A Large Proportion of the Neonatal Iron Pool Is Acquired from the Gestational Diet in a Murine Model.

BACKGROUND: Iron is crucial for growth and development, but excess iron is harmful. Neonatal mice have elevated concentrations of circulating iron, but the source of this iron is unclear. This lack of understanding makes it difficult to optimize early life iron balance. OBJECTIVES: Identify the origins of neonatal tissue-specific iron pools using dietary manipulation and cross-fostering murine models. METHODS: To determine whether tissue-specific neonatal iron was primarily acquired during gestation or after birth, pups born to iron-sufficient or iron-deficient dams were cross-fostered, and tissues were harvested at postnatal days 3-5 to measure iron content. A separate set of female mice were fed a diet enriched with the stable iron isotope 57 (57Fe) for 4 generations to replace naturally abundant liver iron isotope 56 (56Fe) stores with 57Fe. To quantify the proportions of neonatal iron acquired during gestation, pups born to dams with 56Fe or 57Fe stores were cross-fostered, and tissues were harvested at postnatal day 3-5 to determine 56Fe:57Fe ratios by inductively coupled plasma mass spectrometry. Finally, to quantify the proportion of neonatal iron acquired from the maternal diet, female mice with 56Fe or 57Fe stores switched diets upon mating, and pup tissues were harvested on P0 to determine 56Fe:57Fe ratios by inductively coupled plasma mass spectrometry. RESULTS: Perinatal iron deficiency resulted in smaller pups, and gestational iron deficiency resulted in lower neonatal serum and liver iron. Cross-fostering between dams with 56Fe and 57Fe stores demonstrated that ≤70% of neonatal serum, liver, and brain iron were acquired during gestation. Dietary manipulation experiments using dams with 56Fe and 57Fe stores showed that over half of neonatal serum, liver, and brain iron were from the dam's gestational diet rather than preconception iron stores. CONCLUSIONS: This study provides quantitative values for the sources of neonatal iron, which may inform approaches to optimize neonatal iron status.

Precise measurement of Fe isotopes in marine and biological samples by pseudo-high-resolution multi-collector inductively coupled plasma mass spectrometry (MC-ICPMS).

This paper introduces an enhanced technique for analyzing iron isotopes in complex marine and biological samples. A dedicated iron purification method for biological marine matrices, utilizing three ion exchange columns, is validated. The MC-ICPMS in pseudo-high-resolution mode determines precise iron isotopic ratios, with sensitivity improved through the DSN-100 desolvating nebulizer system and Apex-IR. Only 2 µg of iron on DSN versus 1 µg on Apex is needed for six replicates (30-60 times improvement) while 10 to 20 µg is required for a single measurement on a wet system considering the resolution power (Rp) is maintained at 11,000-13,000. The Ni-doping method with a Fe/Ni ratio of 1 yields more accurate isotopic ratios than standard-sample bracketing alone. Measurement reproducibility of triplicate samples from marine biological experiments on MC-ICPMS is ± 0.03‰ (2SD) for δ56Fe and ± 0.07‰ for δ57Fe (2SD). This study introduces a novel iron purification process specifically designed for marine and biological samples, enhancing sensitivity and enabling more reliable measurements with smaller sample sizes and reduced uncertainties. It proposes iron isotopic compositions for biological reference materials, offering a valuable reference dataset in diverse scientific disciplines.

Iron colloids dominate sedimentary supply to the ocean interior.

Dissolution of marine sediment is a key source of dissolved iron (Fe) that regulates the ocean carbon cycle. Currently, our prevailing understanding, encapsulated in ocean models, focuses on low-oxygen reductive supply mechanisms and neglects the emerging evidence from iron isotopes in seawater and sediment porewaters for additional nonreductive dissolution processes. Here, we combine measurements of Fe colloids and dissolved δ56Fe in shallow porewaters spanning the full depth of the South Atlantic Ocean to demonstrate that it is lithogenic colloid production that fuels sedimentary iron supply away from low-oxygen systems. Iron colloids are ubiquitous in these oxic ocean sediment porewaters and account for the lithogenic isotope signature of dissolved Fe (δ56Fe = +0.07 ± 0.07‰) within and between ocean basins. Isotope model experiments demonstrate that only lithogenic weathering in both oxic and nitrogenous zones, rather than precipitation or ligand complexation of reduced Fe species, can account for the production of these porewater Fe colloids. The broader covariance between colloidal Fe and organic carbon (OC) abundance suggests that sorption of OC may control the nanoscale stability of Fe minerals by inhibiting the loss of Fe(oxyhydr)oxides to more crystalline minerals in the sediment. Oxic ocean sediments can therefore generate a large exchangeable reservoir of organo-mineral Fe colloids at the sediment water interface (a "rusty source") that dominates the benthic supply of dissolved Fe to the ocean interior, alongside reductive supply pathways from shallower continental margins.

Anthropogenic Asian aerosols provide Fe to the North Pacific Ocean.

Fossil-fuel emissions may impact phytoplankton primary productivity and carbon cycling by supplying bioavailable Fe to remote areas of the ocean via atmospheric aerosols. However, this pathway has not been confirmed by field observations of anthropogenic Fe in seawater. Here we present high-resolution trace-metal concentrations across the North Pacific Ocean (158°W from 25°to 42°N). A dissolved Fe maximum was observed around 35°N, coincident with high dissolved Pb and Pb isotope ratios matching Asian industrial sources and confirming recent aerosol deposition. Iron-stable isotopes reveal in situ evidence of anthropogenic Fe in seawater, with low δ56Fe (-0.23‰ > δ56Fe > -0.65‰) observed in the region that is most influenced by aerosol deposition. An isotope mass balance suggests that anthropogenic Fe contributes 21-59% of dissolved Fe measured between 35° and 40°N. Thus, anthropogenic aerosol Fe is likely to be an important Fe source to the North Pacific Ocean.

Iron Isotopes in Acid Mine Drainage: Extreme and Divergent Fractionation between Solid (Schwertmannite, Jarosite, and Ferric Arsenate) and Aqueous Species.

Examination of stable Fe isotopes is a powerful tool to explore Fe cycling in a range of environments. However, the isotopic fractionation of Fe in acid mine drainage (AMD) has received little attention and is poorly understood. Here, we analyze Fe isotopes in waters and Fe(III)-rich solids along an AMD flow-path. Aqueous Fe spanned a concentration and δ56Fe range of ∼420 mg L-1 and + 0.04‰ at the AMD source to ∼100 mg L-1 and -0.81‰ at ∼450 m downstream. Aqueous As (up to ∼33 mg L-1) and SO42- (up to ∼2000 mg L-1), like aqueous Fe, decreased in concentration down the flow-path. X-ray absorption spectroscopy indicated that downstream attenuation in aqueous Fe, As, and SO42- was due to the precipitation of amorphous ferric arsenate (AFA), schwertmannite, and jarosite. The Fe(III) in these solids displayed extreme variability in δ56Fe, spanning +3.95‰ in AFA near the AMD source to -1.34‰ in schwertmannite at ∼450 m downstream. Similarly, the isotopic contrast between solid Fe(III) precipitates and aqueous Fe (Δ56Feppt-aq) dropped along the flow-path from about +4.1 to -1.1‰. The shift from positive to negative Δ56Feppt-aq reflects divergence between competing equilibrium versus kinetic fractionation processes.

Large Fractionation in Iron Isotopes Implicates Metabolic Pathways for Iron Cycling in Boreal Shield Lakes.

Stable Fe isotopes have only recently been measured in freshwater systems, mainly in meromictic lakes. Here we report the δ56Fe of dissolved, particulate, and sediment Fe in two small dimictic boreal shield headwater lakes: manipulated eutrophic Lake 227, with annual cyanobacterial blooms, and unmanipulated oligotrophic Lake 442. Within the lakes, the range in δ56Fe is large (ca. -0.9 to +1.8‰), spanning more than half the entire range of natural Earth surface samples. Two layers in the water column with distinctive δ56Fe of dissolved (dis) and particulate (spm) Fe were observed, despite differences in trophic states. In the epilimnia of both lakes, a large Δ56Fedis-spm fractionation of 0.4-1‰ between dissolved and particulate Fe was only observed during cyanobacterial blooms in Lake 227, possibly regulated by selective biological uptake of isotopically light Fe by cyanobacteria. In the anoxic layers in both lakes, upward flux from sediments dominates the dissolved Fe pool with an apparent Δ56Fedis-spm fractionation of -2.2 to -0.6‰. Large Δ56Fedis-spm and previously published metagenome sequence data suggest active Fe cycling processes in anoxic layers, such as microaerophilic Fe(II) oxidation or photoferrotrophy, could regulate biogeochemical cycling. Large fractionation of stable Fe isotopes in these lakes provides a potential tool to probe Fe cycling and the acquisition of Fe by cyanobacteria, with relevance for understanding biogeochemical cycling of Earth's early ferruginous oceans.

Surface Ocean Biogeochemistry Regulates the Impact of Anthropogenic Aerosol Fe Deposition on the Cycling of Iron and Iron Isotopes in the North Pacific.

Distinctively-light isotopic signatures associated with Fe released from anthropogenic activity have been used to trace basin-scale impacts. However, this approach is complicated by the way Fe cycle processes modulate oceanic dissolved Fe (dFe) signatures (δ56Fediss) post deposition. Here we include dust, wildfire, and anthropogenic aerosol Fe deposition in a global ocean biogeochemical model with active Fe isotope cycling, to quantify how anthropogenic Fe impacts surface ocean dFe and δ56Fediss. Using the North Pacific as a natural laboratory, the response of dFe, δ56Fediss, and primary productivity are spatially and seasonally variable and do not simply follow the footprint of atmospheric deposition. Instead, the effect of anthropogenic Fe is regulated by the biogeochemical regime, specifically the degree of Fe limitation and rates of primary production. Overall, we find that while δ56Fediss does trace anthropogenic input, the response is muted by fractionation during phytoplankton uptake, but amplified by other isotopically-light Fe sources.

Methodological Considerations for Investigating Iron Status and Regulation in Exercise and Sport Science Studies.

Iron deficiency is a common health issue in active and athlete populations. Accordingly, research into iron status, regulation, absorption, and iron deficiency treatment strategies is increasing at a rapid rate. However, despite the increase in the quantity of research, various methodological issues need to be addressed as we progress our knowledge in this area. The purpose of this review is to highlight specific considerations for conducting iron-related research in active and athlete populations. First, we discuss the methodological importance of assessment and interpretation of iron status, with reference to blood collection protocols, participant screening procedures, and biomarker selection. Next, we consider numerous variables that should be accounted for in the design of iron-related research studies, such as the iron regulatory hormone hepcidin and its interaction with exercise, in addition to an examination of female physiology and its impact on iron metabolism. Subsequently, we explore dietary iron and nutrient interactions that impact iron regulation and absorption, with recommendations made for optimal methodological control. Consideration is then given to key features of long-term study designs, such as the monitoring of training load, oral iron supplementation, dietary analysis, and general lifestyle factors. Finally, we conclude our recommendations with an exploration of stable iron isotope tracers as a methodology to measure iron absorption. Ultimately, it is our intention that this review can be used as a guide to improve study design, biomarker analysis, and reporting of findings, to maximize the quality of future research outputs in iron-related research focused on active and athlete populations.

Measurement of long-term iron absorption and loss during iron supplementation using a stable isotope of iron (57 Fe).

We report the first measurements of long-term iron absorption and loss during iron supplementation in African children using a stable isotope of iron (57 Fe). After uniform labelling of body iron with 57 Fe, iron absorption is proportional to the rate of decrease in the 57 Fe tracer concentration, while iron loss is proportional to the rate of decrease in the 57 Fe tracer amount. Anaemic Gambian toddlers were given 2 mg 57 Fe orally to equilibrate with total body iron over 8-11 months. After assignment to the positive control arm of the HIGH study, 22 toddlers consumed a micronutrient powder containing 12 mg iron for 12 weeks followed by 12 weeks without iron supplementation. Their daily iron absorption increased 3·8-fold during the iron supplementation period compared to the control period [median (interquartile range, IQR): 1·00 (0·82; 1·28) mg/day vs. 0·26 (0·22; 0·35) mg/day; P = 0·001]. Unexpectedly, during the supplementation period, daily iron loss also increased by 3·4-fold [0·75 (0·55; 0·87) mg/day vs. 0·22 (0·19; 0·29) mg/day; P = 0·005]. Consequently, most (~72%) of the absorbed iron was lost during supplementation. Long-term studies of iron absorption and loss are a promising and accurate method for assessing and quantifying long-term iron balance and may provide a reference method for evaluating iron intervention programs in vulnerable population groups. This study was registered as ISRCTN 0720906.

Constraints on the Cycling of Iron Isotopes From a Global Ocean Model.

Although iron (Fe) is a key regulator of primary production over much of the ocean, many components of the marine iron cycle are poorly constrained, which undermines our understanding of climate change impacts. In recent years, a growing number of studies (often part of GEOTRACES) have used Fe isotopic signatures (δ56Fe) to disentangle different aspects of the marine Fe cycle. Characteristic δ56Fe endmembers of external sources and assumed isotopic fractionation during biological Fe uptake or recycling have been used to estimate relative source contributions and investigate internal transformations, respectively. However, different external sources and fractionation processes often overlap and act simultaneously, complicating the interpretation of oceanic Fe isotope observations. Here we investigate the driving forces behind the marine dissolved Fe isotopic signature (δ56Fediss) distribution by incorporating Fe isotopes into the global ocean biogeochemical model PISCES. We find that distinct external source endmembers acting alongside fractionation during organic complexation and phytoplankton uptake are required to reproduce δ56Fediss observations along GEOTRACES transects. δ56Fediss distributions through the water column result from regional imbalances of remineralization and abiotic removal processes. They modify δ56Fediss directly and transfer surface ocean signals to the interior with opposing effects. Although attributing crustal compositions to sedimentary Fe sources in regions with low organic carbon fluxes improves our isotope model, δ56Fediss signals from hydrothermal or sediment sources cannot be reproduced accurately by simply adjusting δ56Fe endmember values. This highlights that additional processes must govern the exchange and/or speciation of Fe supplied by these sources to the ocean.

Leonardite iron humate and synthetic iron chelate mixtures in Glycine max nutrition.

BACKGROUND: The aim of this work was to study the possible synergic effect between mixtures with iron leonardite humate (L/Fe3+ ) and synthetic chelates iron (Ch/Fe3+ : o,oEDDHA /Fe3+ or HBED/Fe3+ ), and to reevaluate the classical chelate shuttle-effect model. Different molar ratios of L/Fe3+ :Ch/Fe3+ , different doses, and different sampling times were used in hydroponic and soil experiments using soybean (Glycine max) as a model Strategy I crop in calcareous conditions. Ligand competition between the humate and chelating agents was also examined. RESULTS: Iron humate participates in the chelate shuttle mechanism, providing available Fe to the chelating agent and then to the plants, showing a slight synergic effect. After a few days, the contribution of the chelates to the Fe nutrition decreases substantially, but the contribution of the humates is maintained. CONCLUSIONS: The most efficient ratio was two parts of iron humates and one part of iron chelate. In particular, HBED/Fe3+ was the most suitable iron chelate because its lasting effect fits the iron humate long-term effect better. The soluble iron in soil increased and the shoot-to-root iron translocation improved due to a synergic effect by a shuttle effect exerted by iron chelate in the mixture. © 2021 Society of Chemical Industry.

Iron isotopes reveal distinct dissolved iron sources and pathways in the intermediate versus deep Southern Ocean.

As an essential micronutrient, iron plays a key role in oceanic biogeochemistry. It is therefore linked to the global carbon cycle and climate. Here, we report a dissolved iron (DFe) isotope section in the South Atlantic and Southern Ocean. Throughout the section, a striking DFe isotope minimum (light iron) is observed at intermediate depths (200-1,300 m), contrasting with heavier isotopic composition in deep waters. This unambiguously demonstrates distinct DFe sources and processes dominating the iron cycle in the intermediate and deep layers, a feature impossible to see with only iron concentration data largely used thus far in chemical oceanography. At intermediate depths, the data suggest that the dominant DFe sources are linked to organic matter remineralization, either in the water column or at continental margins. In deeper layers, however, abiotic non-reductive release of Fe (desorption, dissolution) from particulate iron-notably lithogenic-likely dominates. These results go against the common but oversimplified view that remineralization of organic matter is the major pathway releasing DFe throughout the water column in the open ocean. They suggest that the oceanic iron cycle, and therefore oceanic primary production and climate, could be more sensitive than previously thought to continental erosion (providing lithogenic particles to the ocean), particle transport within the ocean, dissolved/particle interactions, and deep water upwelling. These processes could also impact the cycles of other elements, including nutrients.

Iron stable isotopes track pelagic iron cycling during a subtropical phytoplankton bloom.

The supply and bioavailability of dissolved iron sets the magnitude of surface productivity for ∼ 40% of the global ocean. The redox state, organic complexation, and phase (dissolved versus particulate) of iron are key determinants of iron bioavailability in the marine realm, although the mechanisms facilitating exchange between iron species (inorganic and organic) and phases are poorly constrained. Here we use the isotope fingerprint of dissolved and particulate iron to reveal distinct isotopic signatures for biological uptake of iron during a GEOTRACES process study focused on a temperate spring phytoplankton bloom in subtropical waters. At the onset of the bloom, dissolved iron within the mixed layer was isotopically light relative to particulate iron. The isotopically light dissolved iron pool likely results from the reduction of particulate iron via photochemical and (to a lesser extent) biologically mediated reduction processes. As the bloom develops, dissolved iron within the surface mixed layer becomes isotopically heavy, reflecting the dominance of biological processing of iron as it is removed from solution, while scavenging appears to play a minor role. As stable isotopes have shown for major elements like nitrogen, iron isotopes offer a new window into our understanding of the biogeochemical cycling of iron, thereby allowing us to disentangle a suite of concurrent biotic and abiotic transformations of this key biolimiting element.

Menopause effect on blood Fe and Cu isotope compositions.

Iron (δ(56) Fe) and copper (δ(65) Cu) stable isotope compositions in blood of adult human include a sex effect, which still awaits a biological explanation. Here, we investigate the effect of menopause by measuring blood δ(56) Fe and δ(65) Cu values of aging men and women. The results show that, while the Fe and Cu isotope compositions of blood of men are steady throughout their lifetime, postmenopausal women exhibit blood δ(65) Cu values similar to men, and δ(56) Fe values intermediate between men and premenopausal women. The residence time of Cu and Fe in the body likely explains why the blood δ(65) Cu values, but not the δ(56) Fe values, of postmenopausal women resemble that of men. We suggest that the Cu and Fe isotopic fractionation between blood and liver resides in the redox reaction occurring during hepatic solicitation of Fe stores. This reaction affects the Cu speciation, which explains why blood Cu isotope composition is impacted by the cessation of menstruations. Considering that Fe and Cu sex differences are recorded in bones, we believe this work has important implications for their use as a proxy of sex or age at menopause in past populations.

Novel Insights into Marine Iron Biogeochemistry from Iron Isotopes.

The micronutrient iron plays a major role in setting the magnitude and distribution of primary production across the global ocean. As such, an understanding of the sources, sinks, and internal cycling processes that drive the oceanic distribution of iron is key to unlocking iron's role in the global carbon cycle and climate, both today and in the geologic past. Iron isotopic analyses of seawater have emerged as a transformative tool for diagnosing iron sources to the ocean and tracing biogeochemical processes. In this review, we summarize the end-member isotope signatures of different iron source fluxes and highlight the novel insights into iron provenance gained using this tracer. We also review ways in which iron isotope fractionation might be used to understand internal oceanic cycling of iron, including speciation changes, biological uptake, and particle scavenging. We conclude with an overview of future research needed to expand the utilization of this cutting-edge tracer.

Iron isotopic fractionation driven by low-temperature biogeochemical processes.

Iron is geologically important and biochemically crucial for all microorganisms, plants and animals due to its redox exchange, the involvement in electron transport and metabolic processes. Despite the abundance of iron in the earth crust, its bioavailability is very limited in nature due to its occurrence as ferrihydrite, goethite, and hematite where they are thermodynamically stable with low dissolution kinetics in neutral or alkaline environments. Organisms such as bacteria, fungi, and plants have evolved iron acquisition mechanisms to increase its bioavailability in such environments, thereby, contributing largely to the iron cycle in the environment. Biogeochemical cycling of metals including Fe in natural systems usually results in stable isotope fractionation; the extent of fractionation depends on processes involved. Our review suggests that significant fractionation of iron isotopes occurs in low-temperature environments, where the extent of fractionation is greatly governed by several biogeochemical processes such as redox reaction, alteration, complexation, adsorption, oxidation and reduction, with or without the influence of microorganisms. This paper includes relevant data sets on the theoretical calculations, experimental prediction, as well as laboratory studies on stable iron isotopes fractionation induced by different biogeochemical processes.

Bioturbation and the δ56Fe signature of dissolved iron fluxes from marine sediments.

We developed a reaction-transport model capable of tracing iron isotopes in marine sediments to quantify the influence of bioturbation on the isotopic signature of the benthic dissolved (DFe) flux. By fitting the model to published data from marine sediments, we calibrated effective overall fractionation factors for iron reduction (-1.3‰), oxidation (+0.4‰), iron-sulfide precipitation (+0.5‰) and dissolution (-0.5‰) and pyrite precipitation (-0.7‰) that agree with literature values. Results show that for bottom-water oxygen concentrations greater than 50 µM, higher bioturbation increased the benthic DFe flux and its δ 56Fe signature. By contrast, for oxygen concentrations less than 50 µM, higher bioturbation decreased the benthic DFe flux and its δ 56Fe signature. The expressed overall fractionation of the benthic DFe flux relative to the δ 56Fe of the iron oxides entering the sediment ranges from -1.67‰ to 0.0‰. On a global scale, the presence of bioturbation increases sedimentary DFe release from approximately 70 G mol DFe yr-1 to approximately 160 G mol DFe yr-1 and decreases the δ 56Fe signature of the DFe flux.

Tracing Fe cycle isotopically in soils based on different land uses: Insight from a typical karst catchment, Southwest China.

Iron (Fe) isotopes can effectively unveil the Fe cycle mechanisms under redox and biological conditions during the weathering and pedogenic processes. Fe contents and Fe isotope compositions (defined as δ56Fe) in the soil profiles under secondary forest land, abandoned cropland and shrubland were investigated in a typical karst area in Southwest China. The results showed that the Fe content ranged from 23.92 to 38.56 g/kg, 21.92 to 33.02 g/kg and 12.98 to 27.93 g/kg, and the δ56Fe levels varied from -0.48 ‰ to 0.21 ‰, -0.24 ‰ to 0.11 ‰ and - 0.11 ‰ to 0.16 ‰ from the secondary forest land, abandoned cropland and shrubland, respectively. The correlation analysis results showed that Fe transportation and isotopic fractionation were regulated by the redox processes through soil pH and soil organic matter (SOM) in the abandoned cropland and shrubland. Heavier Fe isotope may be accumulated in the deeper soil of secondary forest land due to Fe-oxide precipitation. The Fe isotope fractionations were greatly altered by soil organic carbon (SOC) in surface soils due to negative surface charges. Soil pH also plays a key role in enriching lighter Fe in a medium-acidic environment (shrubland) by ligand-controlled dissolution and reductive dissolution. Long-term cultivation in abandoned cropland and grazing in shrubland reshaped the Fe cycle in soil profiles by changing soil pH and SOC contents. However, the similar values of δ56Fe in different land use soils indicated that the agricultural activities have no significant impact on the Fe transformation in karst soil ecosystems. The land utilization is reasonable in the Yinjiang County. This study provided effective data and insightful analysis to understand the Fe cycle processes in the karst soils under varied land uses.

Recruitment and Retention of Urban Pregnant Women to a Clinical Study Administering an Oral Isotope Dietary Tracer.

Introduction: Pregnant women are a vulnerable population that are difficult to engage in clinical research. We report successful recruitment and retention strategies used in a longitudinal pilot study of urban racially/ethnically diverse pregnant women that involved administration of an orally ingested isotope tracer, multiple venipunctures, biopsy of placenta after delivery, and cord or placental blood collection. Materials and Methods: We used direct strategies to recruit English-speaking obese and nonobese pregnant women aged 17-45 years, who were in the third trimester of pregnancy. The study required data collection at 32-34 and 34-36 gestational weeks and delivery. Strategies included frequent personal engagement with participants and staff to build relationships and trust, tangible appreciation, and the study team being present at delivery. In addition, leveraging hospital information technology (IT) services was critical to ensure retention through labor and delivery (LD). Results: A racially (52% Black, 23% White, and 10% other) and ethnically (15% Hispanic or Latinx) diverse sample of pregnant women was enrolled. Of the 52 women enrolled, 85% of women completed all procedures. Conclusions: This is the first report of successful strategies for recruitment and retention of racially/ethnically diverse pregnant women in a longitudinal study requiring oral administration of an isotope tracer. Personal engagement with multiple touch points, starting with recruitment and continuing regularly throughout the third trimester, was the most successful strategy. Creating and maintaining relationships with the LD providers and staff and utilizing hospital IT, including targeted electronic medical record alerts, ensured successful retention for the duration of the study. Trial Registration: Not applicable.

Isotopic reconstruction of iron oxidation-reduction process based on an Archean Ocean analogue.

The chemical composition and redox conditions of the Precambrian ocean are key factors for reconstructing the temporal evolution of atmospheric oxygen through time. In particular, the isotopic composition of iron are useful proxies for reconstructing paleo-ocean environments. Yet, respective processes and related signatures are poorly constrained, hindering the reconstruction of iron redox mechanisms in the Archean ocean. This study centers on Sihailongwan Lake, a stratified water body with a euxinic lower water column considered as an Archean ocean analogue. Results show that the anaerobic oxidation layer is so different from other similar lakes in which dissolved Fe oxidation is present in redoxcline layer. And the fractionation factor between ferrous Fe and iron hydroxide observed in nature water body of Sihailongwan Lake reaches to 2.6‰, which would benefit the production of the oxidations of BIF in sediment. By the spatial distribution of Fe isotope, the benthic water in autumn and the hypolimnetic anoxic water in spring has been identified as iron sulfide zone, where iron isotopic fractionation factor during iron sulfide formation is 1.16‰, accounting for partial scavenging of dissolved Fe(II) with an associated isotopic fractionation. However, pyrite in the sediment records the iron isotopic signal from the redoxcline but not in the iron sulfide or oxide zones of the water column. Above findings indicate that neither the iron isotope fractionation during partial transfer of ferrous iron to iron sulfide nor the partial oxidation of ferrous iron are recorded as pyrite in sedimentary rock. Importantly, the signal of Fe isotopic fractionation in water was archived in the suspended particulate matter and transferred into the sediment, rather than via ferrous iron directly deposited in the sediment. This study reveals that Fe isotopes from modern natural environments are useful proxies for reconstructing iron oxidation-reduction process during Earth's early history.