Biological effects of molybdenum(IV) sulfide nanoparticles and microparticles in the rat after repeated intratracheal administration.

In this study, molybdenum(IV) sulfide (MoS2 ) nanoparticles (97 ± 32 nm) and microparticles (1.92 ± 0.64 µm) stabilized with poly (vinylpolypyrrolidone) (PVP) were administered intratracheally to male and female rats (dose of 1.5 or 5 mg/kg bw), every 14 days for 90 days (seven administrations in total). Blood parameters were assessed during and at the end of the study (hematology, biochemistry including glucose, albumins, uric acid, urea, high density lipoprotein HDL, total cholesterol, triglycerides, aspartate transaminase, and alanine transaminase ALT). Bronchoalveolar lavage fluid (BALF) analyses included cell viability, biochemistry (total protein concentration, lactate dehydrogenase, and glutathione peroxidase activity), and cytokine levels (tumor necrosis factor α, TNF-α, macrophage inflammatory protein 2-alpha, MIP-2, and cytokine-induced neutrophil chemoattractant-2, CINC-2). Tissues were subjected to routine histopathological and electron microscopy (STEM) examinations. No overt signs of chronic toxicity were observed. Differential cell counts in BALF revealed no significant differences between the animal groups. An increase in MIP-2 and a decrease in TNF-α were observed in BALF in the exposed males. The histopathological changes in the lung evaluated according to a developed classification system (based on severity of inflammation, range 0-4, with 4 indicating the most severe changes) showed average histopathological score of 1.33 for animals exposed to nanoparticles and microparticles at the lower dose, 1.72 after exposure to nanoparticles at the higher dose, and 2.83 for animals exposed to microparticles at the higher dose. In summary, it was shown that nanosized and microsized MoS2 can trigger dose-dependent inflammatory reactions in the lungs of rats after multiple intratracheal instillation irrespective of the animal sex. Some evidence indicates a higher lung pro-inflammatory potential of the microform.

Human molybdenum exposure risk in industrial regions of China: New critical effect indicators and reference dose.

Evidence increasingly suggests molybdenum exposure at environmental levels is still associated with adverse human health, emphasizing the necessity to establish a more protective reference dose (RfD). Herein, we conducted a study measuring 15 urinary metals and 30 clinical health indicators in 2267 participants residing near chemical enterprises across 11 Chinese provinces to investigate their relationships. The kidney and cystatin-C emerged as the most sensitive organ and critical effect indicator of molybdenum exposure, respectively. Odds of cystatin-C-defined chronic kidney disease (CKD) in the highest quantile of molybdenum exposure significantly increased by 133.5% (odds ratio [OR]: 2.34, 95% CI: 1.78, 3.11) and 75.8% (OR: 1.76, 95% CI: 1.24, 2.49) before and after adjusting for urinary 14 metals, respectively. Intriguingly, cystatin-C significantly mediated 15.9-89.5% of molybdenum's impacts on liver and lung function, suggesting nephrotoxicity from molybdenum exposure may trigger hepatotoxicity and pulmonary toxicity. We derived a new RfD for molybdenum exposure (0.87 µg/kg-day) based on cystatin-C-defined estimated glomerular filtration rate by employing Bayesian Benchmark Dose modeling analysis. This RfD is significantly lower than current exposure guidance values (5-30 µg/kg-day). Remarkably, >90% of participants exceeded the new RfD, underscoring the significant health impacts of environmental molybdenum exposure on populations in industrial regions of China.

Role of PLC/IP3 /IP3 R axis in excess molybdenum exposure induced apoptosis in duck renal tubular epithelial cells.

Excess molybdenum (Mo) is harmful to animals, but its nephrotoxicity has not been comprehensively explained. To appraise the influences of excess Mo on Ca homeostasis and apoptosis via PLC/IP3 /IP3 R axis, primary duck renal tubular epithelial cells were exposed to 480 µM and 960 µM Mo, and joint of 960 µM Mo and 10 µM 2-APB or 0.125 µM U-73122 for 12 h (U-73122 pretreated for 1 h), respectively. The data revealed that the increment of [Ca2+ ]c induced by Mo mainly originated from intracellular Ca storage. Mo exposure reduced [Ca2+ ]ER , elevated [Ca2+ ]mit , [Ca2+ ]c , and the expression of Ca homeostasis-related factors (Calpain, CaN, CRT, GRP94, GRP78 and CaMKII). 2-APB could effectively reverse subcellular Ca2+ redistribution by inhibiting IP3 R, which confirmed that [Ca2+ ]c overload induced by Mo originated from ER. Additionally, PLC inhibitor U-73122 remarkably mitigated the change, and dramatically reduced the number of apoptotic cells, the expression of Bak-1, Bax, cleaved-Caspase-3/Caspase-3, and notably increased the expression of Bcl-xL, Bcl-2, and Bcl-2/Bax ratio. Overall, the results confirmed that the Ca2+ liberation of ER via PLC/IP3 /IP3 R axis was the main cause of [Ca2+ ]c overload, and then stimulated apoptosis in duck renal tubular epithelial cells.

Molybdenum and cadmium co-induce necroptosis through Th1/Th2 imbalance-mediated endoplasmic reticulum stress in duck ovaries.

Cadmium (Cd) and excess molybdenum (Mo) pose serious threats to animal health. Our previous study has determined that Cd and/or Mo exposure can cause ovarian damage of ducks, while the specific mechanism is still obscure. To further investigate the toxic mechanism of Cd and Mo co-exposure in the ovary, forty 8-day-old female ducks were randomly allocated into four groups for 16 weeks, and the doses of Cd and Mo in basic diet per kg were as follows: control group, Mo group (100 mg Mo), Cd group (4 mg Cd), and Mo + Cd group (100 mg Mo + 4 mg Cd). Cadmium sulfate 8/3-hydrate (CdSO4·8/3H2O) and hexaammonium molybdate ((NH4)6Mo7O24·4H2O) were the origins of Cd and Mo, respectively. At the 16th week of the experiment, all ovary tissues were collected for the detection of related indexes. The data indicated that Mo and/or Cd induced trace element disorders and Th1/Th2 balance to divert toward Th1 in the ovary, which activated endoplasmic reticulum (ER) stress and then provoked necroptosis through triggering RIPK1/RIPK3/MLKL signaling pathway, and eventually caused ovarian pathological injuries and necroptosis characteristics. The alterations of above indicators were most apparent in the joint group. Above all, this research illustrates that Mo and/or Cd exposure can initiate necroptosis through Th1/Th2 imbalance-modulated ER stress in duck ovaries, and Mo and Cd combined exposure aggravates ovarian injuries. This research explores the molecular mechanism of necroptosis caused by Mo and/or Cd, which reveals that ER stress attenuation may be a therapeutic target to alleviate necroptosis.

Coupled Lipidomics and Digital Pathology as an Effective Strategy to Identify Novel Adverse Outcome Pathways in Eisenia fetida Exposed to MoS2 Nanosheets and Ionic Mo.

Molybdenum disulfide (MoS2) nanosheets are increasingly applied in several fields, but effective and accurate strategies to fully characterize potential risks to soil ecosystems are lacking. We introduce a coelomocyte-based in vivo exposure strategy to identify novel adverse outcome pathways (AOPs) and molecular endpoints from nontransformed (NTMoS2) and ultraviolet-transformed (UTMoS2) MoS2 nanosheets (10 and 100 mg Mo/L) on the earthworm Eisenia fetida using nontargeted lipidomics integrated with transcriptomics. Machine learning-based digital pathology analysis coupled with phenotypic monitoring was further used to establish the correlation between lipid profiling and whole organism effects. As an ionic control, Na2MoO4 exposure significantly reduced (61.2-79.5%) the cellular contents of membrane-associated lipids (glycerophospholipids) in earthworm coelomocytes. Downregulation of the unsaturated fatty acid synthesis pathway and leakage of lactate dehydrogenase (LDH) verified the Na2MoO4-induced membrane stress. Compared to conventional molybdate, NTMoS2 inhibited genes related to transmembrane transport and caused the differential upregulation of phospholipid content. Unlike NTMoS2, UTMoS2 specifically upregulated the glyceride metabolism (10.3-179%) and lipid peroxidation degree (50.4-69.4%). Consequently, lipolytic pathways were activated to compensate for the potential energy deprivation. With pathology image quantification, we report that UTMoS2 caused more severe epithelial damage and intestinal steatosis than NTMoS2, which is attributed to the edge effect and higher Mo release upon UV irradiation. Our results reveal differential AOPs involving soil sentinel organisms exposed to different Mo forms, demonstrating the potential of liposome analysis to identify novel AOPs and furthermore accurate soil risk assessment strategies for emerging contaminants.

Exposure to MoS2 nanosheets or bulk activated Kruppel-like factor 4 in 3D Caco-2 spheroids in vitro and mouse intestines in vivo.

MoS2 nanosheets (NSs) are novel 2D nanomaterials (NMs) being used in many important fields. Recently, we proposed the need to evaluate the influences of NMs on Kruppel-like factors (KLFs) even if these materials are relatively biocompatible. In this study, we investigated the influences of MoS2 NSs or bulk on KLF4 signaling pathway in 3D Caco-2 spheroids in vitro and mouse intestines in vivo. Through the analysis of our previous RNA-sequencing data, we found that exposure to MoS2 NSs or bulk activated KLF4 expression in 3D Caco-2 spheroids. Consistently, these materials also activated KLF4-related gene ontology (GO) terms and down-regulated a panel of KLF4-downstream genes. To verify these findings, we repeatedly exposed mice to MoS2 NSs or bulk materials via intragastrical administration (1 mg/kg bodyweight, once a day, for 4 days). It was shown that oral exposure to these materials decreased bodyweight, leading to relatively higher organ coefficients. As expected, exposure to both types of materials increased Mo elements as well as other trace elements, such as Zn, Fe, and Mn in mouse intestines. The exposure also induced morphological changes of intestines, such as shortening of intestinal villi and decreased crypt depth, which may result in decreased intestinal lipid staining. Consistent with RNA-sequencing data, we found that material exposure increased KLF4 protein staining in mouse intestines and decreased two KLF4 downstream proteins, namely extracellular signal-regulated kinase (ERK) and serine/threonine kinase (AKT). We concluded that MoS2 materials were capable to activate KLF4-signaling pathway in intestines both in vivo and in vitro.

Co-exposure to molybdenum and cadmium triggers pyroptosis and autophagy by PI3K/AKT axis in duck spleens.

Excessive amounts of molybdenum (Mo) and cadmium (Cd) are toxicant, but their combined immunotoxicity are not clearly understood. To estimate united impacts of Mo and Cd on pyroptosis and autophagy by PI3K/AKT axis in duck spleens, Mo or/and Cd subchronic toxicity models of ducks were established by feeding diets with different dosages of Mo or/and Cd. Data show that Mo or/and Cd cause oxidative stress by increasing MDA concentration, and decreasing T-AOC, CAT, GSH-Px and T-SOD activities, restrain PI3K/AKT axis by decreasing PI3K, AKT, p-AKT expression levels, which evokes pyroptosis and autophagy by elevating IL-1ß, IL-18 concentrations and NLRP3, Caspase-1, ASC, GSDME, GSDMA, NEK7, IL-1ß, IL-18 expression levels, promoting autophagosomes, LC3 puncta, Atg5, LC3A, LC3B, LC3II/LC3I and Beclin-1 expression levels, and reducing expression levels of P62 and Dynein. Furthermore, the variations of abovementioned indexes are most pronounced in co-treated group. Overall, results reveal that Mo or/and Cd may evoke pyroptosis and autophagy by PI3K/AKT axis in duck spleens. The association of Mo and Cd exacerbates the changes.

2D Materials and Primary Human Dendritic Cells: A Comparative Cytotoxicity Study.

Human health can be affected by materials indirectly through exposure to the environment or directly through close contact and uptake. With the ever-growing use of 2D materials in many applications such as electronics, medical therapeutics, molecular sensing, and energy storage, it has become more pertinent to investigate their impact on the immune system. Dendritic cells (DCs) are highly important, considering their role as the main link between the innate and the adaptive immune system. By using primary human DCs, it is shown that hexagonal boron nitride (hBN), graphene oxide (GO) and molybdenum disulphide have minimal effects on viability. In particular, it is evidenced that hBN and GO increase DC maturation, while GO leads to the release of reactive oxygen species and pro-inflammatory cytokines. hBN and MoS2 increase T cell proliferation with and without the presence of DCs. hBN in particular does not show any sign of downstream T cell polarization. The study allows ranking of the three materials in terms of inherent toxicity, providing the following trend: GO > hBN ≈ MoS2 , with GO the most cytotoxic.

Controlled decoration of nanoceria on the surface of MoS2nanoflowers to improve the biodegradability and biocompatibility inDrosophila melanogastermodel.

In recent years, nanozymes based on two-dimensional (2D) nanomaterials have been receiving great interest for cancer photothermal therapy. 2D materials decorated with nanoparticles (NPs) on their surface are advantageous over conventional NPs and 2D material based systems because of their ability to synergistically improve the unique properties of both NPs and 2D materials. In this work, we report a nanozyme based on flower-like MoS2nanoflakes (NFs) by decorating their flower petals with NCeO2using polyethylenimine (PEI) as a linker molecule. A detailed investigation on toxicity, biocompatibility and degradation behavior of fabricated nanozymes in wild-typeDrosophila melanogastermodel revealed that there were no significant effects on the larval size, morphology, larval length, breadth and no time delay in changing larvae to the third instar stage at 7-10 d for MoS2NFs before and after NCeO2decoration. The muscle contraction and locomotion behavior of third instar larvae exhibited high distance coverage for NCeO2decorated MoS2NFs when compared to bare MoS2NFs and control groups. Notably, the MoS2and NCeO2-PEI-MoS2NFs treated groups at 100µg ml-1covered a distance of 38.2 mm (19.4% increase when compared with control) and 49.88 mm (no change when compared with control), respectively. High-resolution transmission electron microscopy investigations on the new born fly gut showed that the NCeO2decoration improved the degradation rate of MoS2NFs. Hence, nanozymes reported here have huge potential in various fields ranging from biosensing, cancer therapy and theranostics to tissue engineering and the treatment of Alzheimer's disease and retinal therapy.

Accumulation of molybdenum in major organs following repeated oral administration of bis-choline tetrathiomolybdate in the Sprague Dawley rat.

Molybdenum is an essential dietary trace element required for several critical enzyme systems. High intake is associated with toxicity in ruminants and animal studies. The proposed therapeutic use of molybdenum-based drugs poses a potential risk for accumulation through chronic administration of therapeutic doses of this element. The current experiment was designed to study the effect of daily dosing of a molybdenum compound, bis-choline tetrathiomolybdate (TTM), in Sprague Dawley rats using laser ablation inductively coupled plasma time-of-flight mass spectrometry (LA-ICP-ToF-MS) and two dosing levels of TTM for up to 3 months. To investigate if molybdenum accumulation was associated with tissue toxicity, histopathology, haematology and clinical biochemistry markers of toxicity were incorporated into the study design. There were no behavioural signs of toxicity to the rats, and no clinical or anatomic pathology was associated with treatment. The current data did show a progressive accumulation of molybdenum within the adrenal gland, kidneys, liver, spleen, brain and testes. Although this was not associated with tissue toxicity within the 3-month study design, greater exposure over a longer period of time has the potential for producing adverse pathophysiological cellular function. Tissue toxicity, as a result of local excessive accumulation of molybdenum over time, has clear implications for the therapeutic use of molybdenum in humans and demands sensitive monitoring of tissue molybdenum levels to avoid toxicity. The current study highlights the shortcomings of conventional biomonitoring approaches to detect molybdenum accumulation with the goal of avoiding molybdenum-associated toxicity.

Chronic level of exposures to low-dosed MoS2 nanomaterials exhibits more toxic effects in HaCaT keratinocytes.

Molybdenum disulfide nanomaterials (MoS2 NMs) have shown significant role as photocatalysts, lubricating agents and sterilant due to their remarkable physicochemical properties. Because of the increasing demand for MoS2 NMs in numerous industrial domains, greater occupational exposure and subsequent NMs release into environment would be unavoidable. However, much efforts have been made to uncover the biological effects of NMs at unrealistic high concentration or acute duration, placing constraints on setting the realistic occupational exposure thresholds with confidence. In order to fill the current knowledge gap, this study aimed to evaluate the nanotoxicity of MoS2 NMs with or without surface defects under the more realistic exposure mode. Noteworthily, the artificial sweat transformed-occupational exposure-cytotoxicity investigation of MoS2 NMs was established as the main studied line. And the high cellular internalization and augmented oxidative stress triggered by surface defect could be recognized as the main factors for triggering serious cellular damage. Moreover, the HaCaTs exhibited loss of cell membrane integrity, dysfunction of mitochondria, disorder of endoplasmic reticulum and damages of nuclei after chronic exposure, compared with acute exposure. The study provided closely realistic exposure scenarios for NMs which exhibited significant difference from acute toxic investigation, enriching understanding towards real environmental safety of NMs.

Molybdenum and cadmium co-exposure promotes M1 macrophage polarization through oxidative stress-mediated inflammatory response and induces pulmonary fibrosis in Shaoxing ducks (Anas platyrhyncha).

High molybdenum (Mo) and cadmium (Cd) are harmful to the body, but pulmonary toxicity induced by Mo and Cd co-exposure is unknown. To assess the combined impacts of Mo and Cd on fibrosis through M1 polarization in the lung of ducks, 80 healthy 8-day-old Shaoxing ducks (Anas platyrhyncha) were randomly assigned to 4 groups and fed with containing unequal doses of Mo or/and Cd diet. Lung tissues were collected on the 16th week. Results indicated that Mo or/and Cd significantly increased their contents in the lungs, and led to trace elements disorder and histological abnormality, and oxidative stress accompanied by promoting contents of H2 O2 and MDA and decreasing activities of T-SOD, GSH-Px, and CAT, then activated the TLR4/NF-κB/NLRP3 pathway accompanied by upregulating Caspase-1, ASC, IL-18, IL-1ß, TLR4, NF-κB, and NLRP3 expression levels, and disrupted M1/M2 balance to divert toward M1, which evoked the TGF-ß/Smad2/3-mediated fibrosis by elevating TGF-ß1, Smad2, Smad3, COL1A1, α-SMA, and MMP2 expression levels, and decreasing Smad7 and TIMP2 expression levels. The changes of the combined group were most obvious. To sum up, the research demonstrated that Mo or/and Cd may cause macrophages to polarize toward M1 by oxidative stress-mediated the TLR4/NF-κB/NLRP3 pathway, then result in fibrosis through the TGF-ß1/Smad2/3 pathway in duck lungs. Mo and Cd may worsen lung damage.

Long-term impact of the Tyrnyauz tungsten-molybdenum mining and processing factory waste on environmental pollution and children's population.

We studied the consequences of the long-term impact of remediated tailing ponds from the Tyrnyauz tungsten-molybdenum mining and processing factory on the environmental pollution and children living in the area. For more than 60 years, the factory has been engaged in the development of tungsten-molybdenum deposits by open-pit and mine methods and the enrichment of the extracted ore. More than 252,771 thousand tons of waste accumulated in its dumps and tailings ponds. This 170-hectare tailing pond contains more than 125 million tons of waste with arsenic, tungsten, molybdenum and other metals. To examine the possible accumulation of potentially toxic elements in children's bodies, we determined the content of heavy metals in drinking water and in the hair of children. An exfoliated buccal micronucleus test was used to determine the cytogenetic status of children. We did not find significant differences in the content of heavy metals inherent of a tailing pond in children's hair from polluted area compared to the control zone. In buccal cells of children living in the vicinity of the tailings pond, the total number of cytogenetic abnormalities was increased by 4.1 times, the total index of proliferation by 1.5 times, early destruction of the nucleus by 2 times and apoptosis by 1.2 times compared to the clean zone. Thus, we identified a genotoxic and cytotoxic effect on children living in the vicinity of the tailing ponds, which led to an increase in the number of children belonging to the medium- and high-risk groups. No correlations were found between the content of heavy metals in children's hair and the frequency of cells with cytogenetic abnormalities. Weak positive correlation was found between the content of manganese, zinc and copper in children's hair and the indicators of buccal epithelial cell proliferation.

Accidental ingestion of sodium molybdate at the workplace followed by short-term biomonitoring.

INTRODUCTION: Most of the molybdenum (Mo) is used in metallurgical applications, the tetrathiomolybdate form is an experimental chelating agent for Wilson's disease. Human data of acute Mo exposure are lacking and, no report of no-observed-adverse-effect level (NOAEL) has been described until now. Case-study: We report a case of acute occupational exposure to molybdenum, with the related plasma and urine molybdenum concentrations, caused by an accidental ingestion of a sip of an anti-corrosion liquid for metal containing sodium molybdate. Our purpose was to evaluate potential systemic toxicity of molybdenum and to evaluate the dose-response/dose-effect relationship. We estimated the amount of ingested molybdenum to make a mg/kg relationship and performed repeated urine and plasma molybdenum determinations. The patient was hospitalized for three days to monitor possible development of acute symptoms/biochemical alterations. DISCUSSION: We estimated the amount of the sip around 50 ml, with an estimation of a total of 5 gr of sodium molybdate that, for the patient bodyweight of 80 kg, would mean 62,5 mg/kg of ingested Mo. Blood and urine samples collected 2 hours after ingestion showed 50 mcg/L (reference range: 0.43 - 1.8 mcg/L) and 630 mcg/L (refence range: up to 116 mcg/L) of Mo respectively, confirming acute exposure. The patients remained asymptomatic confirming that an estimated oral dose of Mo of 62.5 mg/kg was not associated with adverse effects. CONCLUSIONS: Our value, being extrapolated by a single case, will require further confirmations from other studies to allow a full evaluation of a NOAEL. Nevertheless, it does not preclude its use in evaluating the probable absence of adverse effect in the context of acute Mo exposure.

Dissolution of 2D Molybdenum Disulfide Generates Differential Toxicity among Liver Cell Types Compared to Non-Toxic 2D Boron Nitride Effects.

2D boron nitride (BN) and molybdenum disulfide (MoS2 ) materials are increasingly being used for applications due to novel chemical, electronic, and optical properties. Although generally considered biocompatible, recent data have shown that BN and MoS2 could potentially be hazardous under some biological conditions, for example, during, biodistribution of drug carriers or imaging agents to the liver. However, the effects of these 2D materials on liver cells such as Kupffer cells (KCs), liver sinusoidal endothelial cells, and hepatocytes, are unknown. Here, the toxicity of BN and MoS2 , dispersed in Pluronic F87 (designated BN-PF and MoS2 -PF) is compared with aggregated forms of these materials (BN-Agg and MoS2 -Agg) in liver cells. MoS2 induces dose-dependent cytotoxicity in KCs, but not other cell types, while the BN derivatives are non-toxic. The effect of MoS2 could be ascribed to nanosheet dissolution and the release of hexavalent Mo, capable of inducing mitochondrial reactive oxygen species generation and caspases 3/7-mediated apoptosis in KUP5 cells. In addition, the phagocytosis of MoS2 -Agg triggers an independent response pathway involving lysosomal damage, NLRP3 inflammasome activation, caspase-1 activation, IL-1ß, and IL-18 production. These findings demonstrate the importance of Mo release and the state of dispersion of MoS2 in impacting KC viability.

Facile synthesis of porous MoS2nanofibers for efficient drug delivery and cancer treatment.

Porous MoS2nanofibers were synthesized by electroplating and post-annealing and applied in a responsive drug delivery system. The one-dimensional (1D) MoS2nanofibers displayed a high specific surface area, controllable morphology, and uniform size, serving as a promising drug carrier for chemotherapy. After surface modification with polyethylene glycol (PEG) through PEGylation, the MoS2/PEG composite displayed excellent physical/chemical stability and biocompatibility. More importantly, MoS2/PEG loaded with doxorubicin (DOX) exhibited a controllable release responsive to pH and near-infrared (NIR) irradiation and demonstrated precise DOX dose release. Such remarkable anticancer effects were mainly attributed to outstanding photothermal performance and stability of porous MoS2nanofibers. This work offered a new opportunity of employing porous MoS2nanofibers as drug carriers for effective cancer chemotherapy.

Nanocolloids, but Not Humic Acids, Augment the Phytotoxicity of Single-Layer Molybdenum Disulfide Nanosheets.

Engineered nanomaterials (ENMs), especially transition metal dichalcogenide (TMDC), have received great attention in recent years due to their advantageous properties and applications in various fields and are inevitably released into the environment during their life cycle. However, the effect of natural nanocolloids, widely distributed in the aquatic environment, on the environmental transformation and ecotoxicity of ENMs remains largely unknown. In this study, the effects of natural nanocolloids were compared to humic acid on the environmental transformation and ecotoxicity of single-layer molybdenum disulfide (SLMoS2), a representative TMDC. SLMoS2 with nanocolloids or humic acid (HA) enhanced their dispersion and Mo ion release in deionized water. Nanocolloids induced growth inhibition, reactive oxygen species (ROS) elevation, and cell permeability. Low-toxicity SLMoS2 combined with nanocolloids will enhance the above adverse effects. SLMoS2-nanocolloids induced serious damage (cell distortion and deformation), SLMoS2 internalization, and metabolic perturbation on Chlorella vulgaris (C. vulgaris). In contrast, the addition of HA induced the growth promotion and lower ROS level, inhibited the internalization of SLMoS2, and mitigated metabolic perturbation on C. vulgaris. This work provides insights into the effect of natural nanocolloids on the behaviors and biological risks of ENMs in aquatic environments, deserving substantial future attention.

The combinations of sulfur and molybdenum fertilizations improved antioxidant capacity of grazing Guizhou semi-fine wool sheep under copper and cadmium stress.

Mineral development and metal smelting are the main sources of heavy metal pollution, and copper (Cu) and cadmium (Cd) are the most serious mineral elements in heavy metal pollution. Food chain is the main channel for Cu and Cd to enter human body. Excessive accumulation of Cu and Cd can lead to a variety of diseases and threaten human health. Therefore, it is urgent to repair Cu and Cd-contaminated soil. Previous several studies found that sulfur (S) and molybdenum (Mo) had the effect of alleviating the decrease of antioxidant capacity caused by heavy metal poisoning. To investigate the co-combinations of S and Mo fertilizations on antioxidant capacity of grazing Guizhou semi-fine wool sheep in Cu and Cd-contaminated meadow, and explore the control methods of co-pollutions of Cu and Cd in natural pastures, fertilizing and grazing experiments were carried out in the Wumeng Prairie in the northwest of Guizhou Province, Southwest China. 24 hm2 Cu and Cd-polluted meadows were fenced, and were randomly divided into four groups with 3 replications per group and 2 hm2 per replication. The tested groups included the control group (no fertilizer) and the three treatment groups, applied 40 kg S + 1 kg Mo, 80 kg S + 2 kg Mo, and 120 kg S + 3 kg Mo per hectare for group I, group II, and group III, respectively. 72 healthy Guizhou semi-fine wool sheep (one year old, 33.9 ± 1.2 kg) were randomly assigned to the tested pastures with 18 sheep per group. The grazing experiment lasted for 60 days. The results showed that the contents of Mn, Zn, Mo, and S in herbage in fertilized pastures were higher than that in the control group (P < 0.05). The content of Cu in herbage in fertilized pastures was lower than that in the control group (P < 0.05). The contents of Mn, Zn, Mo, and S in serum of grazing Guizhou semi-fine wool sheep were higher than that in the control group (P < 0.05). The content of Cu in serum of grazing Guizhou semi-fine wool sheep was lower than that in the control group (P < 0.05). The levels of blood Hb, RBC, and PCV, and the activities of serum SOD, GSH-Px, T-AOC, CAT, and Cp in group Ⅲ were higher than that in the control group, group Ⅰ, and group Ⅱ (P < 0.05). The MDA content of sheep in group Ⅲ was lower than that in the other treatment sheep (P < 0.05). In summary, the combinations of S and Mo fertilizers influenced the mineral contents in herbage and serum of grazing Guizhou semi-fine wool sheep. The combinations of 120 kg S + 3 kg Mo fertilizer reduced the toxicity and improved antioxidant capacity of grazing Guizhou semi-fine wool sheep in Cu and Cd-polluted grasslands.

Inhibition of ROS/NLRP3/Caspase-1 mediated pyroptosis alleviates excess molybdenum-induced apoptosis in duck renal tubular epithelial cells.

OBJECTIVE: Excess molybdenum (Mo) is harmful to the body, and the kidney is the vital target organ for Mo exposure. This study focused on the impacts of excess Mo on pyroptosis and the relationship between pyroptosis and apoptosis in kidney. METHODS: The duck renal tubular epithelial cells were treated with (NH4)6Mo7O24·4H2O (0, 480, 720 and 960 µM Mo), N-acetyl-L-cysteine (NAC) (100 µM), Z-YVAD-fluoromethylketone (YVAD) (10 µM) and the combination of Mo and NAC or YVAD for 12 h. The LDH release and IL-1ß, IL-18 contents of cell supernatant were detected by LDH and ELISA kits. The MMP and ROS level were measured using MMP and ROS kits by flow cytometry. The apoptotic rate of cell was detected by AO/EB counterstaining. Pyroptosis and apoptosis-related factors mRNA and protein levels were assayed by real-time qPCR and western blot, respectively. RESULTS: Excessive Mo markedly increased LDH, IL-18, IL-1ß releases and induced overproduction of ROS, pyroptosis-related factors mRNA and protein levels. NAC and YVAD dramatically decreased pyroptosis induced by Mo. Simultaneously, YVAD significantly changed apoptosis-related factors mRNA and protein levels, and reduced cell apoptotic rate. CONCLUSION: Excessive Mo exposure can induce pyroptosis by the ROS/NLRP3/Caspase-1 pathway in duck renal tubular epithelial cells, and restraining pyroptosis of Caspase-1 dependence might weaken excess Mo-induced apoptosis. The study provides theoretical basis for excess Mo exposure nephrotoxic researches on waterfowl and the interplay between pyroptosis and apoptosis highlights a new sight into the mechanism of Mo-induced nephrotoxicity.

Sodium molybdate induces heterophil extracellular traps formation in chicken.

Molybdenum (Mo) is not only an important rare metal that is widely used in industrial production but also an essential trace element for plants and animals. Nevertheless, in Mo polluted areas, excess Mo intake will not only cause gout in humans but also cause diarrhea in livestock and growth inhibition of chickens. Heterophils extracellular traps (HETs) are an important way to clear pathogens in the innate immune system of the chicken. However, the effects of Mo on the innate immune responses of HETs formation in chicken, and the mechanism undergoing this phenomenon remain unknown. In the study, we firstly aim to investigate the effects of sodium molybdate (Na2MoO4) on chicken HETs formation in vitro, and further to explore its related metabolic requirements and molecular mechanisms. Chicken heterophils were cultured with Na2MoO4, and Na2MoO4-induced HETs structures were analyzed by confocal microscopy. Moreover, Na2MoO4-induced HETs were quantified by Quant-iT PicoGreen® dsDNA Assay kits and fluorescence microplate. It has been shown that Na2MoO4 truly triggered HETs-like structures that were composed of DNA decorated with citrullinated histone 3 (citH3) and elastase. The inhibitors of NADPH oxidase, ERK1/2 and p38 MAPK signaling pathway significantly reduced Na2MoO4-induced HETs formation. Further experiments on energy metabolism involving Na2MoO4-induced HETs formation showed that Na2MoO4-induced HETs release was relevant to glucose, and the inhibitors of glycolysis including 3PO, AZD23766 and 3-Bromopyuvic acid, the inhibitors of glucose transport including STF31 and Ritonavir and NSC23766 significantly decreased Na2MoO4-induced HETs formation. In summary, these results demonstrate that Mo does induce chicken HETs formation in vitro, and the formation of HETs is a process relying on glucose transport 1 (GLUT1)，glucose transport 4 (GLUT4), glycolysis, and ROS production depended on the activation of NADPH oxidase, ERK1/2 and p38 signaling pathways, which also reflects the early innate immune responses of chicken against excessive molybdenum intake.