Genotoxic assessment of cerium and magnesium nanoparticles and their ionic forms in Eisenia hortensis coelomocytes by alkaline comet assay.

The present study aimed to evaluate the genotoxic potential of cerium oxide (CeO2 ), magnesium oxide (MgO) nanoparticles and their ionic forms by alkaline comet assay. Eisenia hortensis were exposed to different series of concentrations (25, 50, 100, 200, and 400 µg/ml) of chemicals for 48 h to find LC50 . The LC50 for MgO and CeO2 NPs were 70 and 80 µg/ml. Whereas, the LC50 for their ionic forms were 50 and 70 µg/ml. To assess the potential DNA damage caused by the chosen chemicals, E. hortensis was further exposed for 48 h to the following concentrations, based on their respective LC50s : LC50/2 , LC50 , and 2xLC50 . Comet scores demonstrated the significant increase (p < 0.05) in DNA damage at all concentrations, both for NPs and ionic forms in a concentration-dependent manner. Findings of the present study revealed the genotoxic effects of CeO2 NPs, MgO NPs and their ionic forms on E. hortensis. RESEARCH HIGHLIGHTS: Genotoxic assessment of CeO2 and MgO NPs and their ionic forms was conducted. Characterization of NPs through electron microscopy and alkaline comet assay was performed on E. Hortensis. Highest DNA damage of CeO2 and MgO NPs was observed on earthworm.

Corrosion Resistance and Cytocompatibility of Magnesium-Calcium Alloys Modified with Zinc- or Gallium-Doped Calcium Phosphate Coatings.

In orthopedic surgery, metals are preferred to support or treat damaged bones due to their high mechanical strength. However, the necessity for a second surgery for implant removal after healing creates problems. Therefore, biodegradable metals, especially magnesium (Mg), gained importance, although their extreme susceptibility to galvanic corrosion limits their applications. The focus of this study was to control the corrosion of Mg and enhance its biocompatibility. For this purpose, surfaces of magnesium-calcium (MgCa1) alloys were modified with calcium phosphate (CaP) or CaP doped with zinc (Zn) or gallium (Ga) via microarc oxidation. The effects of surface modifications on physical, chemical, and mechanical properties and corrosion resistance of the alloys were studied using surface profilometry, goniometry, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), nanoindentation, and electrochemical impedance spectroscopy (EIS). The coating thickness was about 5-8 µm, with grain sizes of 43.1 nm for CaP coating and 28.2 and 58.1 nm for Zn- and Ga-doped coatings, respectively. According to EIS measurements, the capacitive response (Yc) decreased from 11.29 to 8.72 and 0.15 Ω-1 cm-2 sn upon doping with Zn and Ga, respectively. The Ecorr value, which was -1933 mV for CaP-coated samples, was found significantly electropositive at -275 mV for Ga-doped ones. All samples were cytocompatible according to indirect tests. In vitro culture with Saos-2 cells led to changes in the surface compositions of the alloys. The numbers of cells attached to the Zn-doped (2.6 × 104 cells/cm2) and Ga-doped (6.3 × 104 cells/cm2) coatings were higher than that on the surface of the undoped coating (1.0 × 103 cells/cm2). Decreased corrosivity and enhanced cell affinity of the modified MgCa alloys (CaP coated and Zn and Ga doped, with Ga-doped ones having the greatest positive effect) make them novel and promising candidates as biodegradable metallic implant materials for the treatment of bone damages and other orthopedic applications.

In Situ Investigation of the Cytotoxic and Interfacial Characteristics of Titanium When Galvanically Coupled with Magnesium Using Scanning Electrochemical Microscopy.

Recently, the cytotoxic properties of galvanically coupled Ti-Mg particles have been shown in different cells. This cytotoxic effect has been attributed mainly to Mg due to its tendency to undergo activation when coupled with Ti, forming a galvanic cell consisting of an anode (Mg) and a cathode (Ti). However, the role of the Ti cathode has been ignored in explaining the cytotoxic effect of Ti-Mg particles due to its high resistance to corrosion. In this work, the role of titanium (Ti) in the cytotoxic mechanism of galvanically coupled Ti-Mg particles was examined. A model galvanic cell (MGC) was prepared to simulate the Mg-Ti particles. The electrochemical reactivity of the Ti sample and the pH change in it due to galvanic coupling with Mg were investigated using scanning electrochemical microscopy (SECM). It was observed that the Ti surface changed from passive to electrochemically active when coupled with Mg. Furthermore, after only 15 min of galvanic coupling with Mg, the pH in the electrolyte volume adjacent to the Ti surface increased to an alkaline pH value. The effects of the galvanic coupling of Ti and Mg, as well as those of the alkaline pH environment, on the viability of Hs27 fibroblast cells were investigated. It was shown that the viability of Hs27 cells significantly diminished when Mg and Ti were galvanically coupled compared to when the two metals were electrically disconnected. Thus, although Ti usually exhibited high corrosion resistance when exposed to physiological environments, an electrochemically active surface was observed when galvanically coupled with Mg, and this surface may participate in electron transfer reactions with chemical species in the neighboring environment; this participation resulted in the increased pH values above its surface and enhanced generation of reactive oxygen species. These features contributed to the development of cytotoxic effects by galvanically coupled Ti-Mg particles.

Impact of land use/land cover changes on water quality and human health in district Peshawar Pakistan.

The quality and quantity of groundwater resources are affected by landuse/landcover (LULC) dynamics, particularly the increasing urbanization coupled with high household wastewater discharge and decreasing open lands. This study evaluates temporal changes of groundwater quality for 2012 and 2019, its relation to Landuse/landcover, and its impact on Peshawar's residents (study area), Pakistan. A total of 105 and 112 groundwater samples were collected from tube wells in 2012 and 2019. Samples were then analyzed for seven standard water quality parameters (i.e., pH, electric conductivity (EC), turbidity, chloride, calcium, magnesium, and nitrate). Patient data for waterborne diseases were also collected for the years 2012 and 2019 to relate the impact of groundwater quality on human health. Landsat satellite images were classified for the years 2012 and 2019 to observe landuse/landcover dynamics concerning groundwater quality. Results manifested a decrease in groundwater quality for the year 2019 compared to 2012 and were more highlighted in highly populated areas. The nitrate concentration level was found high in the vicinity of agricultural areas due to the excessive use of nitrogenous fertilizers and pesticides, and thus the methemoglobinemia patients ratio increased by 14% (48-62% for the year 2012 and 2019, respectively). Besides, Urinary Tract Infections, Peptic Ulcer, and Dental Caries diseases increased due to the high calcium and magnesium concentration. The overall results indicate that anthropogenic activities were the main driver of Spatio-temporal variability in groundwater quality of the study area. The study could help district health administration understand groundwater quality trends, make appropriate site-specific policies, and formulate future health regulations.

Epileptiform activity in mouse hippocampal slices induced by moderate changes in extracellular Mg2+, Ca2+, and K.

BACKGROUND: Rodent brain slices-particularly hippocampal slices-are widely used in experimental investigations of epileptiform activity. Oxygenated artificial cerebrospinal fluid (ACSF) is used to maintain slices in vitro. Physiological or standard ACSF containing 3-3.5 mM K+, 1-2 mM Mg2+, and 1-3 mM Ca2+ generally does not induce population epileptiform activity, which can be induced by ACSF with high K+ (8-10 mM), low Mg2+, or low Ca2+ alone or in combination. While low-Mg2+ ACSF without intentionally added Mg salt but with contaminating Mg2+ (≤ 50-80 µM) from other salts can induce robust epileptiform activity in slices, it is unclear whether such epileptiform activity can be achieved using ACSF with moderately decreased Mg2+. To explore this issue, we examined the effects of moderately modified (m)ACSF with 0.8 mM Mg2+, 1.3 mM Ca2+, and 5.7 mM K+ on induction of epileptiform discharges in mouse hippocampal slices. RESULTS: Hippocampal slices were prepared from young (21-28 days old), middle-aged (13-14 months old), and aged (24-26 months old) C57/BL6 mice. Conventional thin (0.4 mm) and thick (0.6 mm) slices were obtained using a vibratome and pretreated with mACSF at 35-36 °C for 1 h prior to recordings. During perfusion with mACSF at 35-36 °C, spontaneous or self-sustained epileptiform field potentials following high-frequency stimulation were frequently recorded in slices pretreated with mACSF but not in those without the pretreatment. Seizure-like ictal discharges were more common in thick slices than in thin slices. CONCLUSIONS: Prolonged exposure to mACSF by pretreatment and subsequent perfusion can induce epileptiform field potentials in mouse hippocampal slices.

Metallomics Analysis for Assessment of Toxic Metal Burdens in Infants/Children and Their Mothers: Early Assessment and Intervention Are Essential.

Accumulation of toxic metals in infants/children is of serious concern worldwide, from the viewpoint of their harmful effects on the normal growth and development. This metallomics study investigates the extent of toxic metal burdens in infants/children and the relationship to those in their mothers for 77 child/mother pair subjects. For mercury, its geometric mean concentration in infants/children was of similar level to that in their mothers, and a high-significant close correlation was observed between infants/children and their mothers (ß = 0.758, r = 0.539, p < 0.0001). A significant but less intimate mother/child relationship was observed for arsenic (ß = 0.301, r = 0.433), lead (ß = 0.444, r = 0.471) and aluminum (ß = 0.379, r = 0.451). Remarkably, the burden levels of lead, cadmium and aluminum in infants/children were approximately three times higher than those in their mothers (p < 0.0001), and the burden levels in some individuals were several tens of times higher than in the mothers. In contrast, some essential metal levels such as zinc, magnesium and calcium in infants/children were significantly lower than those in their mothers, and 29 individuals (37.7%) in the child subjects were estimated to be zinc-deficient. In addition, significant inverse correlations were observed between zinc and lead (r = -0.267, p = 0.019), and magnesium and arsenic (r = -0.514, p < 0.0001). These findings suggest that these toxic metal burdens and essential metal deficiencies in infants/children are of serious concern for their neurodevelopment, indicating that the early assessment and intervention are crucial. It is expected that larger epidemiological and intervention studies will provide a reasonable and essential pathway for intervention of neurodevelopment disorders.

Elevated Magnesium Concentrations Altered Freshwater Assemblage Structures in a Mesocosm Experiment.

Magnesium (Mg) is a mining-related contaminant in the Alligators Rivers Region of tropical northern Australia. A mesocosm experiment was used to assess Mg toxicity to aquatic freshwater assemblages. Twenty-five 2700-L tubs were arranged, stratified randomly, on the bed of Magela Creek, a seasonally flowing, sandy stream channel in the Alligator Rivers Region of northern Australia. The experiment comprised 5 replicates of 4 nominal Mg treatments, 2.5, 7.5, 23, and 68 mg L-1 , and a control. Phytoplankton biomass, and diatom, zooplankton, and macroinvertebrate assemblages present in the treatment tubs were sampled before and after Mg addition. A significant negative relationship between phytoplankton biomass and Mg was observed 4 wk after Mg addition as measured by chlorophyll a concentrations (r2 = 0.97, p = 0.01). This result was supported by reductions in some major phytoplankton groups in response to increasing Mg concentrations, in the same experiment and from independent field studies. There was a significant negative relationship between zooplankton assemblage similarity (to control) and Mg concentrations (r2 = 0.96, p = 0.002). Seven weeks after Mg addition, macroinvertebrate assemblages were dominated by 3 microcrustacean groups (Ostracoda, Cladocera, and Copepoda), each reaching maximum abundance at intermediate Mg concentrations (i.e., unimodal responses). The responses of phytoplankton and zooplankton were used to derive assemblage effect concentrations (Mg concentrations resulting in x% of the assemblage change [ECx]). Magnesium concentrations resulting in assemblage EC01 values were <3 mg L-1 . Together with candidate guideline values from other laboratory- and field-based lines of evidence, the mesocosm EC01 values were incorporated into a weight-of-evidence framework for a robust regulatory approach to environmental protection. Environ Toxicol Chem 2020;39:1973-1987. © 2020 Commonwealth of Australia. Published by Wiley Periodicals LLC on behalf of SETAC.

TiO2-Induced In Situ Reaction in Graphene Oxide-Reinforced AZ61 Biocomposites to Enhance the Interfacial Bonding.

Graphene oxide (GO) can improve the degradation resistance of biomedical Mg alloy because of its excellent impermeability and outstanding chemical inertness. However, the weak interfacial bonding between GO and Mg matrix leads to easily detaching during degradation. In this study, in situ reaction induced by TiO2 took place in the AZ61-GO biocomposite to enhance the interfacial bonding between GO and Mg matrix. For the specific process, TiO2 was uniformly and tightly deposited onto the GO surface by hydrothermal reaction (TiO2/GO) first and then used for fabricating AZ61-TiO2/GO biocomposites by selective laser melting (SLM). Results showed that TiO2 was in situ reduced by magnesiothermic reaction during SLM process, and the reduzate Ti, on the one hand, reacted with Al in the AZ61 matrix to form TiAl2 and, on the other hand, reacted with GO to form TiC at the AZ61-GO interface. Owing to the enhanced interfacial bonding, the AZ61-TiO2/GO biocomposite showed 12.5% decrease in degradation rate and 10.1% increase in compressive strength as compared with the AZ61-GO biocomposite. Moreover, the AZ61-TiO2/GO biocomposite also showed good cytocompatibility because of the slowed degradation. These findings may provide guidance for the interfacial enhancement in GO/metal composites for biomedical applications.

Microstructure controls the corrosion behavior of a lean biodegradable Mg-2Zn alloy.

Microstructural design was a long-term sustainable development method to improve the biodegradability and mechanical properties of low alloyed biomedical Mg alloys. In this study, the microstructural features (including grain size, deformation twin, deformed grains, sub-grains, and recrystallized grains) of the MZ2 ((Mg-2Zn (wt%)) alloy were controlled by different single-passed rolling reductions at high temperature. Besides the effect of grain size, we found that deformation twins and deformed grains influenced corrosion performance. Grain refinement with uniform distribution, meanwhile reducing the content of deformation twins, deformed grains, and sub-grains, was a practical method to improve both corrosion resistance and mechanical properties of MZ2 alloy. This finding proposed a better understanding of the development of lean biomedical Mg alloys with superior mechanical properties and favorable corrosion resistance. STATEMENT OF SIGNIFICANCE: Current research and development of biomedical Mg focused on alloying methods. The lean biodegradable Mg, which reduced the materials' compositional complexity, was the benefit of development for long-term sustainability. Here, our work revealed the relationship between microstructural features and corrosion resistance of a lean Mg-2Zn alloy during the different single-passed rolling processes. We found that recrystallized fine grains with partially ultra-fine grains could improve both strength and corrosion resistance. This study could give a new understanding of the development of lean biodegradable Mg alloys by using microstructural design to improve the overall performance of biomedical applications.

Associations of exposure to metals with the risk of hypertension among an older population aged 40-75 years in rural southwest China.

Metal exposure has recently been related to the risk of hypertension. However, the association remains unclear and relevant epidemiologic studies are limited. The present study aimed to assess the associations between exposure to metals and the odds of hypertension, as well as blood pressure (BP) levels. A total of 816 participants were enrolled in southwestern China. Hypertension was defined as a systolic BP (SBP) of ≥140 mmHg or diastolic BP (DBP) of ≥90 mmHg, a self-reported physician diagnosis, or current use of antihypertensive medication. Blood samples were used to detect the levels of exposure to metals, ie, magnesium (Mg), calcium (Ca), iron (Fe), zinc (Zn), arsenic (As), cadmium (Cd), copper (Cu) and lead (Pb). Logistic and linear regression models were used to assess the potential associations. The results show that positive trends for elevated odds of hypertension with increasing quartiles of Fe in a polluted area; and of Mg, Ca and Cu in an unpolluted area. Compared with those in the lowest quartiles, participants in the highest quartiles of Fe, Mg and Ca had 2.7-, 9.0- and 5.1-fold increased odds of hypertension, respectively. High blood Fe and Pb levels in the Cd-polluted area, and Mg and Fe in the unpolluted area were found to be related to increasing SBP and DBP levels. Our findings suggest that exposure to Fe and/or Pb in the polluted area; and Mg, Ca and Fe in the unpolluted area might increase the risk of hypertension or elevate BP levels.

Effect of ion doping in silica-based nanoparticles on the hemolytic and oxidative activity in contact with human erythrocytes.

AIM: The aim of this study was the synthesis of ion doped silica-based nanoparticles and the evaluation of their toxic effect on erythrocytes. MATERIALS & METHODS: Their synthesis was performed using the sol-gel method, by the progressive addition of calcium, magnesium and copper ions on pure silica nanoparticles. The toxicity evaluation was based on hemolysis, lipid peroxidation, ROS, H2O2 species and antioxidant enzyme production. RESULTS: The addition of Mg and Cu in the SNs presented better hemocompatibility by protecting erythrocytes from oxidative stress. CONCLUSION: Ion doping with magnesium in the investigated calcium silicate system induces a protective effect in erythrocyte membrane in compare with pure silica nanoparticles.

The bioeffects of degradable products derived from a biodegradable Mg-based alloy in macrophages via heterophagy.

Biodegradable magnesium alloys are promising candidates for use in biomedical applications. However, degradable particles (DPs) derived from Mg-based alloys have been observed in tissue in proximity to sites of implantation, which might result in unexpected effects. Although previous in vitro studies have found that macrophages can take up DPs, little is known about the potential phagocytic pathway and the mechanism that processes DPs in cells. Additionally, it is necessary to estimate the potential bioeffects of DPs on macrophages. Thus, in this study, DPs were generated from a Mg-2.1Nd-0.2Zn-0.5Zr alloy (JDBM) by an electrochemical method, and then macrophages were incubated with the DPs to reveal the potential impact. The results showed that the cell viability of macrophages decreased in a concentration-dependent manner in the presence of DPs due to effects of an apoptotic pathway. However, the DPs were phagocytosed into the cytoplasm of macrophages and further degraded in phagolysosomes, which comprised lysosomes and phagosomes, by heterophagy instead of autophagy. Furthermore, several pro-inflammatory cytokines in macrophages were upregulated by DPs through the induction of reactive oxygen species (ROS) production. To the best of our knowledge, this is the first study to show that DPs derived from a Mg-based alloy are consistently degraded in phagolysosomes after phagocytosis by macrophages via heterophagy, which results in an inflammatory response owing to ROS overproduction. Thus, our research has increased the knowledge of the metabolism of biodegradable Mg metal, which will contribute to an understanding of the health effects of biodegradable magnesium metal implants used for tissue repair. STATEMENT OF SIGNIFICANCE: Biomedical degradable Mg-based alloys have great promise in applied medicine. Although previous studies have found that macrophages can uptake degradable particles (DPs) in vitro and observed in the sites of implantation in vivoin vivo, few studies have been carried out on the potential bioeffects relationship between DPs and macrophages. In this study, we analyzed the bioeffects of DPs derived from a Mg-based alloy on the macrophages. We illustrated that the DPs were size-dependently engulfed by macrophages via heterophagy and further degraded in the phagolysosome rather than autophagosome. Furthermore, DPs were able to induce a slight inflammatory response in macrophages by inducing ROS production. Thus, our research enhances the knowledge of the interaction between DPs of Mg-based alloy and cells, and offers a new perspective regarding the use of biodegradable alloys.

Comparative in vitro study on binary Mg-RE (Sc, Y, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb and Lu) alloy systems.

Correct selection of alloying elements is important for developing novel biodegradable magnesium alloys with superior mechanical and biological performances. In contrast to various reports on nutrient elements (Ca, Zn, Sr, etc.) as alloying elements of biomedical magnesium alloys, there is limited information about how to choose the right rare earth elements (REEs) as alloying elements of magnesium. In this work, 16 kinds of REEs were individually added into Mg, including Sc, Y, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Du, Ho, Er, Tm, Yb and Lu, to fabricate binary Mg-RE model alloys with different composition points. Under the same working history, comparative studies were undertaken and the impact of each kind of rare earth element on the microstructure, mechanical property, corrosion behavior and biocompatibility of Mg were investigated. The corresponding influence level for the 16 kinds of REEs were ranked. The results showed that the second phases were detected in some Mg-RE alloys, which were mainly composed of Mg12RE. By adding different REEs into Mg with proper contents, the mechanical properties of resulting Mg-RE binary alloys could be adjusted in wide range. The corrosion resistance of Mg-light REE alloys was generally better than Mg-heavy REE alloys. As for biocompatibility, Mg-RE model alloys showed no cytotoxic effect on MC3T3-E1 cells. The hemolysis rates of all experimental Mg-RE model alloys were lower than 5% except for Mg-Lu alloy model. In general, the addition of different REEs into Mg could improve its performance from different aspects. This work provides a better understanding on suitable REEs as alloying elements for magnesium, and the future R&D direction on biomedical Mg-RE alloys was proposed. STATEMENT OF SIGNIFICANCE: In contrast to various reports on nutrient elements (Ca, Zn, Sr, etc.) as alloying elements of biomedical magnesium alloys, until now there is limited information about how to choose the right rare earth elements (REEs) as alloying elements of magnesium. In this work, comparative studies were undertaken by individually adding 16 kinds of REEs, including Sc, Y, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Du, Ho, Er, Tm, Yb and Lu, into Mg to fabricate binary Mg-RE model alloys, with different composition points, then the impact of each kind of rare earth element on the microstructure, mechanical property, corrosion behavior and biocompatibility of Mg under the same working history were investigated, and the corresponding influence level for the 16 kinds of REEs were ranked. This work provides a better understanding on suitable REEs as alloying elements for magnesium, and the future R&D direction on biomedical Mg-RE alloys was proposed.

Higher serum magnesium concentration is associated with lower hearing thresholds and risk of hearing loss among a Chinese population.

BACKGROUND AND OBJECTIVES: Hearing loss is a sensory impairment caused by genetic and environmental factors. Previous epidemiological studies of magnesium intake and hearing loss have yielded conflicting results. METHODS AND STUDY DESIGN: We investigated the association between serum magnesium concentrations and hearing loss in a population from the Zhejiang region of China. A cross-sectional study of 3,267 participants aged 18 years and older from five hospitals was conducted from October 2016 to May 2018. An audiometric examination was conducted, and hearing thresholds were computed as pure-tone averages (PTAs) at speech (0.5, 1, 2, and 4 kHz) and high frequencies (3, 4, and 6 kHz). Magnesium concentrations were measured using an inductively coupled plasma mass spectrometer. RESULTS: A linear regression analysis revealed a negative association between magnesium levels and hearing losses from lower to high PTAs. After the adjustment of potential confounders, participants in the highest magnesium quartile had a lower PTA (quartile 4: -1.89%; 95% confidence interval (CI: -3.07 to -0.701); p=0.022) and high PTA (quartile 4: -3.05%; 95% CI: -4.64 to -1.46; p=0.005) than those in the lowest quartile. A logistic regression analysis showed a dose-dependent reduction in the odds of high frequency hearing loss across magnesium quartiles. In model 3, after adjusting for all potential confounders, participants with the highest magnesium quartiles had a 54.0% (OR: 0.460; 95% CI: 0.339-0.587) reduction in the odds of high-frequency hearing loss. CONCLUSIONS: Higher whole blood levels of magnesium in this population were associated with lower hearing thresholds and risk of hearing loss.

Acute and chronic toxicity of magnesium to the early life stages of two tropical freshwater mussel species.

Magnesium (Mg) is a common contaminant in mine water discharges. Although Mg is an essential element in biological processes, increased concentrations from anthropogenic sources can stress aquatic ecosystems. Additionally, studies evaluating the effects of Mg on north Australian freshwater species have indicated that in very soft waters there is a high risk to some species. Freshwater mussels are an ecologically and culturally important taxon in many freshwater environments, but knowledge of their sensitivity to Mg is limited. In the present study, the acute and chronic sensitivity of two freshwater mussel species, Velesunio angasi and an undescribed Velesunio species, to Mg was assessed (using MgSO4) on their early life stages, larval glochidia and post-parasitic juveniles. Acute 24-h exposures with glochidia generated a mean median lethal (LC50) toxicity estimate of 284mg/L for the five tests with V. angasi, and a mean LC50 of 300mg/L for the three tests with Velesunio sp. Mean chronic 14-d toxicity estimates resulting in 50% (EC50) and 10% (EC10) growth rate reductions for juveniles were 241 and 88mg/L respectively for the three tests with V. angasi juveniles, and 232 and 87mg/L respectively for the three tests with Velesunio sp. juveniles. The results represent the first acute and chronic Mg toxicity data for tropical freshwater mussels, and indicated that V. angasi and Velesunio sp. exhibited similar sensitivity and were moderately sensitive to Mg when compared to other tropical species. These results are a valuable contribution to the small existing dataset for Mg toxicity to tropical freshwater species, which can be used to inform water management in areas where Mg is a contaminant of concern, and ensure the protection of these taxa.

Low-intensity ultrasound suppresses low-Mg2+-induced epileptiform discharges in juvenile mouse hippocampal slices.

OBJECTIVE: It has been shown that low-intensity ultrasound (LIUS) can suppress seizures in some laboratory studies. However, the mechanism of the suppression effect of LIUS remains unclear. The goal of this study is to investigate the modulation effects of focused LIUS on epileptiform discharges in mouse hippocampal slices as well as the underlying mechanism. APPROACH: Epileptiform discharges in hippocampal slices of 8 d-old mice were induced by low-Mg2+ artificial cerebrospinal fluid and recorded by a micro-electrode array in vitro. LIUS was delivered to hippocampal slices to investigate its modulation effects on epileptiform discharges. Pharmacological experiments were conducted to study the mechanism of the modulation effects. MAIN RESULTS: LIUS suppressed the amplitude, rate and duration of ictal discharges. For inter-ictal discharges, LIUS suppressed the amplitude but facilitated the rate. LIUS suppressed the spontaneous spiking activities of pyramidal neurons in CA3, and the suppression effect was eliminated by Kaliotoxin. The suppression effect of LIUS on epileptiform discharges was weakened when the perfusion was mixed with Kaliotoxin. SIGNIFICANCE: Those findings demonstrate that LIUS suppresses the epileptiform discharges in 8 d-old mouse hippocampal slices and that its suppression effect can mainly attributed to the activation of mechanosensitive Kv1.1 channels.

Improved corrosion resistance of commercially pure magnesium after its modification by plasma electrolytic oxidation with organic additives.

The optimal mechanical properties render magnesium widely used in industrial and biomedical applications. However, magnesium is highly reactive and unstable in aqueous solutions, which can be modulated to increase stability of reactive metals that include the use of alloys or by altering the surface with coatings. Plasma electrolytic oxidation is an efficient and tuneable method to apply a surface coating. By varying the plasma electrolytic oxidation parameters voltage, current density, time and (additives in the) electrolytic solution, the morphology, composition and surface energy of surface coatings are set. In the present study, we evaluated the influence on surface coatings of two solute additives, i.e. hexamethylenetetramine and mannitol, to base solutes silicate and potassium hydroxide. Results from in vitro studies in NaCl demonstrated an improvement in the corrosion resistance. In addition, coatings were obtained by a two-step anodization procedure, firstly anodizing in an electrolyte solution containing sodium fluoride and secondly in an electrolyte solution with hexamethylenetetramine and mannitol, respectively. Results showed that the first layer acts as a protective layer which improves the corrosion resistance in comparison with the samples with a single anodizing step. In conclusion, these coatings are promising candidates to be used in biomedical applications in particular because the components are non-toxic for the body and the rate of degradation of the surface coating is lower than that of pure magnesium.

Vacuolar Proton Pyrophosphatase Is Required for High Magnesium Tolerance in Arabidopsis.

Magnesium (Mg2+) is an essential nutrient in all organisms. However, high levels of Mg2+ in the environment are toxic to plants. In this study, we identified the vacuolar-type H⁺-pyrophosphatase, AVP1, as a critical enzyme for optimal plant growth under high-Mg conditions. The Arabidopsis avp1 mutants displayed severe growth retardation, as compared to the wild-type plants upon excessive Mg2+. Unexpectedly, the avp1 mutant plants retained similar Mg content to wild-type plants under either normal or high Mg conditions, suggesting that AVP1 may not directly contribute to Mg2+ homeostasis in plant cells. Further analyses confirmed that the avp1 mutant plants contained a higher pyrophosphate (PPi) content than wild type, coupled with impaired vacuolar H⁺-pyrophosphatase activity. Interestingly, expression of the Saccharomyces cerevisiae cytosolic inorganic pyrophosphatase1 gene IPP1, which facilitates PPi hydrolysis but not proton translocation into vacuole, rescued the growth defects of avp1 mutants under high-Mg conditions. These results provide evidence that high-Mg sensitivity in avp1 mutants possibly resulted from elevated level of cytosolic PPi. Moreover, genetic analysis indicated that mutation of AVP1 was additive to the defects in mgt6 and cbl2 cbl3 mutants that are previously known to be impaired in Mg2+ homeostasis. Taken together, our results suggest AVP1 is required for cellular PPi homeostasis that in turn contributes to high-Mg tolerance in plant cells.

Natural variation among Arabidopsis thaliana accessions in tolerance to high magnesium supply.

High magnesium (Mg2+) in some extreme serpentine soils or semi-arid regions is an important factor affecting crop growth and development. Specific loci that form the genetic framework underlying high Mg2+ homeostasis, however, are not well understood. By using GWA mapping on 388 accessions of Arabidopsis thaliana selected from a worldwide collection and genotyped at approximately 250,00 SNPs, we successfully identified 109 and 74 putative genetic regions associated in nutrient traits under normal (1,000 µM) and high Mg2+ (10,000 µM), respectively. Above 90% SNPs associated with nutrients including Mg2+ and only two SNPs shared between normal and high Mg2+. A single strong peak of SNPs associated with Ca concentration corresponding to candidate gene At1g60420 ARABIDOPSIS NUCLEOREDOXIN (AtNRX1) under high Mg2+ was further determined. Compared with wildtype, mutants of Atnrx1-1 and Atnrx1-2 supplied with high Mg2+ had higher Ca concentrations in the plant, and higher cytosolic Ca2+ concentrations during root elongation, as well as higher fresh weight and lateral-root number. This suggests that AtNRX1 was a critical gene negatively regulating Ca uptake under high Mg2+ conditions. The discovery could help to breed/select crops that can adapt to high-Mg2+ soils such as serpentine soils (high ratio of Mg2+: Ca2+) or Mars soil with high levels of magnesium sulfate.

High waterborne Mg does not attenuate the toxic effects of Fe, Mn, and Ba on Na+ regulation of Amazonian armored catfish tamoatá (Hoplosternum litoralle).

Formation water (FoW) is a by-product from oil and gas production and usually has high concentrations of soluble salts and metals. Calcium (Ca) and magnesium (Mg) have been shown to reduce the toxicity of metals to aquatic animals, and previous study showed that high waterborne Ca exerts mild effect against disturbances on Na+ regulation in Amazonian armored catfish tamoatá (Hoplosternum littorale) acutely exposed to high Fe, Mn, and Ba levels. Here, we hypothesized that high Mg levels might also reduce the toxic effects of these metals on Na+ regulation of tamoatá. The exposure to 5% FoW promoted an increase in Na+ uptake and a rapid accumulation of Na+ in all tissues analyzed (kidney