Effects of calcium supplements on oral bioavailability of fluoride in soil based on In Vivo and In Vitro methods.

Dietary calcium (Ca) intake can alleviate fluoride (F) induced fluorosis to maintain bone health. However, it is unclear whether calcium supplements can reduce the oral bioavailability of F present in contaminated soils. Here we evaluated the effects of Ca supplements on F bioavailability in three soils using an in vitro method (Physiologically Based Extraction Test) and an in vivo mouse model. Seven Ca salts, commonly used in calcium supplements, significantly reduced the F bioaccessibility in the gastric and small intestinal phases. Particularly for Ca phosphate at 150 mg Ca supplementation, F bioaccessibility in the small intestinal phase was reduced from 35.1-38.8% to 0.7-1.9% where soluble F concentrations were less than 1 mg/L. Overall, the eight Ca tablets tested in this study showed greater efficiency at decreasing F solubility. The in vitro bioaccessibility after Ca supplementation was consistent with the relative bioavailability of F. As supported by X-ray photoelectron spectroscopy, a possible mechanism is that freed F can be bound by Ca to form insoluble CaF2 and exchanged with OH groups from Al/Fe hydroxide to strongly adsorb F. These findings provide evidence of Ca supplementation in reducing health risks associated soil F exposure.

Spatial Metallomics Reveals Preferable Accumulation of Methylated Selenium in a Single Seed of the Hyperaccumulator Cardamine violifolia†.

Cardamine violifolia is a Se hyperaccumulator found in Enshi, China. In this study, spatial metallomics was applied to visualize the distribution and speciation of Se in a single seed of C. violifolia. It was found that Se reached 1729.89 ± 28.14 mg/kg and the main Se species were SeCys and SeMet in bulk seeds. Further in situ study on a single seed found that the methylated Se species located mostly in the episperm. This is the first visualized evidence of the in situ distribution of methylated Se species in the seeds of C. violifolia. In all, spatial metallomics finds a preferable accumulation of methylated Se species in the seed coat, which deepens the understanding of the tolerance of Se by C. violifolia. The protocol applied in this study may also be used for the understanding of the tolerance of heavy metals/metalloids in other hyperaccumulators.

Nano mercury selenide as a source of mercury for rice.

Mercury (Hg) is a persistent and toxic metal while mercury selenide (HgSe) is generally considered as the environmental sink of Hg in its biogeochemical cycle. Recent studies found nano-sized HgSe (nano-HgSe) could be transformed by certain bacteria. This raises safety concerns about the application of selenium (Se) to curb Hg contamination in farmlands. Therefore, hydroponic experiments were performed in which rice plants were cultured with different concentrations of nano-HgSe and micro-sized HgSe (micro-HgSe) to explore their bioavailability and toxicity. It was found that both nano-HgSe and micro-HgSe did not affect the germination of rice seeds but affected the growth of rice seedlings. However, nano-HgSe could be more readily absorbed by roots and transferred to the aboveground parts compared to micro-HgSe. The highest Hg and Se levels were found to be 5255.67 ± 2496.14 µg/g and 1743.75 ± 61.87 µg/g, respectively in roots when exposed to 5000 mg/L nano-HgSe. Besides, small portion (1.2%) of methylmercury (MeHg) to total Hg was found accumulated in rice stem when exposed to 100 mg/L nano-HgSe, suggesting that nano-HgSe could be decomposed. Furthermore, nano-HgSe exposure brought oxidative damage to rice with decreased chlorophyll content and GSH-Px activity. In all, nano-HgSe was found to be more absorbable, transportable and methylated in rice plant compared to micro-HgSe. This suggests that although Se application in Hg contaminated farmland is an effective way to reduce the bioavailability of Hg, the risk of the possible remobilization of HgSe should not be neglected. Besides, the finding that nano-HgSe can act as an environmental source of Hg for plants deepens the understanding of biogeochemical cycle of Hg. More works are required to study the factors affecting the formation of nano-HgSe in the environment and the mechanisms of Hg methylation in rice plants after exposure to nano-HgSe.

Cardamine violifolia as a potential Hg hyperaccumulator and the cellular responses.

Cardamine violifolia belongs to the Brassicaceae family and is a selenium (Se) hyperaccumulator found in Enshi, China. In this study, C. violifolia was found to accumulate mercury (Hg) in its roots and aboveground parts at concentrations up to 6000 µg/g. In the seedling and mature stages, the bioaccumulation factors (BAFS) of Hg reached 1.8-223, while the translocation factor (TF) for Hg reached 1.5. We observed a significant positive correlation between THg concentrations in plant tissues and those in the soil (r2 = 0.71-0.84). Synchrotron radiation X-ray fluorescence with focused X-ray (µ-SRXRF) showed that Hg was translocated from the roots to shoots through the vascular bundle and was transported through the leaf veins in leaves. Transmission electron microscopy showed that root cells were more tolerant to Hg than leaf cells. These findings provide insights into the mechanisms of Hg hyperaccumulation in C. violifolia. Overall, we demonstrated that C. violifolia is a promising Hg hyperaccumulator that may be used for phytoremediating Hg-contaminated farmlands.

Nano-WSe2 Is Absorbable and Transformable by Rice Plants.

As typical transition metal dichalcogenides (TMDC), tungsten selenide (WSe2) nanosheets (nano-WSe2) are widely used in various fields due to their layered structures and highly tunable electronic and magnetic properties, which results in the unwanted release of tungsten (W) and selenium (Se) into the environment. However, the environmental effects of nano-WSe2 in plants are still unclear. Herein, we evaluated the impacts and fate of nano-WSe2 and micro-WSe2 in rice plants (Oryza sativa L.). It was found that both nano-WSe2 and micro-WSe2 did not affect the germination of rice seeds up to 5000 mg/L but nano-WSe2 affected the growth of rice seedlings with shortened root lengths. The uptake and transportation of WSe2 was found to be size-dependent. Moreover, W in WSe2 was oxidized to tungstate while Se was transformed to selenocysteine, selenomethionine, SeIV and SeVI in the roots of rice when exposed to nano-WSe2, suggesting the transformation of nano-WSe2 in rice plants. The exposure to nano-WSe2 brought lipid peroxidative damage to rice seedlings. However, Se in nano-WSe2 did not contribute to the synthesis of glutathione peroxidase (GSH-Px) since the latter did not change when exposed to nano-WSe2. This is the first report on the impacts and fate of nano-WSe2 in rice plants, which has raised environmental safety concerns about the wide application of TMDCs, such as WSe2 nanosheets.

MnO2-melittin nanoparticles serve as an effective anti-tumor immunotherapy by enhancing systemic immune response.

Cancer vaccines are viewed as a promising immunotherapy to eradicate malignant tumors and aim to elicit the patients' own tumor-specific immune response against tumor cells. However, few cancer vaccines have been applied due to the low immunogenicity of antigen and invalidation of adjuvant. Herein, we designed a tumor microenvironment (TME) responsive MnO2-melittin nanoparticles (M-M NPs). The M-M NPs consumed glutathione and produced •OH via Fenton-like reaction in the mimic TME, specifically caused tumor cell death in vitro, activated cGAS-STING pathway in vitro and promoted the maturation of antigen-presenting cells in vitro and in vivo to elicit systemic anti-tumor immune response including the augmentation of tumor-specific T cells and more productions of pro-inflammatory cytokines and chemokines, which all were stronger than MnO2 NPs and melittin. The anti-tumor effects of M-M NPs were evaluated in three subcutaneous tumor models and the B16-F10 lung metastasis model and the tumor growth and lung metastasis were more obviously inhibited in the M-M NPs treated mice, compared with MnO2 NPs and melittin treatments. More importantly, only M-M NPs promoted the MHC-I cross-dressing by dendritic cells to prime tumor-specific CD8+ T cells and remarkably suppressed the growth of left tumors if express cognate antigen while treating on the right in the bilateral tumor model. Our findings proposed a strategy to enhance the cancer vaccine efficiency which showed great therapeutic effect on tumor immunotherapy.

MALDI-TOF-MS and XAS analysis of complexes formed by metallothionein with mercury and/or selenium.

Mercury (Hg) is highly toxic while selenium (Se) has been found to antagonize Hg. Both Hg and Se have been found to induce metallothioneins (MTs). In this study, the complexes formed by metallothionein-1 (MT-1) with HgCl2 and/or Na2SeO3 was studied using matrix-assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS) and X-ray absorption spectrometry (XAS). MALDI-TOF-MS and XAS indicated the formation of Hg-S bond or Se-S bond when MT-1 reacted with HgCl2 or Na2SeO3, respectively. The bond lengths of Hg-S and coordination number in MT-Hg are 2.41 ± 0.02 Å and 3.10 and in MT-Se are 2.50 ± 0.03 Å and 2.69. A MT-Se-Hg complex was formed when MT-1 reacted with both HgCl2 and Na2SeO3, in which the neighboring atom of Hg is Se, while the neighboring atoms of Se are S and Hg. Our study is an important step towards a better understanding of the interaction of HgCl2 and/or Na2SeO3 with proteins like MT-1.

Ginsenoside Rb3 Alleviates CSE-induced TROP2 Upregulation through p38 MAPK and NF-κB Pathways in Basal Cells.

Smoking-mediated reprogramming of the phenotype and function of airway basal cells (BCs) disrupts airway homeostasis and is an early event in chronic obstructive pulmonary disease (COPD)-associated airway remodeling. Here, we examined the expression and regulation of the transmembrane glycoprotein TROP2 (trophoblast antigen 2), a putative stem cell marker in airway BCs, in lung tissue samples from healthy smokers and healthy nonsmokers and in models in culture to identify therapeutic targets. TROP2 expression was upregulated in the airway epithelia of smokers and positively correlated with the smoking index. In vitro, cigarette smoke extract (CSE) induced TROP2 expression in airway BCs in a time- and dose-dependent manner. The p38 MAPK and NF-κB pathways were also activated by CSE, and their specific antagonists inhibited CSE-induced TROP2 expression. A therapeutic component derived from traditional Chinese medicine, ginsenoside Rb3, inhibited CSE-induced TROP2 expression as well as activation of the p38 MAPK and NF-κB pathways in BCs in monolayer culture. Furthermore, ginsenoside Rb3 prevented the increase in TROP2 expression and antagonized CSE-induced BC hyperplasia and expression of inflammatory factors and epithelial-mesenchymal transition changes in an air-liquid culture model. Thus, CSE-induced TROP2 is a possible biomarker for early changes in the epithelium of smokers, and ginsenoside Rb3 may serve as a therapeutic molecule, preventing the disruption of epithelial homeostasis in COPD.

New generation lipid emulsions increase brain DHA and improve body composition, but not short-term neurodevelopment in parenterally-fed preterm piglets.

New generation, multicomponent parenteral lipid emulsions provide key fatty acids for brain growth and development, such as docosahexaenoic acid (DHA) and arachidonic acid (AA), yet the content may be suboptimal for preterm infants. Our aim was to test whether DHA and AA-enriched lipid emulsions would increase activity, growth, and neurodevelopment in preterm piglets and limit brain inflammation. Cesarean-delivered preterm pigs were given three weeks of either enteral preterm infant formula (ENT) or TPN with one of three parenteral lipid emulsions: Intralipid (IL), SMOFlipid (SMOF) or an experimental emulsion (EXP). Activity was continuously monitored and weekly blood sampling and behavioral field testing performed. At termination of the study, whole body and tissue metrics were collected. Neuronal density was assessed in sections of hippocampus (HC), thalamus, and cortex. Frontal cortex (FC) and HC tissue were assayed for fatty acid profiles and expression of genes of neuronal growth and inflammation. After 3 weeks of treatment, brain DHA content in SMOF, EXP and ENT pigs was higher (P < 0.01) in FC but not HC vs. IL pigs. There were no differences in brain weight or neuron density among treatment groups. Inflammatory cytokine TNFα and IL-1ß expression in brain regions were increased in IL pigs (P < 0.05) compared to other groups. Overall growth velocity was similar among groups, but IL pigs had higher percent body fat and increased insulin resistance compared to other treatments (P < 0.05). ENT pigs spent more time in higher physical activity levels compared to all TPN groups, but there were no differences in exploratory behavior among groups. We conclude that a soybean oil emulsion increased select brain inflammatory cytokines and multicomponent lipid emulsions enriched with DHA and AA in parenteral lipids results in increased cortical DHA and improved body composition without affecting short term neurodevelopmental outcomes.

Selenoprotein P as the major transporter for mercury in serum from methylmercury-poisoned rats.

Selenium (Se) has been found to promote weight gain, decrease hepatic damage, but redistribute mercury (Hg) in brains and livers in methylmercury (MeHg)-poisoned rats. The aims of the present work were to examine the effects of Se on the levels of Hg in serum and the role of serum selenoproteins in binding with Hg in MeHg-poisoned rats. The concentration of Se, Hg and MeHg were studied using ICP-MS and CVAFS. The Hg- and Se-binding selenoproteins were separated and quantified using affinity chromatography with post-column isotope dilution analysis using both enriched 78Se and 199Hg. It was found that Se treatment reduced Hg levels in serum in MeHg-poisoned rats. Among the three separated selenoproteins, the amounts of SelP-bound Hg and Se increased to 73% and 93.6%, from 64.4% and 89.3% of the total Hg and Se, respectively after Se treatment, suggesting that SelP acts as a major transporter for Hg and pool for Se in serum. Over 90% of the total Hg was MeHg in serum, and the molar ratios of MeHg to Se as 1:4 and 1:9 in the formed MeHg-Se-SelP complex in the control and the Se treatment group, respectively. The elevated Se level binding with SelP facilitated the Hg extraction from tissues and organs, as well as its redistribution in brains and livers through blood circulation in the MeHg-poisoned rats. Together, our findings provide direct evidence that serum SelP is the major Hg transporter in MeHg-poisoned rats.