Iron Flux Research Articles

Biomineralization of Fe3+ to Nanosized γFe2O3 by Haloferax alexandrinus GUSF-1

Hypersaline environment is a habitat with extreme osmotic conditions along with low Aw, serving as a home to extremely halophilic and halotolerant bacteria. The hypersaline environments, such as solar salterns located along the rivers, are exposed to fluxes of iron from iron ore transportation and other industrial wastes. The solar salterns often serve as a sink for metal intoxicants. Studies on archaea interaction with metal ions indicate the formation of minerals such as goethite, hematite, rhodochrosite, etc. However, studies exploring haloarchaeal candidates interacting with metals such as Fe3+ in a hypersaline growth condition are scarce. This study unveils for the first time formation of γFe2O3 from Fe3+ by the haloarchaeon, Haloferax sp. GUSF-1 thus implying the significance of the culture synthesizing minerals in hypersaline sediments. γFe2O3 is formed from Fe3+ by the haloarchaeon Haloferax sp. GUSF-1 (GenBank accession no.GU-1KF796625), under microaerophilic growth on sodium acetate. A 50 mg L−1 of Fe2+ and 30.6 mg L−1 of Fe3+ was detected inside the cells. Simultaneously, a brown-colored crystalline material deposited in the culture broth through an iron reductase inhibited by Zn2+ ions. The XRD of the deposit exhibited d values of 2.96, 2.514, 2.086, 1.6, and 1.45, while SEM-EDX displayed cubic and irregularly shaped minute particles with peaks for Fe at 0.6, 6.4, and 6.6 keV, respectively. TEM profiles revealed polycrystalline particles of 12–23 nm in size. Further, the SAED concentric pattern of light scattering with well-defined diffraction spots was consistent and matched with maghemite's crystal structure (γFe2O3). The FTIR spectrum revealed a peak at 1450 cm−1 indicating iron oxyhydroxide formation as an intermediate having γ-FeOOH stretching bond vibrations. Conclusively, this study opens the possibility of the haloarchaea isolated from solar salterns for its exploitation in nanobiotechnology.

The iron chelator, PBT434, modulates transcellular iron trafficking in brain microvascular endothelial cells.

Iron and other transition metals, such as copper and manganese, are essential for supporting brain function, yet over-accumulation is cytotoxic. This over-accumulation of metals, particularly iron, is common to several neurological disorders; these include Alzheimer’s disease, Parkinson’s disease, Friedrich’s ataxia and other disorders presenting with neurodegeneration and associated brain iron accumulation. The management of iron flux by the blood-brain barrier provides the first line of defense against the over-accumulation of iron in normal physiology and in these pathological conditions. In this study, we determined that the iron chelator PBT434, which is currently being developed for treatment of Parkinson’s disease and multiple system atrophy, modulates the uptake of iron by human brain microvascular endothelial cells (hBMVEC) by chelation of extracellular Fe2+. Treatment of hBMVEC with PBT434 results in an increase in the abundance of the transcripts for transferrin receptor (TfR) and ceruloplasmin (Cp). Western blot and ELISA analyses reveal a corresponding increase in the proteins as well. Within the cell, PBT434 increases the detectable level of chelatable, labile Fe2+; data indicate that this Fe2+ is released from ferritin. In addition, PBT434 potentiates iron efflux likely due to the increase in cytosolic ferrous iron, the substrate for the iron exporter, ferroportin. PBT434 equilibrates rapidly and bi-directionally across an hBMVEC blood-brain barrier. These results indicate that the PBT434-iron complex is not substrate for hBMVEC uptake and thus support a model in which PBT434 would chelate interstitial iron and inhibit re-uptake of iron by endothelial cells of the blood-brain barrier, as well as inhibit its uptake by the other cells of the neurovascular unit. Overall, this presents a novel and promising mechanism for therapeutic iron chelation.

Benthic iron flux influenced by climate‐sensitive interplay between organic carbon availability and sedimentation rate in Arctic fjords

AbstractBenthic iron (Fe) fluxes from continental shelf sediments are an important source of Fe to the global ocean, yet the magnitude of these fluxes is not well constrained. Processing of Fe in sediments is of particular importance in the Arctic Ocean, which has a large shelf area and Fe limitation of primary productivity. In the Arctic fjords of Svalbard, glacial weathering delivers high volumes of Fe‐rich sediment to the fjord benthos. Benthic redox cycling of Fe proceeds through multiple pathways of reduction (i.e., dissimilatory iron reduction and reduction by hydrogen sulfide) and re‐oxidation. There are few estimates of the magnitude and controlling factors of the benthic Fe flux in Arctic fjords. We collected cores from two Svalbard fjords (Kongsfjorden and Lilliehöökfjorden), measured dissolved Fe2+ concentrations using a two‐dimensional sensor, and analyzed iron, manganese, carbon, and sulfur species to study benthic Fe fluxes. Benthic fluxes of Fe2+ vary throughout the fjords, with a “sweet spot” mid‐fjord controlled by the availability of organic carbon linked to sedimentation rates. The flux is also impacted by fjord circulation and sea ice cover, which influence overall mineralization rates in the sediment. Due to ongoing Arctic warming, we predict an increase in the benthic Fe2+ flux with reduced sea ice cover in some fjords and a decrease in the Fe2+ flux with the retreat of tidewater glaciers in other regions. Decreasing benthic Fe2+ fluxes in fjords may exacerbate Fe limitation of primary productivity in the Arctic Ocean.

A baseline of terrestrial freshwater and nitrogen fluxes to the Southern California Bight, USA

Time series were compiled of terrestrial nitrogen, phosphorus, carbon, iron, and silica fluxes to the Southern California Bight (SCB), a U.S. West Coast embayment (Sutula et al., 2021). Monitoring data and model output were used to construct a baseline of inputs from direct point source (PS) discharges of wastewater treatment (WWT) effluent (via ocean outfalls) and PS, non-point and natural sources from coastal rivers. The baseline covers 1971—2017 for large WWT plants discharging >50 million gallons per day (MGD) and 1997–2017 for small WWT plants and rivers. PS are the dominant nitrogen source, with contributions of 70% of the total annual freshwater discharge and 95% of nitrogen loads. WWT upgrades have reduced organic nitrogen loads by 73% since 1971. Inorganic nitrogen loads have generally held constant (35–40 Gg y−1) for the large WWT plants. This baseline represents a period prior to extensive wastewater and stormwater recycling that is increasing in the region.

Geochemical Characteristics of Late Ordovician Shales in the Upper Yangtze Platform, South China: Implications for Redox Environmental Evolution

Changes to the redox environment of seawater in the Late Ordovician affect the process of organic matter enrichment and biological evolution. However, the evolution of redox and its underlying causes remain unclear. This paper analyzed the vertical variability of main, trace elements and δ34Spy from a drill core section (well ZY5) in the Upper Yangtze Platform, and described the redox conditions, paleoproductivity and paleoclimate variability recorded in shale deposits of the P. pacificus zone and M. extraordinarius zone that accumulated during Wufeng Formation. The results showed that shale from well ZY5 in Late Ordovician was deposited under oxidized water environment, and there are more strongly reducing bottom water conditions of the M. extraordinarius zone compared with the P. pacificus zone. Excess silica (SiO2(exc)) and substitution index of paleoproductivity (Y) indicated that the P. pacificus zone had higher paleoproductivity whereas the M. extraordinarius zone was lower. The high productivity level controlled O2 release in the shallow water area as well as the oxidation degree of the P. pacificus zone. The decrease of productivity and the relatively stagnant water mass of the inner Yangtze Sea controlled the formation of relatively reduced water conditions in the M. extraordinarius zone. The chemical index of alteration (CIA) results suggested that palaeoclimatic conditions changed from warm and humid to cold and dry climate from the P. pacificus to the M. extraordinarius zones in the study area. A comparative analysis of the published Fe-S-C data for the Xiushan Datianba section showed that in the P. pacificus zone of the inner Yangtze Sea, warm and humid climate conditions drove high productivity, sulphate flux and low reactive iron flux, which promoted the expansion of oxic ocean-surface waters and mid-depth euxinic waters. In the M. extraordinarius zone, the cold and dry climate with significant uplift of the Xiang’e Submarine High led to the relative sea level decline, resulting in low productivity, sulfate flux and high reactive iron flux, which promoted the expansion of the mid-depth ferruginous waters and the shrinkage of oxic ocean-surface waters. The results offered new insights into the co-evolution of continents and oceans, and explained the role of continental weathering and uplift of the Xiang’e Submarine High in the exchange of sulfate flux and nutrients in the redox environment change of inner Yangtze Sea during the Late Ordovician.

Characterization of Iron Metabolism in Mouse Model of Congenital Polycythemia with Human Gain-of-Function Erythropoietin Receptor

Hepcidin (encoded by HAMP), the peptide hormone regulating systemic iron homeostasis, controls iron flux to plasma and thus ensures adequate iron supply for erythropoiesis. Increased erythropoietic activity negatively regulates hepcidin synthesis by the hormone erythroferrone (ERFE) produced by erythroid precursors in response to erythropoietin (EPO). Here we evaluated iron metabolism in a mouse model of polycythemia with augmented erythropoiesis and low EPO levels bearing the gain-of-function polycythemia-causing human EPO receptor gene (mtHEPOR) (Divoky PNAS 2002). The mtHEPOR embryos developed polycythemia around embryonic day (ED) 17.5, followed by unexpected but transient correction of polycythemia in perinatal life (postnatal day 7 - PD7) and reappearance of a polycythemic phenotype at 3-6 weeks of age. (Human patients with the gain-of-function polycythemia-causing human EPOR mutations are also born non-polycythemic and then develop polycythemia within a few weeks of neonatal life). The mtHEPOR mice had reduced Epo levels, augmented EPOR signaling and prolonged activation of Stat5 in erythroblasts when compared to mEpoR mice (Divoky JMolMed 2016). To assess whether developmental changes of erythron in this mouse model correlate with changes in iron metabolism, we determined temporal changes of Erfe and Hamp expression and body iron stores.We found that mtHEPOR mice have increased expression of Erfe at ED 17.5 (7.5-times) and PD7 (4-times) compared to mEpoR controls when normalized to a housekeeping gene beta-actin and independently to erythroid marker glycophorin A. Therefore Erfe in mtHEPOR mice would be increased both because of a higher number of erythroid precursors and because each precursor is producing more Erfe by increased transcription. This corresponds to reduced expression of Hamp in the liver of ED17.5 (4-times) and PD7 mtHEPOR mice (15-times) compared to mEpoR littermates. However, perinatally (PD1), Erfe expression dramatically decreased in mtHEPOR mice (7-times) concomitantly with increased Hamp expression (45-times), and both these factors reached expression levels detected in mEpoR at PD1. Expression of Erfe and Hamp between mtHEPOR and mEpoR mice was also not different in older mice (7 months of age), even though mtHEPOR mice were markedly polycythemic with persistent erythropoietic activity, markedly increased splenic erythropoiesis (the weight of spleens of control animals was 100-180 mg compared to 200-350 mg of mtHEPOR mice), and augmented EPOR-Stat5 signaling. However, mtHEPOR and mEpoR mice differed in transferrin saturation (TSAT) and tissue iron stores. The spleens of mtHEPOR mice had markedly increased iron deposits compared to mEpoR controls and stainable iron could only be detected in the livers of mtHEPOR mice but not in the livers of mEpoR controls. TSAT was elevated in mtHEPOR mice (77±3.2%) when compared to mEpoR (54.7±8.0%), consistent with the iron overload in mtHEPOR mice. Nevertheless, Hamp expression was comparable between mtHEPOR and mEpoR mice. This shows that Hamp expression was unexpectedly normal in respect to the presence of iron overload in mtHEPOR mice at 7 months of age.With further aging (mice 14 months and older), Erfe continued to increase and Hamp continued to decrease in mEpoR mice. In contrast, there was a trend towards decreased Erfe expression while Hamp expression became significantly elevated (2-times) in mtHEPOR mice. These changes were accompanied by a 2.4-fold decline in TSAT in both genotypes, which suggests that aged mEpoR mice develop iron deficiency while mtHEPOR mice remain iron-replete likely due to mobilization of iron from high iron stores.We show that the polycythemic phenotype, as well as Erfe and Hamp expression, in mtHEPOR mice undergoes dynamic changes during ontogenesis. We conclude that further research will be needed to understand the development of iron overload and changes in Erfe and Hamp expression in mtHEPOR mice characterized by erythroid hyperplasia and low Epo levels.Acknowledgment: BK, VD, and MH were supported by the Czech Science Foundation (projects GA15-13732S and GA17-05988S), KONTAKTII project LH15223, and in part by project LTAUSA17142. BK and JS contributed equally to this work. JTP and MH act as equivalent co-senior authors. DisclosuresNo relevant conflicts of interest to declare.

Iron isotope of suspended particulate matter in Zhujiang River, Southwest China: Characteristics, sources, and environmental implications

Understanding the environmental iron cycle influenced by natural and anthropogenic processes is significant to obtain the key information on earth-surface evolution. Iron isotope compositions and elemental compositions of the suspended particulate matter (SPM) in Zhujiang River were investigated to provide key insights for the earth-surface iron cycle. The δ56Fe values of SPM display the range from −0.05‰ to 0.34‰ (averaged 0.19‰) while the iron contents range from 0.73 wt% to 7.63 wt% (averaged 4.15 wt%). The Chemical Index of Alteration (CIA) shows that the main weathering type of SPM is intermediate weathering (mean CIA value: 79.12). While the main chemical weathering types are similar, the δ56Fe values vary dramatically, indicating that chemical weathering is not the governing factor of δ56Fe values of SPM. Furthermore, evidence from the enrichment factors (EF, 0.78 to 1.29) of iron and Zinc isotopes reveals that the iron input from anthropogenic activities is quite limited. The significant correlation between (Fe/Ca)SPM and (Na/Ca)SPM, (Mg/Ca)SPM, (Al/Ca)SPM and (K/Ca)SPM (0.73 < r < 0.99, p < 0.01, n = 22) and the A–CN–K diagram could confirm that clay minerals (especially smectite and illite) are important components of SPM. Meanwhile, the higher enrichment rates of La, Pr and Nd with the increasing iron contents denote heavy minerals (mainly Fe oxides/oxy-hydroxides) are also important compositions of SPM. Based on the isotopic mass balance, it shows that the iron flux of SPM to the oceans during the wet season would reduce the δ56Fe values of the bulk ocean by 0.3%. The present study reports the iron isotope and elemental compositions of Zhujiang SPM and identifies its influencing factors (weathering, anthropogenic inputs, and minerals effect), and also provides a quantitative reference for the intriguing question on the distinct δ56Fe values of oceans, which is beneficial for understanding iron cycle in earth-surface system.

Indoxyl-Sulfate-Induced Redox Imbalance in Chronic Kidney Disease

The accumulation of the uremic toxin indoxyl sulfate (IS) induces target organ damage in chronic kidney disease (CKD) patients, and causes complications including cardiovascular diseases, renal osteodystrophy, muscle wasting, and anemia. IS stimulates reactive oxygen species (ROS) production in CKD, which impairs glomerular filtration by a direct cytotoxic effect on the mesangial cells. IS further reduces antioxidant capacity in renal proximal tubular cells and contributes to tubulointerstitial injury. IS-induced ROS formation triggers the switching of vascular smooth muscular cells to the osteoblastic phenotype, which induces cardiovascular risk. Low-turnover bone disease seen in early CKD relies on the inhibitory effects of IS on osteoblast viability and differentiation, and osteoblastic signaling via the parathyroid hormone. Excessive ROS and inflammatory cytokine releases caused by IS directly inhibit myocyte growth in muscle wasting via myokines’ effects. Moreover, IS triggers eryptosis via ROS-mediated oxidative stress, and elevates hepcidin levels in order to prevent iron flux in circulation in renal anemia. Thus, IS-induced oxidative stress underlies the mechanisms in CKD-related complications. This review summarizes the underlying mechanisms of how IS mediates oxidative stress in the pathogenesis of CKD’s complications. Furthermore, we also discuss the potential role of oral AST-120 in attenuating IS-mediated oxidative stress after gastrointestinal adsorption of the IS precursor indole.

Iron and sulfur cycling in the cGENIE.muffin Earth system model (v0.9.21)

Abstract. The coupled biogeochemical cycles of iron and sulfur are central to the long-term biogeochemical evolution of Earth's oceans. For instance, before the development of a persistently oxygenated deep ocean, the ocean interior likely alternated between states buffered by reduced sulfur (“euxinic”) and buffered by reduced iron (“ferruginous”), with important implications for the cycles and hence bioavailability of dissolved iron (and phosphate). Even after atmospheric oxygen concentrations rose to modern-like values, the ocean episodically continued to develop regions of euxinic or ferruginous conditions, such as those associated with past key intervals of organic carbon deposition (e.g. during the Cretaceous) and extinction events (e.g. at the Permian–Triassic boundary). A better understanding of the cycling of iron and sulfur in an anoxic ocean, how geochemical patterns in the ocean relate to the available spatially heterogeneous geological observations, and quantification of the feedback strengths between nutrient cycling, biological productivity, and ocean redox requires a spatially resolved representation of ocean circulation together with an extended set of (bio)geochemical reactions. Here, we extend the “muffin” release of the intermediate-complexity Earth system model cGENIE to now include an anoxic iron and sulfur cycle (expanding the existing oxic iron and sulfur cycles), enabling the model to simulate ferruginous and euxinic redox states as well as the precipitation of reduced iron and sulfur minerals (pyrite, siderite, greenalite) and attendant iron and sulfur isotope signatures, which we describe in full. Because tests against present-day (oxic) ocean iron cycling exercises only a small part of the new code, we use an idealized ocean configuration to explore model sensitivity across a selection of key parameters. We also present the spatial patterns of concentrations and δ56Fe and δ34S isotope signatures of both dissolved and solid-phase Fe and S species in an anoxic ocean as an example application. Our sensitivity analyses show that the first-order results of the model are relatively robust against the choice of kinetic parameter values within the Fe–S system and that simulated concentrations and reaction rates are comparable to those observed in process analogues for ancient oceans (i.e. anoxic lakes). Future model developments will address sedimentary recycling and benthic iron fluxes back to the water column, together with the coupling of nutrient (in particular phosphate) cycling to the iron cycle.

The detrimental effect of iron on OA chondrocytes: Importance of pro-inflammatory cytokines induced iron influx and oxidative stress.

Iron overload is common in elderly people which is implicated in the disease progression of osteoarthritis (OA), however, how iron homeostasis is regulated during the onset and progression of OA and how it contributes to the pathological transition of articular chondrocytes remain unknown. In the present study, we developed an in vitro approach to investigate the roles of iron homeostasis and iron overload mediated oxidative stress in chondrocytes under an inflammatory environment. We found that pro‐inflammatory cytokines could disrupt chondrocytes iron homeostasis via upregulating iron influx transporter TfR1 and downregulating iron efflux transporter FPN, thus leading to chondrocytes iron overload. Iron overload would promote the expression of chondrocytes catabolic markers, MMP3 and MMP13 expression. In addition, we found that oxidative stress and mitochondrial dysfunction played important roles in iron overload‐induced cartilage degeneration, reducing iron concentration using iron chelator or antioxidant drugs could inhibit iron overload‐induced OA‐related catabolic markers and mitochondrial dysfunction. Our results suggest that pro‐inflammatory cytokines could disrupt chondrocytes iron homeostasis and promote iron influx, iron overload‐induced oxidative stress and mitochondrial dysfunction play important roles in iron overload‐induced cartilage degeneration.

TAM-ing the CIA-Tumor-Associated Macrophages and Their Potential Role in Unintended Side Effects of Therapeutics for Cancer-Induced Anemia.

Cancer-induced anemia (CIA) is a common consequence of neoplasia and has a multifactorial pathophysiology. The immune response and tumor treatment, both intended to primarily target malignant cells, also affect erythropoiesis in the bone marrow. In parallel, immune activation inevitably induces the iron-regulatory hormone hepcidin to direct iron fluxes away from erythroid progenitors and into compartments of the mononuclear phagocyte system. Moreover, many inflammatory mediators inhibit the synthesis of erythropoietin, which is essential for stimulation and differentiation of erythroid progenitor cells to mature cells ready for release into the blood stream. These pathophysiological hallmarks of CIA imply that the bone marrow is not only deprived of iron as nutrient but also of erythropoietin as central growth factor for erythropoiesis. Tumor-associated macrophages (TAM) are present in the tumor microenvironment and display altered immune and iron phenotypes. On the one hand, their functions are altered by adjacent tumor cells so that they promote rather than inhibit the growth of malignant cells. As consequences, TAM may deliver iron to tumor cells and produce reduced amounts of cytotoxic mediators. Furthermore, their ability to stimulate adaptive anti-tumor immune responses is severely compromised. On the other hand, TAM are potential off-targets of therapeutic interventions against CIA. Red blood cell transfusions, intravenous iron preparations, erythropoiesis-stimulating agents and novel treatment options for CIA may interfere with TAM function and thus exhibit secondary effects on the underlying malignancy. In this Hypothesis and Theory, we summarize the pathophysiological hallmarks, clinical implications and treatment strategies for CIA. Focusing on TAM, we speculate on the potential intended and unintended effects that therapeutic options for CIA may have on the innate immune response and, consequently, on the course of the underlying malignancy.

Sodium iodate induces ferroptosis in human retinal pigment epithelium ARPE-19 cells

Sodium iodate (SI) is a widely used oxidant for generating retinal degeneration models by inducing the death of retinal pigment epithelium (RPE) cells. However, the mechanism of RPE cell death induced by SI remains unclear. In this study, we investigated the necrotic features of cultured human retinal pigment epithelium (ARPE-19) cells treated with SI and found that apoptosis or necroptosis was not the major death pathway. Instead, the death process was accompanied by significant elevation of intracellular labile iron level, ROS, and lipid peroxides which recapitulated the key features of ferroptosis. Ferroptosis inhibitors deferoxamine mesylate (DFO) and ferrostatin-1(Fer-1) partially prevented SI-induced cell death. Further studies revealed that SI treatment did not alter GPX4 (glutathione peroxidase 4) expression, but led to the depletion of reduced thiol groups, mainly intracellular GSH (reduced glutathione) and cysteine. The study on iron trafficking demonstrated that iron influx was not altered by SI treatment but iron efflux increased, indicating that the increase in labile iron was likely due to the release of sequestered iron. This hypothesis was verified by showing that SI directly promoted the release of labile iron from a cell-free lysate. We propose that SI depletes GSH, increases ROS, releases labile iron, and boosts lipid damage, which in turn results in ferroptosis in ARPE-19 cells.

Potentially bioavailable iron produced through benthic cycling in glaciated Arctic fjords of Svalbard

The Arctic has the highest warming rates on Earth. Glaciated fjord ecosystems, which are hotspots of carbon cycling and burial, are extremely sensitive to this warming. Glaciers are important for the transport of iron from land to sea and supply this essential nutrient to phytoplankton in high-latitude marine ecosystems. However, up to 95% of the glacially-sourced iron settles to sediments close to the glacial source. Our data show that while 0.6–12% of the total glacially-sourced iron is potentially bioavailable, biogeochemical cycling in Arctic fjord sediments converts the glacially-derived iron into more labile phases, generating up to a 9-fold increase in the amount of potentially bioavailable iron. Arctic fjord sediments are thus an important source of potentially bioavailable iron. However, our data suggests that as glaciers retreat onto land the flux of iron to the sediment-water interface may be reduced. Glacial retreat therefore likely impacts iron cycling in coastal marine ecosystems.

Metabolomic analysis of the egg yolk during the embryonic development of broilers

The chicken egg yolk, which is abundant with lipids, proteins, and minerals, is the major nutrient resource for the embryonic development. In fact, the magnitude and type of yolk nutrients are dynamically changed during the chicken embryogenesis to meet the developmental and nutritional requests at different stages. The yolk nutrients are metabolized and absorbed by the yolk sac membrane and then used by the embryo or other extraembryonic tissues. Thus, understanding the metabolites in the yolk helps to unveil the developmental nutritional requirements for the chicken embryo. In this study, we performed ultra high performance liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS) analysis to investigate the change of metabolites in the egg yolk at embryonic (E) 07, E09, E11, E15, E17, and E19. The results showed that 1) the egg yolk metabolites at E07 and E09 were approximately similar, but E09, E11, E15, E17, and E19 were different from each other, indicating the developmental and metabolic change of the egg yolk; and 2) most of the metabolites were annotated in amino acid metabolism pathways from E11 to E15 and E17 to E19. Especially, arginine, lysine, cysteine, and histidine were continuously increased during the embryonic development, probably because of their effects on the growth promotion and oxidative stress amelioration of the embryo. Interestingly, the ferroptosis was found as one of major processes occurred from E15 to E17 and E17 to E19. Owing to the upregulated expression of acyl-CoA synthetase long-chain family member 4 detected in the yolk sac, we assumed that the ferroptosis of the yolk sac was perhaps caused by the accumulation of reactive oxygen species, which was induced by the large amount of polyunsaturated fatty acids and influx of iron in the yolk. Our findings might offer a novel understanding of embryonic nutrition of broilers according to the developmental changes of metabolites in the egg yolk and may provide new ideas to improve the health and nutrition for prehatch broiler chickens.

MYCN-Amplified Neuroblastoma Is Addicted to Iron and Vulnerable to Inhibition of the System Xc-/Glutathione Axis.

MYCN is amplified in 20% to 25% of neuroblastoma, and MYCN-amplified neuroblastoma contributes to a large percent of pediatric cancer-related deaths. Therapy improvements for this subtype of cancer are a high priority. Here we uncover a MYCN-dependent therapeutic vulnerability in neuroblastoma. Namely, amplified MYCN rewires the cell through expression of key receptors, ultimately enhancing iron influx through increased expression of the iron import transferrin receptor 1. Accumulating iron causes reactive oxygen species (ROS) production, and MYCN-amplified neuroblastomas show enhanced reliance on the system Xc- cystine/glutamate antiporter for ROS detoxification through increased transcription of this receptor. This dependence creates a marked vulnerability to targeting the system Xc-/glutathione (GSH) pathway with ferroptosis inducers. This reliance can be exploited through therapy with FDA-approved rheumatoid arthritis drugs sulfasalazine (SAS) and auranofin: in MYCN-amplified, patient-derived xenograft models, both therapies blocked growth and induced ferroptosis. SAS and auranofin activity was largely mitigated by the ferroptosis inhibitor ferrostatin-1, antioxidants like N-acetyl-L-cysteine, or by the iron scavenger deferoxamine (DFO). DFO reduced auranofin-induced ROS, further linking increased iron capture in MYCN-amplified neuroblastoma to a therapeutic vulnerability to ROS-inducing drugs. These data uncover an oncogene vulnerability to ferroptosis caused by increased iron accumulation and subsequent reliance on the system Xc-/GSH pathway. SIGNIFICANCE: This study shows how MYCN increases intracellular iron levels and subsequent GSH pathway activity and demonstrates the antitumor activity of FDA-approved SAS and auranofin in patient-derived xenograft models of MYCN-amplified neuroblastoma.

Feasibility of platinum recovery from waste automotive catalyst with different carriers via cooperative smelting-collection process

Large amounts of waste automotive catalyst (WAC) containing platinum are generated as the automotive scrapped, which not only wastes platinum resources, but also causes environment impacts if WAC is not addressed. In this research, a novel and effective smelting-collection process for recovering platinum from WAC was proposed. The different WAC carriers (cordierite carrier and alumina carrier) are mixed and subjected to smelting-collection with the addition of collector metal of iron powder and flux agent of CaO. The carrier materials serves as slag constituents, and the addition of extra slagging flux such as SiO2 and Al2O3 was nearly avoided compared to platinum recovery from single WAC carrier. Experimental results indicated that the maximum platinum recovery was over 98%, when cordierite carrier WAC addition, collector metal addition, CaO/SiO2 mass ratio, smelting temperature, and holding time were 80 wt%, 10.5 wt%, 0.5, 1550 °C and 120 min, respectively. After smelting, platinum is concentrated into Fe–Pt alloy, and the glass slag which is believed to be safe to the environment is obtained. The results indicated that platinum content in obtained alloy and glass slag was 0.63 wt% and 9.4 g/t, respectively. This proposed process is an effective and economical approach for recovery platinum from WAC.

Iron Overload Is Associated With Accelerated Progression of Osteoarthritis: The Role of DMT1 Mediated Iron Homeostasis

Objective: Iron overload is common in elderly people which is associated with an increased prevalence of osteoarthritis (OA), but the exact role of iron in the development of OA has not been established. The aim of the present study is to elucidate the connection between iron overload and OA using an iron overloaded mice model, as well as to explore the role of iron homeostasis, iron transporters dependent iron influx in OA pathogenesis.Methods: The iron overloaded mice model was established and OA was surgically induced. OA progression was assessed at 8 weeks after surgery. Next, primary chondrocytes were treated with pro-inflammatory cytokines and iron regulators mediated iron homeostasis were evaluated. Involvement of iron transporters was analyzed using chondrocytes mimicking an osteoarthritis-related phenotype in vitro.Results: Iron overloaded mice exhibited greater cartilage destruction and elevated ADAMTS5 as well as MMP13 expression along with increased iron accumulation and dysregulated iron regulators. Pro-inflammatory cytokines could disturb cellular iron homeostasis via upregulating iron import proteins, TFR1 and DMT1, downregulating iron efflux protein FPN, thus result in cellular iron overload. Among iron transporters, DMT1 was found to play pivotal roles in iron overload induced OA progress. Inhibition of DMT1 suppressed IL-1β induced inflammatory response and ECM degradation via blockade of MAPK and PI3K/AKT/NF-κB pathways.Conclusions: Our results suggest that iron takes parts in the development of OA and cutting iron influx via inhibiting DMT1 activity could be an attractive new target for OA treatment.

Seasonal and Inter Annual Variations between Concentrations and Fluxes of Dissolved and Particulate Organic Carbon, Iron and Manganese from the Northern Dvina River to the White Sea

The paper presents new data on concentrations and fluxes of organic carbon, iron, and manganese in waters of the mouth area of the Northern Dvina River. The work was conducted within the project “Northern Dvina River Marginal Filter Observatory” from May 2015 to May 2019 with monthly collection of water samples. Systematic determinations of the concentrations of the main carrier elements of many trace elements in dissolved and particulate forms were used to establish the average weighted of Corg, Fe, and Mn concentrations. The results of 4 years of systematic investigations established the main regularities of seasonal variations of dissolved and particulate forms of element concentrations and the relationships between. Significant variations were observed not only between concentrations but also between fluxes of elements in both forms. However, more than half the annual fluxes of all elements in all years studied was transported to the sea in the spring flood period. The results also demonstrated significant variations between element concentrations and their fluxes in different years. This is unsurprising, since even during the 4 years of investigations, the difference between water runoff and SPM fluxes in different years was up to, respectively, 1.4 and 2.6 times.

A Rotary-Linear SPM Voice Coil Motor With PM Flux Bridges for Output Performance Improvement

This paper proposes a rotary-linear surface-mounted permanent magnet (PM) voice coil motor (RL-SVCM) with PM flux bridges in place of the iron flux bridges in a traditional RL-SVCM for enhancing average torque and force ripple but slight damage of torque ripple and average linear force. The iron flux bridges in a basic RL-SVCM cannot participate in the generation of rotary torque. In contrast, the PM flux bridges in the proposed RL-SVCM can participate in the generation of rotary torque. The magnetic equivalent circuit (MEC) is used to analyze the magnetic circuits of the basic and proposed models. The results explain the reasons for the performance improvements achieved by the proposed motor. The finite element method (FEM) is used to derive the precise output performance of the basic and proposed motors. Additionally, a prototype of the proposed RL-SVCM with PM flux bridges was manufactured for experimental verification. Close agreement between the experimental results and FEM results validates the feasibility of the proposed RL-SVCM.

Decreasing brain iron in multiple sclerosis: The difference between concentration and content in iron MRI.

Increased brain iron concentration is often reported concurrently with disease development in multiple sclerosis (MS) and other neurodegenerative diseases. However, it is unclear whether the higher iron concentration in patients stems from an influx of iron into the tissue or a relative reduction in tissue compartments without much iron. By taking into account structural volume, we investigated tissue iron content in the deep gray matter (DGM) over 2 years, and compared findings to previously reported changes in iron concentration. 120 MS patients and 40 age‐ and sex‐matched healthy controls were included. Clinical testing and MRI were performed both at baseline and after 2 years. Overall, iron content was calculated from structural MRI and quantitative susceptibility mapping in the thalamus, caudate, putamen, and globus pallidus. MS patients had significantly lower iron content than controls in the thalamus, with progressive MS patients demonstrating lower iron content than relapsing–remitting patients. Over 2 years, iron content decreased in the DGM of patients with MS, while it tended to increase or remain stable among controls. In the thalamus, decreasing iron content over 2 years was associated with disability progression. Our study showed that temporally increasing magnetic susceptibility in MS should not be considered as evidence for iron influx because it may be explained, at least partially, by disease‐related atrophy. Declining DGM iron content suggests that, contrary to the current understanding, iron is being removed from the DGM in patients with MS.