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Phosphate removal technology has faced significant challenges due to the growing global population and agricultural inputs. Lanthanum-based adsorbents (LBA) have gained attention because of their high efficiency in removing phosphate. While the LBA has been studied since the 1990 s, most of the related research has focused on theoretical aspects rather than practical applications. This review will demonstrate the various types of LBA available on the market and how different factors, such as temperature, pH, natural organic matter (NOM), inorganic ions, and initial phosphate concentration, affect the variation in phosphate removal. Additionally, the mechanism of phosphate removal by LBA, including ion exchange, ligand exchange, electrostatic interactions, Lewis acid base interactions, and H-bonding, will be examined. From the standpoint of practical application, this review thoroughly examines not only the mechanism of phosphate removal by LBA but also the analysis of currently available LBA, determining its potential toxicity to humans and crops, as well as phosphate recovery following adsorbent use. LBA, which can also be used as fertilizer, is efficient at removing phosphate and has low toxicity. However, their efficiency in removing phosphorus is affected by coexisting substances such as pH, temperature, and NOM. We provide suggestions for future directions in LBA research based on the current body of knowledge. [Display omitted] • Comprehensive review of the mechanism of phosphate removal by LBA. • Summarized the different kinds of LBA differences and characteristics. • Consideration of the factors affecting the effect of LBA and coexisting substances. • The reuse of LBA and phosphorus recovery were examined. • Considered the toxicity of LBA to humans and plants in practical terms. [ABSTRACT FROM AUTHOR]

The mode of action, bioaccumulation potential and toxicity of Rare Earth Elements (REE), with several applications in the technology, medical and agricultural fields, are still understudied. The nitrates acute effects on single exposures, binary and ternary mixtures of lanthanum (La), neodymium (Nd) and samarium (Sm) on Lactuca sativa lettuce seed germination and wet biomass in an artificial soil (AS) and an Ultisol were assessed. Germination (EC 50 ), wet biomass (IC 50 ) and germination inhibition (% GI) were evaluated. EC 50 values show La was the most toxic in Ultisol, Sm in AS, and Nd appears with intermediate values on both substrates. The IC 50 , both single and mixed, decreased from 3- to 181-fold with increasing test concentrations in relation to the control in AS, while increases in Ultisol were observed, followed by decreases at higher doses which may be associated with the low-dose stimulation effect (hormesis). Our findings may be used to subsidize REE risk assessment studies and reinforce the hormesis effect to prevent the use of high application of REE fertilizers, avoiding the accumulation of REE in agricultural soils., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The accumulation of rare earth elements (REEs) in the global environment poses a threat to plant health and ecosystem stability. Stomata located on leaves serve as the primary site for plant responses to REE-related threats. This study focused on lanthanum [La(III)], a prevalent REE in the atmospheric environment. Using interdisciplinary techniques, it was found that La(III) (≤80 µM) interfered with the fundamental rhythms of stomatal opening, related gene expression, and evapotranspiration in plants. Specifically, when exposed to low concentrations of La(III) (15 and 30 µM), the expression levels of six genes were increased, stomatal opening was enhanced, and the evapotranspiration rate was accelerated. The interference on stomatal rhythms was enhanced with higher concentrations of La(III) (60 and 80 µM), increasing the expression levels of six genes, stomatal opening, and evapotranspiration rate. To counter the interference of low concentrations of La(III) (15 and 30 μM), plants accelerated nutrient replenishment through La(III)-induced endocytosis, which the redundant nutrients enhanced photosynthesis. However, replenished nutrients failed to counter the disruption of plant biological rhythms at higher concentrations of La(III) (60 and 80 μM), thus inhibiting photosynthesis due to nutrient deficit. The interference of La(III) on these biological rhythms negatively affected plant health and ecosystem stability., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Given the widespread applications in industrial and agricultural production, the health effects of rare earth elements (REEs) have garnered public attention, and the genotoxicity of REEs remains unclear. In this study, we evaluated the genetic effects of lanthanum nitrate, a typical representative of REEs, with guideline-compliant in vivo and in vitro methods. Genotoxicity assays, including the Ames test, comet assay, mice bone marrow erythrocyte micronucleus test, spermatogonial chromosomal aberration test, and sperm malformation assay were conducted to assess mutagenicity, chromosomal damage, DNA damage, and sperm malformation. In the Ames test, no statistically significant increase in bacterial reverse mutation frequencies was found as compared with the negative control. Mice exposed to lanthanum nitrate did not exhibit a statistically significant increase in bone marrow erythrocyte micronucleus frequencies, spermatogonial chromosomal aberration frequencies, or sperm malformation frequencies compared to the negative control (P > 0.05). Additionally, after a 24-h treatment with lanthanum nitrate at concentrations of 1.25, 5, and 20 μg/ml, no cytotoxicity was observed in CHL cells. Furthermore, the comet assay results indicate no significant DNA damage was observed even after exposure to high doses of lanthanum nitrate (20 μg/ml). In conclusion, our findings suggest that lanthanum nitrate does not exhibit genotoxicity., Competing Interests: Declaration of Competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

pH reduction (Low pH), microplastic (MP), and lanthanum (La) are substantial stressors due to their increasing trends in marine ecosystems and having adverse effects on marine species. This study investigates the single and combined effects of those stressors (Low pH: 7.45, polyethylene MP: 26 μg L -1 , and La: 9 μg L -1 ) on the physiology and histology of sea urchin Arbacia lixula. Regarding physiological results, while the coelomocytes' quantity was slightly affected by stressors, their viability was significantly affected. The coelomocyte count and viability were suppressed most in Low pH-MP-La treatment. The stressors did not impact the respiration rate. According to the histological examination results, the crypt (villi-like structure) was shorter, and epithelial layers were thinner in single and dual stress treatments like MP, Low pH, Low pH-La, and MP-La. Overall, we suggest that the combination of variable types of those stressors causes negative effects on sea urchin's physiology and histology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Persistent molecules, such as pesticides, herbicides, and pharmaceuticals, pose significant threats to both the environment and human health. Advancements in developing efficient photocatalysts for degrading these substances can play a fundamental role in remediating contaminated environments, thereby enhancing safety for all forms of life. This study investigates the enhancement of photocatalytic efficiency achieved by incorporating La 3+ into Ag 3 PO 4 , using the co-precipitation method in an aqueous medium. These materials were utilized in the photocatalytic degradation of Rhodamine B (RhB) and Ciprofloxacin (CIP) under visible light irradiation, with monitoring conducted through high-performance liquid chromatography (HPLC). The synthesized materials exhibited improved stability and photodegradation levels for RhB. Particularly noteworthy was the 2% La 3+ -incorporated sample (APL2), which achieved a 32.6% mineralization of CIP, nearly three times higher than pure Ag 3 PO 4 . Toxicological analysis of the residue from CIP photodegradation using the microalga Raphidocelis subcapitata revealed high toxicity due to the leaching of Ag  +  ions from the catalyst. This underscores the necessity for cautious wastewater disposal after using the photocatalyst. The toxicity of the APL2 photocatalysts was thoroughly assessed through comprehensive toxicological tests involving embryo development in Danio rerio, revealing its potential to induce death and malformations in zebrafish embryos, even at low concentrations. This emphasizes the importance of meticulous management. Essentially, this study adeptly delineated a thorough toxicological profile intricately intertwined with the photocatalytic efficacy of newly developed catalysts and the resultant waste produced, prompting deliberations on the disposal of degraded materials post-exposure to photocatalysts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Lanthanum (La), the second most abundant rare earth element (REE) is emerging as an environmental issue, with the potential to impact ecosystems and human health. Major sources of soil contamination by La include agricultural, and industrial activities. Lanthanum is non-essential for plant growth but accumulates in various plant parts. The uptake of La by plants is intricately influenced by various factors such as soil pH, redox potential, cation exchange capacity, presence of organic acids and rhizosphere composition. These factors significantly impact the availability and absorption of La ions. Lanthanum impact on plants depends on soil characteristics, cultivated species, developmental stage, La concentration, treatment period, and growth conditions. Excessive La concentrations affect cell division, DNA structure, nutrient uptake, and photosynthesis and induce toxicity symptoms. Plants employ detoxification mechanisms like vacuolar sequestration, osmolyte synthesis, and antioxidant defense system. However, higher concentrations of La can overwhelm these defense mechanisms, leading to adverse effects on plant growth and development. Further, accumulation of La in plants increases the risk for human exposure. Strategies to mitigate La toxicity are, therefore, vital for ecosystem protection. The application of phytoremediation, supplementation, chelation, amendments, and biosorption techniques contributes to the mitigation of La toxicity. This review provides insights into La sources, uptake, toxicity, and alleviation strategies in plants. Identifying research gaps and discussing advancements aims to foster a holistic understanding and develop effective strategies for protecting plant health and ecosystem resilience against La contamination., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Lanthanum (La) is widely used in modern industry and agriculture because of its unique physicochemical properties and is broadly exposed in the population. Some studies have shown that La may have some effects on adipogenesis, but there is a lack of related in vivo evidence. In this study, the effects of La(NO 3 ) 3 on adipogenesis and its associated mechanism were studied using C57BL/6J mouse model. The results showed that La(NO 3 ) 3 exposure caused a decrease in body weight and the percentage of fat content in mice. In addition, the adipose marker molecules and specific adipogenic transcription factors decreased in both white adipose tissue (WAT) and brown adipose tissue (BAT). Detection of signaling pathway-related molecules revealed that canonical wnt/β-catenin pathway-related molecules were upregulated in both adipose tissues. In summary, in vivo exposure to La(NO 3 ) 3 might inhibited adipogenesis in mice, possibly through upregulation of the canonical Wnt/β-catenin signaling pathway., (© 2023 John Wiley & Sons, Ltd.)

Nephrotoxicity is a common adverse effect induced by various chemicals, necessitating the development of reliable toxicity screening models for nephrotoxicity assessment. In this study, we assessed a group of nephrotoxicity indicators derived from different toxicity pathways, including conventional endpoints and kidney tubular injury biomarkers such as clusterin (CLU), kidney injury molecule-I (KIM-1), osteopontin (OPN), and neutrophil gelatinase-associated lipocalin (NGAL), using HK-2 and induced pluripotent stem cells (iPSCs)-derived renal proximal tubular epithelial-like cells (PTLs). Among the biomarkers tested, OPN emerged as the most discerning and precise marker. The predictive potential of OPN was tested using a panel of 10 nephrotoxic and 5 non-nephrotoxic compounds. The results demonstrated that combining OPN with the half-maximal inhibitory concentration (IC 50 ) enhanced the diagnostic accuracy in both cellular models. Additionally, PTLs cells showed superior predictive efficacy for nephrotoxicity compared to HK-2 cells in this investigation. The two cellular models were utilized to evaluate the nephrotoxicity of lanthanum. The findings indicated that lanthanum possesses nephrotoxic properties; however, the degree of nephrotoxicity was relatively low, consistent with the outcomes of in vivo experiments., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Lanthanum (La) and cerium (Ce), rare earth elements with physical properties similar to calcium (Ca), are generally considered non-toxic when used appropriately. However, their ions possess anti-tumor capabilities. This investigation explores the potential applications and mechanisms of LaCl 3 or CeCl 3 treatment in triple-negative breast cancer (TNBC) cell lines. TNBC, characterized by the absence of estrogen receptor (ERα), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) expression, is prone to early metastasis and resistant to hormone therapy. Our results demonstrate that La/Ce treatment reduces cell growth, and when combined with cisplatin, it synergistically inhibits cell growth and the PI3K/AKT pathway. La and Ce induce oxidative stress by disrupting mitochondrial function, leading to protein oxidation. Additionally, they interfere with protein homeostasis and induce nucleolar stress. Furthermore, disturbance in F-actin web formation impairs cell migration. This study delves into the mechanism by which calcium-like elements La and Ce inhibit breast cancer cell growth, shedding light on their interference in mitochondrial function, protein homeostasis, and cytoskeleton assembly., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Cadmium (Cd) and lead (Pb) accumulate easily in leafy vegetables and can harm human health. Lanthanum (La) have been used to improve agricultural yield and quality, but the effect of La application on Cd/Pb enrichment in leafy vegetables remains incomplete currently. A previous study reported that the endocytosis in lettuce leaf cells can be activated by La, leading to an increase in Pb accumulation in lettuce leaves. However, it has not been investigated whether foliar application of La enhances root cellular endocytosis and promotes its uptake of Cd and Pb. In this study, the influence of La on the uptake of Cd and Pb, Cd bioaccessibility, and the safety risks of cultivating lettuce under Cd and Pb stress were explored. It was found that La increased Cd (16-30 % in shoot, 16-34 % in root) and Pb (25-29 % in shoot, 17-23 % in root) accumulation in lettuce. The increased accumulation of Cd and Pb could be attributed to La-enhanced endocytosis. Meanwhile, La enhanced the toxicity of both Cd and Pb, inhibited lettuce growth, and aggravated the damage to the photosynthetic and antioxidant systems. Finally, gastrointestinal simulation experiments showed that La increased the Cd bioaccessibility in both gastric and intestinal phase by 7-108 % and 9-87 %, respectively. These results offer valuable insights into the safety of REEs for agricultural applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Rare earth elements (REEs) are emerging as an anticipated pollution in the environment due to their active use in many areas. However, the effects of REEs on the photosynthesis of rice have not been thoroughly explored. Therefore, this study emphasizes how high levels of La(III) affect the thylakoid membrane of rice seedlings, thereby inhibiting photosynthesis and growth. Here, we reported that rice plants treated with La(III) exhibited an increase in La accumulation in the leaves, accompanied by a decrease in chlorophyll content and photosynthetic capacity. La(III) exposure decreased Mg content in leaves, but possibly increased other nutrients including Cu, Mn, and Zn through systemic endocytosis. K-band and L-band appeared in the fluorescence OJIP transients, indicating La(III) stress destroyed the donor and receptor sides of photosystem II (PSII). Numerous reaction centers (RC/CS m ) were inactivated by La(III) treatment, which resulted in a reduction in electron transport capacity (decreased ET o /RC and ET o /CS m ) and an increase in the dissipation of the excess excitation energy by heat (increased DI o /RC and DI o /CS m ). The BN-PAGE analysis of thylakoid membrane protein complexes showed that La(III) induced the degradation of supercomplexes, PSII core, LHCII, PSI core, LHCI, and F1-ATPase binding Cyt b 6 f complex. Collectively, this study revealed that La(III) causes significant degradation of thylakoid membrane proteins, thereby promoting the decomposition of photosynthetic complexes, ultimately destroying the chloroplast structure and reducing the photosynthetic performance of rice seedlings., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The increasing demand for rare earth elements (REEs) in modern applications has drawn significant attention. REEs can be introduced into the environment through REE-containing fertilizers, abandoned REE-rich equipment, and mining, persisting and impacting soil quality, nutrient cycles, and plant growth. Scientists have raised concerns about REEs entering the food chain from the environment and eventually accumulating in organisms. Decades of experimental evidence have shown that these effects include inhibited growth, impaired liver function, and alterations in children's intelligence quotients. However, there exists a paucity of research that has elucidated the metabolic-level biological impacts of REEs. In our study, Caenorhabditis elegans (C. elegans) was used as a model organism to investigate physiological and inherent metabolic changes under exposure to different concentrations of REEs. The diet bacteria of nematodes play a key role in their life and development. Therefore, we investigated the influence of bacterial activity on the nematodes' response to REE exposure. We observed a concentration-dependent accumulation of REEs in nematodes, which consequently led to a reduction in lifespan and alterations in body length. Exposure to a mixed solution of REEs, in comparison to a single REE solution, resulted in greater toxicity toward nematodes. The metabolic results showed that the above changes were closely related to REE-induced amino acid metabolism disorder, membrane disturbance, DNA damage, and oxidative stress. Of note, the presence of living bacteria elicits REE effects in C. elegans. These findings highlight the potential intrinsic metabolic changes occurring in nematodes under REE exposure. Our study raises awareness of the exposure risks associated with REEs, provides valuable insight into the metabolic-level biological impacts of REEs and contributes to the development of effective mitigation strategies to reduce potential risks to human health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

While our awareness of the toxicity of rare earth elements to aquatic organisms increases, our understanding of their direct interaction and accumulation remains limited. This study describes the acute toxicity of lanthanum (La) and gadolinium (Gd) in Daphnia magna neonates and discusses potential modes of action on the basis of the respective patterns of biodistribution. Ecotoxicological bioassays for acute toxicity were conducted and dissolved metal concentrations at the end of the tests were determined. The results showed a significant difference in nominal EC 50 (immobility) between La (>30 mg L -1 ) and Gd (13.93 (10.92 to 17.38) mg L -1 ). Daphnids that were then exposed to a concentration close to the determined EC 50 of Gd (15 mg L -1 , nominal concentration) for 48 h and 72 h were studied by synchrotron micro and nano-X-ray fluorescence to evaluate the biodistribution of potentially accumulated metals. X-ray fluorescence analyses showed that La was mainly found in the intestinal track and appeared to accumulate in the hindgut. This accumulation might be explained by the ingestion of solid La precipitates formed in the media. In contrast, Gd could only be detected in a small amount, if at all, in the intestinal tract, but was present at a much higher concentration in the tissues and became more pronounced with longer exposure time. The solubility of Gd is higher in the media used, leading to higher dissolved concentrations and uptake into tissue in ionic form via common metal transporting proteins. By studying La and Gd biodistribution in D. magna after an acute exposure, the present study has demonstrated that different uptake pathways of solid and dissolved metal species may lead to different accumulation patterns and toxicity.

Lanthanum (La) is a natural rare-earth element that can damage the central nervous system and impair learning and memory. However, its neurotoxic mechanism remains unclear. In this study, adult female rats were divided into 4 groups and given distilled water solution containing 0%, 0.125%, 0.25%, and 0.5% LaCl 3 , respectively, and this was done from conception to the end of the location. Their offspring rats were used to establish animal models to investigate LaCl 3 neurotoxicity. Primary neurons cultured in vitro were treated with LaCl 3 and infected with LKB1 overexpression lentivirus. The results showed that LaCl 3 exposure resulted in abnormal axons in the hippocampus and primary cultured neurons. LaCl 3 reduced the expression of LKB1, p-LKB1, STRAD and MO25 proteins, and directly or indirectly affected the expression of LKB1, leading to decreased activity of LKB1-MARK2 and LKB1-STK25-GM130 pathways. This study indicated that LaCl 3 exposure could interfere with the normal effects of LKB1 in the brain and downregulate LKB1-MARK2 and LKB1-STK25-GM130 signaling pathways, resulting in abnormal axon in offspring rats., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Rare earth elements (REEs) cerium (Ce) and lanthanum (La) and their combination were tested across a concentration range, from toxic (10 -4 to 10 -5  M) to lower concentrations (10 -6 to 10 -8  M) for their effects on sea urchin (Sphaerechinus granularis) sperm. A significantly decreased fertilization rate (FR) was found for sperm exposed to 10 -5  M Ce, La and their combination, opposed to a significant increase of FR following 10 -7 and 10 -8  M REE sperm exposure. The offspring of REE-exposed sperm showed significantly increased developmental defects following sperm exposure to 10 -5  M REEs vs. untreated controls, while exposure to 10 -7 and 10 -8  M REEs resulted in significantly decreased rates of developmental defects. Both of observed effects-on sperm fertilization success and on offspring quality-were closely exerted by Ce or La or their combination., (© 2023. The Author(s).)

Lanthanum (La) as a rare earth element is widely used in agriculture, industry, and medicine. It has been suggested in several studies that La might influence glycolipid metabolism in vivo. In this study, we used 3T3-L1 preadipocytes as in vitro cell model to elucidate the effects of La(NO 3 ) 3 on adipogenesis and the underlying mechanisms. The results showed that La(NO 3 ) 3 could inhibit the adipogenic differentiation of 3T3-L1 preadipocytes, which showed a decrease in lipid accumulation and the downregulation of specific adipogenic transcription factors. La(NO 3 ) 3 exerted its inhibitory effect mainly at the early differentiation stage. Furthermore, La(NO 3 ) 3 influenced the S-phase entry and cell cycle process during the mitotic clonal expansion and regulated the phosphorylation of signal transducer and activator of transcription 3 (STAT3) and expressions of the proteins in phosphatidylinositol 3-kinase (PI3K)/Akt pathway at the early stage of differentiation. Besides, La(NO 3 ) 3 upregulated the expressions of wnt10b mRNA and β-catenin protein and promoted the nucleus translocation of β-catenin. Additionally, we found that La(NO 3 ) 3 could promote the growth of 3T3-L1 preadipocytes both with and without MDI (3-isobutyl-1-methylxanthine [IBMX], dexamethasone [Dex], and insulin) stimulation. Collectively, these results indicated that La(NO 3 ) 3 could inhibit adipogenesis in 3T3-L1 preadipocytes and influence cell proliferation., (© 2022 John Wiley & Sons Ltd.)

The increasing use of Rare Earth Elements (REE) in emerging technologies, medicine and agriculture has led to chronic aquatic compartment contamination. In this context, this aimed to evaluate the acute toxic effects of lanthanum (La), neodymium (Nd) and samarium (Sm), as both single and binary and ternary mixtures on the survival of the microcrustacean Daphnia similis. A metal solution medium with (MS) and without EDTA and cyanocobalamin (MSq) as chelators was employed as the assay dilution water to assess REE bioavailability effects. In the single exposure experiments, toxicity in the MS medium decreased following the order La > Sm > Nd, while the opposite was noted for the MSq medium, which was also more toxic than the MS medium. The highest MS toxicity was observed for the binary Nd + La (1:1) mixture (EC 50 48 h of 11.57 ± 1.22 mg.L -1 ) and the lowest, in the ternary Sm + La + Nd (2:2:1) mixture (EC 50 48 h 41.48 ± 1.40 mg.L -1 ). The highest toxicity in the MSq medium was observed in the single assays and in the binary Sm + Nd (1:1) mixture (EC 50 48 h 10.60 ± 1.57 mg.L -1 ), and the lowest, in the ternary Sm + La + Nd (1:2:2) mixture (EC 50 48 h 36.76 ± 1.54 mg.L -1 ). Concerning the MS medium, 75 % of interactions were additive, 19 % antagonistic, and 6 % synergistic. In the MSq medium, 56 % of interactions were synergistic and 44 % additive. The higher toxicity observed in the MSq medium indicates that the absence of chelators can increase the concentrations of more toxic free ions, suggesting that the MS medium should be avoided in REE assays. Additive interactions were observed in greater or equivalent amounts in both media and were independent of elemental mixture ratios. These findings improve the understanding of environmental REE effects, contributing to the establishment of future guidelines and ecological risk calculations., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The versatile applicability of rare earth elements (REEs) especially lanthanum (La) in diverse fields, has led to large-scale mineral exploitation globally, inevitably resulting in substantial release of La into environment. As emerging anthropogenic environmental contaminant, La-induced toxicological effects and potential ecotoxicological implications in relation to realistic levels of La in aquatic ecosystems are becoming major concerns. To address these issues, Daphnia magna was selected as a prototype, and toxicity tests were conducted to explore the effects of La exposure on life-history characteristics and fecundity fitness, as showcased by quantitative variations from the individual level to population scale. In parallel, to further denote transgenerational caloric impacts of parental La exposure, bioenergetic profiles on newborn neonates were concurrently determined by measuring macromolecule forms in terms of proteins, glycogens and lipids to quantify nutritional alterations at progeny level. The results revealed that low-dose La exposure slightly stimulated the demographic potential and nutritional responses, exhibiting dose-dependent hormesis-like effects and promising non-toxicological potential to Daphnia, whereas high-dose La exposure of greater than 59.2 µg La L  -   1 , conspicuously imposed detrimental effects on quantity and quality of offspring, i.e. not only reducing body size, lifespan expectancy and reproductive output in a concentration-dependent way and resulting in lower population fitness by a dynamic life-table analysis, but eventually leading to the decrease of nutritional qualities and caloric contents on neonates. Taken together, these two-phase findings regarding the dose-related shift from hormesis to inhibition not only provided valuable insights into the complicated biological outcomes of La effects on environmentally-relevant organisms, but experimentally highlighted the significant implications of considering environmental and nutritional consequences in ecologically assessing the La-triggered risk at environmentally realistic occurrences, particularly on gradient scenarios crossing upstream and downstream of highly complex mining watersheds., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Light rare earth elements (LREEs) have been long used in agriculture (i.e., mainly via aerially applied LREE fertilizers) based on the fact that low-dose LREEs promote plant growth. Meanwhile, the toxic effects of low-dose LREEs on organisms have also been found. However, the cellular and molecular mechanism of low-dose LREEs acting on organisms remain unclear. Plants are at the beginning of food chains, so it is critical to uncover the cellular and molecular mechanism of low-dose LREEs on plants. Here, lanthanum (La) and soybean were the representatives of LREEs and plants, respectively. The effects of low-dose La on soybean leaves were investigated, and the stimulatory effect and mechanism of low-dose LREEs on leaf cells were revealed. Specifically, clathrin-mediated endocytosis (CME) activated by low-dose La is an influx channel for La in soybean leaf cells. The intracellular La and La-activated CME jointly disturbed multiple forms of intracellular homeostasis, including metallic element homeostasis, redox homeostasis, gene expression homeostasis. The disturbed homeostasis either stimulated cell growth or caused damage to the plasma membrane of soybean leaf cells. These results provide new insights for clarifying the cellular and molecular mechanisms of low-dose LREEs as a class of stimulators instead of nutrients to stimulate plants., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Lanthanum (La) is one of the most abundant emergent rare earth elements. Its release into the environment is enhanced by its use in various industrial applications. In the aquatic environment, emerging contaminants are one of the stressors with the ability to compromise the fitness of its inhabitants. Warming and acidification can also affect their resilience and are another consequence of the growing human footprint on the planet. However, from information gathered in the literature, a study on the effects of ocean warming, acidification, and their interaction with La was never carried out. To diminish this gap of knowledge, we explored the effects, combined and as single stressors, of ocean warming, acidification, and La (15 μg L -1 ) accumulation and elimination on the surf clam (Spisula solida). Specimens were exposed for 7 days and depurated for an additional 7-day period. Furthermore, a robust set of membrane-associated, protein, and antioxidant enzymes and non-enzymatic biomarkers (LPO, HSP, Ub, SOD, CAT, GPx, GST, TAC) were quantified. Lanthanum was bioaccumulated after just one day of exposure, in both control and climate change scenarios. A 7-day depuration phase was insufficient to achieve control values and in a warming scenario, La elimination was more efficient. Biochemical response was triggered, as highlighted by enhanced SOD, CAT, GST, and TAC levels, however as lipoperoxidation was observed it was insufficient to detoxify La and avoid damage. The HSP was largely inhibited in La treatments combined with warming and acidification. Concomitantly, lipoperoxidation was highest in clams exposed to La, warming, and acidification combined. The results highlight the toxic effects of La on this bivalve species and its enhanced potential in a changing world., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The increasing use of rare earth elements (REEs) in electric and electronic equipment has been associated with the presence of these elements in aquatic systems. The present study aimed to evaluate the toxicity of two REEs, Lanthanum (La) and Gadolinium (Gd), towards the mussel species Mytilus galloprovincialis. For this, the toxicity was assessed after a short-term exposure (14 days) to an environmentally relevant concentration of each element (10 μg/L), followed by a recovery period (14 days) in the absence of any contaminant. The measured biomarkers included energy-related parameters, activity of antioxidant and biotransformation enzymes, indicators of oxidative damage, levels of oxidized glutathione and neurotoxicity. After exposure mussels accumulated more La (0.54 μg/g) than Gd (0.15 μg/g). After recovery higher concentration decrease was observed for Gd (≈40% loss) compared to La exposed mussels (≈30% loss) which may be associated with lower detoxification capacity of mussels previously exposed to La. Mussels increased their metabolism (i.e., higher electron transport system activity) only after the exposure to Gd. Exposure to La and Gd resulted into lower energy expenditure, while when both elements were removed glycogen and protein concentrations decreased to values observed in non-contaminated mussels. Antioxidant and biotransformation capacity was mainly increased in the presence of Gd. This defense response avoided the occurrence of cellular damage but still loss of redox balance was found regardless the contaminant, which was re-established after the recovery period. Neurotoxicity was only observed in the presence of Gd with no effects after the recovery period. Results showed that a short-term exposure to La and especially to Gd can exert deleterious effects that may compromise specific biochemical pathways in aquatic species, such as M. galloprovincialis, but under low concentrations organisms can be able to re-establish their biochemical status to control levels after a recovery period., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The increasing exploitation and application of rare earth elements (REEs) may induce hazardous risks to freshwater aquatic organisms. Due to the lack of water quality criteria (WQC) and sufficient reliable toxicity data, little information is available on the ecological risk of REEs in surface water. In this study, lanthanum (La) toxicity data were collected from published toxicological studies, and the data quality was assessed using a toxicological data reliability assessment tool. To obtain more toxicity data, Daphnia magna, Cyprinus carpio, and Dania rerio embryos were selected as surrogate species, and an interspecies correlation estimation (ICE) model was used to predict the toxicity of La for untested species. The species sensitivity distributions (SSDs) of La toxicity and WQC were investigated. Differences were observed in the hazardous concentrations for 5% of species (HC 5 ), but no statistically significant differences were noted in the SSD curves between the measured acute toxicity data and the predicted data. For the SSDs constructed from the measured toxicity data, the ICE-predicted toxicity data and all acute data supplemented with the ICE-predicted data, the acute WQC values of La were 88, 1022 and 256 μg/L, respectively. According to the SSD and corresponding HC 5 of chronic toxicity data, the chronic WQC was 14 μg/L. The results provide a scientific reference for establishing WQC for freshwater aquatic organisms and ecological risk assessments of REEs., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Lanthanum, a major rare earth element, can exert detrimental effects on the adult immune system, but its developmental immunotoxicity (DIT) remains obscure. This study was designed to evaluate the DIT of lanthanum nitrate (LN) and the self-recovery of LN-induced DIT 21 days following cessation of exposure. BALB/c pregnant dams were exposed to 0, 0.1, 1, and 10 mg/kg body weight/day LN by gavage during gestation and lactation. Results showed that in male offspring, LN markedly inhibited the adaptive immunity at postanal day 21 (PND21) and the inhibitory effect on cellular immunity continued to PND42 (after three weeks of self-recovery). In female offspring, LN suppressed cellular immunity at both PND21 and PND42. Moreover, decreased relative organ weight of thymus, humoral immunity and proportion of double-positive T cells in thymus were also observed at PND42. Bcl-xl protein level decreased in thymus of female at PND42, while the level of β-catenin increased. These changes might contribute to accelerating the degeneration and weight loss of thymus. Overall, in-utero and postanal exposure to LN could induce impairments of immunity in offspring, especially the female, and adaptive immunosuppression would persist throughout development into adulthood. The LOAEL of LN for DIT should be 1 mg/kg., (Copyright © 2022. Published by Elsevier B.V.)

Studies dealing with Rare Earth Elements (REE) ecotoxicological behavior are scattered and with potential conflicting results. Climate change impacts on aquatic biota and is known to modify contaminants toxicokinetic. Nevertheless, the current knowledge on the potential interactions between climate change and REE is virtually non-existent. Therefore, we focus our research on La and Gd as representatives of Light and Heavy REE that also are of great environmental concern. Experiments on different mediums (fresh-, brackish- and seawater) were designed to run at present-day and near-future conditions (T°=+4 °C, pH=△-0.4). Sampling was taken at different time scales from minutes to hours for one day. The main challenge was to evaluate the availability of La and Gd under environmental conditions closely related to climate changes scenarios. Furthermore, this study will contribute to the baseline knowledge by which future research towards understanding REE patterns and toxicity will build upon. Lanthanum and Gd behave differently with salinity. Temperature also affects the availability of dissolved La in freshwater. On the other hand, pH reduction causes the decrease of Gd in freshwater. In this medium, concentrations reduce sharply, presumably due to sorption processes or precipitates. In the brackish water experiment only the dissolved La levels in the Warming (T°=+4 °C) and Warming & Acidification (T°=+4 °C, pH=△0.4) diminished significantly through time. Dissolved La and Gd levels in seawater were relatively constant with time. The speciation of both elements is also of great relevance for ecotoxicological experiments. The trivalent free ions (La 3+ and Gd 3+ ) were the most common species in the trials. However, as ionic strength increases, the availability of other complexes rose, which should be subject of great attention for upcoming ecotoxicological studies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Lanthanum can induce neurotoxicity and impair cognitive function; therefore, research on the mechanism by which the ability to learning and memory is decreased by lanthanum is vitally important for protecting health. Microglia are a type of neuroglia located throughout the brain and spinal cord that play an important role in the central nervous system. When overactive, these cells can cause the excessive production of inflammatory cytokines that can damage neighboring neurons. The purpose of this study was to explore the effect of lanthanum in the form of lanthanum chloride (LaCl 3 ) on learning and the memory of mice and determine whether there is a relationship between hippocampal neurons or learning and memory damage and excessive production of inflammatory cytokines. Four groups of pregnant Chinese Kun Ming mice were exposed to 0, 18, 36, or 72 mM LaCl 3 in their drinking water during lactation. The offspring were then exposed to LaCl 3 in the breast milk at birth until weaning and then exposed to these concentrations in their drinking water for 2 months after weaning. The results showed that LaCl 3 impaired learning and memory in mice and injured their neurons, activated the microglia, and significantly overregulated the mRNA and protein expression of tumor necrosis factor alpha, interleukin (IL)-1β, IL-6, monocyte chemoattractant protein-1, and nitric oxide in the hippocampus. The results of this study suggest that lanthanum can impair learning and memory in mice, possibly by over-activating the microglia., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

The industrial and agricultural applications of rare earth elements (REEs) lead to considerable REE emissions into environment. Yet, little is known about the molecular-level effects and interactions of REEs in terrestrial plants. Herein, the individual and joint effects of La and Ce in Triticum aestivum were investigated using mass spectrometry-based metabolomics. Metabolic effect level index (MELI) was utilized as a readable endpoint for quantifying mixture interactions. Exposure to single La/Ce at environmentally relevant levels induced significant dose-dependent metabolic changes. The highly overlap of differential metabolites and perturbed pathways of La and Ce suggested their similar mode of action. Exposure to La-Ce mixtures did not induce additional metabolic pathway perturbation. Specifically, metabolism of amino sugar and nucleotide sugar, starch and sucrose, fructose and mannose, glycerophospholipid and purine were disrupted for both single and binary exposures. These results, together with physiological indicators, point to REE-induced oxidative stress, energy expenditure, DNA damage and membrane disturbance. The MELI calculations showed that La and Ce interacted synergistically at the overall metabolic level, which could be causally linked to synergistic interaction at the individual level (root elongation). This work proved metabolomics could be an important and effective strategy for interpreting toxicity and interactions of REE mixtures., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Rare earth elements inevitably release into the soil due to their widespread application. However, it is unclear how they affect the soil animals. The study surveyed the growth and physiological responses of earthworm (Eisenia fetida) exposed into artificial soils spiked with La, Ce, and their mixture, and actual mine soil collected from an abandoned La-Ce mining area (Mianning, Sichuan). The results showed that the 1000-1200 mg/kg combined exposure in two soils induced significant histopathological and phenotypic changes of earthworms. Concentration significantly affected the superoxide dismutase (SOD), peroxidase (POD), malondialdehyde (MDA), and protein of E. fetida and the effects differentiated with the prolonging duration. These indicators were negatively affected under the La stress ≥800 mg/kg (SOD, POD, and protein), the 1200 mg/kg (SOD), Ce stress ≥1000 mg/kg (protein), and the combination ≥800 mg/kg (SOD, POD) and ≥1000 mg/kg (protein). Artificial combination had -15.04% (SOD), 8.87% (POD), 5.64% (MDA), and -8.34% (protein) difference compared with the contamination soil, respectively. Overall, E. fetida respond sensitively under the La and Ce stress, the antioxidant defense system and the lipid peroxidation were stimulated, and the artificial soil might overestimate eco-toxicological effect., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Lanthanum is one of REEs documented to have neurotoxicity that led to learning and memory ability impairments. However, the mechanisms underlying La-induced neurotoxicity remain largely unexplored. Autophagy is a self-balancing and self-renewal process that degrades damaged organelles and macromolecules through lysosomal pathway. Importantly, appropriate autophagy levels have protective effects against harmful stress, while excessive autophagy has been demonstrated to be implicated in neurological diseases. ER is close to mitochondria at specific sites with a reported distance of 10-30 nm. The functional domains between the two organelles, called MAM, have been associated with autophagosome synthesis. In this study, the pregnant Wistar rats were randomly divided into four groups and given distilled water solution containing 0%, 0.125%, 0.25%, and 0.5% LaCl 3 for drinking during gestation and lactation. The pups were exposed to LaCl 3 via the maternal placenta and three-week lactation. Experimental results showed that LaCl 3 decreased spatial learning and memory ability of offspring rats, decreased tethering protein complexes expression of MAM, damaged MAM structure, up-regulated NOX4 expression which led to active ROS-AMPK-mTOR signaling pathway. Our findings suggest that decreased spatial learning and memory ability induced by LaCl 3 may be related to the abnormally autophagy regulated by tethering protein complexes of MAM., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Rare earth elements (REEs) are widely used in the industry, agriculture, biomedicine, aerospace, etc, and have been shown to pose toxic effects on animals, as such, studies focusing on their biomedical properties are gaining wide attention. However, environmental and population health risks of REEs are still not very clear. Also, the REEs damage to the nervous system and related molecular mechanisms needs further research. In this study, the L1 and L4 stages of the model organism Caenorhabditis elegans were used to evaluate the effects and possible neurotoxic mechanism of lanthanum(III) nitrate hexahydrate (La(NO 3 ) 3 ·6H 2 O). For the L1 and L4 stage worms, the 48-h median lethal concentrations (LC 50 s) of La(NO 3 ) 3 ·6H 2 O were 93.163 and 648.0 mg/L respectively. Our results show that La(NO 3 ) 3 ·6H 2 O induces growth inhibition and defects in behavior such as body length, body width, body bending frequency, head thrashing frequency and pharyngeal pumping frequency at the L1 and L4 stages in C. elegans. The L1 stage is more sensitive to the toxicity of lanthanum than the L4 stage worms. Using transgenic strains (BZ555, EG1285 and NL5901), we found that La(NO 3 ) 3 ·6H 2 O caused the loss or break of soma and dendrite neurons in L1 and L4 stages; and α-synuclein aggregation in L1 stage, indicating that Lanthanum can cause toxic damage to dopaminergic and GABAergic neurons. Mechanistically, La(NO 3 ) 3 ·6H 2 O exposure inhibited or activated the neurotransmitter transporters and receptors (glutamate, serotonin and dopamine) in C. elegans, which regulate behavior and movement functions. Furthermore, significant increase in the production of reactive oxygen species (ROS) was found in the L4 stage C. elegans exposed to La(NO 3 ) 3 ·6H 2 O. Altogether, our data show that exposure to lanthanum can cause neuronal toxic damage and behavioral defects in C. elegans, and provide basic information for understanding the neurotoxic effect mechanism and environmental health risks of rare earth elements., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Among the environmental emerging concern rare earth elements, lanthanum (La) is one of the most common and reactive. Lanthanum is widely used in numerous modern technologies and applications, and its intense usage results in increasing discharges into the environment, with potentially deleterious consequences to earthlings. Therefore, we exposed the important food resource and powerful monitoring tool Manila clam to two environmentally relevant concentrations of La (0.3 µg L -1 and 0.9 µg L -1 ) for 6 days, through water, to assess the bioaccumulation pattern in the gills, digestive gland, and remaining body. The La bioaccumulation was measured after 1 (T1), 2 (T2), and 6 (T6) days of exposure. Lanthanum was bioaccumulated after 2 days, and the levels increased in all tissues in a dose-dependent manner. When exposed to 0.3 µg L -1 , the enrichment factor pattern was gills > body > digestive gland. However, when exposed to 0.9 µg L -1 , the pattern appears to change to gills > digestive gland > body. Tissue portioning appears to be linked with exposed concentration: In higher exposure levels, digestive gland seems to gain importance, probably associated with detoxification mechanisms. Here, we describe for the first time La bioaccumulation in these different tissues in a bivalve species. Future studies dealing with the bioaccumulation and availability of La should connect them with additional water parameters (such as temperature, pH, and major cations)., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Autophagy is a lysosome dependent degradation pathway occurring in eukaryotic cells. Autophagy ensures balance and survival mechanism of cells during harmful stress. Excessive or weak autophagy leads to abnormal function and death in some cases. Lanthanum (La), a rare earth element (REE), damages the central nervous system (CNS) and promotes learning and memory dysfunction. However, underlying mechanism has not been fully elucidated. La induces oxidative stress, inhibits Nrf2/ARE and Akt/mTOR signaling pathways, and activates JNK/c-Jun and JNK/Foxo signaling pathways, resulting in abnormal induction of autophagy in rat hippocampus. In addition, La activates PINK1- Parkin signaling pathway and induces mitochondrial autophagy. However, the relationship between La and autophagy in rat neurons at the cellular level has not been explored previously. The aim of this study was to explore adverse effects of La. Primary culture of rat neurons were exposed to 0 mmol/L, 0.025 mmol/L, 0.05 mmol/L and 0.1 mmol/L lanthanum chloride (LaCl 3 ). The results showed that La upregulates p-AMPK, inhibits levels of p-Akt and p-mTOR, increases levels of autophagy related proteins (Beclin1 and LC3B-II), and downregulates expression of p-Bcl-2 and p62. Upstream and downstream intervention agents of autophagy were used to detect autophagy flux to verify accuracy of our results. Electron microscopy results showed significant increase in the number of autophagosomes in LaCl 3 exposed groups. These findings imply that LaCl 3 inhibits Akt/mTOR signaling pathway and activates AMPK/mTOR signaling pathway, resulting in abnormal autophagy in primary cultured rat cortical neurons. In addition, LaCl 3 induces neuronal damage through excessive autophagy., (Copyright © 2021. Published by Elsevier Ltd.)

The multiplicity and wide variety of applications of electrical and electronic equipment has largely increased with the technological and economic progress and, in consequence, the amount of generated waste of electrical and electronic equipment (WEEE). Due to inappropriate processing and disposal of WEEE, different chemical elements and compounds, including rare-earth elements such as Lanthanum (La) have been released in the environment. Nevertheless, the environmental risks resulting from La presence are almost unknown, especially in marine systems, which may be challenged by foreseen climate changes such as water salinity shifts. Within this context, the present study aimed to understand the combined effects of salinity and La by assessing biochemical alterations in mussels Mytilus galloprovincialis exposed to La (0 and 10 μg/L) at different salinity levels (20, 30 and 40). A decrease in salinity caused a wide range of biochemical changes to both non-contaminated and contaminated organisms, such as metabolism, antioxidant and biotransformation defenses activation, associated to hypotonic stress. Furthermore, the decrease in salinity enhanced the effects of La exposure seen as an increase on lipid and protein cellular damage in those exposed, probably due to free metal ions increase at lower salinities, resulting in a higher bioaccumulation and toxicity. In general, La exposure caused cellular damage and inhibition of antioxidant defenses in contaminated mussels when compared to non-contaminated ones, with cellular damages being higher at the lowest salinity. Overall, the present study highlights the need to investigate the presence and impacts of emerging contaminants of WEEE source at environmental relevant concentrations, not just at present but also under forecasted climate change scenarios, thus providing a more realistic environmental risk assessment., Competing Interests: Declaration of competing interest The Authors whose names are listed immediately below certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers' bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or nonfinancial /interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (Copyright © 2021 Elsevier B.V. All rights reserved.)

This paper investigates the effect of lanthanum (La) on lipid deposition and Wnt10b signaling in the liver of male zebrafish with exposure of 0, 10, 20, and 30 μmol/L La. It suggests that La can be accumulated in liver, and its treatments decrease the activities and gene expression of enzymes related to fatty acid synthesis. The levels of total cholesterol (TC), triglyceride (TG), and nonesterified fatty acids (NEFA) as well as the size of lipid droplets are decreased by La treatments. Moreover, La treatments affect the composition of fatty acids and the content of nutrient elements. Meanwhile, they also induce the gene expression of wnt10b, β-catenin, pparα, and pparγ, but inhibit gsk-3β gene expression in liver. Further study on the result of wnt10b gene interference shows that Wnt10b/β-catenin signaling plays a crucial role in the regulatory process of hepatic lipid deposition. Taken together, our observations suggest that La accumulation affects lipid deposition in the liver of male zebrafish, and Wnt10b signaling pathway may be involved in this process., (Copyright © 2021. Published by Elsevier B.V.)

Significant release of rare earth elements (REEs) into the environment is mainly due to active or abandoned mining sites, but their presence is globally increasing due to their use in several industrial sectors. The effects on primary producers as Raphidocelis subcapitata are still limited. This research focused on La and Ce as the two most widespread REEs that can be currently found up to hundreds of μg/L in water and wastewater. Microalgae were exposed to La and Ce for 3 days (pH = 7.8) (short-term exposure) to derive the effective concentrations inhibiting the growth on 10% (EC10) of the exposed population. EC10 values (0.5 mg/L of La and 0.4 mg/L of Ce) were used for the 28 days long-term exposure (renewal test) to observe after 7, 14, 21, and 28 days on a multi-endpoint basis microalgae growth inhibition (GI), biomarkers of stress (reactive oxygen species (ROS), superoxide dismutase (SOD), and catalase (CAT)), and bioconcentration. Results evidenced that La and Ce EC10 increased GI (day 28) up to 38% and 28%, respectively. ROS, CAT, and SOD activities showed differential responses from day 7 to day 14, 21, and 28, suggesting, in most of the cases, that La and Ce effects were counteracted (i.e., being the values at day 28 not significantly different, p > 0.05, from the relative negative controls), except for La-related ROS activities. La and Ce significantly bioconcentrated in microalgae populations up to 2- and 5-fold (i.e., at day 28 compared to day 7), in that order. Bioconcentrated La and Ce were up to 3157 and 1232 μg/g dry weight (day 28), respectively. These results suggested that low La and Ce concentrations can be slightly toxic to R. subcapitata having the potential to be bioaccumulated and potentially transferred along the food web., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Due to the wide application of rare-earth elements (REEs) in the last decades, lanthanum has increasingly entered the environment and has gradually accumulated in the human body through the food chain. Lanthanum is worth paying attention in terms of food safety. Although the genotoxicity of lanthanum has been studied in vitro, data on its DNA damage in vivo rodent are limited, moreover, which have also presented some controversy. This study aimed to conduct an in vivo rodent alkaline comet assay, and as a companion test to the lanthanum nitrate carcinogenicity test. We conducted an oral gavage experiment for 180 days (26 weeks) to test for the persistence of DNA damage of long-term low-dose accumulation of lanthanum nitrate (12.5, 25, and 50 mg/kg body weight), in F1 hybrid C57-ras transgenic mice (CB6F1) by using alkaline comet assay in the blood and liver. The comet assay revealed that all the tested concentrations of lanthanum nitrate did not induce DNA damage in any of the tissues investigated, whereas DNA damage was induced in the positive control group. These results could indicate that lanthanum nitrate can accumulate in tissues and organs of the mice after exposure, and does not possess DNA damage in C57-ras transgenic mice after repeated treatments at oral doses up to 50 mg/kg·BW for 26 weeks; also, it did not cause pathological changes in the liver of the mice., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

The alteration of rare earth elements (REEs) biogeochemical cycles has increased the potential effects related to their environmental exposure in a one-health perspective. Cerium (Ce), gadolinium (Gd), lanthanum (La), and neodymium (Nd) are frequently related to technological applications and their environmental concentrations are already in the μg/kg - mg/kg (i.e., or L) range depending on the considered matrices. The effect of Ce, Gd, La, and Nd was investigated in a simulated AMD (0.01-10.22 mg/L) at pH 4 and 6 considering a battery of photosynthetic organisms (Raphidocelis subcapitata, Lepidium sativum, and Vicia faba) according to a multiple-endpoint approach (growth inhibition, germination index, and mutagenicity). According to modelled chemical speciation, the considered elements were mostly in the trivalent free form (86-88%) at pH 4. Gd, La, and Nd exerted the most relevant toxic effect at pH 4. The pH 6 scenario evidenced a reduction in REEs toxicity level. Mutagenicity was detected only at pH 4 by Gd (up to 3-fold compared to negative controls), La and Nd, while Ce did not show any adverse effect. Toxic effects due to Ce, Gd, La, and Nd can be reduced by controlling the pH, but several gaps of knowledge still remain about their uptake and trophic transfer, and long-term effects on targeted species., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Rare earth elements (REEs) are emerging as a serious threat to ecological safety due to their increasing accumulation in environments. The accumulation of REEs in environments has significantly increased its accumulation in the leaves of edible plants. However, the accumulation pathway of REEs in the leaves of edible plants are still unknown. In this study, lanthanum [La(III), a widely used and accumulated REE] and four edible plants (soybean, lettuce, pakchoi, and celery) with short growth cycles were selected as research objects. By using interdisciplinary research techniques, we found that low-dose La(III) activated endocytosis (mainly the clathrin-mediated endocytosis) in the leaf cells of four edible plants, which provided an accumulation pathway for low-dose La in the leaf cells of these edible plants. The accumulation of La in the leaf cells was positively correlated with the intensity of endocytosis, while the intensity of endocytosis was negatively correlated with the density of leaf trichomes. In addition to the accumulation of La, low-dose La(III) also brought other risks. For example, the harmful element (Pb) can also be accumulated in the leaf cells via La(III)-activated endocytosis; the homeostasis of the essential elements (K, Ca, Fe, Mg) was disrupted, although the chlorophyll synthesis and the growth of these leaf cells were accelerated; and the expression of stress response genes (GmNAC20, GmNAC11) in soybean leaves was increased. These results provided an insight to further analyze the toxicity and mechanism of REEs in plants, and sounded the alarm for the application of REEs in agriculture., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Soluble lanthanum (La)(Ⅲ) species that have been extensively used as fertilizers in agriculture can potentially get into the human body through foods and environment. Most soluble La(Ⅲ) species can rapidly transform into insoluble La(Ⅲ) species under physiological conditions, however, their potential biological behavior and chronic toxicity are rarely investigated. In the present study, insoluble La(Ⅲ) species formed under physiological condition were identified as nanoscale or microscale particles, and their major components were found to experience biotransformation process upon contact with cells. Insoluble La(Ⅲ) species could adhere to extracellular membrane or be internalized into cells, capable of activating a nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome. The underlying mechanism could be ascribed to K + efflux and lysosomal rupture because these insoluble La(Ⅲ) species locating at extracellular membrane could reduce the unsaturated fatty acids of cell membrane, leading to potassium (K + ) efflux, and those internalized into cells could consume the phospholipids of lysosomal membrane, leading to lysosomal rupture. Mice daily drinking soluble La(Ⅲ) species to mimic drinking tea process for 90 days were found to present NLRP3 inflammasome activation in liver and kidney, as a result of chronic fibrosis, which is potentially correlated to insoluble La(Ⅲ) species formation., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Lanthanum nanoparticles are widely used in industry, agriculture, and biomedicine. Over 900 kg of lanthanum is annually released into the environment only in Europe, 50 times higher than the metals, mercury, and cadmium's environmental spread. Human health risk associated with long-term exposure to the abundant lanthanum nanoparticles is a concerning environmental issue. Due to lanthanum's ability to disrupt the main biological barriers and interrupt various cells' hemostasis, they seem to cause severe disruptions to various tissues. This review opens a new perspective regarding the cellular and molecular interaction of nanosized and ionic lanthanum with the possible toxicity on the nervous system and other tissues that would show lanthanum nanoparticles' potential danger to follow in toxicological science.

The massive application of rare earth elements (REEs) in electronic industries cause their inevitable release into the environment; however, its effects on soil biota remain largely unaddressed. We investigated the E. fetida detoxification potential of nano and bulk La 2 O 3 and Yb 2 O 3 and their potential impact on biochemical and genetic markers at 50, 100, 200, 500 and 1000 mg kg -1 concentration. We found that earthworms bioremediate 3-15% La 2 O 3 and Yb 2 O 3 contaminated soil at low and medium levels, while this potential was limited at higher levels. Nano and bulk La 2 O 3 and Yb 2 O 3 treatment induced neurotoxicity in earthworm by inhibiting acetylcholinesterase by 49-65% and 22-36% at 500 and 1000 mg kg -1 , respectively. Nano La 2 O 3 proved to be highly detrimental, mainly through oxidative stress and subsequent failure of antioxidant system. Nano La 2 O 3 and Yb 2 O 3 at 100 mg kg -1 significantly down-regulated the expression of annetocin mRNA in the parental and progeny earthworms by 50% and 20%, which is crucial for earthworm reproduction. Similarly, expression level of heat shock protein 70 (HSP70) and metallothionein was significantly upregulated in both generations at medium exposure level. Histological observations showed that nano REEs at 200 mg kg -1 induced drastic changes in the intestinal epithelium and typhlosole of E. fetida. To date, our results enhance the understanding of interaction between REEs and earthworms., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Toxicity of lanthanides is generally regarded as low, and they even have been suggested to be beneficial at low concentrations. This research was conducted to investigate effects of Lanthanum (La) on Desmodesmus quadricauda, a freshwater green microalga. The algal cultures were treated with nanomolar La concentrations under controlled environmentally relevant conditions. Intracellular localization of La was analyzed with μXRF tomography in frozen-hydrated samples. At sublethal concentration (128 nM) La was in hotspots inside the cells, while at lethal 1387 nM that led to release of other ions (K, Zn) from the cells, La filled most of the cells. La had no clear positive effects on growth or photosynthetic parameters, but increasing concentrations led to a dramatic decrease in cell counts. Chlorophyll fluorescence kinetic measurements showed that La led to the inhibition of photosynthesis. Maximal photochemical quantum yield of the PSII reaction center in dark-adapted state (F v /F m ) decreased at > 4.3 nM La during the 2nd week of treatment. Minimum dark-adapted fluorescence quantum yield (F 0 ) increased at > 13.5 nM La during the 2nd week of treatment except for control (0.2 nM La, baseline from chemicals) and 0.3 nM La. NPQ at the beginning of the actinic light phase showed significant increase for all the treatments. Metalloproteomics by HPLC-ICPMS showed that La binds to a >500 kDa soluble protein complex already in the sub-nM range of La treatments, in the low nM range to a small-sized (3 kDa) soluble peptide, and at >100 nM La additionally binds to a 1.5 kDa ligand., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Nanoparticles have a great potential to increase the therapeutic efficiency of several cancer therapies. This research examines the potential for silver-doped lanthanum manganite nanoparticles to enhance radiation therapy to target radioresistant brain cancer cells, and their potential in combinational therapy with magnetic hyperthermia. Magnetic and structural characterisation found all dopings of nanoparticles (NPs) to be pure and single phase with an average crystallite size of approximately 15 nm for undoped NPs and 20 nm for silver doped NPs. Additionally, neutron diffraction reveals that La 0.9 Ag 0.1 MnO 3 (10%-LAGMO) NPs exhibit residual ferromagnetism at 300 K that is not present in lower doped NPs studied in this work, indicating that the Curie temperature may be manipulated according to silver doping. This radiobiological study reveals a completely cancer-cell selective treatment for LaMnO 3 , La 0.975 Ag 0.025 MnO 3 and La 0.95 Ag 0.05 MnO 3 (0, 2.5 and 5%-LAGMO) and also uncovers a potent combination of undoped lanthanum manganite with orthovoltage radiation. Cell viability assays and real time imaging results indicated that a concentration of 50 μg/mL of the aforementioned nanoparticles do not affect the growth of Madin-Darby Canine Kidney (MDCK) non-cancerous cells over time, but stimulate its metabolism for overgrowth, while being highly toxic to 9L gliosarcoma (9LGS). This is not the case for 10%-LAGMO nanoparticles, which were toxic to both non-cancerous and cancer cell lines. The nanoparticles also exhibited a level of toxicity that was regulated by the overproduction of free radicals, such as reactive oxygen species, amplified when silver ions are involved. With the aid of fluorescent imaging, the drastic effects of these reactive oxygen species were visualised, where nucleus cleavage (an apoptotic indicator) was identified as a major consequence. The genotoxic response of this effect for 9LGS and MDCK due to 10%-LAGMO NPs indicates that it is also causing DNA double strand breaks within the cell nucleus. Using 125 kVp orthovoltage radiation, in combination with an appropriate amount of NP-induced cell death, identified undoped lanthanum manganite as the most ideal treatment. Real-time imaging following the combination treatment of undoped lanthanum manganite nanoparticles and radiation, highlighted a hinderance of growth for 9LGS, while MDCK growth was boosted. The clonogenic assay following incubation with undoped lanthanum manganite nanoparticles combined with a relatively low dose of radiation (2 Gy) decreased the surviving fraction to an exceptionally low (0.6 ± 6.7)%. To our knowledge, these results present the first biological in-depth analysis on silver-doped lanthanum manganite as a brain cancer selective chemotherapeutic and radiation dose enhancer and as a result will propel its first in vivo investigation., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Rhizosphere microbes are essential partners for plant stress tolerance. Recent studies indicate that arbuscular mycorrhizal fungi (AMF) can facilitate the revegetation of soils contaminated by heavy metals though interacting with rhizosphere microbiome. However, it is unclear how AMF affect rhizosphere microbiome to improve the growth of plant under rare earth elements (REEs) stress. AMF (Claroideoglomus etunicatum) was inoculated to maize grown in soils spiked with Lanthanum (0 mg kg -1 , La0; 10 mg kg -1 , La10; 100 mg kg -1 , La100; 500 mg kg -1 , La500). Plant biomass, nutrient uptake, REE uptake and rhizosphere bacterial and fungal community were evaluated. The results indicated that La100 and La500 decreased significantly root colonization rates and nutrition uptake (K, P, Ca and Mg content). La500 decreased significantly α-diversity indexes of bacterial and fungal community. AMF enhanced significantly the shoot and root fresh and dry weight of maize in all La treatments (except for the root fresh and dry weight of La0 and La10 treatment). For La100 and La500 treatments, AMF increased significantly nutrition uptake (K, P, Ca and Mg content) in shoot of maize by 27.40-441.77%. For La500 treatment, AMF decreased significantly shoot La concentration by 51.53% in maize, but increased significantly root La concentration by 30.45%. In addition, AMF decreased bacterial and fungal Shannon index in La0 treatment, but increased bacterial Shannon index in La500 treatment. Both AMF and La500 affected significantly the bacterial and fungal community composition, and AMF led to more influence than La. AMF promoted the enrichment of bacteria, including Planomicrobium, Lysobacter, Saccharothrix, Agrococcus, Microbacterium, Streptomyces, Penicillium and other unclassified genus, and fungi (Penicillium) in La500, which showed the function for promoting plant growth and tolerance of heavy metal. The study revealed that AMF can regulate the rhizosphere bacterial and fungal composition and foster certain beneficial microbes to enhance the tolerance of maize under La stress. Phytoremediation assisted by AMF is an attractive approach to ameliorate REEs-contaminated soils., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

With the widespread application of rare earth elements (REEs) in environment safety, food and medicine, they accumulate in the ecosystem and different human organs where REEs exert certain biological effects. Low dose REEs are proved to perform antioxidant effects, while high concentration can cause oxidative stress. However, scant information about rational doses and underlying mechanism of REEs as oxidants/antioxidants were illustrated. To elucidate these problems, here we performed a study that the ICR mice were received 0.1, 0.2, 1.0, 2.0 and 20.0 mg/kg lanthanum nitrate (La(NO 3 ) 3 ) by gavage for 30 days, and then were given 12 mL/kg ethanol once to undergo acute ethanol-induced oxidative stress. The antioxidant enzymes, antioxidants, peroxides and related proteins in Keap 1/Nrf2/p62 signaling pathway were measured. The results showed that La(NO 3 ) 3 inhibited hepatic morphological alternations by histopathological examination. Meanwhile, elevated superoxide dismutase (SOD) and glutathione (GSH), coupled with decreased alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA) and protein carbonyl (PC) were observed in serum and liver tissues of mice by enzyme-linked immunosorbent assay test. Furthermore, western blot analysis demonstrated that oxidative stress was alleviated due to enhanced NF-E2-related factor 2 (Nrf2) and phosphorylated p62 expressions as well as lower Kelch-like ECH-associated protein-1 (Keap 1), followed by the activation of heme oxygenase 1 (HO-1), NAD(P)H quinone oxidoreductase 1 (NQO-1) and glutamate cysteine ligase, catalytic (GCLC) proteins. Our findings clearly highlighted that La(NO 3 ) 3 could restore the redox homeostasis disrupted by ethanol through provoking Keap 1/Nrf2/p62 signaling pathway, and the optimal dosages were 1.0 and 2.0 mg/kg., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Lanthanum is a rare-earth element that has been used in various fields including medicine, agriculture and industry. Previously, in utero lanthanum exposure to dams was shown to alter neurobehavior and neurotransmitter levels in rat offspring; however, the effects of postweaning exposure to lanthanum on neurological behavior is still limited. The purpose of this study was to investigate the effects of postweaning exposure to lanthanum on neurological behavior during early adulthood in rats. Rats were orally exposed to 0, 2, 20, 60 mg/kg BW of lanthanum nitrate from postnatal day (PND) 24 to PND60. Our results indicated that lanthanum treatment significantly decreased body weight and food intake. Morris water maze test results showed that lanthanum significantly decreased escape latency and travel distance. Lanthanum treatment also significantly decreased grip strength, hindlimb strength, and running time & distance in motor activity test. Further results showed that lanthanum treatment significantly decreased plasma neurotransmitter levels of acetylcholine and norepinephrine as well as the number of neurons in the CA1 area of the hippocampus. These results suggest that postweaning exposure to lanthanum have adverse effects on neurobehaviors and the central nervous system, with no-observed-adverse-effect level at 2 mg/kg BW and benchmark dose lower confidence limit at 1.7 mg/kg BW., (Copyright © 2020 Elsevier B.V. All rights reserved.)

China is the world's largest rare earth producer and exporter, previous studies have shown that rare earth elements can cause oxidative damage in animal testis. However, the molecular mechanisms underlying these observations have yet to be elucidated. In this paper, male mice were fed with different doses (10, 20, and 40 mg/kg BW) of LaCl 3 for 90 consecutive days, regulatory role of nuclear factor erythroid-2 related factor 2 (Nrf-2)/antioxidant response element (ARE) pathway in testicular oxidative stress induced by LaCl 3 were investigated. Analysis showed that LaCl 3 exposure could lead to severe testicular pathological changes and apoptosis in spermatogenic cells, it up-regulated the peroxidation of lipids, proteins and DNA, and induced the excessive levels of reactive oxygen species (ROS) production in mouse testis, reduced the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and glutathione S epoxide transferase (GST) as well as the glutathione (GSH) content. Furthermore, exposure to LaCl 3 also downregulated the expression of Nrf2 and its target gene products, including heme oxygenase 1 (HO-1), glutamate-cysteine ligase catalytic subunit (GCLC), NAD(P)H dehydrogenase [quinine] 1(NQO1), protein kinase C (PKC), and phosphatidylinositol 3-kinase (PI3K), but upregulated the expression of Kelch-like ECH-related protein 1 (Keap1) in damaged mouse testes. Collectively, our data imply that the oxidative damage induced by LaCl 3 in testis was related to inhibition of the Nrf-2/AREs pathway activation., (© 2020 Wiley Periodicals LLC.)

Increasing rare earth element (REE) mining and refining activities have led to a considerable release of these substances into aquatic environment, yet the knowledge of their impacts on aquatic organisms is still limited. Here, we explored the developmental effects of 16 REEs (concentration ranged from 0.46 to 1000 mg/L) to zebrafish embryos and highlighted the adverse effects of lanthanum (La) and praseodymium (Pr). Among the multiple developmental parameters measured, the significant effects on swimming behavior and cardiac physiology were the most prominent. Transcriptomic analysis of La and Pr at concentrations of 1.1 to 10 mg/L revealed their rather uniform effects at molecular levels. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis revealed that among others, notch, glutamate, and serotonin signaling, as well as cardiac hypertrophy and cardiac muscle contraction, were significantly affected. These changes of neural signaling were consistent with behavior effects observed and supported by neurotransmitter changes and thus provide a reasonable molecular mechanistic explanation. Furthermore, increased DNA damage and apoptotic activity at high concentrations were observed, especially in the heart. They may contribute to explain the observed adverse morphological and physiological outcomes, such as pericardial edema. The effect concentrations observed in the present study were comparable to the concentrations of REE residues at highly contaminated sites (several mg/L), indicating ecotoxicological effects at environmentally relevant concentrations. Overall, the present data help to clarify the potential developmental toxicity of REEs that was not yet fully recognized and thus contribute to their environmental risk assessment.

Rare earth elements (REEs) have caused bioaccumulation and adverse health effects attributed to extensive application. The penetrability of REEs across the blood-brain barrier (BBB) contributes to their neurotoxicity process, but potential mechanisms affecting BBB integrity are still obscure. The present study was designed to investigate the effects of lanthanum on BBB adheren junctions and the actin cytoskeleton in vitro using bEnd.3 cells. After lanthanum chloride (LaCl3, 0.125, 0.25 and 0.5 mM) treatment, cytotoxicity against bEnd.3 cells was observed accompanied by increased intracellular Ca2+. Higher paracellular permeability presented as decreased TEER (transendothelial electrical resistance) and increased HRP (horse radish peroxidase) permeation, and simultaneously reduced VE-cadherin expression and F-actin stress fiber formation caused by LaCl3 were reversed by inhibition of ROCK (Rho-kinase) and MLCK (myosin light chain kinase) using inhibitor Y27632 (10 μM) and ML-7 (10 μM). Moreover, chelating overloaded intracellular Ca2+ by BAPTA-AM (25 μM) remarkably abrogated RhoA/ROCK and MLCK activation and downstream phosphorylation of MYPT1 (myosin phosphatase target subunit 1) and MLC2 (myosin light chain 2), therefore alleviating LaCl3-induced BBB disruption and dysfunction. In conclusion, this study indicated that lanthanum caused endothelial barrier hyperpermeability accompanied by loss of VE-cadherin and rearrangement of the actin cytoskeleton though intracellular Ca2+-mediated RhoA/ROCK and MLCK pathways.