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Small (Weinheim An Der Bergstrasse,... Aug 20222D layered molybdenum disulfide (MoS ) nanomaterials are a promising platform for biomedical applications, particularly due to its high biocompatibility...
2D layered molybdenum disulfide (MoS ) nanomaterials are a promising platform for biomedical applications, particularly due to its high biocompatibility characteristics, mechanical and electrical properties, and flexible functionalization. Additionally, the bandgap of MoS can be engineered to absorb light over a wide range of wavelengths, which can then be transformed into local heat for applications in photothermal tissue ablation and regeneration. However, limitations such as poor stability of aqueous dispersions and low accumulation in affected tissues impair the full realization of MoS for biomedical applications. To overcome such challenges, herein, multifunctional MoS -based magnetic helical microrobots (MoSBOTs) using cyanobacterium Spirulina platensis are proposed as biotemplate for therapeutic and biorecognition applications. The cytocompatible microrobots combine remote magnetic navigation with MoS photothermal activity under near-infrared irradiation. The resulting photoabsorbent features of the MoSBOTs are exploited for targeted photothermal ablation of cancer cells and on-the-fly biorecognition in minimally invasive oncotherapy applications. The proposed multi-therapeutic MoSBOTs hold considerable potential for a myriad of cancer treatment and diagnostic-related applications, circumventing current challenges of ablative procedures.
Topics: Disulfides; Infrared Rays; Molybdenum; Nanostructures; Phototherapy
PubMed: 35867042
DOI: 10.1002/smll.202203821 -
Chemistry (Weinheim An Der Bergstrasse,... Feb 2022Nitrogenase is the only enzyme in nature that can fix N from the air. The active cofactor of the leading form of this enzyme contains seven irons and one molybdenum...
Nitrogenase is the only enzyme in nature that can fix N from the air. The active cofactor of the leading form of this enzyme contains seven irons and one molybdenum connected by sulfide bridges. In several recent experimental studies, it has been suggested that the cofactor is very flexible, and might lose one of its sulfides during catalysis. In this study, the possible loss of a sulfide has been investigated by model calculations. In previous studies, we have shown that there should be four activation steps before catalysis starts, and this study is based on that finding. It was found here that, after the four reductions in the activation steps, a sulfide will become very loosely bound and can be released in a quite exergonic step with a low barrier. The binding of N has no part in that release. In our previous studies, we suggested that the central carbide should be protonated three times after the four activation steps. With the new finding, there will instead be a loss of a sulfide, as the barrier for the loss is much lower than the ones for protonating the carbide. Still, it is suggested here that the carbide will be protonated anyway, but only with one proton, in the E to E step. A very complicated transition state for H formation involving a large structural change was obtained. The combined step, with a loss of H and binding of N , is calculated to be endergonic by +2.3 kcal mol ; this is in excellent agreement with experiments in which an easily reversible step has been found.
Topics: Molybdenum; Nitrogen; Nitrogenase; Oxidation-Reduction; Protons; Sulfides
PubMed: 35098591
DOI: 10.1002/chem.202103745 -
The Journal of Biological Chemistry Feb 2022The molybdenum/tungsten-bis-pyranopterin guanine dinucleotide family of formate dehydrogenases (FDHs) plays roles in several metabolic pathways ranging from carbon...
The molybdenum/tungsten-bis-pyranopterin guanine dinucleotide family of formate dehydrogenases (FDHs) plays roles in several metabolic pathways ranging from carbon fixation to energy harvesting because of their reaction with a wide variety of redox partners. Indeed, this metabolic plasticity results from the diverse structures, cofactor content, and substrates used by partner subunits interacting with the catalytic hub. Here, we unveiled two noncanonical FDHs in Bacillus subtilis, which are organized into two-subunit complexes with unique features, ForCE1 and ForCE2. We show that the formate oxidoreductase catalytic subunit interacts with an unprecedented partner subunit, formate oxidoreductase essential subunit, and that its amino acid sequence within the active site deviates from the consensus residues typically associated with FDH activity, as a histidine residue is naturally substituted with a glutamine. The formate oxidoreductase essential subunit mediates the utilization of menaquinone as an electron acceptor as shown by the formate:menadione oxidoreductase activity of both enzymes, their copurification with menaquinone, and the distinctive detection of a protein-bound neutral menasemiquinone radical by multifrequency electron paramagnetic resonance (EPR) experiments on the purified enzymes. Moreover, EPR characterization of both FDHs reveals the presence of several [Fe-S] clusters with distinct relaxation properties and a weakly anisotropic Mo(V) EPR signature, consistent with the characteristic molybdenum/bis-pyranopterin guanine dinucleotide cofactor of this enzyme family. Altogether, this work enlarges our knowledge of the FDH family by identifying a noncanonical FDH, which differs in terms of architecture, amino acid conservation around the molybdenum cofactor, and reactivity.
Topics: Electron Spin Resonance Spectroscopy; Formate Dehydrogenases; Formates; Guanine; Molybdenum; Vitamin K 2
PubMed: 34748728
DOI: 10.1016/j.jbc.2021.101384 -
Applied and Environmental Microbiology Sep 2023All nitrogen-fixing bacteria and archaea (diazotrophs) use molybdenum (Mo) nitrogenase to reduce dinitrogen (N) to ammonia, with some also containing vanadium (V) and...
All nitrogen-fixing bacteria and archaea (diazotrophs) use molybdenum (Mo) nitrogenase to reduce dinitrogen (N) to ammonia, with some also containing vanadium (V) and iron-only (Fe) nitrogenases that lack Mo. Among diazotrophs, the regulation and usage of the alternative V-nitrogenase and Fe-nitrogenase in methanogens are largely unknown. contains , , and gene clusters encoding putative Mo-nitrogenase, V-nitrogenase, and Fe-nitrogenase, respectively. This study investigated nitrogenase expression and growth by in response to fixed nitrogen, Mo/V availability, and CRISPRi repression of the , , and/or gene clusters. The availability of Mo and V significantly affected growth of with N but not with NHCl. exhibited the fastest growth rate and highest cell yield during growth with N in medium containing Mo, and the slowest growth in medium lacking Mo and V. qPCR analysis revealed the transcription of the operon is only moderately affected by depletion of fixed nitrogen and Mo, whereas and transcription increased significantly when fixed nitrogen and Mo were depleted, with removal of Mo being key. Immunoblot analysis revealed Mo-nitrogenase is detected when fixed nitrogen is depleted regardless of Mo availability, while V-nitrogenase and Fe-nitrogenase are detected only in the absence of fixed nitrogen and Mo. CRISPRi repression studies revealed that V-nitrogenase and/or Fe-nitrogenase are required for Mo-independent diazotrophy, and unexpectedly that the expression of Mo-nitrogenase is also required. These results reveal that alternative nitrogenase production in is tightly controlled and dependent on Mo-nitrogenase expression. IMPORTANCE Methanogens and closely related methanotrophs are the only archaea known or predicted to possess nitrogenase. Methanogens play critical roles in both the global biological nitrogen and carbon cycles. Moreover, methanogens are an ancient microbial lineage and nitrogenase likely originated in methanogens. An understanding of the usage and properties of nitrogenases in methanogens can provide new insight into the evolution of nitrogen fixation and aid in the development nitrogenase-based biotechnology. This study provides the first evidence that a methanogen can produce all three forms of nitrogenases, including simultaneously. The results reveal components of Mo-nitrogenase regulate or are needed to produce V-nitrogenase and Fe-nitrogenase in methanogens, a result not seen in bacteria. Overall, this study provides a foundation to understand the assembly, regulation, and activity of the alternative nitrogenases in methanogens.
Topics: Nitrogenase; Molybdenum; Methanosarcina; Nitrogen; Nitrogen Fixation; Archaea
PubMed: 37695043
DOI: 10.1128/aem.01033-23 -
Angewandte Chemie (International Ed. in... Dec 2022Alkene metathesis catalyzed by enantiopure metal alkylidene complexes enables exceptionally versatile strategies to products with configurationally-defined...
Alkene metathesis catalyzed by enantiopure metal alkylidene complexes enables exceptionally versatile strategies to products with configurationally-defined stereocenters. Desymmetrization processes thereby provide reliable stereoselective routes to aliphatic structures, while the differentiation of aromatic stereogenic units remained an outstanding challenge. Herein, we describe the feasibility of alkene metathesis to catalytically control stereogenic axes by traceless arene formation. Stereodynamic trienes are selectively converted into corresponding binaphthalene atropisomers upon exposure to a chiral molybdenum catalyst. Remarkably, stereoselective arene-forming metathesis allows enantioselectivities of up to 98 : 2 e.r. and excellent yields. As the disconnection of each bond of an aromatic target is retrosynthetically conceivable, it is anticipated that forging arenes by means of stereoselective metathesis will enable versatile approaches for the synthesis of a broad range of molecular topologies with precisely defined configuration.
Topics: Alkenes; Stereoisomerism; Catalysis; Molybdenum; Coordination Complexes
PubMed: 36283028
DOI: 10.1002/anie.202211168 -
NanoImpact Jan 2023MoS has been increasingly used in place of graphene as a flexible and multifunctional 2D material in many biomedical applications such as cancer detection and drug...
MoS has been increasingly used in place of graphene as a flexible and multifunctional 2D material in many biomedical applications such as cancer detection and drug delivery, which makes it crucial to evaluate downstream compatibility in human immune cells. Molybdenum is a component of stainless-steel stent implants and has previously been implicated in stent hypersensitivity. In view of this, it is important to ascertain the effect of MoS on allergy-relevant cells. Basophils are a less commonly used immune cell type. Unlike mast cells, basophils can be easily derived from primary human blood and can act as a sentinel for allergy. However, merely testing any one type of MoS in basophils could result in different biological results. We thus decided to compare 2D MoS from the two companies BeDimensional© (BD) and Biograph Solutions (BS), manufactured with two different but commonly exploited methods (BD, deoxycholate surfactant in a high-pressure liquid exfoliation, and BS using glycine in ball-milling exfoliation) to elucidate immunological end-points common to both MoS and to demonstrate the need for biological verification for end-users who may require a change of supplier. We report higher histamine production in human basophils with MoS. No effects on either surface basophil activation markers CD63 and CD203c or reactive oxygen species (ROS) production and cell viability were observed. However, different cytokine production patterns were evidenced. IL-6 and IL-1β but not TNF and GM-CSF were increased for both MoS. BS-MoS increased IL-4, while BD-MoS decreased IL-4 and increased IL-13. Molybdate ion itself only increased IL-1β and IL-4. Deoxycholate surfactant decreased viability at 18 h and increased ROS upon basophil activation. Therefore, these results demonstrate the safety of MoS in human basophils in general and highlight the importance of considering manufacturer additives and variability when selecting and investigating 2D materials such as MoS.
Topics: Humans; Basophils; Molybdenum; Interleukin-4; Reactive Oxygen Species; Hypersensitivity; Deoxycholic Acid
PubMed: 36626980
DOI: 10.1016/j.impact.2023.100451 -
Ecotoxicology and Environmental Safety Oct 2021Mineral 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...
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 hm Cu and Cd-polluted meadows were fenced, and were randomly divided into four groups with 3 replications per group and 2 hm 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.
Topics: Animals; Antioxidants; Cadmium; Copper; Fertilization; Humans; Molybdenum; Sheep; Sulfur; Wool
PubMed: 34280842
DOI: 10.1016/j.ecoenv.2021.112520 -
PloS One 2022Trace mineral imbalances can have significant effects on animal health, reproductive success, and survival. Monitoring their status in wildlife populations is,...
Trace mineral imbalances can have significant effects on animal health, reproductive success, and survival. Monitoring their status in wildlife populations is, therefore, important for management and conservation. Typically, livers and kidneys are sampled to measure mineral status, but biopsies and lethal-sampling are not always possible, particularly for Species at Risk. We aimed to: 1) determine baseline mineral levels in Northern Mountain caribou (Rangifer tarandus caribou; Gmelin, 1788) in northwestern British Columbia, Canada, and 2) determine if hair can be used as an effective indicator of caribou mineral status by evaluating associations between hair and organ mineral concentrations. Hair, liver, and kidney samples from adult male caribou (nHair = 31; nLiver, nKidney = 43) were collected by guide-outfitters in 2016-2018 hunting seasons. Trace minerals and heavy metals were quantified using inductively-coupled plasma mass spectrometry, and organ and hair concentrations of same individuals were compared. Some organ mineral concentrations differed from other caribou populations, though no clinical deficiency or toxicity symptoms were reported in our population. Significant correlations were found between liver and hair selenium (rho = 0.66, p<0.05), kidney and hair cobalt (rho = 0.51, p<0.05), and liver and hair molybdenum (rho = 0.37, p<0.10). These findings suggest that hair trace mineral assessment may be used as a non-invasive and easily-accessible way to monitor caribou selenium, cobalt, and molybdenum status, and may be a valuable tool to help assess overall caribou health.
Topics: Animals; British Columbia; Cobalt; Forests; Hair; Male; Molybdenum; Reindeer; Selenium; Trace Elements
PubMed: 35763458
DOI: 10.1371/journal.pone.0269441 -
The Biochemical Journal May 2018The molybdenum cofactor (Moco) is a redox-active prosthetic group found in the active site of Moco-dependent enzymes, which are vitally important for life. Moco...
The molybdenum cofactor (Moco) is a redox-active prosthetic group found in the active site of Moco-dependent enzymes, which are vitally important for life. Moco biosynthesis involves several enzymes that catalyze the subsequent conversion of GTP into cyclic pyranopterin monophosphate (cPMP), molybdopterin (MPT), adenylated MPT (MPT-AMP), and finally Moco. While the underlying principles of cPMP, MPT, and MPT-AMP formation are well understood, the molybdenum insertase (Mo-insertase)-catalyzed final Moco maturation step is not. In the present study, we analyzed high-resolution X-ray datasets of the plant Mo-insertase Cnx1E that revealed two molybdate-binding sites within the active site, hence improving the current view on Cnx1E functionality. The presence of molybdate anions in either of these sites is tied to a distinctive backbone conformation, which we suggest to be essential for Mo-insertase molybdate selectivity and insertion efficiency.
Topics: Amino Acid Sequence; Binding Sites; Catalysis; Catalytic Domain; Coenzymes; Eukaryota; Metalloproteins; Molybdenum; Molybdenum Cofactors; Mutation; Protein Conformation; Pteridines; Sequence Homology
PubMed: 29717023
DOI: 10.1042/BCJ20170935 -
International Journal of Molecular... Nov 2020The ideal immunosuppressive regimen should provide for excellent immunosuppression with no side effects. Yet, current immunosuppressive therapy regimens commonly used in...
The Effects of Immunosuppressive Treatment during Pregnancy on the Levels of Potassium, Iron, Chromium, Zinc, Aluminum, Sodium and Molybdenum in Hard Tissues of Female Rats and Their Offspring.
The ideal immunosuppressive regimen should provide for excellent immunosuppression with no side effects. Yet, current immunosuppressive therapy regimens commonly used in clinical applications fail to meet this criterion. One of the complications caused by immunosuppressive drugs is mineralization disorders in hard tissues. In this study, we evaluated the effects of three immunosuppressive therapies used after transplantation on the levels of potassium, iron, chromium, zinc, aluminum, sodium and molybdenum in the bones and teeth of female rats and their offspring. The study was conducted on 32 female Wistar rats, subjected to immunosuppressive regimens (cyclosporine A, mycophenolate mofetil and prednisone; tacrolimus, mycophenolate mofetil and prednisone; and cyclosporine A, everolimus and prednisone). The hard tissues of rats were analyzed using inductively coupled plasma optical emission spectrometry (ICP-OES, ICAP 7400 Duo, Thermo Scientific) equipped with a concentric nebulizer and a cyclonic spray chamber. All the immunosuppressive regimens included in the study affected the concentrations of the studied minerals in hard tissues of female rats and their offspring. The therapy based on cyclosporine A, everolimus and prednisone led to a decline in the levels of iron in bone, zinc in teeth, and molybdenum in the bone and teeth of mothers, while in the offspring, it caused a decline of bone potassium, with a decrease in iron and increase of molybdenum in teeth. Moreover, the regimen caused an increase in aluminum and chromium in the teeth and aluminum in the bones of the offspring, and consequently, it seems to be the therapy with the most negative impact on the mineral metabolism in hard tissues.
Topics: Aluminum; Animals; Bone and Bones; Chromium; Female; Immunosuppressive Agents; Iron; Minerals; Molybdenum; Organ Specificity; Potassium; Pregnancy; Rats, Wistar; Sodium; Zinc
PubMed: 33261165
DOI: 10.3390/ijms21239038