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During the spring of 2024, 33 members of a group of Gulf War I veterans wounded in depleted uranium (DU) friendly-fire incidents were seen at the Baltimore VA Medical Center for surveillance related to their combat exposure. The cohort was assessed with a protocol which includes exposure monitoring for total and isotopic uranium (U) concentrations in urine and a comprehensive assessment of health outcomes including measures of bone metabolism and bone mineral density (BMD). An audiometry examination of the cohort was added to assess for acoustic trauma and toxic metal effects in this surveillance episode marking over 30 years since this exposure event. Elevated urine U concentrations were detected in cohort members with retained DU shrapnel fragments. In addition, a measure of bone resorption, N-telopeptide, determined in urine, exhibited a significant increase in the high DU sub-group. In addition, and similar to our previous surveillance report, a significant decrease was found in bone mass in the high DU sub-group compared to the low DU sub-group. It has been 30 years since the first surveillance visit occurred. An aging cohort of military veterans continues to demonstrate few U-related adverse health effects in known target organs attributed to U toxicity exposure. The new finding of impaired BMD in older cohort members has now been detected in three consecutive surveillance visits. This is a biologically plausible outcome related to the diminished bone mass in those with an elevated DU burden in combination with advancing age. The accumulating U burden derived from fragment absorption over time and the effect of aging on bone mineral loss recommends that our surveillance efforts need to continue. Our findings enable early detection of bone effects and other signs of target organ insult, which may occur when tissue injury thresholds are reached in the future and thus, permitting indicated medical management. [ABSTRACT FROM AUTHOR]

Uranium (U) released from U mining and spent nuclear fuel reprocessing in the nuclear industry, nuclear accidents and military activities as a primary environmental pollutant (e.g., drinking water pollution) is a threat to human health. Kidney is one of the main target organs for U accumulation, leading to nephrotoxicity mainly associated with the injuries in proximal tubular epithelial cells (PTECs). Transient receptor potential mucolipin 1 (TRPML1) is a novel therapeutic target for nephrotoxicity caused by acute or chronic U poisoning. We herein investigate the therapeutic efficacy of ML-SA5, a small molecule agonist of TRPML1, in U-induced nephrotoxicity in acute U intoxicated mice. We demonstrate that delayed treatment with ML-SA5 enhances U clearance from the kidneys via urine excretion by activating lysosomal exocytosis, and thereby attenuates U-induced kidney dysfunction and cell death/apoptosis of renal PTECs in acute U intoxicated mice. In addition, ML-SA5 promotes the nuclear translocation of transcription factor EB (TFEB) in renal PTECs in acute U intoxicated mice. Mechanistically, ML-SA5 triggers the TRPML1-mediated lysosomal calcium release and consequently induces TFEB activation in U-loaded renal PTECs-derived HK-2 cells. Moreover, knockdown of TRPML1 or TFEB abolishes the effects of ML-SA5 on the removal of intracellular U and reduction of the cellular injury/death in U-loaded HK-2 cells. Our findings indicate that pharmacological activation of TRPML1 is a promising therapeutic approach for the delayed treatment of U-induced nephrotoxicity via the activation of the positive feedback loop of TRPML1 and TFEB and consequent the induction of lysosomal exocytosis., 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 Masson SAS.. All rights reserved.)

Transformation represents one of the most important pathways for the horizontal transfer of antibiotic resistance genes (ARGs), which enables competent bacteria to acquire extracellular ARGs from the surrounding environment. Both heavy metals and irradiation have been demonstrated to influence the bacterial transformation process. However, the impact of ubiquitously occurring radioactive heavy metals on the transformation of ARGs remains largely unknown. Here, we showed that a representative radioactive nuclide, uranium (U), at environmental concentrations (0.005-5 mg/L), improved the transformation frequency of resistant plasmid pUC19 into Escherichia coli by 0.10-0.85-fold in a concentration-dependent manner. The enhanced ARGs transformation ability under U stress was demonstrated to be associated with reactive oxygen species (ROS) overproduction, membrane damage, and up-regulation of genes related to DNA uptake and recombination. Membrane permeability and ROS production were the predominant direct and indirect factors affecting transformation ability, respectively. Our findings provide valuable insight into the underlying mechanisms of the impacts of U on the ARGs transformation process and highlight concerns about the exacerbated spread of ARGs in radioactive heavy metal-contaminated ecosystems, especially in areas with nuclear activity or accidents., 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.)

Aim: This study aimed to evaluate the protective effect of soybean extract (SE) against uranium-induced lung injury in rats., Materials and Methods: A rat lung injury model was established through nebulized inhalation of uranyl nitrate. Pretreatment with SE or sterile water (control group) by gavage for seven days before uranium exposure and until the experiment endpoints. The levels of uranium in lung tissues were detected by ICP-MS. Paraffin embedding-based hematoxylin & eosin staining and Masson's staining for the lung tissue were performed to observe the histopathological imaging features. A public database was utilized to analyze the network pharmacological association between SE and lung injury. The expression levels of proteins indicating fibrosis were measured by enzyme-linked immunosorbent assay. RNA-seq transcriptomic and LC-MS/MS targeted metabolomics were conducted in lung tissues., Results: Uranium levels in the lung tissues were lower in SE-pretreated rats than in the uranium-treated group. Inflammatory cell infiltration and the deposition of extracellular matrix were attenuated, and the levels of alpha-smooth muscle actin, transforming growth factor beta1, and hydroxyproline decreased in SE-pretreated rats compared to the uranium-treated group. Active ingredients of SE were related to inflammation, oxidative stress, and drug metabolism. A total of 67 differentially expressed genes and 39 differential metabolites were identified in the SE-pretreated group compared to the uranium-treated group, focusing on the drug metabolism-cytochrome P450, glutathione metabolism, IL-17 signaling pathway, complement, and coagulation cascades., Conclusions: These findings suggest that SE may ameliorate uranium-induced pulmonary inflammation and fibrosis by regulating glutathione metabolism, chronic inflammation, and immune regulation., 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 Masson SAS.. All rights reserved.)

Uranium, a heavy metal and primordial radionuclide, is present in surface waters and soils both naturally and due to industrial activities. Uranium is known to be toxic to plants and its uptake and toxicity can be influenced by multiple factors such as pH and the presence of different ions. However, the precise role of the different ions in uranium uptake is not yet known. Here we investigated whether calcium influences uranium uptake and toxicity in the terrestrial plant Arabidopsis thaliana. To this end, A. thaliana plants were exposed to different calcium and uranium concentrations and furthermore, calcium channels were blocked using the calcium channel blocker lanthanum chloride (LaCl 3). Fresh weight, relative growth rate, concentration of nutrients and uranium and gene expression of oxidative stress-related genes and calcium transporters were determined in roots and shoots. Calcium affected plant growth and oxidative stress in both control (no uranium) and uranium-exposed plants. In shoots, this was influenced by the total calcium concentration, but not by the different tested uranium concentrations. Uranium in turn did influence calcium uptake and distribution. Uranium-exposed plants grown in a medium with a higher calcium concentration showed an increase in gene expression of NADPH oxidases RBOHC and RBOHE and calcium transporter CAX7 after uranium exposure. In roots, these calcium-dependent responses in gene expression were not observed. This indicates that calcium indeed affects uranium toxicity, but only in shoots. In addition, a clear influence of uranium and LaCl 3 (separately and combined) on the expression of calcium transporters was observed. • Roots respond to uranium oxidative stress in a calcium-independent manner. • Calcium concentration in the medium modulates uranium responses in shoots. • Shoots with high calcium concentrations were more susceptible to uranium stress. [ABSTRACT FROM AUTHOR]

Sunflower (Helianthus annuus) can potentially be used for uranium (U) phytoremediation. However, the factors influencing the absorption of U and its subsequent distribution within plant tissues remain unclear, including the effect of silicon (Si) which is known to increase metal tolerance. Here, using hydroponics, the effect of Si on the distribution and speciation of U in sunflower was examined using synchrotron-based X-ray fluorescence and fluorescence-X-ray absorption near-edge spectroscopy. It was found that ∼88 % of U accumulates within the root regardless of treatments. Without the addition of Si, most of the U appeared to bind to epidermis within the roots, whereas in the leaves, U primarily accumulated in the veins. The addition of Si alleviated U phytotoxicity and decreased U concentration in sunflower by an average of 60 %. In the roots, Si enhanced U distribution in cell walls and impeded its entry into cells, likely due to increased callose deposition. In the leaves, Si induced the sequestration of U in trichomes. However, Si did not alter U speciation and U remained in the hexavalent form. These results provide information on U accumulation and distribution within sunflower, and suggest that Si could enhance plant growth under high U stress., 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.)

Uranium pollution in aquatic ecosystems poses a threat to organisms. However, the metabolism and toxicity of uranium along aquatic food chains remain unknown. Here, we established an artificial aquatic ecosystem to investigate the fate of uranium along the food chain and reveal its potential toxicity. The results displayed a dose- and time-dependent toxicity of uranium on algae, leading to cell deformation and impeding cell proliferation. When uranium-exposed algae are ingested by fish, uranium tends to concentrate in the intestinal system and bones of fish. Comparatively, direct water uranium exposure resulted in a remarkable uranium accumulation in the head, skin, and muscles of fish, suggesting different toxicity depending on distinct exposure pathways. High-level uranium pollution (20 mg L -1 ) intensifies the toxicity to fish through food intake compared to direct water exposure. It has also revealed that approximately 25 % and 20 % of U(VI) were reduced to lower valence forms during its accumulation in algae and fish, respectively, and over 10 % of U(IV, VI) converted to U(0) ultimately, through which uranium toxicity was mitigated due to the lower solubility and bioavailability. Overall, this study provides new insights into the fate of uranium during its delivery along the aquatic food chain and highlights the risks associated with consuming uranium-contaminated aquatic products., 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.)

In this study, the biological effects of U(VI) exposure on lung epithelial cells were investigated by MTT assay, immunofluorescence, flow cytometry, and Western blotting. U(VI)-induced stress triggers oxidative stress in cells, activates MAPK signaling pathways, and promotes inflammation. Additionally, U(VI) causes damage to the cell membrane structure and severe DNA injury, impacting the accuracy of transcription and translation. The results demonstrate that U(VI) exposure significantly inhibits cell proliferation and migration. This is attributed to the disruption of the PI3K/AKT/GSK-3β/β-catenin signaling pathway and the reduction in CyclinD1 expression, leading to a delayed cell cycle, decreased growth rate, mitochondrial damage, and reduced energy metabolism. This study provides a comprehensive understanding of the molecular mechanisms underlying uranium-induced cellular toxicity in lung epithelial cells., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Wencheng Song reports financial support was provided by National Natural Science Foundation of China. If there are other authors, they 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.)

The addressing this question in udder tissue (main target of the metal) and test here if uranium U at low concentrations could also be a pro-oxidant. The research deals with different groups of grass-fed cows in several locations where the same phenomenon represents a case from Basra/Iraq. The histopathological examination of the udder in cows with (U) revealed hemangiomatous transformation. For the uranium, experts used a sodium iodide instrument to perform measurements and analyzed samples of cow udders as these organs are most affected by uranium. The tissues were being inflamed and they would die, becoming degenerated and necrotic (inflammatory). But, if given in high doses leads to the formation of different tumors: GGFL (gentle giants famous large udders) or clear cell carcinoma, Sarcomatoid type RCC. There is toxic uranium in the levels of grass that cattle consume and as a result there) cause defense allergies prevail over cows it is easy to induce oxidative pressure within their udders. However, even under (U) doses restraint stressors are seldom found to have additional negative effects at baseline value but the additive influence of these is never ruled out.

Environmental or occupational exposure to natural uranium can have adverse health effects, with its chemical toxicity being mainly directed towards the kidneys and skeleton. This has led to the development of chelating agents to remove uranium from the human body, including the ligand 3,4,3-LI(1,2-HOPO). We have developed a new in vitro assay to assess the efficacy of 3,4,3-LI(1,2-HOPO) in attenuating uranium-induced bone cell damage. This approach uses osteoclasts whose formation and function are altered by exposure to uranium. This assay is an interesting and effective alternative to animal methods for assessing the efficacy and safety of new uranium decorporants., 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 B.V. All rights reserved.)

Uranium (U) contamination of rice is an urgent ecological and agricultural problem whose effective alleviation is in great demand. Sphingopyxis genus has been shown to remediate heavy metal-contaminated soils. Rare research delves into the mitigation of uranium (U) toxicity to rice by Sphingopyxis genus. In this study, we exposed rice seedlings for 7 days at U concentrations of 0, 10, 20, 40, and 80 mg L -1 with or without the Sphingopyxis sp. YF1 in the rice nutrient solution. Here, we firstly found YF1 colonized on the root of rice seedlings, significantly mitigated the growth inhibition, and counteracted the chlorophyll content reduction in leaves induced by U. When treated with 1.1 × 10 7  CFU mL -1 YF1 with the amendment of 10 mg L -1 U, the decrease of U accumulation in rice seedling roots and shoots was the largest among all treatments; reduced by 39.3% and 32.1%, respectively. This was associated with the redistribution of the U proportions in different organelle parts, leading to the alleviation of the U damage to the morphology and structure of rice root. Interestingly, we found YF1 significantly weakens the expression of antioxidant enzymes genes (CuZnSOD,CATA,POD), promotes the up-regulation of metal-transporters genes (OsHMA3 and OsHMA2), and reduces the lipid peroxidation damage induced by U in rice seedlings. In summary, YF1 is a plant-probiotic with potential applications for U-contaminated rice, benefiting producers and consumers., 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 Masson SAS. All rights reserved.)

Human exposure to high concentrations of uranium is a major concern due to the risk of developing numerous internal organ malignancies over time. In addition to the numerous attributes of uranium in the nuclear power industry, the radiological characteristics and chemical toxicity of uranium present a substantial risk to human health. This study aims to evaluate potential negative health impacts associated with the ingestion of uranium through drinking water in the Noida and Greater Noida region within the Gautam Buddha districts of Uttar Pradesh (India), due to extreme industrial revolution in this geological location. The mean concentration of uranium in drinking water of the examined area was estimated to range from 0.23 to 78.21 µg l -1 . The hair compartment biokinetic model is used to estimate the retention and radiological doses of uranium in distinct organs and tissues. Studies on time-dependent factors revealed variations in uranium retention, with lower levels observed in the Gastrointestinal Tract (GIT) region and higher levels on cortical bone surfaces causes the skeletal deformities. The kidney, liver, and other soft tissues (OST) exhibited a non-saturation pattern in the retention of uranium via exposure of drinking water. The age-wise non-carcinogenic and carcinogenic doses were estimated for the health hazards studies. The outcome of this study will be useful for water resource management authorities to supply safe potable water to the local residents., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Depleted uranium (DU) retains the radiological toxicities, which accumulates preferentially in the kidneys. Hedgehog (Hh) pathway plays a critical role in tissue injury. However, the role of Hh in DU-induced nephrotoxicity was still unclear. This study was carried out to investigate the effect of Gli2, which was an important transcription effector of Hh signaling, on DU induced nephrotoxicity. To clarify it, CK19 positive tubular epithelial cells specific Gli2 conditional knockout (KO) mice model was exposed to DU, and then histopathological damage and Hh signaling pathway activation was analyzed. Moreover, HEK-293 T cells were exposed to DU with Gant61 or Gli2 overexpression, and cytotoxicity of DU as analyzed. Results showed that DU caused nephrotoxicity accompanied by activation of Hh signaling pathway. Meanwhile, genetic KO of Gli2 reduced DU-induced nephrotoxicity by normalizing biochemical indicators and reducing Hh pathway activation. Pharmacologic inhibition of Gli1/2 by Gant61 reduced DU induced cytotoxicity by inhibiting apoptosis, ROS formation and Hh pathway activation. However, overexpression of Gli2 aggravated DU-induced cytotoxicity by increasing the levels of apoptosis and ROS formation. Taken together, these results revealed that Hh signaling negatively regulated DU-inducted nephrotoxicity, and that inhibition of Gli2 might serve as a promising nephroprotective target for DU-induced kidney injury., (© 2024 Wiley Periodicals LLC.)

The influence of uranium (U) mining on the fungal diversity (FD) and communities (FC) structure was investigated in this work. Our results revealed that soil FC richness and FD indicators obviously decreased due to U, such as Chao1, observed OTUs and Shannon index (P<0.05). Moreover, the abundances of Mortierella, Gibberella, and Tetracladium were notably reduced in soil samples owing to U mining activities (P<0.05). In contrast, the abundances of Cadophora, Pseudogymnoascus, Mucor, and Sporormiella increased in all soil samples after U mining (P<0.05). Furthermore, U mining not only dramatically influenced the Plant&#95;Pathogen guild and Saprotroph and Pathotroph modes (P<0.05), but also induced the differentiation of soil FC and the enrichment of the Animal&#95;Pathogen-Soil&#95;Saprotroph and Endophyte guilds and Symbiotroph and Pathotroph Saprotroph trophic modes. In addition, various fungal populations and guilds were enriched to deal with the external stresses caused by U mining in different U mining areas and soil depths (P<0.05). Finally, nine U-tolerant fungi were isolated and identified with a minimum inhibitory concentration range of 400-600 mg/L, and their adsorption efficiency for U ranged from 11.6% to 37.9%. This study provides insights into the impact of U mining on soil fungal stability and the response of fungi to U mining activities, as well as aids in the screening of fungal strains that can be used to promote remediation of U mining sites on plateaus., 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.)

Background: Uranium exposure remains an important environmental legacy and physiological health concern, with hundreds of abandoned uranium mines located in the Southwestern United States largely impacting underserved indigenous communities. The negative effects of heavy metals on barrier permeability and inhibition of intestinal epithelial healing have been described; however, transcriptomic changes within the intestinal epithelial cells and impacts on lineage differentiation are largely unknown., Objectives: Herein, we sought to determine the molecular and cellular changes that occur in the colon in response to uranium bearing dust (UBD) exposure., Methods: Human colonoids from three biologically distinct donors were acutely exposed to UBD then digested for single cell RNA sequencing to define the molecular changes that occur to specific identities of colonic epithelial cells. Validation in colonoids was assessed using morphological and imaging techniques., Results: Human colonoids acutely exposed to UBD exhibited disrupted proliferation and hyperplastic differentiation of the secretory lineage cell, enteroendocrine cells (EEC). Single-cell RNA sequencing also showed more EEC subtypes present in UBD-exposed colonoids., Discussion: These findings highlight the significance of crypt-based proliferative cells and secretory cell differentiation using human colonoids to model major colonic responses to uranium-bearing particulate dust exposure. https://doi.org/10.1289/EHP13855.

Background: Humans are exposed to uranium (U) in a variety of applications. Both animal and observational human studies support an associated U nephrotoxicity. Few statistical syntheses of the human data have been performed and these analyses are limited in the types of exposures considered., Objectives: This study aims to evaluate the state of current evidence and to expand on existing meta-analyses by systematically evaluating kidney-associated causes of mortality in multiple U-exposed populations. This study also aims to evaluate the effect of U exposure on kidney function and biomarkers of kidney injury., Methods: The published and grey literature were systematically reviewed for studies that reported Standardized Mortality Ratios (SMR) for kidney cancer, chronic nephritis/nephrosis, all-cause mortality, diabetes, all circulatory/heart disease, and/or ischemic heart disease in U-exposed humans. Studies that reported kidney biomarker measures for U-exposed versus control subjects were identified separately., Results: 36 studies were included. The studies were parsed into subgroups based on setting of exposure. Analysis of kidney cancer and chronic nephritis/nephrosis mortality demonstrated an SMR of 0.93 (95CI: 0.82-1.05) and 0.82 (95CI: 0.70-0.96), respectively. The other clinical outcomes evaluated also demonstrated mortality deficits in exposed relative to unexposed individuals. Subgroup analyses demonstrated similar mortality deficits. Conversely, biomarker analyses suggested better kidney function in the controls, but none of these differences reached significance., Discussion: Given that most of the included mortality studies were conducted in occupational populations, the mortality deficits observed in our analyses were likely due to the healthy-worker effect. Additionally, our analyses of kidney biomarkers were severely limited by low precision due to a low number of available studies and small study-size. Future work needs to evaluate the progression of chronic and to end-stage kidney disease in community-based populations to better assess the full impact of prolonged chronic U exposure on kidney outcomes., 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 Inc. All rights reserved.)

In a longitudinal study of 6,158 Kuwaiti children, we selected 94 for salivary metabolomic analysis who were neither obese (by waist circumference) nor metabolic syndrome (MetS) positive (

Uranium accumulation in the kidneys and bones following internal contamination results in severe damage, emphasizing the pressing need for the discovery of actinide decorporation agents with efficient removal of uranium and low toxicity. In this work, cinnamic acid (3-phenyl-2-propenoic acid, CD), a natural aromatic carboxylic acid, is investigated as a potential uranium decorporation ligand. CD demonstrates markedly lower cytotoxicity than that of diethylenetriaminepentaacetic acid (DTPA), an actinide decorporation agent approved by the FDA, and effectively removes approximately 44.5% of uranyl from NRK-52E cells. More importantly, the results of the prompt administration of the CD solution remove 48.2 and 27.3% of uranyl from the kidneys and femurs of mice, respectively. Assessments of serum renal function reveal the potential of CD to ameliorate uranyl-induced renal injury. Furthermore, the single crystal of CD and uranyl compound (C 9 H 7 O 2 ) 2 ·UO 2 (denoted as UO 2 -CD) reveals the formation of uranyl dimers as secondary building units. Thermodynamic analysis of the solution shows that CD coordinates with uranyl to form a 2:1 molar ratio complex at a physiological pH of 7.4. Density functional theory (DFT) calculations further show that CD exhibits a significant 7-fold heightened affinity for uranyl binding in comparison to DTPA.

Diluted treated effluent from the McClean Lake uranium mill in northern Saskatchewan is released into Vulture Lake, which flows into the east basin of McClean Lake; this input could potentially cause a variety of disturbances to the aquatic systems. This study aimed to determine the potential effects of diluted effluent exposure (metals and major ions) on benthic macroinvertebrates in Vulture Lake and McClean Lake. Two monitoring locations located in Vulture Lake and eight in McClean Lake were used for collection water, sediment, and benthic macroinvertebrates. Complementary surface water bioassays were performed with larvae of the midge Chironomus dilutus using lake water from selected sites. Results indicated that total macroinvertebrate abundance and Margalef index (MI) did not follow the diluted effluent pattern. In addition, while the MI from artificial substrate samplers showed higher values in Vulture Lake and lower values at McClean Lake sites 4 and 5 (closer to effluent diffuser), the values recorded for sediment grab samples registered lower indices in Vulture Lake and higher values for sites 4 and 5. The final model from a Generalized Additive Modelling (GAM) approach suggested that electrical conductivity (EC), selenium (Se), and chloride (Cl) in water, and total organic carbon (TOC) and cadmium (Cd) in sediment are key variables that collectively may have influenced macroinvertebrate community composition at the study sites. Finally, across all test endpoints in the bioassays, exposure to lake water from Vulture Lake and McClean Lake had no statistically significant effects on C. dilutus., 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 Elsevier Inc. All rights reserved.)

Radionuclide uranium is a great threat to human health, due to its high chemical toxicity and radioactivity. Finding suitable uranium decorporation to reduce damage caused by uranium internal contamination is an important aspect of nuclear emergency response. However, the poor selectivity and/or high toxicity of the only excretory promoter approved by Food and Drug Administration (FDA) is an obvious disadvantage. Herein, we choose an edible natural product, the traditional Chinese medicine called Perilla frutescens (PF), which has wide sources and can be used as an excellent and effective uranyl decorporation. In vivo uranium decorporation assays illustrate the removal efficiency of uranium in kidney were 68.87% and 43.26%, in femur were 56.66% and 54.53%, by the test of prophylactic and immediate administration, respectively. Cell level experiments confirmed that it had better biocompatibility than CaNa 3 -DTPA (CaNa 3 -diethylenetriamine pentaacetate, a commercial actinide excretion agent). In vitro static adsorption experiments exhibited that its excellent selectivity sorption for uranyl. All those results findings would provide new research insights about natural product for uranyl decorporation., 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 Elsevier Ltd. All rights reserved.)

In a longitudinal study of 6,158 Kuwaiti children, we selected 94 for salivary metabolomic analysis who were neither obese (by waist circumference) nor metabolic syndrome (MetS) positive (<3 diagnostic features). Half (43) remained healthy for 2 years. The other half (51) were selected because they became obese and MetS positive 2 years later. In the half becoming obese, metabolomic analysis revealed that the level of salivary N1-Methyl-2-pyridone-5-carboxamide (2PY) had the highest positive association with obesity (p = 0.0003, AUC = 0.72) of 441 salivary biochemicals detected. 2PY is a recognized uremic toxin. Also, 2PY has been identified as a biomarker for uranium uptake. Considering that a relatively recent military conflict with documented uranium contamination of the area suggests that this weight gain could be a toxicological effect of long-time, low-level uranium ingestion. Comparison of salivary 2PY in samples from the USA and Kuwait found that only Kuwait samples were significantly related to obesity. Also, the geographic distribution of both reported soil radioactivity from 238U and measured salivary 2PY was highest in the area where military activity was highest. The prevalence pattern of adult diabetes in Kuwait suggests that a transient diabetogenic factor has been introduced into the Kuwaiti population. Although we did not measure uranium in our study, the presence of a salivary biomarker for uranium consumption suggests potential toxicity related to obesity in children. [ABSTRACT FROM AUTHOR]

Background and Aims: The global incidence of renal cell cancer is increasing annually and the causes are multifactorial. Early diagnosis and successful urological procedures with partial or total nephrectomy can be life-saving. However, only up to 10% of RCC patients present with characteristic clinical symptoms. Over 60% are detected incidentally in routine ultrasound examination. The question of screening and preventive measures greatly depends on the cause of the tumor development. For the latter reason, this review focuses on etiology, pathophysiology and risk factors for renal neoplasm. Methods: A literature search using the databases Medscape, Pubmed, UpToDate and EBSCO from 1945 to 2015. Results and Conclusions: Genetic predisposition/hereditary disorders, obesity, smoking, various nephrotoxic industrial chemicals, drugs and natural/manmade radioactivity all contribute and enviromental risks are a serious concern in terms of prevention and the need to screen populations at risk. Apropos treatment, current oncological research is directed to blocking cancer cell division and inhibiting angiogenesis based on a knowledge of molecular pathways.

Uranium has both radiotoxicity and chemical toxicity. Low enriched uranium is mainly chemically toxic, the kidney is the target organ of uranium chemical toxicity. However, due to the differences among species and the mixed effects of chemical toxicity and radiotoxicity, the dose effect relationship of uranium is not clear, and the current standards in China do not provide chemical toxicity limits for uranium workplaces. This paper reviews the data of acute and chronic human uranium exposure, dose effect relationship and renal injury risk prediction literature at home and abroad, providing reference for the health protection of uranium workers and the establishment of chemical limits in uranium workplaces.

A variety of processes, both natural and anthropogenic, can have a negative impact on surface waters, which in turn can be detrimental to human and environmental health. Few studies have considered the ecotoxicological impacts of concurrently occurring contaminants, and that is particularly true for mixtures that include contaminants of emerging concern (CEC). Motivated by this knowledge gap, the present study considers the potential ecotoxicity of environmentally relevant contaminants in the representative aquatic plant Lemna minor (common duckweed), a model organism. More specifically, biological effects associated with exposure of L. minor to a ubiquitous radionuclide (uranium [U]) and a fluorinated organic compound (perfluorooctanoic acid [PFOA], considered a CEC), alone and in combination, were monitored under controlled laboratory conditions. Lemna minor was grown for 5 days in small, aerated containers. Each treatment consisted of four replicates with seven plants each. Treatments were 0, 0.3, and 3 ppb PFOA; 0, 0.5, and 5 ppb U; and combinations of these. Plants were observed daily for frond number and signs of chlorosis and necrosis. Other biological endpoints examined at the conclusion of the experiment were chlorophyll content and antioxidant capacity. In single-exposure experiments, a slight stimulatory effect was observed on frond number at 0.3 ppb PFOA, whereas both concentrations of U had a detrimental effect on frond number. In the dual-exposure experiment, the combinations with 5 ppb U also had a detrimental effect on frond number. Results for chlorophyll content and antioxidant capacity were less meaningful, suggesting that environmentally relevant concentrations of PFOA and U have only subtle effects on L. minor growth and health status. Environ Toxicol Chem 2023;42:2412-2421. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC., (© 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.)

Abstract Uranium toxicity depends on its chemical properties rather than on its radioactivity and involves its interaction with macromolecules. Here, a systematic survey of the structural features of the uranyl sites observed in protein crystal structures deposited in the Protein Data Bank is reported. Beside the two uranyl oxygens, which occupy the axial positions, uranium tends to be coordinated by five other oxygen atoms, which occupy the equatorial vertices of a pentagonal bipyramid. Even if one or more of these equatorial positions are sometime empty, they can be occupied only by oxygen atoms that belong to the carboxylate groups of Glu and Asp side-chains, usually acting as monodentate ligands, to water molecules, or to acetate anions. Although several uranium sites appear undefined or unrefined, with a single uranium atom that lacks the two uranyl oxygen atoms, this problem seems to become less frequent in recent years. However, it is clear that the crystallographic refinements of the uranyl sites are not always well restrained and a better parametrization of these restraints seems to be necessary. Graphical abstract Uranium toxicity depends on its chemical properties rather than on its radioactivity and involves its interaction with macromolecules. Here, a systematic survey of the structural features of the uranyl sites observed in protein crystal structures deposited in the Protein Data Bank is reported. Unlabelled Image Highlights • Uranium chemical toxicity is related to uranium-protein interactions. • Stereochemistry of uranyl interaction with protein • Only water and carboxylate oxygens as donor atoms • Preferred stereochemistry: pentagonal bipyramid • Few examples of uranyl aggregation [ABSTRACT FROM AUTHOR]

A small group of Gulf War I veterans wounded in depleted uranium (DU) friendly-fire incidents have been monitored in a clinical surveillance program since 1993. During the spring of 2017, 42 members of the cohort were evaluated with a protocol which includes exposure monitoring for total and isotopic uranium concentrations in urine and a comprehensive assessment of health outcomes including measures of bone metabolism, and for participants >50 years, bone mineral density (BMD) determination. Elevated urine U concentrations were observed in cohort members with retained DU shrapnel fragments. Only the mean serum estradiol concentration, a marker of bone metabolism, was found to be significantly different for lower-vs- higher urine U (uU) cohort sub-groups. For the first time, a significant deficit in BMD was observed in the over age 50, high uU sub-group. After more than 25 years since first exposure to DU, an aging cohort of military veterans continues to exhibit few U-related adverse health effects in known target organs of U toxicity. The new finding of reduced BMD in older cohort members, while biologically plausible, was not suggested by other measures of bone metabolism in the full (all ages) cohort, as these were predominantly within normal limits over time. Only estradiol was recently found to display a difference as a function of uU grouping. As BMD is further impacted by aging and the U-burden from fragment absorption accrues in this cohort, a U effect may be clarified in future surveillance visits. [ABSTRACT FROM AUTHOR]

Natural deposits and human-caused releases of uranium have led to its contamination in the nature. Toxic environmental contaminants such as uranium that harm cerebral processes specifically target the brain. Numerous experimental researches have shown that occupational and environmental uranium exposure can result in a wide range of health issues. According to the recent experimental research, uranium can enter the brain after exposure and cause neurobehavioral problems such as elevated motion related activity, disruption of the sleep-wake cycle, poor memory, and elevated anxiety. However, the exact mechanism behind the factor for neurotoxicity by uranium is still uncertain. This review primarily aims on a brief overview of uranium, its route of exposure to the central nervous system, and the likely mechanism of uranium in neurological diseases including oxidative stress, epigenetic modification, and neuronal inflammation has been described, which could present the probable state-of-the-art status of uranium in neurotoxicity. Finally, we offer some preventative strategies to workers who are exposed to uranium at work. In closing, this study highlights the knowledge of uranium's health dangers and underlying toxicological mechanisms is still in its infancy, and there is still more to learn about many contentious discoveries. • Uranium exposure can cause several health issues. • Uranium can enter the central nervous system either via BBB or olfactory bulb. • Uranium can trigger several neurodegenerative diseases. • The probable mechanism of action of Uranium exposure in the central nervous system. [ABSTRACT FROM AUTHOR]

Uranium and fluoride enrichment in groundwater along alluvial plains pose a severe threat to living beings like cancer, fluorosis and crop yield as witnessed around semi-arid southwest Punjab, India. In-situ groundwater was examined for major ions, stable isotopes and trace metals to understand the hydrogeochemical processes, contaminant origin and health risks around SW Punjab, India. Groundwater from a freshly drilled bore well is found to be hard, alkaline, and saline with total dissolved solids and salinity up to 1300 and 1500 mg L−1, respectively. Fluoride (up to 4 mg L−1) and uranium (up to 90.07 μg L−1) contents exceed permissible limits in most samples and originated from fertilizer inputs and aquifer leaching. Uranium contents decline with depth, while fluoride remains invariable. Decreased U contents are inferred to be caused by U(VI) reduction to U(IV) as evidenced by an increase in Fe2+ vs. Fe3+, S2− vs. S6+ and N3− vs. N5+ with depth. NaHCO 3 , NaCl + NaHCO 3 and NaCl are the dominant water types for shallow (<38 m), intermediate (49–83 m) and deeper groundwater (105–128 m) with Na+ and HCO 3 − as the dominant cations and anions, respectively. Silicate weathering majorly controlled the groundwater geochemistry together with a partial contribution from cation exchange processes. Unsuitability for drinking and irrigation use is envisaged for all depths, while deeper groundwater is safe in regard to radiological risk. δ18O and δD variations are suggestive of evaporation dominance in shallow groundwater, while intermediate groundwater witness canal and groundwater mixing and deeper groundwater are recharged through higher altitude. [Display omitted] • Alkaline and saline groundwater with high dissolved solids and unsafe for direct use. • Na+, HCO 3 − and Cl− constitute the dominant ions with NaHCO 3 and NaCl water types. • Silicate weathering and cation exchange dominantly control hydrogeochemistry. • δ18O/δD signify evaporation, canal-groundwater mixing and high altitude recharge. • Fertilizer inputs and aquifer soil leaching combinedly contribute excess U and F. [ABSTRACT FROM AUTHOR]

The contamination of uranium in aquatic ecosystems has raised growing global concern. However, the understanding of its chronic effects on aquatic organisms is limited, particularly with regards to transgenerational toxicity. In this study, we evaluated the maternal transfer risk of uranium using zebrafish. Sexually mature female zebrafish were exposed to 2 and 20 ng/g of uranium-spiked food for 28 days. The induced bioconcentration, thyroid disruption, and oxidative stress in both the adults (F0) and their embryos (F1) were further investigated. Element analysis showed that uranium was present in both F0 and F1, with higher concentrations observed in F1, indicating significant maternal offloading to the offspring. Meanwhile, an increased malformation and decreased swim speed were observed in the F1. Thyroid hormone analysis revealed significant decreases in the levels of triiodothyronine (T3) in both the F0 adults and F1 embryos, but thyroxine (T4) was not significantly affected. Additionally, the activities of antioxidant defenses, including catalase (CAT) and superoxide dismutase (SOD), and the expression of glutathione (GSH) and malondialdehyde (MDA) were significantly altered in the F0 and F1 larvae at 120 hpf. The hypothalamic-pituitary-thyroid (HPT) axis, oxidative stress, and apoptosis-related gene transcription expression were also significantly affected in both generations. Taken together, these findings highlight the importance of considering maternal transfer in uranium risk assessments., 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.)

Uranium is a contaminate in the underground water in many regions of the world, which poses health risks to the local populations through drinking water. Although the health hazards of natural uranium have been concerned for decades, the controversies about its detrimental effects continue at present since it is still unclear how uranium interacts with molecular regulatory networks to generate toxicity. Here, we integrate transcriptomic and metabolomic methods to unveil the molecular mechanism of lipid metabolism disorder induced by uranium. Following exposure to uranium in drinking water for twenty-eight days, aberrant lipid metabolism and lipogenesis were found in the liver, accompanied with aggravated lipid peroxidation and an increase in dead cells. Multi-omics analysis reveals that uranium can promote the biosynthesis of unsaturated fatty acids through dysregulating the metabolism of arachidonic acid (AA), linoleic acid, and glycerophospholipid. Most notably, the disordered metabolism of polyunsaturated fatty acids (PUFAs) like AA may contribute to lipid peroxidation induced by uranium, which in turn triggers ferroptosis in hepatocytes. Our findings highlight disorder of lipid metabolism as an essential toxicological mechanism of uranium in the liver, offering insight into the health risks of uranium in drinking water., 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 Elsevier Ltd. All rights reserved.)

Uranium (U) is a well-known nephrotoxicant which forms precipitates in the lysosomes of renal proximal tubular epithelial cells (PTECs) after U-exposure at a cytotoxic dose. However, the roles of lysosomes in U decorporation and detoxification remain to be elucidated. Mucolipin transient receptor potential channel 1 (TRPML1) is a major lysosomal Ca 2+ channel regulating lysosomal exocytosis. We herein demonstrate that the delayed administration of the specific TRPML1 agonist ML-SA1 significantly decreases U accumulation in the kidney, mitigates renal proximal tubular injury, increases apical exocytosis of lysosomes and reduces lysosomal membrane permeabilization (LMP) in renal PTECs of male mice with single-dose U poisoning or multiple-dose U exposure. Mechanistic studies reveal that ML-SA1 stimulates intracellular U removal and reduces U-induced LMP and cell death through activating the positive TRPML1-TFEB feedback loop and consequent lysosomal exocytosis and biogenesis in U-loaded PTECs in vitro. Together, our studies demonstrate that TRPML1 activation is an attractive therapeutic strategy for the treatment of U-induced nephrotoxicity., (© 2023. The Author(s).)

The intricate dynamics of inorganic polyphosphate (polyP) in response to phosphorus (P) limitation and metal exposure typical of contaminated aquatic environments is poorly understood. Cyanobacteria are important primary producers in aquatic environments that are exposed to P stringency as well as metal contamination. There is a growing concern regarding migration of uranium, generated as a result of anthropogenic activities, into the aquatic environments owing to high mobility and solubility of stable aqueous complexes of uranyl ions. The polyP metabolism in cyanobacteria in context of uranium (U) exposure under P limitation has hardly been explored. In this study, we analyzed the polyP dynamics in a marine, filamentous cyanobacterium Anabaena torulosa under combination of variable phosphate concentrations (overplus and deficient) and uranyl exposure conditions typical of marine environments. Polyphosphate accumulation (polyP + ) or deficient (polyP - ) conditions were physiologically synthesized in the A. torulosa cultures and were ascertained by (a) toulidine blue staining followed by their visualization using bright field microscopy and (b) scanning electron microscopy in combination with energy dispersive X-ray spectroscopy (SEM/EDX). On exposure to 100 μM of uranyl carbonate at pH 7.8, it was observed that the growth of polyP + cells under phosphate limitation was hardly affected and these cells exhibited larger amounts of uranium binding as compared to polyP - cells of A. torulosa. In contrast, the polyP - cells displayed extensive lysis when exposed to similar U exposure. Our findings suggest that polyP accumulation played an important role in conferring uranium tolerance in the marine cyanobacterium, A. torulosa. The polyP-mediated uranium tolerance and binding could serve as a suitable strategy for remediation of uranium contamination in aquatic environments., 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 Elsevier Ltd. All rights reserved.)

Uranium and thorium are heavy metals, and all of their isotopes are radioactive, so it is impossible to study chemical effects entirely independent of the radiation effects. In the present study, we tried to compare the chemo- and radiotoxicity of both metals, taking into account deterministic radiation damages reflected by acute radiation sickness and stochastic radiation damages leading to long-term health impairments (e.g., tumor induction). We made at first a literature search on acute median lethal doses that may be expected to be caused by chemical effects, as even acute radiation sickness as a manifestation of acute radiotoxicity occurs with latency. By simulations based on the biokinetic models of the International Commission on Radiological Protection and using the Integrated Modules for Bioassay Analysis software, we determined the amounts of uranium at different enrichment grades and thorium-232 leading to a short-term red bone marrow equivalent dose of 3.5 Sv considered to cause 50% lethality in humans. Different intake pathways for incorporation were considered, and values were compared to the mean lethal doses by chemotoxicity. To assess stochastic radiotoxicity, we calculated the uranium and thorium amounts leading to a committed effective dose of 200 mSv that is often considered critical. Mean lethal values for uranium and thorium are in the same order of magnitude so that the data do not give evidence for substantial differences in acute chemical toxicity. When comparing radiotoxicity, the reference units (activity in Bq or weight in g) must always be taken into account. The mean lethal equivalent dose to the red bone marrow of 3.5 Sv is reached by lower activities of thorium compared to uranium in soluble compounds. However, for uranium as well as thorium-232, acute radiation sickness is expected only after incorporation of amounts exceeding the mean lethal doses by chemotoxicity. Thus, acute radiation sickness is not a relevant clinical issue for either metal. Concerning stochastic radiation damages, thorium-232 is more radiotoxic than uranium if incorporating the same activities. Using weight units for comparison show that for soluble compounds, thorium-232 is more radiotoxic than low-enriched uranium in the case of ingestion but even more toxic than high-enriched uranium after inhalation or intravenous administration. For insoluble compounds, the situation differs as the stochastic radiotoxicity of thorium-232 ranges between depleted and natural uranium. For acute effects, the chemotoxicity of uranium, even at high enrichment grades, as well as thorium-232 exceeds deterministic radiotoxicity. Simulations show that thorium-232 is more radiotoxic than uranium expressed in activity units. If the comparison is based on weight units, the rankings depend on the uranium enrichment grades and the route of intake., (© 2023. The Author(s).)

Uranium (U) phytotoxicity is an inherently difficult problem in the phytoremediation of U-contaminated environments. Plant chelating and antioxidant systems play an authoritative role in resistance to abiotic stress. To reveal the toxicity of U, the changes of chelating system, osmoregulatory substances and antioxidant systems in Vicia faba roots were studied after short-term (24 h) U exposure. The results indicated that the development of lateral roots and root activity of V. faba were significantly inhibited with U accumulation. Compared with the control, plant chelating systems showed significant positive effects after U exposure (15 - 25 μM). Osmoregulatory substances (proline and soluble protein) increasingly accumulated in roots with increasing U concentration, and O 2 - and H 2 O 2 rapidly accumulated after U exposure (15 - 25 μM). Thus, the contents of malondialdehyde (MDA), a marker of lipid peroxidation, were also significantly increased. Antioxidant systems were activated after U exposure but were inhibited at higher U concentrations (15 - 25 μM). In summary, although the chelating, osmotic regulation and antioxidant systems in V. faba were activated after short-term U exposure, the antioxidases (CAT, SOD and POD) were inhibited at higher U concentrations (15 - 25 μM). Therefore, the root cells were severely damaged by peroxidation, which eventually resulted in inhibited activity and arrested root development., (© 2023. The Author(s) under exclusive licence to The Botanical Society of Japan.)

Uranium is chemo- and radiotoxic element which can cause multifactorial health hazards. Natural and anthropogenic uranium contamination raises concerns about potential public health problems. Natural contamination plays a significant role with regard to uranium exposure in the general population, whereas anthropogenic contamination leads to occupational uranium exposure, particularly in nuclear industry workers. In this review, we present a state-of-the-art status concerning uranium-induced health risks with a focus on epidemiological findings of uranium processing and enrichment plant workers. We provide a general overview of physicochemical properties of uranium and analytical methods for measuring or monitoring uranium, describe environmental and occupational exposure scenarios, and discuss the challenges for objectively investigating risks from uranium exposure., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Background A small group of Gulf War I veterans wounded in depleted uranium (DU) friendly-fire incidents have been monitored for health changes in a clinical surveillance program at the Veterans Affairs Medical Center, Baltimore since 1994. Methods During the spring of 2015, an in-patient clinical surveillance protocol was performed on 36 members of the cohort, including exposure monitoring for total and isotopic uranium concentrations in urine and a comprehensive assessment of health outcomes. Results On-going mobilization of U from embedded fragments is evidenced by elevated urine U concentrations. The DU isotopic signature is observed principally in participants possessing embedded fragments. Those with only an inhalation exposure have lower urine U concentration and a natural isotopic signature. Conclusions At 25 years since first exposure to DU, an aging cohort of military veterans continues to show no U-related health effects in known target organs of U toxicity. As U body burden continues to accrue from in-situ mobilization from metal fragment depots, and increases with exposure duration, critical tissue-specific U concentration thresholds may be reached, thus recommending on-going surveillance of this veteran cohort. [ABSTRACT FROM AUTHOR]

Background and Aims. The global incidence of renal cell cancer is increasing annually and the causes are multifactorial. Early diagnosis and successful urological procedures with partial or total nephrectomy can be life-saving. However, only up to 10% of RCC patients present with characteristic clinical symptoms. Over 60% are detected incidentally in routine ultrasound examination. The question of screening and preventive measures greatly depends on the cause of the tumor development. For the latter reason, this review focuses on etiology, pathophysiology and risk factors for renal neoplasm. Methods. A literature search using the databases Medscape, Pubmed, UpToDate and EBSCO from 1945 to 2015. Results and Conclusions. Genetic predisposition/hereditary disorders, obesity, smoking, various nephrotoxic industrial chemicals, drugs and natural/manmade radioactivity all contribute and enviromental risks are a serious concern in terms of prevention and the need to screen populations at risk. Apropos treatment, current oncological research is directed to blocking cancer cell division and inhibiting angiogenesis based on a knowledge of molecular pathways. [ABSTRACT FROM AUTHOR]

A combination of synchrotron-based elemental analysis and acute toxicity tests was used to investigate the biodistribution and adverse effects in Daphnia magna exposed to uranium nanoparticle (UNP, 3-5 nm) suspensions or to uranium reference (U ref ) solutions. Speciation analysis revealed similar size distributions between exposures, and toxicity tests showed comparable acute effects (UNP LC 50 : 402 μg L -1 [336-484], U ref LC 50 : 268 μg L -1 [229-315]). However, the uranium body burden was 3- to 5-fold greater in UNP-exposed daphnids, and analysis of survival as a function of body burden revealed a ∼5-fold higher specific toxicity from the U ref exposure. High-resolution X-ray fluorescence elemental maps of intact, whole daphnids from sublethal, acute exposures of both treatments revealed high uranium accumulation onto the gills (epipodites) as well as within the hepatic ceca and the intestinal lumen. Uranium uptake into the hemolymph circulatory system was inferred from signals observed in organs such as the heart and the maxillary gland. The substantial uptake in the maxillary gland and the associated nephridium suggests that these organs play a role in uranium removal from the hemolymph and subsequent excretion. Uranium was also observed associated with the embryos and the remnants of the chorion, suggesting uptake in the offspring. The identification of target organs and tissues is of major importance to the understanding of uranium and UNP toxicity and exposure characterization that should ultimately contribute to reducing uncertainties in related environmental impact and risk assessments.

During nuclear fuel processing, workers can potentially be exposed to repeated inhalations of uranium compounds. Uranium nephrotoxicity is well documented after acute uranium intake, but it is controversial after long-term or protracted exposure. This study aims to analyze the nephrotoxicity threshold after repeated uranium exposure through upper airways and to investigate the resulting uranium biokinetics in comparison to reference models. Mice (C57BL/6J) were exposed to uranyl nitrate (0.03-3 mg/kg/day) via intranasal instillation four times a week for two weeks. Concentrations of uranium in urines and tissues were measured at regular time points (from day 1 to 91 post-exposure). At each exposure level, the amount of uranium retained in organs/tissues (kidney, lung, bone, nasal compartment, carcass) and excreta (urine, feces) reflected the two consecutive weeks of instillation except for renal uranium retention for the highest uranium dose. Nephrotoxicity biomarkers, KIM-1, clusterin and osteopontin, are induced from day 4 to day 21 and associated with changes in renal function (arterial fluxes) measured using non-invasive functional imaging (Doppler-ultrasonography) and confirmed by renal histopathological analysis. These results suggest that specific biokinetic models should be developed to consider altered uranium excretion and retention in kidney due to nephrotoxicity. The threshold is between 0.25 and 1 mg/kg/day after repeated exposure to uranium via upper airways., (© 2023. The Author(s).)

The kidney is the main organ affected by acute depleted uranium (DU) toxicity. The mechanism of nephrotoxicity induced by DU is complex and needs to be further explored. This study aimed to elucidate the function of mitochondrial dysfunction in nephrotoxicity generated by DU and confirm the latent mechanism. We verified that DU (2.5-10 mg/kg) caused mitochondrial dysfunction in male rat kidneys and decreased ATP content and the mitochondrial membrane potential. In addition, melatonin (20 mg/kg), as an antioxidant, alleviated DU-induced oxidative stress and mitochondrial dysfunction in male rats, further reducing kidney damage caused by DU. These results indicate that mitochondrial dysfunction plays a vital role in DU nephrotoxicity. When ethylmalonic encephalopathy 1 (ETHE1) was knocked down, DU-induced oxidative stress and mitochondrial dysfunction were increased, and renal injury was aggravated. When exogenous ETHE1 protein was applied to renal cells, the opposite changes were observed. We also found that ETHE1 knockdown increased the expression of NF-E2-related factor 2 (Nrf2), a vital oxidative stress regulator, and its downstream molecules heme oxygenase-1 (HO-1) and NADPH quinone oxidoreductase 1 (NQO1). Nrf2 knockout also aggravated DU-induced oxidative stress, mitochondrial dysfunction, and kidney damage. In conclusion, DU causes oxidative stress and antioxidant defense imbalance in renal cells through the ETHE1/Nrf2 pathway, further causing mitochondrial dysfunction and ultimately leading to nephrotoxicity., 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 Elsevier B.V. All rights reserved.)

Uranium contamination is a widespread problem caused by natural and anthropogenic activities. Although microorganisms thrive in uranium-contaminated environments, little is known about the actual molecular mechanisms mediating uranium resistance. Here, we investigated the resistance mechanisms driving the adaptation of Cupriavidus metallidurans NA4 to toxic uranium concentrations. We selected a spontaneous mutant able to grow in the presence of 1 mM uranyl nitrate compared to 250 µM for the parental strain. The increased uranium resistance was acquired via the formation of periplasmic uranium-phosphate precipitates facilitated by the increased expression of a genus-specific small periplasmic protein, PrsQ 2 , regulated as non-cognate target of the CzcS 2 -CzcR 2 two-component system. This study shows that bacteria can adapt to toxic uranium concentrations and explicates the complete genetic circuit behind the adaptation., 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 B.V. All rights reserved.)

Uranium (U) toxicity is known to be highly dependent on U speciation and bioavailability. To assess the impact of uranium on plants, a growth inhibition test was set up in the freshwater macrophyte Lemna minor . First growth media with different compositions were tested in order to find a medium fit for testing U toxicity in L . minor . Following arguments were used for medium selection: the ability to sustain L . minor growth, a high solubility of U in the medium and a high percentage of the more toxic U-species namely UO 2 2 + . Based on these selection criteria a with a low phosphate concentration of 0.5 mg L −1 and supplemented with 5 mM MES (2-(N-morpholino)ethanesulfonic acid) to ensure pH stability was chosen. This medium also showed highest U toxicity compared to the other tested media. Subsequently a full dose response curve for U was established by exposing L . minor plants to U concentrations ranging from 0.05 μM up to 150 μM for 7 days. Uranium was shown to adversely affect growth of L . minor in a dose dependent manner with EC10, EC30 and EC50 values ranging between 1.6 and 4.8 μM, 7.7–16.4 μM and 19.4–37.2 μM U, respectively, depending on the growth endpoint. Four different growth related endpoints were tested: frond area, frond number, fresh weight and dry weight. Although differences in relative growth rates and associated ECx-values calculated on different endpoints are small (maximal twofold difference), frond area is recommended to be used to measure U-induced growth effects as it is a sensitive growth endpoint and easy to measure in vivo allowing for measurements over time. [ABSTRACT FROM AUTHOR]

Anthropogenic activities have led to a widespread uranium (U) contamination in many countries. The toxic effects of U at the cellular level have mainly been investigated at a pH around 5.5, the optimal pH for hydroponically grown plants. However, since the speciation of U, and hence its toxicity, is strongly dependent on environmental factors such as the pH, it is important to investigate the effects of U at different environmentally relevant pH levels. Although U is poorly translocated from the roots to the shoots, resulting in a low U concentration in the leaves, it has been demonstrated that toxic effects in the leaves were already visible after 1 day exposure at pH 5.5, although only when exposed to relatively high U concentrations (100 μM). Therefore, the present study aimed to analyse the effects of different U concentrations (ranging from 0 to 100 μM) at pH 4.5 in leaves of Arabidopsis thaliana plants. Results indicate that U induces early senescence in A. thaliana leaves as was suggested by a decreased expression of CAT2 accompanied by an induction of CAT3 expression, a decreased CAT capacity and an increased lipid peroxidation. In addition, miRNA398b/c is involved in the regulation of the SOD response in the leaves. As such, an increased MIR398b/c expression was observed leading to a decreased transcript level of CSD1 / 2 . Finally, the biosynthesis of ascorbate was induced after U exposure. This can point towards an important role for this metabolite in the scavenging of reactive oxygen species under U stress. [ABSTRACT FROM AUTHOR]

Uranium (U) is a nonessential and toxic heavy metal and radioactive element. Nitric oxide (NO) and hydrogen peroxide (H 2 O 2 ) are intimately involved in the growth, development and metabolic function of plant cells. In addition to possible toxic activities, a role for these signalling molecules in the regulation of plant responses to toxic metals has been proposed. Here, we investigated the synthesis of NO and H 2 O 2 in Arabidopsis thaliana seedlings exposed to 25 μM U. We demonstrated that U induces NO and H 2 O 2 production in the roots and leaves. Addition of the NO releasing compound, sodium nitroprusside (SNP) as well as the NO synthase inhibitor (L-NAME) to the plants, resulted in a decrease of the U-induced NO production and both alleviated U toxicity as indicated by plant growth (leaf area and biomass). Treatment with L-NAME further resulted in the disappearance of the U-induced H 2 O 2 in the shoots of the plants. It appears that generation of NO and H 2 O 2 is intimately linked in the toxicity response of U-exposed A. thaliana plants. [ABSTRACT FROM AUTHOR]

The chemical speciation of uranium (U), and hence its toxicity, is strongly dependent on pH. However, oxidative stress responses after U exposure have mainly been investigated in Arabidopsis thaliana plants at pH 5.5, the ideal pH for growing plants in a hydroponic setup. As the pH of pore water can vary strongly, the aim of this study is to investigate oxidative stress responses induced in roots of A. thaliana plants exposed to different U concentrations at pH 4.5 and hence at a high free uraynl (UO 2 2+ ) concentration. In addition to analyzing growth reduction, effects were analysed at enzyme, metabolite and genetic level. Results indicate that U is highly toxic at low pH resulting in a significant decrease in fresh weight (EC50 value for root growth reduction: 28.14 ± 1.59 μM U). In addition, no intact RNA could be extracted from the roots exposed to 75 and 100 μM U and the ascorbate concentrations could not be determined in roots exposed to 50, 75 or 100 μM U indicating that the roots are seriously damaged. Concerning the antioxidative defence system, the involvement of miRNA398b/c in the regulation of the superoxide dismutase (SOD) response was observed after U exposure. As such, a significant increase in MIR398b / c expression was observed, accompanied by a decreased copper/zinc SOD ( CSD1 / 2 ) expression. The latter was compensated by an increased expression of iron SOD ( FSD1 ) to maintain the SOD capacity in the plastids. While the involvement of miRNA398b/c was already reported before under copper or cadmium stress, this is the first time that it is reported for U. [ABSTRACT FROM AUTHOR]

To evaluate the environmental impact of uranium (U) contamination, it is important to investigate the effects of U at ecologically relevant conditions. Since U speciation, and hence its toxicity, strongly depends on environmental pH, the present study aimed to investigate dose-dependent effects of U at pH 7.5. Arabidopsis thaliana plants (Mouse-ear Cress) were exposed for three days to different U concentrations at pH 7.5. In the roots, the increased capacities of ascorbate peroxidase and glutathione reductase indicate an important role for the ascorbate-glutathione cycle during U-induced stress. However, a significant decrease in the ascorbate redox state was observed after exposure to 75 and 100 µM U, indicating that those roots are severely stressed. In accordance with the roots, the ascorbate-glutathione cycle plays an important role in the antioxidative defence systems in A. thaliana leaves exposed to U at pH 7.5 as the ascorbate and glutathione biosynthesis were upregulated. In addition, small inductions of enzymes of the antioxidative defence system were observed at lower U concentrations to counteract the U-induced stress. However, at higher U concentrations it seems that the antioxidative defence system of the leaves collapses as reductions in enzyme activities and gene expression levels were observed. [ABSTRACT FROM AUTHOR]