Iron Deposition Research Articles

Long-term pulmonary iron oxide nanoparticles exposure disrupts hepatic iron-lipid homeostasis and increases plaque vulnerability in ApoE−/− mice

Iron oxide nanoparticles (Fe3O4 NPs) have attracted great attention due to their extensive applications, which warranted their environmental concerns. Although recent advances have proposed the relevance of Fe3O4 NPs to cardiovascular disease, the intrinsic mechanisms underlying the effects of NPs remain indistinct. ApoE−/− mice were chosen as a long-term exposure model to explore the immanent association between respiratory exposure to Fe3O4 NPs and the development of cardiovascular diseases. Pulmonary exposure to 20 nm and 200 nm Fe3O4 NPS resulted in significant lung injury, and pulmonary histopathological examination displayed inflammatory cell infiltration, septal thickening and alveolar congestion. Intriguingly, liver iron deposition and variations in the hepatic lipid homeostasis were found in Fe3O4 NPs-exposed mice, eventually leading to dyslipidemia, hinting the potential cardiovascular toxicity of Fe3O4 NPs. In addition, we not only found that Fe3O4 NPs exposure increased aortic plaque area, but also increased M1 macrophages in the plaque, which yielding plaque vulnerability in ApoE−/− mice Of note, 20 nm Fe3O4 NPs showed enhanced capability on the progression of atherosclerosis than 200 nm Fe3O4 NPs. This study may propose the potential mechanism for adverse cardiovascular disease induced by Fe3O4 NPs and provide convincing evidence for the safety evaluation of Fe3O4 NPs.

Research on the clinical factors of cardiac iron deposition in children with beta-thalassemia major

Magnetic resonance imaging (MRI) T2* is the gold standard for detecting iron deposition in cardiac tissue, but the technique has limitations and cannot be fully performed in paediatric thalassemia patients. The aim of this study was to analyse clinical data to identify other predictors of cardiac iron deposition. A retrospective analysis was performed on 370 children with β-TM. According to the cardiac MRI results, patients were allocated to a cardiac deposition group and noncardiac deposition group. Multivariate analysis revealed that genotype and corrected QT interval were associated with cardiac iron deposition, indicating that the-β0/β0 genotype conferred greater susceptibility to cardiac iron deposition. Receiver operating characteristic curve (ROC) analysis was performed, and the area under the curve (AUC) of genotype was 0.651. The AUC for the corrected QT interval was 0.711, at a cut-off value of 418.5 ms. ROC analysis of the combined genotype and corrected QT interval showed an AUC of 0.762 with 81.3% sensitivity and 64.7% specificity. Compared to patients with the β+/β+ and β0β+ genotypes, β0β0 children with β-TM were more likely to have cardiac iron deposition. Conclusion: The genotype and QTc interval can be used to predict cardiac iron deposition in children with β-TM who are unable to undergo MRI T2 testing.

INCIDENCE OF DILATED CARDIOMYOPATHY IN PATIENTS OF THALASSEMIA MAJOR RECEIVING DEFERASIROX AND DEFEROXAMINE AS CHELATORS

The objective of this study was to determine the frequency of dilated cardiomyopathy in patients with β-thalassemia major who received treatment with deferasirox and deferoxamine. A descriptive cross-sectional study was conducted in the Department of Paediatrics, Combined Military Hospital, Rawalpindi, from May 2022 to January 2023. All 746 paediatric patients aged between 4 to 18 years, of both genders, who had been diagnosed with β-thalassemia major and had received chelation with either deferasirox or deferoxamine for at least one continuous year were included. Patients who were non-compliant with treatment based on history or suffered from concurrent chronic cardiopulmonary, renal (including proteinuria), hepatic, or neoplastic disease, those who suffered from malabsorption syndromes, or those who had undergone gastrointestinal surgery were excluded. All patients underwent a 2D echocardiographic study to document cardiac dilatation and measurement of ejection fraction. Dilated cardiomyopathy was defined as dilating one or both heart ventricles with an ejection fraction of less than 40%. Patients were divided into two groups: those who had received deferasirox and those who had received deferoxamine. Data was analyzed using SPSS 26.0. The study population had a median age of 8.00 (IQR: 5.00) years, with a male majority of 384 (51.5%). The median time on chelation therapy was 23.00 (IQR: 10.00) months, while the median age at first transfusion was 12.00 (IQR: 7.00) months. The median number of lifetime transfusions was 60.50 (IQR: 33.00), while only 431 (57.8%) patients had received chelator therapy previously. Out of the total sample population, 36 (4.8%) patients had dilated cardiomyopathy, of whom 22 (5.9%) occurred with deferasirox while 14 (3.8%) were seen with deferoxamine (p=0.172). The study concluded that the frequency of dilated cardiomyopathy secondary to iron deposition in the myocardium of patients with β-thalassemia major on deferasirox for at least one year was similar to those using deferoxamine for the same minimum period.

Apatite trace elements and O-Sr isotopes reveal different magmatic sources of Fe-Ti oxide deposits in the eastern Tianshan, NW China

Magmatic Fe-Ti oxide deposits are one of the most important iron deposit in eastern Tianshan, NW China, and their ore-forming mechanism remains obscure. Here, we use trace elements and O-Sr isotopes of apatite from two representative magmatic Fe-Ti oxide deposits (Niumaoquan and Weiya) in the eastern Tianshan to constrain the genesis of ore formation. The apatites from the Niumaoquan Fe-Ti oxide ores exhibit higher Eu/Eu* values, lower Mn contents, and larger REE variations than those from the Weiya Fe-Ti oxide ores, indicating a protracted evolution process of the Niumaoquan ore-forming magmas under a relatively reduced condition. Specifically, the apatites from the Niumaoquan Fe-Ti oxide ores can be divided into two groups: Group 1 with relatively low REE contents, low 87Sr/86Sr ratios (0.70574–0.70641) and high δ18O values (5.1–5.6‰), and Group 2 with relatively high REE contents, high 87Sr/86Sr ratios (0.70703–0.70792) and low δ18O values (2.8–3.3‰). The Group 1 apatites formed by early crystallization in the mantle, while the Group 2 apatites formed by assimilation of low δ18O-high 87Sr/86Sr altered rocks during magmas emplacement en route to the continental crust. Unlike the Niumaoquan apatites, the apatites from the Weiya Fe-Ti oxide ores have relatively homogeneous, high δ18O values (8.3‰-9.1‰) and 87Sr/86Sr ratios (0.70798–0.70848), indicating involvement of continental crustal materials in their mantle sources. Combined with previous studies, we suggest that the Niumaoquan and the Weiya Fe-Ti oxide deposits formed in a non-plume tectonic setting but they originated from different magmatic sources. Our study highlights that trace elements and O-Sr isotopes of apatite can be used as powerful tools to constrain the source characteristics and ore-forming processes of magmatic Fe-Ti oxide deposits.

Chemical and mineralogical properties of Lejja Nsukka iron ore deposits

The ore deposits obtained from Dunoka, Amankwo and Umuakpo in Lejja Nsukka were found to be iron silicate in nature. They were analysedby XRD, XRF, AAS and the ores were found to contain 60.59% Fe, 64.81%Fe and 64.67%Fe respectively. These ores when compared to those iron ore producing nations, they were classified as medium-grade iron ore. Other elements like titanium, magnesium and manganese were present and could be mined for commercial use. Chemical analysis of the ore samples showed that traces of phosphorous of ≤ 0.0079% and were free from the deleterious elements, sulphur and arsenic.

Going Going Gonad: Assessing Iron Staining Impact on Fertility for Patients with Sickle Cell Disease

Introduction: Medical advances in the care of patients with sickle cell disease (SCD) and other hemoglobinopathies have allowed for the focus of care to shift and incorporate long-term quality of life metrics, such as fertility. Concerns for reproductive health in patients with SCD stem from the underlying disease itself as well as from medical therapies that are offered such as hydroxyurea, chronic red blood cell transfusions, and stem cell transplant (SCT). Iron deposition from chronic transfusions in other tissues is known to result in end organ damage and lifelong consequences. While little is known about iron overload and fertility, one study noted testicular iron deposition on MRI in pubertal males with transfusion-dependent beta-thalassemia; results were notable for lower sperm concentrations and a lower percentage of sperm with normal morphology, indicating that iron overload likely has an impact on fertility for patients. Iron deposition has not been studied in the pre-pubertal hemoglobinopathy population. Fertility counseling in this patient population does not often occur until patients are considering SCT as a curative therapy option, as the conditioning regimens for SCT are gonadotoxic. Without a good understanding of the impact of chronic transfusions on fertility for patients with hemoglobinopathies, it is difficult to determine the optimal time to offer fertility preservation to families. We aim to assess iron overload on testicular tissue to gain a better understanding of the impact that medical management and chronic transfusions can have on fertility for a patient with SCD. Methods: Our study is a cross-sectional evaluation of patients with SCD who underwent testicular tissue cryopreservation (TTC) as a part of a multicenter research protocol through the University of Pittsburgh Medical Center (UPMC) prior to SCT. As part of the TTC protocol, each patient provided a small piece of tissue for research, with the remaining cryopreserved for patient use. All samples were evaluated for the presence of germ cells. For this study, demographics, treatment data, imaging results, and labs pertinent to hormonal profile and iron status were obtained. All samples from patients with SCD and thalassemia will undergo additional pathology review to evaluate for the presence of germ cells and iron. At the time of this abstract, the tissue for two patients had been analyzed. Results: Banked research tissue from UPMC includes 77 patients with SCD and 21 patients with beta thalassemia major. Of the 77 SCD patient samples, 42 were found to have germ cells, 34 have not yet been analyzed and 1 had no germ cells present. Of the 21 samples from patients with beta thalassemia major, 17 were found to have germ cells, 3 were not yet analyzed and 1 had no germ cells present. To date, we have obtained pathology review on two patients, both with Hb SS genotype and were on the maximum tolerated dose of hydroxyurea prior to TTC. Patient 1 had been on hydroxyurea for 7 years and had 13 units of blood transfusions, and Patient 2 on hydroxyurea for 4 years and 6units of blood transfusions prior to TTC. Both patients were found to have normal testicular tissue histopathology with presence of germ cells and without evidence of iron on staining (Table 1). Conclusions: Based on our preliminary data it can be noted that patients without significant iron burden, based on low ferritin and a limited transfusion history may not have a significant impact on their testicular histopathology with their iron staining being negative. We will expand our patient cohort to include patients who have a severe disease course requiring more blood transfusions to determine whether this is associated with increased iron deposition in their testicular tissue and/or reduced germ cell numbers. This information will allow teams to optimize the timing of fertility discussions and possible preservation in this patient population, even outside of curative treatment.

RBC Exchange Transfusion As an Adjunct Therapy to Control Iron Overload in Patients with Transfusion-Dependent Thalassemia

Background Patients with transfusion-dependent thalassemia (TDT) require red blood cell (RBC) transfusions as frequently as every 2-4 weeks to maintain a pre-transfusion hemoglobin of 9.0-10.5 g/dL for patients without cardiac complications. Chronic RBC transfusions increase body iron stores leading to iron deposition in liver, pancreatic, and cardiac tissues. Deferoxamine, deferiprone, and deferasirox are the iron chelators currently licensed for clinical use to manage iron overload in TDT patients with side effects ranging from nausea to nephrotoxicity and hearing loss. RBC exchange transfusion (RBCX), particularly in conjunction with isovolumic hemodilution, has been utilized for patients with sickle cell disease as a means of stabilizing iron overload. The 2015 ASFA Red Blood Cell Exchange consensus supports RBCX to reduce or prevent iron overload in sickle cell disease. Review of literature shows that RBCX can be beneficial as an acute intervention for patients with TDT and pulmonary hypertension however there is a paucity of literature documenting chronic RBCX use in TDT patients with iron overload. Case series This series presents five patients with TDT who were transitioned from chronic simple RBC transfusions to chronic RBCX after developing treatment-refractory iron overload as evidenced by serum ferritin elevation. Patients were treated on a transfusion schedule with a pre-transfusion goal hemoglobin of 9.5g/dL or higher and interval 4-6 weeks. Patient A is a 14 year-old male who developed significant iron overload (peak ferritin of 7077) on deferasirox 20 mg/kg/day and MRI T2 imaging suggestive of iron deposition. After transition to RBCX, ferritin decreased significantly with a post-RBCX mean of 1382. Blood utilization was 4200 ml three months pre-RBCX and 5625 ml three months post-RBCX. Patient B is a 23 year-old male with a peak ferritin of 1310 prior to RBCX on 23 mg/kg/day of deferasirox complicated by mild hearing loss. Serum ferritin has shown stabilization, with a mean post-RBCX ferritin of 880. Blood utilization was 2400 ml three months pre-RBCX and 8100 ml three months post-RBCX. Patient C is a 17 year-old male with a peak ferritin of 1400 with deferasirox management complicated by acute renal injury. Mean serum ferritin of 633 post-RBCX. Blood utilization was 1200 ml three months pre-RBCX and 5200 ml three months post-RBCX. Patient D is a 17 year-old male managed on 23 mg/kg/day of deferasirox with a peak ferritin of 3060 on pre-RBCX. The patient transitioned to chronic RBCX with mean serum ferritin of 1073. Blood utilization was 1800 ml three months pre-RBCX and 7700 ml three months post-RBCX. Patient E is a 17 year-old male with peak ferritin of 3404 despite 20 mg/kg/day of deferasirox prior to chronic RBCX. Mean serum ferritin after transition to RBCX was found to be 1282. Blood utilization was 1500 ml three months pre-RBCX and 4900 ml three months post-RBCX. All 5 patients have tolerated RBC exchange procedures without complications. Serum ferritin levels pre- and post-RBC exchange were trended pre- and post- RBCX (Figure 1). Serum ferritins were averaged together for each patient to obtain an equal number of time points considered prior to and after starting RBCX therapy. Descriptive statistics (Table 1) were used to summarize average ferritin levels for the patient group. A Wilcoxon signed-rank test was performed to assess the median difference in ferritin level from pre-RBCX to post-RBCX. All analyses were conducted in SAS version 9.4. P <0.05 is considered statistically significant. Median pre-RBCX ferritin level for the study group is 2489.3 (Inter-quartile range (IQR): 1190.0, 2659.0). The median post-RBCX ferritin level for the series is 1329.3 (IQR: 941.0, 1711.0). After subtracting the post-RBCX ferritin level from the pre-RBCX ferritin level, the median change for the group is 457 (IQR: 249.0, 1160.0) (p=0.06). Conclusion This case series documents the successful clinical application of chronic RBCX in TDT patients as a means of stabilizing serum ferritin levels over time. Mean ferritin levels were significantly lower, clinically, after transitioning from chronic simple RBC transfusion to RBCX (Table 1), though analysis is limited due to cohort size. Blood utilization increased after transitioning to RBCX. Next steps in evaluating our practice for the patient group will be to evaluate iron deposition status with MRI T2* imaging.

The Effect of Ferritin Level on Respiratory Functions in Patients with β-Thalassemia Major

Introduction-Purpose β-thalassemia major (β-TM) is an autosomal recessive disorder caused by mutations in the β-globin gene of hemoglobin. The disease is characterized by splenomegaly due to ineffective erythropoiesis, iron accumulation signs in tissues as a result of increased iron absorption, bone expansion due to increased erythropoietic activity, and decreased tissue oxygenation. One of the effected organ can be the lungs due to excessive iron deposition in these patients. The current study aimed to investigate the effect of serum ferritin level, which is known as a marker of iron accumulation in tissues, on pulmonary function tests (PFT) in patients with β-TM. Methods and Materials Patients aged ≥6 years who were regularly followed in the pediatric hematology section of Mersin City Research and Training Hospital with a diagnosis of β-TM were included. All patients received regular blood transfusion and iron chelation therapy. Study participants underwent PFT prior to blood transfusion in the pediatric pulmonology section Results A total of 43 patients with β-TM were studied. Included patients were divided into two groups according to the mean annual ferritin level; low ferritin group if below 2000 ml/ng and high ferritin group if above 2000 ml/ng. The low ferritin group was consisted of 19 patients and the high ferritin group was consisted of 24 patients. The characteristics of these two groups are shown in Table 1. There were no statistical significance in age, gender, body mass index, age at diagnosis, mean annual hemoglobin, splenectomy, cardiac involvement and oxygen saturation among both groups, but the number of annual transfusion was significantly higher in the high ferritin group than lower ferritin group. When PFT parameters of both groups were compared, FVC (forced vital capacity) was statistically lower in the high ferritin group compared to the low ferritin group. Other parameters included FEV 1 (forced expiratory volume in 1 second), FEV 1/FVC ratio, PEF (peak expiratory flow) and FEF 25-75 (forced expiratory flow between 25% and 75% of vital capacity) were similar among groups. (Table 2) Discussion Patients with β-TM may accumulate iron in the interstitial area of the lungs which can lead fibrosis and impaired lung function over time. There are several studies investigated lung dysfunction and its etiology in these patients. Although the results of the studies are varied, the majority of them reported a restrictive pattern of respiratory dysfunction in thalassemia patients. Additionally, some studies showed the presence of mild or moderate obstruction in small airways and decrease in diffusion capacity with the increase of alveolar-capillary membrane thickness at advanced ages. In the present study, we found that patients with β-TM who had high ferritin level showed restrictive type lung function compared to those with low ferritin level. There were no difference among the groups in obstructive parameters (i.e. FEV 1, FEV 1/FVC, FEF 25-75) of PFT. In the literature, studies investigating PFT in patients with high ferritin levels had variable results, impaired or no change, in pulmonary status. In conclusion, loss of respiratory function and impaired tissue oxygenation in patients with β-TM may develop over time due to iron deposition in the interstitial area. PFT assessment of these patients is essential and recommended for the detection of early lung disease. Routine PFT follow in patients with β-TM of high ferritin values is highly important.

6 The Moderating Role of Physical Activity on Hippocampal Iron Deposition and Memory Outcomes in Typically Aging Older Adults

Objective:Quantitative Susceptibility Mapping (QSM) is an MRI-based technique that sensitively measures in-vivo iron deposition via relaxation and magnetic susceptibility of brain tissue. Iron is essential for brain homeostasis, including oxidative metabolism, formation and maintenance of neural networks, and myelin synthesis. While increased levels of iron deposition occur during normal aging, high levels may have detrimental effects. Previous work has linked excessive brain iron accumulation to oxidative stress, beta-amyloid and tau toxicity, neurodegeneration, and cognitive dysfunction, particularly memory loss. Physical activity, on the other hand, correlates with higher synaptic integrity and memory performance, even in the presence of neuropathology. To date, it is unknown how physical activity may affect iron deposition-related cognition changes. We examined the moderating role of physical activity on the relationship between QSM hippocampal iron deposition and verbal memory in typically aging adults.Participants and Methods:62 cognitively unimpaired older adults from the UCSF Memory and Aging Center (age mean(SD) = 78.34(7.28) years; 56% women; education mean(SD) = 17.94(1.72) years; 85% non-Hispanic White) completed neuropsychological testing and brain MRI during annual research visits, followed by Fitbit™ physical activity monitoring for 30 days. Average total daily steps were aggregated. Participants completed 3T Prisma neuroimaging with QSM, and regional iron deposition levels were quantified. All subjects also underwent diffusion tensor imaging (fractional anisotropy). Verbal memory was assessed via long delay free recall scores from the California Verbal Learning Test II (CVLT-II). Linear regression examined verbal memory as a function of hippocampal QSM (bilateral), physical activity, and their interaction. Models covaried for age, sex, and education. Additional models separately examined left and right hippocampal QSM, as well as subcortical QSM to determine lateralization and specificity of verbal memory effects to hippocampal iron deposition, respectively.Results:Univariably, higher bilateral hippocampal QSM correlated with worse verbal memory (r= 0.35; p= 0.015). Adjusting for demographics, physical activity moderated the relationship between bilateral hippocampal QSM and verbal memory (ß= 0.41, p= 0.011), such that at higher levels of physical activity, the negative relationship between hippocampal QSM and verbal memory was significantly attenuated. Results persisted when adjusting for DTI integrity of the uncinate fasciculus and fornix white matter tracts. Lateralization models were both significant, suggesting that results were not dominantly driven by either left (ß= 0.34, p= 0.048), or right (ß=0.31, p= 0.035) hippocampal QSM. In contrast, subcortical QSM did not correlate with memory performance (r= 0.13, p > 0.05) or interact with physical activity on verbal memory outcomes (p > 0.05).Conclusions:Physical activity significantly moderated the negative relationship between hippocampal QSM and verbal memory performance. Higher exercise engagement may buffer the adverse effect of hippocampal iron deposition on memory, potentially through its role in maintenance of myelin and synaptic integrity and/or protecting against other neurotoxic events (e.g., oxidative stress, neuronal cell death). Our results support that physical activity continues to be a modifiable risk factor that may offer a protective role in neurobiological pathways of memory and cognitive decline.

Shenshuaifu Granule Attenuates Acute Kidney Injury by Inhibiting Ferroptosis Mediated by p53/SLC7A11/GPX4 Pathway.

Acute kidney injury (AKI) is a common clinical condition resulting in a rapid decline in renal function, and requires improvement in effective preventive measures. Ferroptosis, a novel form of cell death, is closely related to AKI. Shenshuaifu granule (SSF) has been demonstrated to prevent AKI through suppressing inflammation and apoptosis. This study aimed to explore whether SSF can inhibit ferroptosis in AKI. Active ingredients in SSF were detected through HPLC-MS/MS, and their binding abilities with ferroptosis were evaluated by molecular docking. Then, male C57/BL/6J mice were randomly divided into control, cisplatin, and cisplatin+SSF groups. In the latter two groups, mice were intraperitoneally injected with 20 mg/kg of cisplatin. For five consecutive days prior to cisplatin injection, mice in the cisplatin+SSF group were gavaged with 5.2 g/kg of SSF per day.72 h after cisplatin injection, the mice were sacrificed. Serum creatinine (SCr) and blood urea nitrogen (BUN) were measured to evaluate renal function. H&E and PAS staining were used to observe pathological damage of kidney. Cell death was observed by TUNEL staining, and iron accumulation in kidneys of mice was detected by Prussian blue staining. Western blotting, immunohistochemistry, and immunofluorescence were used to investigate the presence of inflammation, oxidative stress, mitochondrial dysfunction, iron deposition, and lipid peroxidation in mouse kidneys. Active ingredients in SSF had strong affinities with ferroptosis. SSF reduced SCr (p<0.01) and BUN (p<0.0001) levels, pathological damage (p<0.0001), dead cells in the tubular epithelium (p<0.0001) and iron deposition (p<0.01) in mice with cisplatin induced AKI. And SSF downregulated macrophage infiltration (p<0.01), the expressions of high mobility group box 1 (HMGB1, p<0.05) and interleukin (IL)-17 (p<0.05), upregulated superoxide dismutase (SOD) 1 and 2 (p<0.01), and catalase (CAT, p<0.05), and alleviated mitochondrial dysfunction (p<0.05). More importantly, SSF regulated iron transport and intracellular iron overload and reduced the expression of ferritin (p<0.05). Moreover, it downregulated the expressions of cyclo-oxygenase-2 (Cox-2, p<0.001), acid CoA ligase 4 (ACSL4, p<0.05), and solute carrier family 7, member 11 (SLC7A11, p<001), upregulated glutathione peroxidase 4 (GPX4, p<0.01) and p53 (p<0.01), and decreased 4-hydroxynonenal (4-HNE) level (p<0.001). SSF attenuates AKI by inhibiting ferroptosis mediated by p53/SLC7A11/GPX4 pathway.

Improved Elevated Temperature Performance of LiFePO4/Graphite Cell by Blending NMC640 in Cathode

Physical mixtures of LiMn2O4 (LMO) and NMC active cathode materials is a well-known strategy in commercial batteries to achieve better cycling and storage performance than cells with a pure LMO cathode. In this work, we demonstrated a similar synergic effect in LiFePO4(LFP)/NMC640 cathode material blends. Blending LFP with NMC640 in the weight ratio of 90% to 10% lead to improvements in cycling and storage compared to cells with LFP alone. A clear linear coordination between capacity loss and iron deposition on the graphite anode was observed in these blended cells. This work shows that blending NMC in LFP cathode is a promising strategy to improve the high-temperature stability of LFP/graphite cells for long-term operation.

ЖЕЛЕЗОРУДНЫЙ БАССЕЙН КУРСКОЙ МАГНИТНОЙ АНОМАЛИИ. ИСТОРИЯ ВЕЛИЧАЙШЕГО ОТКРЫТИЯ ПЕРВОЙ ПОЛОВИНЫ ХХ В. В РОССИИ. Ч. I. ПРИРОДНЫЙ ФЕНОМЕН КУРСКОЙ ГУБЕРНИИ

In April 2023, exactly 100 years have passed since the iron-ore core was taken from a well drilled in the Shchigry area of Kursk province, thereby the secret of the Kursk magnetic anomaly nature was revealed and the beginning of the world’s largest iron-ore deposits development was marked. This article is devoted to the history of one of the greatest discoveries of geologists of the first half of the 20th century, full of action-packed and dramatic events.

Cortical Iron Deposition Is Associated with Kidney Fibrosis and Can Be Assessed by Magnetic Resonance Imaging

Cortical Iron Deposition Is Associated with Kidney Fibrosis and Can Be Assessed by Magnetic Resonance Imaging

MTORC1 Inhibitor Rapamycin Inhibits Growth of Cerebral Cavernous Malformation in Adult Mice.

Cerebral cavernous malformations (CCMs) are vascular malformations that frequently cause stroke. CCMs arise due to loss of function in one of the genes that encode the CCM complex, a negative regulator of MEKK3-KLF2/4 signaling in vascular endothelial cells. Gain-of-function mutations in PIK3CA (encoding the enzymatic subunit of the PI3K (phosphoinositide 3-kinase) pathway associated with cell growth) synergize with CCM gene loss-of-function to generate rapidly growing lesions. We recently developed a model of CCM formation that closely reproduces key events in human CCM formation through inducible CCM loss-of-function and PIK3CA gain-of-function in mature mice. In the present study, we use this model to test the ability of rapamycin, a clinically approved inhibitor of the PI3K effector mTORC1, to treat rapidly growing CCMs. We show that both intraperitoneal and oral administration of rapamycin arrests CCM growth, reduces perilesional iron deposition, and improves vascular perfusion within CCMs. Our findings further establish this adult CCM model as a valuable preclinical model and support clinical testing of rapamycin to treat rapidly growing human CCMs.

Devising of a method for improving anode capacity for an all-iron flow battery

A comprehensive study of the impact of electrode design and iron deposition mechanism on the enhancement of the capacity of an all-iron redox flow battery (AIFB) has been conducted. The research is focused on revealing the complex interaction between electrode architecture, iron deposition behaviour, and battery capacity. Using a developed experimental setup, five different electrode designs are investigated. These designs include variations in the arrangement of carbon felt (CF) and non-woven fabric (NWF) layers and critical factors affecting iron deposition. Battery charge and discharge experiments were carried out under controlled conditions, simulating practical operating regimes with a current density of 50 mA/cm² and a compression ratio of 80%. The results demonstrate the influence of electrode design on iron deposition and, consequently, on battery capacity. The electrode configuration with two layers of CF and two layers of NWF exhibits a specific capacity exceeding 700 mA·h/cm². Analysis using scanning electron microscopy (SEM) complements the capacity determination results by providing valuable information about the spatial distribution of iron on the electrode surfaces. Furthermore, quantitative analysis using ZAF correction reveals uniform models of iron deposition on the surface of electrode E, indicating its potential for optimizing AIFB performance. This study provides a comprehensive understanding of the relationship between electrode design, iron deposition behaviour, and AIFB capacity. The results offer insights for improving electrode configurations, ultimately contributing to the development of efficient energy storage solutions

The Importance of Dynamic Iron Deposition in Projecting Climate Change Impacts on Pacific Ocean Biogeochemistry

AbstractDeposition of mineral dust plays an important role in upper‐ocean biogeochemical processes, particularly by delivering iron to iron‐limited regions. Here we examine the impact of dynamically changing iron deposition on tropical Pacific Ocean biogeochemistry in fully coupled earth system model projections under several emissions scenarios. Projected end‐of‐21st‐century increases in central tropical Pacific dust and iron deposition strengthen with increasing emissions/radiative forcing, and are aligned with projected soil moisture decreases in adjacent land areas and precipitation increases over the equatorial Pacific. Increased delivery of soluble iron results in a reduction in, and eastward contraction of, equatorial Pacific phytoplankton iron limitation and shifts primary production and particulate organic carbon flux projections relative to a high emissions projection (SSP5‐8.5) wherein soluble iron deposition is prescribed as a static climatology. These results highlight modeling advances in representing coupled land‐air‐sea interactions to project basin‐scale patterns of ocean biogeochemical change.

Non-magmatic sulfur source of hydrothermal colloform pyrite: Insights from the Jinshandian iron skarn deposit, Daye district, eastern China

Colloform pyrite occurs widely in many ore deposits in the Middle–Lower Yangtze River Metallogenic Belt (MLYRMB) in eastern China, but its genesis is still debated. In this study, we present detailed textures and geochemical compositions of newly identified colloform pyrite (Py1) and late coarse-grained pyrite (Py2) from the Jinshandian iron skarn deposit in the Daye district to decipher the genesis of the pyrite grains. Colloform pyrite is composed of nanometer-sized (<1 μm) grains, showing typical colloform textures, and occurs as interstitial fillings between magnetite grains. In contrast, Py2 commonly has a large grain size (up to 200 μm) and is usually distributed along the margins of colloform pyrite. These two types of pyrite have relatively high Co/Ni (1.24–13.36) ratios. δ34SCDT values of Py1 (17.22‰–20.63‰, mean 19.42‰) and Py2 (18.96‰–19.95‰, mean 19.43‰) are close to those of gypsum (anhydrite) from evaporites in the Daye district, indicating the incorporation of evaporite-derived materials into the formation of colloform pyrite. On the basis of the textures, trace-element compositions, and sulfur isotope characteristics of the colloform pyrite, it is inferred that this pyrite from the Jinshandian iron deposit is of hydrothermal origin. The sulfur isotope composition of colloform pyrite from Jinshandian is heavier relative to other magmatic-hydrothermal colloform pyrites, which indicates colloform pyrite could formed in diverse hydrothermal fluids (magmatic to no-magmatic fluid). Our study further confirmed that hydrothermal colloform pyrite has widely occurred in Fe and Cu-Au deposits associated with the Cretaceous magmatism in the MLYRMB.

Assessing the Uncertainty in Lithology, Grades and Recoverable Resources in an Iron Deposit in Southern Cameroon

Assessing the Uncertainty in Lithology, Grades and Recoverable Resources in an Iron Deposit in Southern Cameroon

The neuropathology of intimate partner violence

Lifelong brain health consequences of traumatic brain injury (TBI) include the risk of neurodegenerative disease. Up to one-third of women experience intimate partner violence (IPV) in their lifetime, often with TBI, yet remarkably little is known about the range of autopsy neuropathologies encountered in IPV. We report a prospectively accrued case series from a single institution, the New York City Office of Chief Medical Examiner, evaluated in partnership with the Brain Injury Research Center of Mount Sinai, using a multimodal protocol comprising clinical history review, ex vivo imaging in a small subset, and comprehensive neuropathological assessment by established consensus protocols. Fourteen brains were obtained over 2 years from women with documented IPV (aged 3rd–8th decade; median, 4th) and complex histories including prior TBI in 6, nonfatal strangulation in 4, cerebrovascular, neurological, and/or psychiatric conditions in 13, and epilepsy in 7. At autopsy, all had TBI stigmata (old and/or recent). In addition, white matter regions vulnerable to diffuse axonal injury showed perivascular and parenchymal iron deposition and microgliosis in some subjects. Six cases had evidence of cerebrovascular disease (lacunes and/or chronic infarcts). Regarding neurodegenerative disease pathologies, Alzheimer disease neuropathologic change was present in a single case (8th decade), with no chronic traumatic encephalopathy neuropathologic change (CTE-NC) identified in any. Findings from this initial series then prompted similar exploration in an expanded case series of 70 archival IPV cases (aged 2nd–9th decade; median, 4th) accrued from multiple international institutions. In this secondary case series, we again found evidence of vascular and white matter pathologies. However, only limited neurodegenerative proteinopathies were encountered in the oldest subjects, none meeting consensus criteria for CTE-NC. These observations from this descriptive exploratory study reinforce a need to consider broad co-morbid and neuropathological substrates contributing to brain health outcomes in the context of IPV, some of which may be potentially modifiable.

Evaluation of intracranial physiological calcifications in Computed Tomography

Introduction: Intracranial physiological calcifications are not related to any pathological conditions, rather they are due to the normal deposition of calcium or iron in the different parts of the brain. Computed Tomography (CT) scan is superior to all other modalities in terms of sensitivity in the detection of intracranial physiological calcifications. The objective of the study was to evaluate the frequency and location of intracranial physiological calcifications and also study them according to age and gender.&#x0D; Methods: A prospective cross-sectional study with a purposive sampling technique was conducted from November 2020 to February 2021 at the Department of Radiology and Imaging. CT scan images of every age group were reviewed from the base of the skull to the vertex excluding images with intracranial pathologies, injuries, artifacts, contrast enhancement and the patients with follow-up scans. Data were analyzed using SPSS version 25. Descriptive analysis was primarily preferred accompanied by inferential statistics.&#x0D; Results: Out of 412 patients, 60.7% were male and the mean age was 41.16 ±19.915 years. The total number of calcifications was 795. 92.8% of patients showed calcifications. Males had a higher number of calcifications. The highest number of calcifications was seen in the age group 20-30. The highest calcification was seen in the pineal gland (76%) followed by the choroid plexus (70.4%) and the lowest in the caudate nucleus (0.38%). The earliest age of calcification was 8 years. There was a significant relationship between the increase in age and the increase in calcification (p&lt;0.05). There was also a significant difference between male and female calcifications (p&lt;0.05).&#x0D; Conclusion: This study can be useful for clinicians to differentiate normal physiological intracranial calcifications from pathological calcification which will reduce misinterpretation of the calcifications.