Marbofloxacin combined with heavy rare-earth ions makes better candidates for veterinary drugs: crystal structure and bio-activity studies.

Marbofloxacin (MB) is a newly developed fluoroquinolone antibiotic used especially as a veterinary drug. It may be regarded as the improved version of enrofloxacin owing to its antibacterial activity, enhanced bioavailability, and pharmacokinetic-pharmacodynamic (PK-PD) properties. In this study, nine heavy rare-earth ions (Y, Gd, Tb, Dy, Ho, Er, Tm, Yb, and Lu) were selected in light of their potential antibacterial activity and satisfactory biosafety to afford the corresponding rare-earth metal complexes of MB: the MB-Ln series. Their chemical structures and coordination patterns were characterized using IR spectroscopy, HRMS, TGA, and X-ray single-crystal diffraction analysis. Our results confirmed that all the MB-Ln complexes yielded the coincident coordination modes with four MB ligands coordinating to the Ln(III) center. In vitro antibacterial screening on five typical bacteria strains revealed that the MB-Ln complexes exhibited antibacterial activities comparable with MB, as indicated by the MIC/MBC values, in which Escherichia coli and Salmonella typhi were the most sensitive ones to MB-Ln. Furthermore, the MB-Ln complexes were found to be much less toxic in vivo than MB, as suggested by the evaluated LD50 (50% lethal dose) values. All the MB-Ln series complexes fell in the LD50 range of 5000-15 000 mg kg-1, while the LD50 value of MB was only 1294 mg kg-1. Furthermore, MB-Lu, as the selected representative of MB-Ln, could effectively inhibit the activity of DNA gyrase, the same as MB, suggesting the primary antibacterial mechanism of the MB-Ln series. The results demonstrated the good prospects and potential of metal-based veterinary drugs with better drug performance.

A double rare earth doped CD nanoplatform for nanocatalytic/starving-like synergistic therapy with GSH-depletion and enhanced reactive oxygen species generation.

Cancer has been one of the principal diseases threatening human health in the world. Traditional chemotherapy, radiotherapy and surgery in clinical applications have some disadvantages, such as inefficiency, low specificity, and serious side effects. Therefore, some emerging synergistic therapies have been developed for more accurate diagnosis and more efficient treatment of cancer. Herein, novel Ce-Gd@CDs-GOx nanozymes were obtained by combining magnetic resonance/fluorescence (MR/FL) imaging and nanocatalytic/starving-like synergistic therapy for tumor tissue imaging and efficient cancer treatment. The as-prepared Ce-Gd@CDs-GOx nanozymes with a diameter of 25.0 ± 0.8 nm exhibited favorable physiological stability, negligible toxicity, bright fluorescence and strong T1-weighted MR imaging (MRI) performance (10.97 mM-1 s-1). Moreover, the nanozymes could not only cut off the nutrient supply of tumor cells, but also generate ROS to synergistically enhance antitumor efficacy. The coexistence of Ce3+/Ce4+ in Ce-Gd@CDs-GOx endowed them with attractive capacity for alleviating hypoxia and enhancing GSH consumption to induce the apoptosis of tumor cells. Furthermore, most of the 4T1 cells treated with Ce-Gd@CDs-GOx nanozymes were damaged in the CCK-8 and Calcein-AM/PI staining assays, indicating the excellent efficiency of intracellular synergistic therapy. In summary, this study offered a promising strategy to design a nanoplatform for MR/FL imaging-guided nanocatalytic and starvation-like synergistic therapy of cancer.

Regulatory actions of rare earth elements (La and Gd) on the cell cycle of root tips in rice seedlings (Oryza sativa L.).

The continuous expansion of the application of rare earth elements (REEs) in various fields has attracted attention to their biosafety. At present, the molecular mechanisms underlying the biological effects of REEs are unclear. In this study, the effects of lanthanum (La) and gadolinium (Gd) on cell cycle progression in the root tips of rice seedlings were investigated. Low concentrations of REEs (0.1 mg L-1) induced an increase in the number of cells in the prophase and metaphase, while high concentrations of REEs (10 mg L-1) induced an increase in the number of cells in the late and terminal stages of the cell cycle, and apoptosis or necrosis. Additionally, low concentrations of REEs induced a significant increase in the expression of the cell cycle factors WEE1, CDKA;1, and CYCB1;1, and promoted the G2/M phase and accelerated root tip growth. However, at high REEs concentrations, the DNA damage response sensitized by BRCA1, MRE11, and TP53 could that prevent root tip growth by inhibiting the transcription factor E2F, resulting in obvious G1/S phase transition block and delayed G2/M phase conversion. Furthermore, by comparing the biological effect mechanisms of La and Gd, we found that these two REEs share regulatory actions on the cell cycle of root tips in rice seedlings.

pH-responsive Mannose-modified ferrocene Metal-Organic frameworks with rare earth for Tumor-targeted synchronous Chemo/Chemodynamic therapy.

The combination of chemodynamic therapy (CDT) and chemotherapy is a promising strategy to achieve enhanced anticancer effects. Metal-organic frameworks (MOFs), as multifunctional drug delivery vehicles, have received extensive attention in the biomedical field. Carbohydrate has excellent biocompatibility and targeting ability, which can be used as a targeting ligand due to a specific recognition with glycoprotein receptors that overexpress on cancer cell membranes. Herein, the pH-responsive mannose-modified ferrocene MOFs with rare earth metal were synthesized via coordination-driven self-assembly of 1,1'-Ferrocenedicarboxylic acid and ytterbium chloride. Subsequently, DOX@Fc-MOFs-Mann nanoparticles (NPs) were obtained by loading doxorubicin (DOX) and modifying mannose (Mann), where DOX@Fc-MOFs-Mann NPs were able to precisely target HepG2 cells via mannose receptor and slowly decompose in the acidic environment of tumor to release ferrocene, DOX, and Yb3+. Fe2+ in ferrocene effectively activated Fenton reaction to produce high levels of reactive oxygen species (ROS) for irreversible induction of cell apoptosis or necroptosis. Combined with the chemotherapy (CT) ability of DOX, Yb3+ further induced cell death through its own toxicity to successfully achieved the rare earth metal synergistic CDT and CT combination therapy. This synergistic CDT and CT strategy not only opens up new horizons for rare earth metals in biomedical applications but also provides new inspiration into the construction of glycosyl-modified MOFs.

Biodegradable freestanding rare-earth nanosheets promote multimodal imaging and delivers CRISPR-Cas9 plasmid against tumor.

Designing nanomaterials for bio-imaging and drug delivery for advanced cancer therapy with biodegradability and biocompatibility is a promising but challenging frontier. Herein, we assembled biodegradable and biocompatible ultrathin rare-earth erbium/dysprosium nanosheets that improve contrast in multimodal bio-imaging settings (MRI and X-ray CT) and deliver CRISPR-Cas9 plasmid to treat tumors.

Pourbaix-Guided Mineralization and Site-Selective Photoluminescence Properties of Rare Earth Substituted B-Type Carbonated Hydroxyapatite Nanocrystals.

Rare-earth labeling in biological apatite could provide critical information for the pathologic transition (osteoclastic) and physiologic regeneration (osteogenesis) of bone and teeth because of their characteristic site-sensitive fluorescence in different coordinative conditions of various tissues in many biological processes. However, the rare-earth labeling method for biological apatites, i.e., carbonated-hydroxyapatite, has been rarely found in the literature. In this paper, we report a Pourbaix-diagram guided mineralizing strategy to controllable carbonation and doping of rare-earth ions in the hydroxyapatite (HA) lattice. The carbonation process of hydroxyapatite was achieved by controllable mineralization in hydrothermal condition with K2CO3 as the carbonate source, which results into the pure B-type carbonated hydroxyapatite (CHA) with tunable carbonate substitution degree. All of the as-synthesized materials crystalized into P63/m (No. 176) space group with the lattice parameter of a decreases and c increases with the increasing of carbonate content in the reactants. Structural refinement results revealed that the substitution of planar CO32- is superimposed on one of the faces of PO43- tetrahedral sub-units with a rotation angle of 30° in reference to c-axis. All of the hydrothermally synthesized CHA nanocrystals show hexagonal rod-like morphology with the length of 70-110 nm and diameter of 21-35 nm, and the decreasing length/diameter ratio from 3.61 to 2.96 from low to high carbonated level of the samples. Five rare-earth cations, of Pr3+, Sm3+, Eu3+, Tb3+, and Ho3+, were used as possible probe ions that can be doped into either HA or CHA lattice. The site-preference of Tb3+ doping is the same in the crystallographic site of HA and CHA according to characteristic emission peaks of 5D4-7Fj (j = 3-6) transitions in their photoluminescent spectroscopy. Our work provides a controllable carbonation method for rare-earth labeling hydroxyapatite nanomaterials with potential biologically active implant powders for bone repair and tissue regeneration.

Rare-Earth Metal Complexes of the Antibacterial Drug Oxolinic Acid: Synthesis, Characterization, DNA/Protein Binding and Cytotoxicity Studies.

"Drug repositioning" is a current trend which proved useful in the search for new applications for existing, failed, no longer in use or abandoned drugs, particularly when addressing issues such as bacterial or cancer cells resistance to current therapeutic approaches. In this context, six new complexes of the first-generation quinolone oxolinic acid with rare-earth metal cations (Y3+, La3+, Sm3+, Eu3+, Gd3+, Tb3+) have been synthesized and characterized. The experimental data suggest that the quinolone acts as a bidentate ligand, binding to the metal ion via the keto and carboxylate oxygen atoms; these findings are supported by DFT (density functional theory) calculations for the Sm3+ complex. The cytotoxic activity of the complexes, as well as the ligand, has been studied on MDA-MB 231 (human breast adenocarcinoma), LoVo (human colon adenocarcinoma) and HUVEC (normal human umbilical vein endothelial cells) cell lines. UV-Vis spectroscopy and competitive binding studies show that the complexes display binding affinities (Kb) towards double stranded DNA in the range of 9.33 × 104 - 10.72 × 105. Major and minor groove-binding most likely play a significant role in the interactions of the complexes with DNA. Moreover, the complexes bind human serum albumin more avidly than apo-transferrin.

Synthesis, structural characterization and antitumor activity of six rare earth metal complexes with 8-hydroxyquinoline derivatives.

The rare earth metal Gd(III), Yb(III), Lu(III), Eu(III), Tb(III) and Ho(III) complexes 1-6 with 2-((2-(pyridin-2-yl)hydrazono)methyl)quinolin-8-ol (H-L) as ligands were synthesized. The in vitro cytotoxicity assay indicated that the cytotoxicity of 1 was equivalent to cisplatin and higher than that of H-L and other complexes towards T24 tumor cells. The mechanism study indicated that 1 caused significant up-regulation of the proteins p27, p21 and p53 in T24 cells and cell cycle arrest in G2 phase. In addition, 1 induced effective T24 cells apoptosis via mitochondrial dysfunction pathway, which was indicated by changes in mitochondrial membrane potential (Δψ), reactive oxygen species (ROS), intracellular Ca2+ and the mitochondria-related proteins (including cytochrome C (Cyt C), B-cell lymphoma-2 (Bcl-2), Bcl-2-associated x (Bax) and apoptotic protease activating factor-1 (Apaf-1)). Moreover, 1 could activate caspase-3/8/9 in T24 cells. Therefore, complex 1 is a promising and potent anticancer drug candidate.

Anti-tumor effect of synthetic baicalin-rare earth metal complex drugs on SMMC-7721 cells.

Baicalin (BC)-rare earth metal complexes [BMCs (BC-Ce, BC-La, and BC-Y)] were synthesized by a complexation coordination method. A mouse tumor model with SMMC-7721 cells was used to examine BMCs for their anti-tumor activities in vivo. The results show that the three new BMCs, Na3Ce (C21H16O11)3·10H2O, Na2La (C21H16O11)2·8H2O, and Na2Y (C21H16O11)2·6H2O significantly inhibited SMMC-7721 cell proliferation, since the BMCs may induce the tumor apoptosis in a dose-dependent manner through decreasing cell membrane fluidity and mitochondrial membrane potential depolarization, blocking of the cell cycle at the G2/M phase, and increasing the expression of Bax and reducing the expression of Bcl-2. The effectiveness order of these three BCMs was as follows: BC-Ce > BC-La > BC-Y > BC. It is concluded that BC-Ce, BC-La, and BC-Y possess potent anti-tumor effects and may be a novel group of anti-tumor drugs. The novel baicalin-rare earth metal complexes (BMC) were synthesized, the anti-tumor effects of the BMC on SMMC-7721 cell analyzed comprehensively.

Toxicological effects of the rare earth element neodymium in Mytilus galloprovincialis.

The wide range of applications of rare earth elements (REE) is leading to their occurrence in worldwide aquatic environments. Among the most popular REE is Neodymium (Nd), being widely used in permanent magnets, lasers, and glass additives. Neodymium-iron-boron (NdFeB) magnets is the main application of Nd since they are used in electric motors, hard disk drives, speakers and generators for wind turbines. Recent studies have already evaluated the toxic potential of different REE, but no information is available on the effects of Nd towards marine bivalves. Thus, the present study evaluated the biochemical alterations caused by Nd in the mussel Mytilus galloprovincialis exposed to this element for 28 days. The results obtained clearly demonstrated that Nd was accumulated by mussels, leading to mussel's metabolic capacity increase and GLY expenditure, in an attempt to fuel up defense mechanisms. Antioxidant and biotransformation defenses were insufficient in the elimination of ROS excess, resulting from the presence of Nd and increased electron transport system activity, which caused cellular damages (measured by lipid peroxidation) and loss of redox balance (assessed by the ratio between reduced and oxidized glutathione). The results obtained clearly highlight the potential toxicity of REEs and, in particular of Nd, with impacts at cellular level, which may have consequences in mussel's survival, growth and reproduction, affecting mussel's population.

Synthesis of Catechin-Rare Earth Complex with Efficient and Broad-Spectrum Anti-Biofilm Activity.

Biofilm is the crucial reason of clinical infections. Herein, green tea based polyphenol (catechin) and rare earth (RE) metal ions were employed for the preparation of catechin-RE complexes with significant anti-biofilm properties. The complexes were characterized by FT-IR, Raman spectroscopy, X-ray photoelectron spectroscopy (XPS) and dynamic light scattering (DLS), which suggested that catechin coordinated with RE3+ through its ortho phenolic hydroxy groups. The prepared catechin-RE showed significant effects in anti-biofilm growth against P. aeruginosa (Gram-negative bacteria), S. sciuri (Gram-positive bacteria), and A. niger (fungi), which significantly exceeded the utilization of catechin or RE3+ . Morphological observations indicated that catechin supplied cell affinity to transfer RE3+ and helped to damage cell membrane, which act as a carrier to exert cytotoxicity of RE3+ to realize anti-biofilm. Differential gene expression analysis described gene expression changes induced by catechin-RE, including 56, 272 and 2160 downregulated genes for P. aeruginosa, S. sciuri and A. niger, respectively, which suggested critical changes in cellular metabolism, growth and other processes. These results illustrate the outstanding superiority of catechin-RE complexes in anti-infection aspect, i. e., the green tea based rare earth complexes are promising candidates for anti-biofilm applications to address serious challenges in the prevention of multiple infections.

Polypyrrole-based double rare earth hybrid nanoparticles for multimodal imaging and photothermal therapy.

Nanotheranostic agents that can simultaneously provide real-time tracking and accurate treatment at tumor sites are playing an increasingly important role in medicine. Herein, a novel polypyrrole (PPy)-based theranostic agent containing double rare-earth elements (PPy@BSA-Gd/Dy NPs) was successfully synthesized via an integrated strategy combining biomineralization and oxidation polymerization. The obtained PPy@BSA-Gd/Dy NPs with a diameter of approximately 59.48 ± 6.12 nm exhibited excellent solubility, long-term stability, superior biocompatibility, and negligible toxicity. Importantly, due to its intrinsic paramagnetic and strong X-ray attenuation ability, this agent demonstrated brilliant imaging performance in both T1/T2-weighted magnetic resonance imaging (MRI) and X-ray computed tomography (CT) imaging in vitro and vivo. Additionally, with an excellent photothermal conversion efficiency (26.61%) upon irradiation by an 808 nm laser, this theranostic agent showed significant photothermal cytotoxicity against HeLa cells and 4T1 cells in vitro and antitumor efficacy through intravenous injection in vivo. Meanwhile, biodistribution and blood circulation were also used to explore its fate in vivo. In summary, this study highlighted the versatility and practicability of PPy@BSA-Gd/Dy NPs and also suggested that the agent may be a promising candidate for T1/T2-weighted MRI/CT tri-modal imaging guided photothermal cancer therapy.

Arabinogalactan protein-rare earth element complexes activate plant endocytosis.

Endocytosis is essential to all eukaryotes, but how cargoes are selected for internalization remains poorly characterized. Extracellular cargoes are thought to be selected by transmembrane receptors that bind intracellular adaptors proteins to initiate endocytosis. Here, we report a mechanism for clathrin-mediated endocytosis (CME) of extracellular lanthanum [La(III)] cargoes, which requires extracellular arabinogalactan proteins (AGPs) that are anchored on the outer face of the plasma membrane. AGPs were colocalized with La(III) on the cell surface and in La(III)-induced endocytic vesicles in Arabidopsis leaf cells. Superresolution imaging showed that La(III) triggered AGP movement across the plasma membrane. AGPs were then colocalized and physically associated with the µ subunit of the intracellular adaptor protein 2 (AP2) complexes. The AGP-AP2 interaction was independent of CME, whereas AGP's internalization required CME and AP2. Moreover, we show that AGP-dependent endocytosis in the presence of La(III) also occurred in human cells. These findings indicate that extracellular AGPs act as conserved CME cargo receptors, thus challenging the current paradigm about endocytosis of extracellular cargoes.

Rare earth elements regulate the endocytosis and DNA methylation in root cells of Arabidopsis thaliana.

With increasing application of rare earth elements (REEs), the resulting environmental safety has attracted extensive attention. When REEs act on plant leaves, REEs can initiate endocytosis in leaf cells, causing more REEs enter plant cells and then severe damage to plants. But when REEs directly act on plant roots, whether and how REEs affect the endocytosis in root cells remain unknown. Here, we characterized effects of lanthanum [La(III)], a REE with high accumulation in environment, on the endocytosis in root cells of Arabidopsis thaliana, and revealed effect mechanism from the perspective of DNA methylation. We found that La(III) enhanced the endocytosis in root cells and the extent of enhancement depended on the dose and time of La(III) exposure: 160 µM > 80 µM >30 µM (12 h); 80 µM > 30 µM >160 µM (24 h); 24 h  > 12 h. La(III)-enhanced endocytosis in root cells resulted from DNA methylation, which was closely related to the expression level of genes encoding DNA methylases/demethylases: CMT3, DRM2 and DNMT2 for 12 h, MET1, CMT1, CMT2, CMT3, DRM2, DNMT2, ROS1, DME, DML2, DML5a, and DML5b for 24 h. Conversely, enhanced endocytosis also promoted the expression level of genes encoding DNA methylases/demethylases. Our findings provide references for understanding the mechanisms by which REEs impact plants.

High Affinity to Skeleton Rare Earth Doped Nanoparticles for Near-Infrared II Imaging.

As a newly noninvasive emerging modality, NIR-II fluorescence imaging (1000-1700 nm) has many advantages over conventional visible and NIR-I imaging (700-900 nm). Unfortunately, only a few NIR-II fluorophores are suitable for bone imaging. Here, we report an NIR-II fluorophore based on DSPE-mPEG encapsulated rare earth doped nanoparticles (RENPs@DSPE-mPEG), which shows inherent affinity to bone without linking any targeting ligands, and thus, it provides an alternative noninvasive and nonradiation strategy for skeletal system mapping and bone disease diagnoses. Interestingly, within the NIR-II window, imaging at a longer wavelength (1345 nm) provides a higher resolution and signal-to-noise ratio than imaging at 1064 nm, even though the quantum yield at 1064 nm is 2-fold higher than that at 1345 nm. Besides bone imaging, RENPs@DSPE-mPEG show an imaging application in blood vessels and lymph nodes. Importantly, RENPs@DSPE-mPEG can be internalized by circulating white blood cells. This finding may open a window to increase efficient nanoparticle delivery in the fields such as immunotherapy and improve the diagnostic and therapeutic efficacy of cancer-targeted nanoparticles in clinical applications.

Cytotoxicity, dose-enhancement and radiosensitization of glioblastoma cells with rare earth nanoparticles.

Glioblastoma is a heterogeneous disease with multiple genotypic origins. Despite treatment protocols such as surgery, radiotherapy and chemotherapy, the prognosis for patients remains poor. This study investigates the cytotoxic and radiation dose-enhancing and radiosensitizing ability of five rare earth oxide nanoparticles, in two different immortalized mammalian cell lines; U-87 MG and Mo59K. Significant cytotoxicity was observed in U-87 MG cells when exposed to Nd2O3 and La2O3. Autophagy was also detected in cells after incubation with Nd2O3. Radiosensitization was observed in U-87 MG when incubated with Gd2O3, CeO2-Gd and Nd2O3:Si. Importantly, these elements did not cause any intrinsic toxicity in the absence of irradiation and so could be considered biocompatible. The Gd2O3 and CeO2-Gd nanoparticles were also seen to generate ROS in U-87 MG cells after irradiation. Furthermore, the Mo59K and U-87 MG cells responded very differently to exposure to the rare earth nanoparticles. This may indicate the importance of the genotype of cells in the successful use of rare earth oxides for treatment.

A novel evaluation of the effect of lanthanum exposure on plant populations.

The accumulation of rare earth elements (REEs) in the environment has recently become a new environmental problem. There have been many studies about the effects of REEs on plant at the individual, organ, cellular and genetic levels. Plants exist in populations under natural conditions, but little is known about the effects of REEs on plant populations. In this study, the effects of lanthanum (III) [La(III)] on the root module growth of soybean (Glycine max L) populations at different densities were investigated by simulating La(III) pollution. Results showed that at La(III) concentrations of 0.40 and 1.20 mM, both the root module growth parameters and leaf photosynthesis parameters were decreased, with 1.20 mM of La(III) causing a more significant decrease. In addition, the above parameters in low-density soybean populations decreased more significantly than those in high-density soybean populations. The above results show that the inhibitory effects of 0.40 and 1.20 mM of La(III) on the growth of root modules are closely related to the inhibition of photosynthesis in soybean population. Moreover, the inhibitory effect of La(III) on the growth of root modules of soybean population is enhanced as the La(III) concentration increases, while is weakened as plant population density increases. This study would provide a reference for the further research on the ecotoxicology of REEs, and show a new perspective and basis for the objective assessment of the environmental risks of REEs. ONE SENTENCE SUMMARY: La(III) pollution affects the root module growth and photosynthesis in soybean populations, and the effects vary depending on soybean population densities.

Mitochondrial specific photodynamic therapy by rare-earth nanoparticles mediated near-infrared graphene quantum dots.

Photodynamic therapy (PDT) has been proposed in cancer treatment for decades, but its clinical translation is significantly impeded by the low yield of ROS, poor tissue penetration depth of most current photosensitizers, and short lifetime of ROS. These limitations directly affect the therapeutic effect of PDT in cancer therapy. Here we proposed a new strategy by collaboratively integrating rare-earth doped upconversion nanoparticles (UCNP) with graphene quantum dot (GQD) for highly efficacious PDT, based on the merits of UCNP, which can emit UV-vis light under near-infrared light (NIR) excitation, and GQD, which can produce 1O2 efficiently. For GQD-decorated UCNP nanoparticles (UCNP-GQD), the emission light from UCNP can further excite GQD with prominent 1O2 generation for NIR-triggered PDT. Furthermore, a hydrophilic rhodamine derivative, TRITC, is covalently tethered to afford the resultant UCNP-GQD/TRITC, possessing distinct mitochondrial targeting property. Thus mitochondrial specific PDT with in-situ1O2 burst in mitochondria induces sharp decrease of mitochondrial membrane potential, which initiates the tumor cell apoptosis irreversibly. Importantly, in vivo experiments demonstrate the tumor inhibition of mitochondrial targeting UCNP-GQD/TRITC with improved therapeutic efficiency compared with non-targeting UCNP-GQD. The proposed strategy highlights the advantages of precision organelles-specific PDT in cancer therapy.

Uptake and effect of rare earth elements on gene expression in Methylosinus trichosporium OB3b.

It is well known that Methylosinus trichosporium OB3b has two forms of methane monooxygenase (MMO) responsible for the initial conversion of methane to methanol, a cytoplasmic (soluble) methane monooxygenase and a membrane-associated (particulate) methane monooxygenase, and that copper strongly regulates expression of these alternative forms of MMO. More recently, it has been discovered that M. trichosporium OB3b has multiple types of the methanol dehydrogenase (MeDH), i.e. the Mxa-type MeDH (Mxa-MeDH) and Xox-type MeDH (Xox-MeDH), and the expression of these two forms is regulated by the availability of the rare earth element (REE), cerium. Here, we extend these studies and show that lanthanum, praseodymium, neodymium and samarium also regulate expression of alternative forms of MeDH. The effect of these REEs on MeDH expression, however, was only observed in the absence of copper. Further, a mutant of M. trichosporium OB3b, where the Mxa-MeDH was knocked out, was able to grow in the presence of lanthanum, praseodymium and neodymium, but was not able to grow in the presence of samarium. Collectively, these data suggest that multiple levels of gene regulation by metals exist in M. trichosporium OB3b, but that copper overrides the effect of other metals by an as yet unknown mechanism.

Antibacterial, Antifungal and Nematicidal Activities of Rare Earth Ions.

Despite the name, rare earth elements are relatively abundant in soil. Therefore, these elements might interact with biosphere during the history of life. In this study, we have examined the effect of rare earth ions on the growth of bacteria, fungi and soil nematode. All rare earth ions, except radioactive promethium that we have not tested, showed antibacterial and antifungal activities comparable to that of copper ions, which is widely used as antibacterial metals in our daily life. Rare earth ions also have nematicidal activities as they strongly perturb the embryonic development of the nematode, Caenorhabditis elegans. Interestingly, the nematicidal activity increased with increasing atomic number of lanthanide ions. Since the rare earth ions did not show high toxicity to the human lymphoblastoid cell line or even stimulate the growth of the cultured cells at 1 mM, it raised the possibility that we can substitute rare earth elements for the antibacterial metals usually used because of their safety.