Iron and ferritin effects on intensive care unit mortality:A metaanalysis

BACKGROUND The effect of serum iron or ferritin parameters on mortality among critically ill patients is not well characterized.AIM To determine the association between serum iron or ferritin parameters and mortality among critically ill patients.METHODS Web of Science,Embase,PubMed,and Cochrane Library databases were searched for studies on serum iron or ferritin parameters and mortality among critically ill patients.Two reviewers independently assessed,selected,and abstracted data from studies reporting on serum iron or ferritin parameters and mortality among critically ill patients.Data on serum iron or ferritin levels,mortality,and demographics were extracted.RESULTS Nineteen studies comprising 125490 patients were eligible for inclusion.We observed a slight negative effect of serum ferritin on mortality in the United States population[relative risk(RR)1.002;95%CI:1.002-1.004].In patients with sepsis,serum iron had a significant negative effect on mortality(RR=1.567;95%CI:1.208-1.925).CONCLUSION This systematic review presents evidence of a negative correlation between serum iron levels and mortality among patients with sepsis.Furthermore,it reveals a minor yet adverse impact of serum ferritin on mortality among the United States population.

Iron and Heart Failure: Current Concepts and Emerging Pharmacological Paradigms

Background: Emerging evidence has recognized that anemia and iron deficiency are recurrent comorbidities in chronic heart failure (HF) and several trials have established that iron administration improves myocardial asset and clinical scenario in HF. Purpose: Recent acquisitions suggest that iron deficiency represents a concrete bias in the pathogenetic mechanism of chronic HF, so we have investigated the putative role of the hepcidin/ferroportin axis in the cardiovascular setting to advocate novel pharmacological and clinical approaches. Methods: Here, after an excursus on iron metabolism, we first reviewed the ongoing studies on novel iron targeted compounds. Then, we summarize large clinical interventional studies conducted on patient suffering from iron deficiency and HF which have tested the effects of drugging iron regard QoL, hospitalizations and cardiovascular death. Results: Novel compounds such as hepcidin agonist (PTG 300), synthetic human hepcidin (LJPC-401) and anti FPN (Vamifeport) are ongoing in iron overloaded patients, while the hepcidin blocker (PRS-080) is under investigation in anemic patients. Noteworthy, novel insights could arise from the results of a Phase IV interventional study regarding the modification of hepcidin pathway in a large cohort of HF patients (n = 1992) by sodium glucose cotransporter 2 inhibitors. To date, several studies highlight the beneficial effect of iron administration in cardiovascular setting and latest evidences consider hepcidin level as a novel biomarker of cardiac injury and atherosclerosis. Conclusions: We advocate that data from ongoing studies will suggest novel iron targeted therapies for diagnosis, prognosis and therapy transferable in selected heart failed patients.

Parenteral iron therapy in children with iron deficiency anemia

Iron deficiency anemia(IDA)continues to be a global public health problem.Oral iron is the universally accepted first-line therapy,and most children have a prompt and favorable response to oral formulations.In subsets of children who fail to respond due to intolerance,poor adherence,or inadequate intestinal absorption,parenteral iron is indicated.Despite numerous studies in adults with IDA of diverse etiologies,pediatric studies on parenteral iron use are very limited.Although mostly retrospective and small,these studies have documented the efficacy and safety profile of intravenous iron formulations.In this editorial the author comments on the most important published data and underscores the need to seriously consider parenteral iron use in children unresponsive to oral therapy.

Iron regulatory protein 1: the deadly switch of ferroptosis

Ferroptosis,an iron-dependent cell death:Ferroptosis is a type of regulated necrosis,characterized by redox-active iron accumulation and increased free radical production derived by Fenton chemistry,that triggers oxidation of polyunsaturated fatty acids in phospholipids,loss of cellular membranes integrity,and leakage of intracellular contents.

Iron-Deficiency Anemia Management in Gynecological Surgery: A Review of Current Evidence and Best Practices

Purpose: Due to the high prevalence of iron deficiency anemia in women undergoing gynecological surgeries and its association with worse postoperative results, it is necessary to identify and treat anemia preoperatively. However, although anemia and iron deficiency are significant global health problems, there are still disparities in the recognition and implementation of “Patient Blood Management” (PBM) as a comprehensive approach to mitigating the risks associated with these diseases. The purpose of the study is to review best practices for the treatment of anemia based on the Enhanced Recovery After Surgery (ERAS) protocol and PBM recommendations. Methods: This study reviewed the literature on preoperative iron deficiency anemia in patients undergoing gynecological surgery. We identified references through searches in PubMed using relevant search terms. Results: Among the various strategies used in PBM, perhaps the most important is the early detection and management of anemia. In gynecological surgery, there are several approaches to reducing perioperative blood loss, highlighting the use of gonadotropin-releasing hormone (GnRH) agonists (aGnRh) and antifibrinolytics. Oral and intravenous iron supplementation can be performed in addition to blood transfusion to treat anemia. Conclusion: Addressing preoperative and postoperative anemia through systematic correction, following the guidelines of the ERAS protocol and PBM guidelines, is essential to improving perioperative outcomes in women undergoing gynecological surgery.

Recent Developments in Metallic Degradable Micromotors for Biomedical and Environmental Remediation Applications

Synthetic micromotor has gained substantial attention in biomedicine and environmental remediation.Metal-based degradable micromotor composed of magnesium(Mg),zinc(Zn),and iron(Fe)have promise due to their nontoxic fuel-free propulsion,favorable biocompatibility,and safe excretion of degradation products Recent advances in degradable metallic micromotor have shown their fast movement in complex biological media,efficient cargo delivery and favorable biocompatibility.A noteworthy number of degradable metal-based micromotors employ bubble propulsion,utilizing water as fuel to generate hydrogen bubbles.This novel feature has projected degradable metallic micromotors for active in vivo drug delivery applications.In addition,understanding the degradation mechanism of these micromotors is also a key parameter for their design and performance.Its propulsion efficiency and life span govern the overall performance of a degradable metallic micromotor.Here we review the design and recent advancements of metallic degradable micromotors.Furthermore,we describe the controlled degradation,efficient in vivo drug delivery,and built-in acid neutralization capabilities of degradable micromotors with versatile biomedical applications.Moreover,we discuss micromotors’efficacy in detecting and destroying environmental pollutants.Finally,we address the limitations and future research directions of degradable metallic micromotors.

Iron supplementation during malaria infection in pregnancy and childhood:A review

Malaria presents a significant global public health challenge,with severe malarial anaemia being a primary manifestation of the disease.The understanding of anaemia caused by malaria remains incomplete,making the treatment more complex.Iron is a crucial micronutrient essential for haemoglobin synthesis,oxygen delivery,and other vital metabolic functions in the body.It is indispensable for the growth of human beings,as well as bacteria,protozoa,and viruses in vitro and in vivo.Iron deficiency is among the most common nutritional deficiencies and can have detrimental effects during developmental stages of life.Malaria-induced iron deficiency occurs due to the hemolysis of erythrocytes and the suppression of erythropoiesis,leading to anaemia.Meeting iron requirements is particularly critical during pivotal life stages such as pregnancy,infancy,and childhood.Dietary intake alone may not suffice to meet adequate iron requirements,thus highlighting the vital role of iron supplementation.While iron supplementation can alleviate iron deficiency,it can exacerbate malaria infection by providing additional iron for the parasites.However,in the context of pregnancy and childhood,iron supplementation combined with malaria prevention and treatment has been shown to be beneficial in improving birth outcomes and ensuring proper growth and development,respectively.This review aims to identify the role and impact of iron supplementation in malaria infection during the life stages of pregnancy and childhood.

Revealing the atomic mechanism of diamond–iron interfacial reaction

Diamond,with ultrahigh hardness,high wear resistance,high thermal conductivity,and so forth,has attracted worldwide attention.However,researchers found emergent reactions at the interfaces between diamond and ferrous materials,which significantly affects the performance of diamond-based devices.Herein,combing experiments and theoretical calculations,taking diamond–iron(Fe)interface as a prototype,the counter-diffusion mechanism of Fe/carbon atoms has been established.Surprisingly,it is identified that Fe and diamond first form a coherent interface,and then Fe atoms diffuse into diamond and prefer the carbon vacancies sites.Meanwhile,the relaxed carbon atoms diffuse into the Fe lattice,forming Fe_(3)C.Moreover,graphite is observed at the Fe_(3)C surface when Fe_(3)C is over-saturated by carbon atoms.The present findings are expected to offer new insights into the atomic mechanism for diamondferrous material's interfacial reactions,benefiting diamond-based device applications.

Green Synthesis of Iron(Ⅱ,Ⅲ)-polyphenol Nanoparticles and Their Adsorption of Malachite Green

Three kinds of iron nanoparticles(FeNPs)were prepared via green route based on pomegranate(PG),green tea(GT),and mulberry(ML)extracts under ambient conditions.The obtained materials were characterized by scanning electron microscopy(SEM),transmission electronic microscopy(TEM),X-ray energy-dispersive spectrometer(EDS),X-ray diffraction(XRD),fourier transform infrared spectroscopy(FTIR),and X-ray photoelectron spectroscopy(XPS)techniques.The experimental results show that FeNPs were in the form of amorphous iron(Ⅱ,Ⅲ)-polyphenol complex with different dispersity and morphologies.GT-Fe has the smallest size range of 25-35 nm,PG-Fe has a moderate size-distribution of 30-40 nm,while ML-Fe formed a tuberous net-type with a sheeting structure.PG-Fe displays the highest removal efficiency of 90.2%in 20 min towards cationic dye of malachite green(16.6%by ML-Fe and 69.3%by GT-Fe),which is attributed to its highest polyphenol content,lowest zeta potential,as well as the most Fe^(2+)on the surface of FeNPs.The removal mechanism was mainly induced by electrostatic adsorption based on pH and zeta potential tests.

Next Generation Nutrition: Genomic and Molecular Breeding Innovations for Iron and Zinc Biofortification in Rice

Global efforts to address malnutrition and hidden hunger, particularly prevalent in low- and middle-income countries, have intensified, with a focus on enhancing the nutritional content of staple crops like rice. Despite serving as a staple for over half of the world's population, rice falls short in meeting daily nutritional requirements, especially for iron(Fe) and zinc(Zn). Genetic resources, such as wild rice species and specific rice varieties, offer promising avenues for enhancing Fe and Zn content. Additionally, molecular breeding approaches have identified key genes and loci associated with Fe and Zn accumulation in rice grains. This review explores the genetic resources and molecular mechanisms underlying Fe and Zn accumulation in rice grains. The functional genomics involved in Fe uptake, transport, and distribution in rice plants have revealed key genes such as OsFRO1, OsIRT1, and OsNAS3. Similarly, genes associated with Zn uptake and translocation, including OsZIP11 and OsNRAMP1, have been identified. Transgenic approaches, leveraging transporter gene families and genome editing technologies, offer promising avenues for enhancing Fe and Zn content in rice grains. Moreover, strategies for reducing phytic acid(PA) content, a known inhibitor of mineral bioavailability, have been explored, including the identification of low-PA mutants and natural variants. The integration of genomic information, including whole-genome resequencing and pan-genome analyses, provides valuable insights into the genetic basis of micronutrient traits and facilitates targeted breeding efforts. Functional genomics studies have elucidated the molecular mechanisms underlying Fe uptake and translocation in rice. Furthermore, transgenic and genome editing techniques have shown promise in enhancing Fe and Zn content in rice grains through the manipulation of key transporter genes. Overall, the integration of multi-omics approaches holds significant promise for addressing global malnutrition and hidden hunger by enhancing the nutritional quality of rice, thereby contributing to improved food and nutritional security worldwide.

TGF-β-regulated different iron metabolism processes in the development and cisplatin resistance of ovarian cancer

The impact of different iron metabolism processes(DIMP)on ovarian cancer remains unclear.In this study,we employed various gene chips and databases to investigate the role of DIMP in the initiation and development of ovarian cancer.cBioPortal was used to determine mutations in DIMP-associated genes in ovarian cancer.Kaplan-Meier plotter was used to examine the influence of DIMP on the prognosis of ovarian cancer.By analyzing 1669 serous ovarian cancer cases,we identified a range of mutations in iron metabolism genes,notably in those coding for the transferrin receptor(19%),melanotransferrin(19%),and ceruloplasmin(10%)in the iron import process,and glucose-6-phosphate isomerase(9%),hepcidin antimicrobial peptide(9%),metal regulatory transcription factor 1(8%),and bone morphogenetic protein 6(8%)in the iron regulation process.Compared to the unaltered group,the group with gene alterations exhibited a higher tumor mutation burden count(43 vs.54)and more advanced histologic grade(78.19%vs.87.90%).Compared to the normal ovarian counterparts,a reduction in expression was observed in 9 out of the 14 genes involved in iron utilization and 4 out of the 5 genes involved in iron export in ovarian cancer;in contrast,an increase in expression was observed in 2 out of the 3 genes involved in iron storage in ovarian cancer.Furthermore,in cisplatin-resistant cells compared to cisplatin-sensitive ones,the expression of all genes in iron storage and 13 out of 14 genes in iron import was decreased,while that of 8 out of the 10 genes in iron utilization was increased.In addition,survival curve analysis indicated that a higher expression in the majority of genes in the iron import process(12/21),or a reduced expression in most genes in the iron export process(4/5)correlated with poor progression-free survival.Additionally,TGF-βcould regulate the expression of most iron metabolism-associated genes;particularly,expression of genes involved in the iron storage process(2/2)was inhibited after TGF-β1 or TGF-β2 treatment.In conclusion,DIMP plays multifaceted roles in the initiation,chemo-resistance,and prognosis of ovarian cancer.Therapeutically targeting DIMP may pave the way for more tailored treatment approaches for ovarian cancer.

Bulk geochemistry,Rb-Sr,Sm-Nd,and stable O-H isotope systematics of the Metzimevin high-grade iron ore deposit,Mbalam iron ore district,southern Cameroon

Bulk geochemistry,Sr,Nd,and O-H isotope systematics are reported for the first time on banded iron formation(BIF)-hosted high-grade iron ore at the northwestern segment of Congo Craton(CC).Located in Mbalam iron ore district,Southern Cameroon,Metzimevin iron ore deposit is a hematite-magnetite BIF system,dominated by SiO_(2)+Fe_(2)O_(3)(97.1 to 99.84 wt%),with low concentrations of clastic elements e.g.,Al_(2)O_(3),TiO_(2),and HFSE,depicting a nearly pure chemical precipitate.The REE+Y signature of the iron deposit displays strong positive Eu anomaly,strong negative Ce anomaly,and chondritic to superchondritic Y/Ho ratios,suggestive of formation by mixed seawater-high temperature hydrothermal fluids in oxidising environment.The^(87)Sr/^(86)Sr ratios of the BIF are higher than the maximum^(87)Sr/^(86)Sr evolution curves for all Archean reservoirs(bulk silicate earth,Archean crust and Archean seawater),indicating involvement of continentally-derived components during BIF formation and alteration.TheƐ_(Nd)(t)(+2.26 to+3.77)and Nd model age indicate that chemical constituents for the BIF were derived from undifferentiated crustal source,between 3.002 and 2.88 Ga.The variable and diverse O and H isotope data(−1.9‰to 17.3‰and−57‰to 136‰respectively)indicate that the Metzimevin iron ore formed initially from magmatic plumes and later enriched by magmatic-metamorphic-modified meteoric fluids.Mass balance calculations indicate mineralisation by combined leaching and precipitation,with an average iron enrichment factor of>2.67 and SiO_(2)depletion factor of>0.99.This is associated with an overall volume reduction of 28.27%,reflecting net leaching and volume collapse of the BIF protholith.

Nanoscale Zero-Valent Iron(nZVI)for Heavy Metal Wastewater Treatment:A Perspective

Industries such as non-ferrous metal smelting discharge billions of gallons of highly toxic heavy metal wastewater(HMW)worldwide annually,posing a severe challenge to conventional wastewater treatment plants and harming the environment.HMW is traditionally treated via chemical precipitation using lime,caustic,or sulfide,but the effluents do not meet the increasingly stringent discharge standards.This issue has spurred an increase in research and the development of innovative treatment technologies,among which those using nanoparticles receive particular interest.Among such initiatives,treatment using nanoscale zero-valent iron(nZVI)is one of the best developed.While nZVI is already well known for its site-remediation use,this perspective highlights its application in HMW treatment with metal recovery.We demonstrate several advantages of nZVI in this wastewater application,including its multifunctionality in sequestrating a wide array of metal(loid)s(>30 species);its capability to capture and enrich metal(loid)s at low concentrations(with a removal capacity reaching 500 mg·g^(-1)nZVI);and its operational convenience due to its unique hydrodynamics.All these advantages are attributable to nZVI’s diminutive nanoparticle size and/or its unique iron chemistry.We also present the first engineering practice of this application,which has treated millions of cubic meters of HMW and recovered tons of valuable metals(e.g.,Cu and Au).It is concluded that nZVI is a potent reagent for treating HMW and that nZVI technology provides an eco-solution to this toxic waste.

Diffusion and reaction mechanism of limestone and quartz in fluxed iron ore pellet roasting process

The increase to the proportion of fluxed pellets in the blast furnace burden is a useful way to reduce the carbon emissions in the ironmaking process.In this study,the interaction between calcium carbonate and iron ore powder and the mineralization mechanism of fluxed iron ore pellet in the roasting process were investigated through diffusion couple experiments.Scanning electron microscopy with energy dispersive spectroscopy was used to study the elements’diffusion and phase transformation during the roasting process.The results indicated that limestone decomposed into calcium oxide,and magnetite was oxidized to hematite at the early stage of preheating.With the increase in roasting temperature,the diffusion rate of Fe and Ca was obviously accelerated,while the diffusion rate of Si was relatively slow.The order of magnitude of interdiffusion coefficient of Fe_(2)O_(3)-CaO diffusion couple was 10^(−10) m^(2)·s^(−1) at a roasting temperature of 1200℃for 9 h.Ca_(2)Fe_(2)O_(5) was the initial product in the Fe_(2)O_(3)-CaO-SiO_(2) diffusion interface,and then Ca_(2)Fe_(2)O_(5) continued to react with Fe_(2)O_(3) to form CaFe_(2)O_(4).With the expansion of the diffusion region,the sillico-ferrite of calcium liquid phase was produced due to the melting of SiO_(2) into CaFe_(2)O_(4),which can strengthen the consolidation of fluxed pellets.Furthermore,andradite would be formed around a small part of quartz particles,which is also conducive to the consolidation of fluxed pellets.In addition,the principle diagram of limestone and quartz diffusion reaction in the process of fluxed pellet roasting was discussed.

Efficacy and Safety of Iron Isomaltoside Compared with an Oral Iron Supplement in the Management of Patients with Iron Deficiency Anemia

Objective: To evaluate the treatment outcome of iron isomaltoside compared with an oral iron supplement in the management of iron deficiency anemia (IDA). Methods: The study included patients with IDA who visited the Outpatient Clinic of the Department of Hematology, the Affiliated Hospital of Qingdao University from October 2021 to August 2022 and met the inclusion and exclusion criteria. According to the actual application of iron supplementation, the patients were divided into two groups: iron isomaltoside treatment group and oral iron treatment group. Baseline measurements were collected before the start of treatment, and measurements were collected subsequently at intervals of 1 week, 1 month, and 3 months. The hematological parameters analyzed included Hemoglobin (Hb), Mean corpuscular hemoglobin (MCH), Mean Hemoglobin content (MCH), Mean corpuscular Hemoglobin concentration (MCHC), and Platelet (Plt). Safety data and adverse event profiles were recorded. Results: Intra-group comparisons: After 1 month of treatment, the Hb significantly improved (P 0.05). Inter-group comparisons: The biochemical parameters were significantly improved (P 0.05) in the iron isomaltoside group compared with those in the oral iron group after 1 month of iron supplementation in patients with mild and moderate anemia. Adverse reactions were tolerable for the patients in both iron isomaltoside group and oral iron group. Only 1 patient in iron isomaltoside group developed anaphylactic shock during medication and recovered after aggressive rescue. Conclusions: Iron isomaltoside which increases Hb more rapidly compared with the oral iron supplementation has few adverse reactions and good acceptance.

New process for treating boron-bearing iron ore by flash reduction coupled with magnetic separation

Boron is an important industrial raw material often sourced from minerals containing different compounds that cocrystallize,which makes it difficult to separate the mineral phases through conventional beneficiation.This study proposed a new treatment called flash reduction-melting separation(FRMS)for boron-bearing iron concentrates.In this method,the concentrates were first flash-reduced at the temperature under which the particles melt,and the slag and the reduced iron phases disengaged at the particle scale.Good reduc-tion and melting effects were achieved above 1550℃.The B_(2)O_(3) content in the separated slag was over 18wt%,and the B content in the iron was less than 0.03wt%.The proposed FRMS method was tested to investigate the effects of factors such as ore particle size and tem-perature on the reduction and melting steps with and without pre-reducing the raw concentrate.The mineral phase transformation and morphology evolution in the ore particles during FRMS were also comprehensively analyzed.

The efficiency and safety evaluation of hemoglobin hydrolysate as a non-heme iron fortifier

Hemoglobin hydrolysate is derived from the enzymatic degradation of hemoglobin.This work aimed to evaluate whether hemoglobin hydrolysate promotes the absorption of non-heme iron and the safety of absorbed iron in mice by analyzing the iron binding content,iron circulation,and liver homeostasis.We found that hemoglobin hydrolysate promoted the absorption of non-heme iron with high efficiency in duodenum by spontaneously binding non-heme iron during digestion,and increased hepatic iron content by up-regulating divalent metal transporter 1,zinc transporter 14,but hepatic iron content only increased at 3 weeks.Duodenal iron entered the blood through ferroportin without restriction at 3 weeks,and excessive iron entered the liver and then affected the hepatocyte membranes permeability and lipid synthesis through oxidative stress.With the prolongation of dietary intervention,the up-regulated hepcidin acted on the ferroportin to restrict excess iron from entering the blood,and then the hepatic homeostasis recovered.In addition,hemoglobin hydrolysate enhanced the hepatic antioxidant capacity.Taken together,hemoglobin hydrolysate has a strong ability to promote the absorption of non-heme iron in vivo,and the absorbed iron is relatively safe due to the regulation of hepcidin.

Deciphering the iron enigma: Navigating the complexities of iron metabolism in critical illness

Iron is a double-edged sword!Despite being essential for numerous physiological processes of the body,a dysregulated iron metabolism can result in tissue da-mage,exaggerated inflammatory response,and increased susceptibility to infection with certain pathogens that thrive in iron-rich environment.During sepsis,there is an alteration of iron metabolism,leading to increased transport and uptake into cells.This increase in labile iron may cause oxidative damage and cellular injury(ferroptosis)which progresses as the disease worsens.Critically ill patients are often complicated with systemic inflammation which may contribute to multiple organ dysfunction syndrome or sepsis,a common cause of mortality in intensive care unit.Originally,ferritin was known to play an important role in the hematopoietic system for its iron storage capacity.Recently,its role has emerged as a predictor of poor prognosis in chronic inflammation and critical illnesses.Apart from predicting the disease outcome,serum ferritin can poten-tially reflect disease activity as well.

Correlations of transcranial sonography of substantia nigra characteristics with MRI iron deposition on substantia nigra in patients with Parkinson disease

Objective To explore the correlations of transcranial sonography of substantia nigra(SN-TCS)characteristics with MRI iron deposition on substantia nigra in patients with Parkinson disease(PD).Methods Data of SN-TCS and craniocerebral MRI in 120 PD patients were retrospectively analyzed.The patients were divided into iron deposition positive group(positive group,n=46)and iron deposition negative group(negative group,n=74)according to quantitative susceptibility mapping(QSM)value.Then parameters of SN-TCS and MRI were compared between groups(both P<0.05),and correlation analysis were also performed.Results The proportion of high echo positive,strong echo area and QSM value of substantia nigra,as well as of hyper-substantia nigra area/midbrain area(S/M)in positive group were all higher than those in negative group(all P<0.001).No significant difference of midbrain area was found between groups(P>0.05).Strong echo area of substantia nigra and S/M based on SN-TCS were both low-medium positively correlated with substantia nigra QSM value showed on MRI(r=0.497,0.529,both P<0.001).Conclusion SN-TCS characteristics of PD patients were correlated with MRI iron deposition on substantia nigra,among which strong echo area and S/M were valuable for evaluating iron deposition on substantia nigra.

Responses of growth performance,antioxidant function,small intestinal morphology and mRNA expression of jejunal tight junction protein to dietary iron in yellow-feathered broilers

This study aimed to investigate the dose-effect of iron on growth performance,antioxidant function.intestinal morphology,and mRNA expression of jejunal tight junction protein in 1-to21-d-old yellow-feathered broilers.A total of 7201-d-old yellow-feathered maleb roilers were allocated to 9 treatments with 8 replicate cages of 10 birds per cage.The dietary treatments were consisted of a basal diet(contained 79.6 mg Fe kg^(-1))supplemented with 0,20,40,60,80,160,320,640,and 1,280 mg Fe kg^(-1)in the form of FeSO_(4)·7H_(2)O.Compared with the birds in the control group,birds supplemented with 20mg Fe kg^(-1)had higher average daily gain(ADG)(P<0.0001).Adding 640 and 1,280 mg Fe kg^(-1)significantly decreased ADG(P<0.0001)and average daily feed intake(ADFI)(P<0.0001)compared with supplementation of 20mg Fe kg^(-1).Malondialdehyde(MDA)concentration in plasma and duodenum increased linearly(P<0.0001),but MDA concentration in liver and jejunum increased linearly(P<0.05)or quadratically(P<0.05)with increased dietary Fe concentration.The villus height(VH)in duodenum and jejunum,and the ratio of villus height to crypt depth(V/C)in duodenum decreased linearly(P?0.05)as dietary Feincreased.As dietary Fe increased,the jejunal relative mRNA abundance of claudin-1 decreased linearly(P=0.001),but the jejunal relative mRNA abundance of zona occludens-1(ZO-1)and occludin decreased linearly(P?0.05)or quadratically(P?0.05).Compared with the supplementation of 20 mg Fe kg^(-1),the supplementation of640 mg Fe kg^(-1)or higher increased(P?0.05)MDA concentrations in plasma,duodenum,and jejunum,decreased VH in the duodenum and jejunum,and the addition of 1,280 mg Fe kg^(-1)reduced(P?0.05)the jejunal tight junction protein(claudin-1,ZO-1,occludin)mRNA abundance.In summary,640 mg of supplemental Fe kg^(-1)or greater was associated with decreased growth performance,increased oxidative stress,disrupted intestinal morphology,and reduced mRNA expression of jejunal tight junction protein.