never be used in vitro to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) nature. Hence, we aimed to establish a novel in vitro system to effectively assess the PK and PD of these kinds of prodrugs. METHODS: Co-culture cellular models were established by simultaneously using colorectal cancer (CRC) and hepatocarcinoma cell lines in one system. Cell Counting Kit-8 (CCK-8) and flow cytometric analysis were used to evaluate cell viability and apoptosis, respectively. Apoptosis-related protein expression levels were measured using western blot analysis. A selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for cellular PK in co-culture models. RESULTS: CAP had little anti-proliferative effect on the five monolayer CRC cell lines (SW480, LoVo, HCT-8, HCT-116 and SW620) or the hepatocarcinoma cell line (HepG2). However, CAP exerted marked anti-tumor activities on each of the CRC cell lines in the co-culture models containing both CRC and hepatocarcinoma cell lines, although its effect on the five CRC cell lines varied. Moreover, after pre-incubation of CAP with HepG2 cells, the culture media containing the active metabolites of CAP also showed an anti-tumor effect on the five CRC cell lines, indicating the crucial role of hepatic cells in the activation of CAP. CONCLUSION: The simple and cost­effective co-culture models with both CRC and hepatocarcinoma cells could mimic the in vivo process of a prodrug dependent on metabolic conversion to active metabolites in the liver, providing a valuable strategy for evaluating the PK and PD characteristics of CAP-like prodrugs in vitro at the early stage of drug development.

Strengthened erosion resistance of compacted bentonite by layered double hydroxide: A new electrostatic interaction-based approach.

For the geological repository of high-level radioactive waste (HLW) built in granitic host rock，the control of buffer material (compacted bentonite) erosion and subsequent loss caused by groundwater in granite fissures is an unresolved problem of major concern. We propose here new insight into enhancing the erosion resistance of compacted bentonite by means of its electrostatic interaction with oppositely-charged layered double hydroxide (LDH). The interaction between bentonite and LDH was studied by dropwise addition of colloidal LDH into colloidal bentonite suspension, during which the variation in electrical conductivity, zeta potential and particle size proved a strong interaction between these two materials. Interestingly, in addition to their aggregation, intercalated structures of LDH and montmorillonite were found in the composite (BEN@LDH) by a combined characterization of X-ray diffraction (XRD) and high resolution transmission electron microscopy (HR-TEM), and were confirmed by density functional theory (DFT) calculation. Colloid generation of compacted BEN@LDH under ultrasonic conditions is negligible comparing with that of compacted bentonite, indicating a significantly higher erosion resistance. Besides, a small amount of LDH by mechanically mixing with bentonite (mass ratio 1:99) can also effectively improve the erosion resistance of compacted bentonite. Moreover, BEN@LDH displayed stronger retention performance towards U(VI) and Se(IV) than bentonite under near-neutral/weakly alkaline conditions. Our results indicate that LDH is a promising additive in compacted bentonite, and this approach may be extended to common geotechnical structures built with clays and soils.

The Interleukin-6/Signal Transducer and Activator of Transcription-3/Cystathionine γ-Lyase Axis Deciphers the Transformation Between the Sensitive and Resistant Phenotypes of Breast Cancer Cells.

Drug resistance of cancer cells is associated with redox homeostasis. The mechanism of acquired resistance of cancer cells to antitumor drugs is not well understood. Our previous studies revealed that drug resistance and highly expressed P-glycoprotein (P-gp) of MCF-7 breast cancer cells was dependent on intracellular redox homeostasis and declined capacity for scavenging reactive oxygen species (ROS). Recently, we observed that, unlike nontumorigenic cells MCF-10A, three tumorigenic breast cancer cells (MCF-7S, BT474, MDA-MB-231) reprogrammed their metabolism, highly expressed cystathionine-γ-lyase (CTH), and acquired a particular specialty to use methionine (Met) to synthesize glutathione (GSH) through the transsulfuration pathway. Interestingly, doxorubicin (adriamycin) further reprogrammed metabolism of MCF-7 cells sensitive to adriamycin (MCF-7S) and induced them to be another MCF-7 cell line resistant to adriamycin (MCF-7R) with dramatically downregulated CTH. The two MCF-7 cell lines showed distinctly different phenotypes in terms of intracellular GSH, ROS levels, expression and activity of P-gp and CTH, and drug resistance. We showed that CTH modulation or the methionine supply brought about the interconversion between MCF-7S and MCF-7R. Methionine deprivation or CTH silencing induced a resistant MCF-7R and lowered paclitaxel activity, yet methionine supplementation or CTH overexpression reversed the above effects, induced a sensitive phenotype of MCF-7S, and significantly increased the cytotoxicity of paclitaxel both in vitro and in vivo. Interleukin-6 (IL-6)/signal transducer and activator of transcription-3 (STAT3) initiated CTH expression and activity, and the effect on the resistant phenotype was exclusively dependent on CTH and ROS. This study suggests that the IL-6/STAT3/CTH axis plays a key role in the transformation between sensitive and resistant MCF-7 cells. SIGNIFICANCE STATEMENT: Cystathionine γ-lyase (CTH) plays a key role in transformation between the sensitive and resistant phenotypes of MCF-7 cells and is dependent on the interleukin-6 (IL-6)/signal transducer and activator of transcription-3 (STAT3) signaling axis. Modulation of the transsulfuration pathway on CTH or IL-6/STAT3 or methionine supplementation is beneficial for reversing the resistance of MCF-7 cells, which indicates a clinical translation potential.

Mechanisms of bentonite colloid aggregation, retention, and release in saturated porous media: Role of counter ions and humic acid.

In the subsurface environment, colloids play an important role in pollutant transport by acting as the carriers. Understanding colloid release, transport, and deposition in porous media is a prerequisite for evaluating the potential role of colloids in subsurface contaminant transport. In this work, the aggregation, retention, and release of bentonite colloid in saturated porous sand media were investigated by kinetic aggregation and column experiments, the correlation and mechanism of these processes were revealed by combining colloid filtration theory, interaction energy calculation and density functional theory. The results showed that the retention and release of colloids were closely related to the dispersion stability and filtration effect. Multivalent cations with higher mineral affinity reduced the colloid stability, and the dispersion stability and mobility of the colloid were greatly improved by humic acid due to the enhancement of electrostatic repulsion and steric hindrance effects. The primary minimum interaction was found to contribute more to irreversible colloid retention in a Ca2+ system, while the secondary energy minimum was found to be responsible for colloid release with the occurrence of transient solution chemistry. The deposited colloid aggregates could be redistributed and released when the solution chemistry became favorable towards dispersion. These findings provide essential insight into the environmental colloid fate as well as a vital reference for the risk of colloid-driven transport of contaminants in the subsurface aquifer environment.

Multiple investigations of aqueous Eu(III)-oxalate complexes: the reduction in coordination number and validation of spectral linear correlation.

Detailed information on the An(iii)/Ln(iii) complexation properties in solution is essential for separation chemistry and the prediction of their potential for radionuclide migration from nuclear waste repositories into natural aquifers. In the present study, to better reveal and confirm the structural information of [Eu(Ox)x (H2O)h-2x]3-2x (h = 8, 9; x = 0-3) aqueous species, especially the variable coordination number (CN), and explore the validity of the spectral linear correlation between the luminescence lifetime and the residual hydration number in the first coordination sphere of Eu(iii) compounds in solution, a comparison between the spectral results and the theoretical calculations in a wide parametric space in terms of the pH value and oxalate concentration was carried out by combining time-resolved luminescence spectroscopy (TRLS) with speciation modelling and density functional theory (DFT) calculations. We have found direct and clear evidence for the 9-fold to 8-fold coordination number reduction of Eu(iii) atoms upon coordination with more than one oxalate in an aqueous medium, and as well systematically validated the applicability of the spectral linear correlation in an aqueous system (otherwise solid state) involving multiple species with the support of relatively reliable and clear speciation modelling.

Colloidal stability and correlated migration of illite in the aquatic environment: The roles of pH, temperature, multiple cations and humic acid.

The mobility and environmental risk of colloids and associated pollutants are dependent on their dispersion stability under various conditions. In this work, the stability and correlated migration of illite colloids (IC) were systematically investigated over a wide range of aquatic chemistry conditions. The results showed that IC was aggregation favorable at low pH, low temperature and high ionic strength. The critical coagulation concentration (CCC) of IC increased exponentially with increasing values of r/Z3, following the Schulze-Hardy and Hofmeister series. Humic acid (HA) greatly mitigated colloid aggregation since the attachment of HA on IC surface increased the steric hindrance and electrostatic potential, and the enhancement of stability was linearly correlated with the HA concentration. The Derjaguin-Landau-Verwey-Overbeek (DLVO) model revealed that the interaction force deriving from van der Waals forces and electrostatic double-layer energy evolved as the aquatic chemistry varied, and the reduction in repulsion force between particles facilitated the colloid collision and then aggregation. The migration of IC in the porous sand column was highly correlated with the dispersion stability and filtration effect, the agglomerated colloids were redispersed and released when conditions favored dispersion. The illite colloids acted as efficient carriers for Eu(III) transport. These findings are essential for improving the understanding of the geological fate of environmental colloids and associated radionuclides.

Emerging Mechanisms and Disease Implications of Ferroptosis: Potential Applications of Natural Products.

Ferroptosis, a newly discovered form of regulatory cell death (RCD), has been demonstrated to be distinct from other types of RCD, such as apoptosis, necroptosis, and autophagy. Ferroptosis is characterized by iron-dependent lipid peroxidation and oxidative perturbation, and is inhibited by iron chelators and lipophilic antioxidants. This process is regulated by specific pathways and is implicated in diverse biological contexts, mainly including iron homeostasis, lipid metabolism, and glutathione metabolism. A large body of evidence suggests that ferroptosis is interrelated with various physiological and pathological processes, including tumor progression (neuro)degenerative diseases, and hepatic and renal failure. There is an urgent need for the discovery of novel effective ferroptosis-modulating compounds, even though some experimental reagents and approved clinical drugs have been well documented to have anti- or pro-ferroptotic properties. This review outlines recent advances in molecular mechanisms of the ferroptotic death process and discusses its multiple roles in diverse pathophysiological contexts. Furthermore, we summarize chemical compounds and natural products, that act as inducers or inhibitors of ferroptosis in the prevention and treatment of various diseases. Herein, it is particularly highlighted that natural products show promising prospects in ferroptosis-associated (adjuvant) therapy with unique advantages of having multiple components, multiple biotargets and slight side effects.

Prolonged effect associated with inflammatory response observed after exposure to low dose of tritium ß-rays.

Background: The value of relative biological effectiveness of tritium increases at low dose domain, which results in the suspicion of weighting factor of 1 for tritium after low dose exposure. Thus, present study was carried out to analyze the differences in the cellular responses at early and late period between low dose of tritium ß-rays and γ-rays radiation.Methods: MCF-10A cells were exposed to low dose of tritium ß-rays or γ-rays, then cellular behaviors, such as DNA double strand breaks (DSBs), apoptosis, reactive oxygen species (ROS) level and inflammatory relevant gene expression were analyzed at early and late period post-irradiation.Results: At early period the elimination of DSB foci produced by HTO is longer than γ-rays. High ROS level and a continual change of cell cycle distribution are observed in HTO radiation group. Based on the results of RNA sequencing, Ingenuity Pathway Analysis (IPA) indicates TNFR1 signaling and production of nitric oxide and ROS are activated as an acute response at 24 h post radiation. Moreover, it also shows a disturbance in cholesterol biosynthesis. The results of 30 days point that there is a lasting active inflammatory response, accompanying with a persistent high expression of relevant cytokines, such as TNF and IL1R.Conclusion: Compared to an acute response induced by γ-rays, a persistent inflammatory response exists in HTO-irradiated cells when cultured for 30 days, which might be related to accumulation of tritium in the form of organically bound tritium (OBT) in cellular DNA or lipids.

Au/SBA-15 catalyst prepared by ozone treatment and importance of negatively charged gold in CO oxidation by DRIFTS.

There is a lack of consensus on the charge state of active gold species in catalytic CO oxidation reaction. Herein, Au/SBA-15 catalyst was prepared by room temperature ozone treatment. Through diffuse reflectance Fourier-transform infrared spectroscopy (DRIFTS), two different gold species, Au0 and Auδ- with CO adsorption at about 2112 cm-1 and 2077 cm-1, were observed on Au/SBA-15. In CO oxidation mixture, the 2077 cm-1 band is completely attenuated while the 2112 cm-1 band retains some intensity. CO-Auδ- bonding is weaker than that of CO-Au0, but CO-Auδ- exhibits higher reactivity towards oxygen. Ozone treatment produces AuOx nanoparticles that is not stable and decomposes to metallic Au gradually. To our best knowledge, this is the first time to identify the presence and importance of Auδ- species for "inert" SiO2 supported gold catalyst.

Organ-on-a-chip: the next generation platform for risk assessment of radiobiology.

Organ-on-a-chip devices have been widely used in biomedical science and technology, for example for experimental regenerative medicine and precision healthcare. The main advantage of organ-on-a-chip technology is the facility to build a specific human model that has functional responses on the level of organs or tissues, thereby avoiding the use of animal models, as well as greatly improving new drug discovery processes for personal healthcare. An emerging application domain for organs-on-chips is the study of internal irradiation for humans, which faces the challenges of the lack of a clear model for risk estimation of internal irradiation. We believe that radiobiology studies will benefit from organ-on-a-chip technology by building specific human organ/tissues in vitro. In this paper, we briefly reviewed the state-of-the-art in organ-on-a-chip research in different domains, and conclude with the challenges of radiobiology studies at internal low-dose irradiation. Organ-on-a-chip technology has the potential to significantly improve the radiobiology study as it can mimic the function of human organs or tissues, and here we summarize its potential benefits and possible breakthrough areas, as well as its limitations in internal low-dose radiation studies.

Method for determination of Pu isotopes in soil and sediment samples by inductively coupled plasma mass spectrometry after simple chemical separation using TK200 resin.

Plutonium has been extensively studied in the environment, for the purpose of radiological assessment, environmental behavior study and nuclear emergency response. To determine Pu isotopes in environmental soil and sediment, a novel analytical method was established in this study using a new type of extraction resin, TK200 resin. Firstly an investigation was performed to study the extraction behaviors of Pu, U, Th, Hg, Tl, Pb, Bi and Hf on TK200 resin. On the basis of the results, a new chromatographic procedure was then proposed to separate Pu from the elements that interfere the accurate determination of Pu isotopes by mass spectrometry. Owing to the excellent separation efficiency between Pu and interfering elements (IEs) of the developed procedure, high decontamination factors (DFs) were obtained for IEs, e.g. the DF(U) (>7.5 × 107) was the highest reported value. The separation procedure was finally combined with HNO3 leaching, CaF2/LaF3 coprecipitation and sector field-inductively coupled plasma mass spectrometry (SF-ICPMS) measurement to establish a complete method. The established method was evaluated by analyzing four standard reference materials (soil, sediment), and the results showed that both 239+240Pu activity and 240Pu/239Pu isotopic ratio were accurately determined, with stable and high Pu chemical recoveries (81-91%). The whole analytical method only took about 15 h, and the limits of detection were calculated to be 0.13-0.24 fg g-1 for Pu isotopes (for 2 g soil or sediment), guaranteeing the rapid determination of ultra-trace level Pu in soil and sediment samples.

Boron-Transition-Metal Triple-Bond FB≡MF2 Complexes.

The boron-transition-metal triple-bond complexes FB≡MF2 (M= Ir, Os, Re, W, Ta) were trapped in excess solid neon and argon through metal atom reactions with boron trifluoride and identified by matrix isolation infrared spectroscopy and quantum chemical calculations. The FB≡MF2 molecule features very high 11B-F stretching frequencies at 1586.6 cm-1 (Ir), 1526.6 cm-1 (Os), 1505.5 cm-1 (Re), and 1453.2 cm-1 (W), respectively. The very high strength of B≡M bonds with triple-bonding character is confirmed by EDA-NOCV calculations and the active molecular orbital and NBO analysis. The experimental observation of FB stabilization by heavy transition-metal atoms with triple bonds opens the door to design new boron-transition-metal complexes.

Microfluidic Cell Trapping for Single-Cell Analysis.

The single-cell capture microfluidic chip has many advantages, including low cost, high throughput, easy manufacturing, integration, non-toxicity and good stability. Because of these characteristics, the cell capture microfluidic chip is increasingly becoming an important carrier on the study of life science and pharmaceutical analysis. Important promises of single-cell analysis are the paring, fusion, disruption and analysis of intracellular components for capturing a single cell. The capture, which is based on the fluid dynamics method in the field of micro fluidic chips is an important way to achieve and realize the operations mentioned above. The aim of this study was to compare the ability of three fluid dynamics-based microfluidic chip structures to capture cells. The effects of cell growth and distribution after being captured by different structural chips and the subsequent observation and analysis of single cells on the chip were compared. It can be seen from the experimental results that the microfluidic chip structure most suitable for single-cell capture is a U-shaped structure. It enables single-cell capture as well as long-term continuous culture and the single-cell observation of captured cells. Compared to the U-shaped structure, the cells captured by the microcavity structure easily overlapped during the culture process and affected the subsequent analysis of single cells. The flow shortcut structure can also be used to capture and observe single cells, however, the shearing force of the fluid caused by the chip structure is likely to cause deformation of the cultured cells. By comparing the cell capture efficiency of the three chips, the reagent loss during the culture process and the cell growth state of the captured cells, we are provided with a theoretical support for the design of a single-cell capture microfluidic chip and a reference for the study of single-cell capture in the future.

Distinctive distributions and migrations of 239+240Pu and 241Am in Chinese forest, grassland and desert soils.

The vertical distributions and downward migrations of the global fallout derived 239+240Pu and 241Am in diverse types of Chinese soils (forest, grassland and desert) were studied. The mean 239+240Pu and 241Am activity concentrations in the investigated soil cores were 0.28-0.69 mBq/g and 0.13-0.37 mBq/g, respectively, while the accumulative inventories were 61.53-138.99 Bq/m2 for 239+240Pu and 28.29-61.05 Bq/m2 for 241Am. The convection-dispersion equation (CDE) was used to calculate the migration parameters of 239+240Pu and higher apparent dispersion coefficients (D) were observed for the acidic forest soils compared with the alkaline grassland and desert soils; meanwhile a compartment model was employed to compare the migration of 239+240Pu and 241Am in successive soil layers which showed that the migration behaviors of 239+240Pu and 241Am were rather similar; both velocities were less than 0.3 cm/y in diverse types of soils and these findings were compatible with those of short-term laboratory simulation experiments in China.

Isoflavones enhance pharmacokinetic exposure of active lovastatin acid via the upregulation of carboxylesterase in high-fat diet mice after oral administration of Xuezhikang capsules.

Xuezhikang capsule (XZK) is a traditional Chinese medicine that contains lovastatin (Lv) for hyperlipidemia treatment, although it has fewer side effects than Lv. However, the pharmacokinetic mechanisms contributing to its distinct efficacy and low side effects are unclear. Mice were fed a high-fat diet (HFD) for 6 weeks to induce hyperlipidemia. We first conducted the pharmacokinetic studies in HFD mice following oral administration of Lv (10 mg/kg, i.g.) and found that HFD remarkably decreased the active form of Lv (the lovastatin acid, LvA) exposure in the circulation system, especially in the targeting organ liver, with a declined conversion from Lv to LvA, whereas the Lv (responsible for myotoxicity) exposure in muscle markedly increased. Then we compared the pharmacokinetic profiles of Lv in HFD mice after the oral administration of XZK (1200 mg/kg, i.g.) or an equivalent dose of Lv (10 mg/kg, i.g.). A higher exposure of LvA and lower exposure of Lv were observed after XZK administration, suggesting a pharmacokinetic interaction of some ingredients in XZK. Further studies revealed that HFD promoted the inflammation and inhibited carboxylesterase (CES) activities in the intestine and the liver, thus contributing to the lower transformation of Lv into LvA. In contrast, XZK inhibited the inflammation and upregulated CES in the intestine and the liver. Finally, we evaluated the effects of monacolins and phytosterols, the fractional extracts of isoflavones, on inflammatory LS174T or HepG2 cells, which showed that isoflavones inhibited inflammation, upregulated CES, and markedly enhanced the conversion of Lv into LvA. For the first time, we provide evidence that isoflavones and Lv in XZK act in concert to enhance the efficacy and reduce the side effects of Lv.

The pharmacokinetics study of ginkgolide A, B and the effect of food on bioavailability after oral administration of ginkgolide extracts in beagle dogs.

Ginkgolides are the primarily active components in Ginkgo products that are popular worldwide. However, few studies have evaluated the bioavailability of ginkgolides and the effects of food on it after oral administration of ginkgolides. In this article, pharmacokinetics and absolute bioavailability of the primary components in ginkgolide extracts were evaluated in beagle dogs. For the first time, we showed that the fed dogs had significantly increased area under the concentration-time curve and peak concentration relative to the fasted dogs based on the data from both the prototype form and total lactones of ginkgolide A (GA) and ginkgolide B (GB). In terms of the free form of the prototype ginkgolides, the absolute bioavailabilities of GA and GB were 34.8 and 5.2% in the fasted dogs, respectively, which significantly increased to an average of 78.6 and 17.0%, respectively, in the fed dogs. In terms of acidified total lactones, the absolute bioavailabilities of GA and GB were 7.5 and 14.5% in the fed dogs, and the percentages declined to 4.1 and 3.7% in the fasted dogs, respectively. It was suggested that administration of ginkgolides after meals could promote the in vivo exposure and the bioavailability of GA and GB, and hence potentially enhance therapeutic outcomes.

A study of electric field distribution in Benjamin type proportional counter using finite element method.

Tissue equivalent proportional counters (TEPCs)  are commonly based on the Benjamin type of concept. Initially the electric field is optimized by pulse height measurement methods and only one optimum solution was established at that time. In this paper, the electric field distribution is analyzed and optimized using a three-dimensional finite element method. The calculations show that the characteristics of the radial electric field distribution of this type of counters can be equated to cylindrical counters using a pair of appropriate field shaping electrode. Furthermore, the paper analyzes the axial electric field distribution and the possibility of achieving a uniform electric field along its anode while reducing the size of Benjamin type proportional counter design down to 1/10 of currently feasible values with respect to the thinnest available anode wire diameters.

Facile Low-Temperature Synthesis of Cellulose Nanocrystals Carrying Buckminsterfullerene and Its Radical Scavenging Property in Vitro.

Buckminsterfullerene (C60), known for its strong radical scavenging properties, has been studied extensively for its biomedical applications. Its clinical use would be promoted by novel functionalization of C60 with the aid of drug delivery carriers based on nanoparticle technologies. Cellulose nanocrystals (CNCs) have recently been exploited as a promising nanoplatform for drug delivery, owing to their intriguing attributes such as nanoscale dimensions, low toxicity, broad chemical-modifying capacity, and biocompatibility. Herein, cellulose nanocrystals carrying buckminsterfullerene (CNC-C60) have been synthesized via amine functionalization of CNCs and subsequent grafting of C60 onto the surface of amine-terminated CNCs. FTIR and XPS measurements confirmed the success of the synthesis, which was further evidently supported by TGA analysis. Given atomic compositions of samples by elemental analysis, we figured out a C60 content of 0.17 mmol/g of CNC-C60, equivalent to 34 C60 molecules/1000 anhydroglucose units (AGU). Afterward, CNC-C60 was evaluated for its antiradical effects on scavenging hydroxyl radicals in vitro. The ease of synthesis and significant radical scavenging activity make CNC-C60 a promising novel antioxidant agent for biomedical use.

Effect of humic acid on uranium(VI) retention and transport through quartz columns with varying pH and anion type.

Humic acid (HA)1 is ubiquitous in the environment and is an important factor in the migration behavior of U(VI) in the geological medium. The present work investigated the effect of HA on the migration behavior of U(VI) using quartz column experiments at different pH values and in the presence of various anions. The U(VI) adsorption characteristics and speciation were also studied to illuminate further the migration behavior of U(VI). Our results indicated that, at pH 6.0, HA slightly increased the migration velocity of U(VI) during the initial phase and reduced the quantity of eluted U(VI) because of the formation of HA-U(VI). The relative concentration (c/c0) of U(VI)was higher in the HA-U system at pH 8.0 than that at pH 5.0 because of the higher solubility of HA in basic solutions and the difference in charge of HA-U(VI). In the U-HA-anion system at pH 6.0, the breakthrough pore volumes (PVs2) of U(VI) in electrolytes containing Cl- and SO42- anions (PV = 8) are much higher than for solutions containing phosphate (PV = 3), while the HA migration behavior was not significantly affected by the type of anion. Thus, the fast migration of U(VI) under HA and phosphate was attributed to phosphate rather than HA. This result suggests that phosphate should be given more attention in predictions of U(VI) migration, especially in regions with high groundwater phosphate content.