Metals/bisulfite system involved generation of 24-sulfonic-25-ene ginsenoside Rg1, a potential quality control marker for sulfur-fumigated ginseng.

Ginseng is a most popular health-promoting food with ginsenosides as its main bioactive ingredients. Illegal sulfur-fumigation causes ginsenosides convert to toxic sulfur-containing derivatives, and reduced the efficacy/safety of ginseng. 24-sulfo-25-ene ginsenoside Rg1 (25-ene SRg1), one of the sulfur-containing derivatives, is a potential quality control marker of fumigated ginseng, but with low accessibility owing to its unknown generation mechanism. In this study, metals/bisulfite system involved generation mechanism was investigated and verified. The generation of 25-ene SRg1 in sulfur-fumigated ginseng is that SO2, formed during sulfur-fumigation, reacted with water and ionized into HSO3-. On the one hand, under the metals/bisulfite system, HSO3- generates HSO5- and free radicals which converted ginsenoside Rg1 to 24,25-epoxide Rg1; on the other hand, as a nucleophilic group, HSO3- reacted with 24,25-epoxide Rg1 and further dehydrated to 25-ene SRg1. This study provided a technical support for the promotion of 25-ene SRg1 as the characteristic quality control marker of sulfur-fumigated ginseng.

Catalytic Metal Ion-Substrate Coordination during Nonenzymatic RNA Primer Extension.

Nonenzymatic template-directed RNA copying requires catalysis by divalent metal ions. The primer extension reaction involves the attack of the primer 3'-hydroxyl on the adjacent phosphate of a 5'-5'-imidazolium-bridged dinucleotide substrate. However, the nature of the interaction of the catalytic metal ion with the reaction center remains unclear. To explore the coordination of the catalytic metal ion with the imidazolium-bridged dinucleotide substrate, we examined catalysis by oxophilic and thiophilic metal ions with both diastereomers of phosphorothioate-modified substrates. We show that Mg2+ and Cd2+ exhibit opposite preferences for the two phosphorothioate substrate diastereomers, indicating a stereospecific interaction of the divalent cation with one of the nonbridging phosphorus substituents. High-resolution X-ray crystal structures of the products of primer extension with phosphorothioate substrates reveal the absolute stereochemistry of this interaction and indicate that catalysis by Mg2+ involves inner-sphere coordination with the nonbridging phosphate oxygen in the pro-SP position, while thiophilic cadmium ions interact with sulfur in the same position, as in one of the two phosphorothioate substrates. These results collectively suggest that during nonenzymatic RNA primer extension with a 5'-5'-imidazolium-bridged dinucleotide substrate the interaction of the catalytic Mg2+ ion with the pro-SP oxygen of the reactive phosphate plays a crucial role in the metal-catalyzed SN2(P) reaction.

Fluorescent Protein-Based Sensors for Detecting Essential Metal Ions across the Tree of Life.

Genetically encoded fluorescent metal ion sensors are powerful tools for elucidating metal dynamics in living systems. Over the last 25 years since the first examples of genetically encoded fluorescent protein-based calcium indicators, this toolbox of probes has expanded to include other essential and non-essential metal ions. Collectively, these tools have illuminated fundamental aspects of metal homeostasis and trafficking that are crucial to fields ranging from neurobiology to human nutrition. Despite these advances, much of the application of metal ion sensors remains limited to mammalian cells and tissues and a limited number of essential metals. Applications beyond mammalian systems and in vivo applications in living organisms have primarily used genetically encoded calcium ion sensors. The aim of this Perspective is to provide, with the support of historical and recent literature, an updated and critical view of the design and use of fluorescent protein-based sensors for detecting essential metal ions in various organisms. We highlight the historical progress and achievements with calcium sensors and discuss more recent advances and opportunities for the detection of other essential metal ions. We also discuss outstanding challenges in the field and directions for future studies, including detecting a wider variety of metal ions, developing and implementing a broader spectral range of sensors for multiplexing experiments, and applying sensors to a wider range of single- and multi-species biological systems.

Dependence of n-Type Metal-Oxide Gas Sensor Response on the Pressure of Oxygen and Reducing Gases.

The adsorption of oxygen and its reaction with target gases are the basis of the gas detection mechanism by using metal oxides. Here, we present a theoretical analysis of the sensor response, within the ionosorption model, for an n-type polycrystalline semiconductor. Our goal of our work is to reveal the mechanisms of gas sensing from a fundamental point of view. We revisit the existing models in which the sensor response presents a power-law behavior with a reducing gas partial pressure. Then, we show, based on the Wolkenstein theory of chemisorption, that the sensor response depends not only on the reducing gas partial pressure but also on the oxygen partial pressure. We also find that the obtained sensor response does not explicitly depend on the grain size, and if it does, it is exclusively through the rate constants related to the involved reactions.

Fast-Response and Low-Power Self-Heating Gas Sensor Using Metal/Metal Oxide/Metal (MMOM) Structured Nanowires.

With the escalating global awareness of air quality management, the need for continuous and reliable monitoring of toxic gases by using low-power operating systems has become increasingly important. One of which, semiconductor metal oxide gas sensors have received great attention due to their high/fast response and simple working mechanism. More specifically, self-heating metal oxide gas sensors, wherein direct thermal activation in the sensing material, have been sought for their low power-consuming characteristics. However, previous works have neglected to address the temperature distribution within the sensing material, resulting in inefficient gas response and prolonged response/recovery times, particularly due to the low-temperature regions. Here, we present a unique metal/metal oxide/metal (MMOM) nanowire architecture that conductively confines heat to the sensing material, achieving high uniformity in the temperature distribution. The proposed structure enables uniform thermal activation within the sensing material, allowing the sensor to efficiently react with the toxic gas. As a result, the proposed MMOM gas sensor showed significantly enhanced gas response (from 6.7 to 20.1% at 30 ppm), response time (from 195 to 17 s at 30 ppm), and limit of detection (∼1 ppm) when compared to those of conventional single-material structures upon exposure to carbon monoxide. Furthermore, the proposed work demonstrated low power consumption (2.36 mW) and high thermal durability (1500 on/off cycles), demonstrating its potential for practical applications in reliable and low-power operating gas sensor systems. These results propose a new paradigm for power-efficient and robust self-heating metal oxide gas sensors with potential implications for other fields requiring thermal engineering.

Tunable Oxidized-Chitin Hydrogels with Customizable Mechanical Properties by Metal or Hydrogen Ion Exposure.

This study focuses on the optimization of chitin oxidation in C6 to carboxylic acid and its use to obtain a hydrogel with tunable resistance. After the optimization, water-soluble crystalline ß-chitin fibrils (ß-chitOx) with a degree of functionalization of 10% were obtained. Diverse reaction conditions were also tested for α-chitin, which showed a lower reactivity and a slower reaction kinetic. After that, a set of hydrogels was synthesized from ß-chitOx 1 wt.% at pH 9, inducing the gelation by sonication. These hydrogels were exposed to different environments, such as different amounts of Ca2+, Na+ or Mg2+ solutions, buffered environments such as pH 9, PBS, pH 5, and pH 1, and pure water. These hydrogels were characterized using rheology, XRPD, SEM, and FT-IR. The notable feature of these hydrogels is their ability to be strengthened through cation chelation, being metal cations or hydrogen ions, with a five- to tenfold increase in their storage modulus (G'). The ions were theorized to alter the hydrogen-bonding network of the polymer and intercalate in chitin's crystal structure along the a-axis. On the other hand, the hydrogel dissolved at pH 9 and pure water. These bio-based tunable hydrogels represent an intriguing material suitable for biomedical applications.

Reversible pH-Gated MXene Membranes with Ultrahigh Mono-/Divalent-Ion Selectivity.

Artificial ion channel membranes hold high promise in water treatment, nanofluidics, and energy conversion, but it remains a great challenge to construct such smart membranes with both reversible ion-gating capability and desirable ion selectivity. Herein, we constructed a smart MXene-based membrane via p-phenylenediamine functionalization (MLM-PPD) with highly stable and aligned two-dimensional subnanochannels, which exhibits reversible ion-gating capability and ultrahigh metal ion selectivity similar to biological ion channels. The pH-sensitive groups within the MLM-PPD channel confers excellent reversible Mg2+-gating capability with a pH-switching ratio of up to 100. The mono/divalent metal-ion selectivity up to 1243.8 and 400.9 for K+/Mg2+ and Li+/Mg2+, respectively, outperforms other reported membranes. Theoretical calculations combined with experimental results reveal that the steric hindrance and stronger PPD-ion interactions substantially enhance the energy barrier for divalent metal ions passing through the MLM-PPD, and thus leading to ultrahigh mono/divalent metal-ion selectivity. This work provides a new strategy for developing artificial-ion channel membranes with both reversible ion-gating functionality and high-ion selectivity for various applications.

Multistress Interplay: Time and Duration of Ocean Acidification Modulate the Toxicity of Mercury and Other Metals.

The current understanding of multistress interplay assumes stresses occur in perfect synchrony, but this assumption is rarely met in the natural marine ecosystem. To understand the interplay between nonperfectly overlapped stresses in the ocean, we manipulated a multigenerational experiment (F0-F3) to explore how different temporal scenarios of ocean acidification will affect mercury toxicity in a marine copepod Pseudodiaptomus annandalei. We found that the scenario of past acidification aggravated mercury toxicity but current and persistent acidification mitigated its toxicity. We specifically performed a proteomics analysis for the copepods of F3. The results indicated that current and persistent acidification initiated the energy compensation for development and mercury efflux, whereas past acidification lacked the barrier of H+ and had dysfunction in the detoxification and efflux system, providing a mechanistic understanding of mercury toxicity under different acidification scenarios. Furthermore, we conducted a meta-analysis on marine animals, demonstrating that different acidification scenarios could alter the toxicity of several other metals, despite evidence from nonsynchronous scenarios remaining limited. Our study thus demonstrates that time and duration of ocean acidification modulate mercury toxicity in marine copepods and suggests that future studies should move beyond the oversimplified scenario of perfect synchrony in understanding multistress interaction.

Formation of Supplementary Metal-Binding Centers in Proteins under Stress Conditions.

In many proteins, supplementary metal-binding centers appear under stress conditions. They are known as aberrant or atypical sites. Physico-chemical properties of proteins are significantly changed after such metal binding, and very stable protein aggregates are formed, in which metals act as "cross-linking" agents. Supplementary metal-binding centers in proteins often arise as a result of posttranslational modifications caused by reactive oxygen and nitrogen species and reactive carbonyl compounds. New chemical groups formed as a result of these modifications can act as ligands for binding metal ions. Special attention is paid to the role of cysteine SH-groups in the formation of supplementary metal-binding centers, since these groups are the main target for the action of reactive species. Supplementary metal binding centers may also appear due to unmasking of amino acid residues when protein conformation changing. Appearance of such centers is usually considered as a pathological process. Such unilateral approach does not allow to obtain an integral view of the phenomenon, ignoring cases when formation of metal complexes with altered proteins is a way to adjust protein properties, activity, and stability under the changed redox conditions. The role of metals in protein aggregation is being studied actively, since it leads to formation of non-membranous organelles, liquid condensates, and solid conglomerates. Some proteins found in such aggregates are typical for various diseases, such as Alzheimer's and Huntington's diseases, amyotrophic lateral sclerosis, and some types of cancer.

Predicting the Structure of Enzymes with Metal Cofactors: The Example of [FeFe] Hydrogenases.

The advent of deep learning algorithms for protein folding opened a new era in the ability of predicting and optimizing the function of proteins once the sequence is known. The task is more intricate when cofactors like metal ions or small ligands are essential to functioning. In this case, the combined use of traditional simulation methods based on interatomic force fields and deep learning predictions is mandatory. We use the example of [FeFe] hydrogenases, enzymes of unicellular algae promising for biotechnology applications to illustrate this situation. [FeFe] hydrogenase is an iron-sulfur protein that catalyzes the chemical reduction of protons dissolved in liquid water into molecular hydrogen as a gas. Hydrogen production efficiency and cell sensitivity to dioxygen are important parameters to optimize the industrial applications of biological hydrogen production. Both parameters are related to the organization of iron-sulfur clusters within protein domains. In this work, we propose possible three-dimensional structures of Chlorella vulgaris 211/11P [FeFe] hydrogenase, the sequence of which was extracted from the recently published genome of the given strain. Initial structural models are built using: (i) the deep learning algorithm AlphaFold; (ii) the homology modeling server SwissModel; (iii) a manual construction based on the best known bacterial crystal structure. Missing iron-sulfur clusters are included and microsecond-long molecular dynamics of initial structures embedded into the water solution environment were performed. Multiple-walkers metadynamics was also used to enhance the sampling of structures encompassing both functional and non-functional organizations of iron-sulfur clusters. The resulting structural model provided by deep learning is consistent with functional [FeFe] hydrogenase characterized by peculiar interactions between cofactors and the protein matrix.

Changes in Endogenous Essential Metal Homeostasis in the Liver and Kidneys during a Six-Month Follow-Up Period after Subchronic Cadmium Exposure.

Cadmium (Cd) is one of the most dangerous environmental pollutants. Its mechanism of action is multidirectional; among other things, it disrupts the balance of key essential elements. The aim of this study was to assess how cumulative exposure to Cd influences its interaction with selected essential elements (Cu, Zn, Ca, and Mg) in the kidney and liver during long-term observation (90 and 180 days) after subchronic exposure of rats (90 days) to Cd at common environmental (0.09 and 0.9 mg Cd/kg b.w.) and higher (1.8 and 4.5 mg Cd/kg b.w.) doses. Cd and essential elements were analyzed using the F-AAS and GF-AAS techniques. It was shown that the highest bioaccumulation of Cd in the kidney occurred six months after the end of exposure, and importantly, the highest accumulation was found after the lowest Cd dose (i.e., environmental exposure). Organ bioaccumulation of Cd (>21 µgCd/g w.w. in the kidney and >6 µgCd/g w.w. in the liver) was accompanied by changes in the other studied essential elements, particularly Cu in both the kidney and liver and Zn in the liver; these persisted for as long as six months after the end of the exposure. The results suggest that the critical concentration in human kidneys (40 µgCd/g w.w.), currently considered safe, may be too high and should be reviewed, as the observed long-term imbalance of Cu/Zn in the kidneys may lead to renal dysfunction.

Trace metal transfer to passerines inhabiting wastewater treatment wetlands.

Wastewater treatment wetlands are cost-effective strategies for remediating trace metals in industrial effluent. However, biogeochemical exchange between wastewater treatment wetlands and adjacent environments provides opportunities for trace metals to cycle in surrounding ecosystems. The transfer of trace metals to wildlife inhabiting treatment wetlands must be considered when evaluating wetland success. Using passerine birds as bioindicators, we conducted a multi-tissue analysis to investigate the mobilization of zinc, copper, and lead derived from wastewater to terrestrial wildlife in treatment wetlands and surrounding habitat. In addition, we evaluate the strength of relationships between metal concentrations in non-lethal (blood and feathers) and lethal (muscle and liver) sample types for estimation of toxicity risk. From July 2020 to August 2021, 177 passerines of seven species were captured at two wetlands constructed to treat industrial wastewater and two reference wetlands in the coastal plain of South Carolina. Feather, blood, liver, and muscle samples from each bird were analyzed for fourteen metals using inductively coupled plasma mass spectrometry and direct mercury analysis. Passerines inhabiting wastewater treatment wetlands accumulated higher concentrations of zinc in liver, copper in blood, and lead in feathers than passerines in reference wetlands, but neither blood nor feather concentrations were correlated with internal tissue concentrations. Of all the detected metals, only mercury in the blood showed a strong predictive relationship with mercury in internal tissues. This study indicates that trace metals derived from wastewater are bioavailable and exported to terrestrial wildlife and that passerine biomonitoring is a valuable tool for assessing metal transfer from treatment wetlands. Regular blood sampling can reveal proximate trace metal exposure but cannot predict internal body burdens for most metals.

Elevated cobalt levels in metal-on-polyethylene knee megaprostheses: a prospective 1-year cohort study of 56 patients with hip and knee megaprostheses.

BACKGROUND AND PURPOSE: Concerns have emerged regarding elevated levels of cobalt and chromium in patients with metal-on-metal megaprostheses. This prospective study aims to identify systemic cobalt and chromium levels in metal-on-polyethylene knee and hip megaprostheses and their associations with other factors. METHODS: 56 patients underwent knee or hip megaprosthesis surgery at 2 sarcoma centers. Serum cobalt and chromium levels were measured preoperatively and thrice within the first year using inductively coupled plasma mass spectrometry. RESULTS: A statistically significant difference in serum cobalt levels (1.4 ppb; 95% confidence interval [CI] 0.0-3.3) was observed 1 year after knee megaprosthesis surgery compared with preoperative levels. In contrast no difference in chromium levels was observed after 1 year compared with preoperative levels (0.05 ppb; CI 0.0-0.8). An association between younger age, higher eGFR, and increased cobalt levels was observed. No significant correlations were found between ion levels and resection length or the number of modular connections. CONCLUSION: We found elevated serum ion levels in metal-on-polyethylene knee megaprostheses in contrast to metal-on-polyethylene hip megaprostheses. Furthermore, a positive correlation between cobalt and chromium levels, and between cobalt and eGFR was identified, along with a negative correlation between cobalt and age. This study highlights the importance of monitoring systemic cobalt and chromium levels in patients with megaprostheses.

Metal Ion-Induced Unusual Stability of the Metastable Vesicle-like Intermediates Evolving during the Self-Assembly of Phenylalanine: Prominent Role of Surface Charge Inversion.

The underlying mechanism and intermediate formation in the self-assembly of aromatic amino acids, peptides, and proteins remain elusive despite numerous reports. We, for the first time, report that one can stabilize the intermediates by tuning the metal ion-amino acid interaction. Microscopic and spectroscopic investigations of the self-assembly of carboxybenzyl (Z)-protected phenylalanine (ZF) reveal that the bivalent metal ions eventually lead to the formation of fibrillar networks similar to blank ZF whereas the trivalent ions develop vesicle-like intermediates that do not undergo fibrillation for a prolonged time. The time-lapse measurement of surface charge reveals that the surface charge of blank ZF and in the presence of bivalent metal ions changes from a negative value to zero, implying unstable intermediates leading to the fibril network. Strikingly, a prominent charge inversion from an initial negative value to a positive value in the presence of trivalent metal ions imparts unusual stability to the metastable intermediates.

Comparative evaluation on wear resistance of metal sleeve, sleeve-free resin, and reinforced sleeve-free resin implant guide: An in vitro study.

BACKGROUND: In-office three-dimensional (3D) printers and metal sleeveless surgical guides are becoming a major trend recently. However, metal sleeve-free designs are reported to be more prone to distortion which might lead to variation in the inner diameter of the drill hole and cause deviation and inaccuracy in the placement of the implant. Carbon fiber nanoparticles are reported to improve the properties of 3D printing resin material in industrial application. AIM: The purpose of the study is to evaluate and compare the wear resistance of 3D-printed implant guides with metal sleeve, sleeve-free, and reinforced sleeve-free resin to the guide drill. MATERIALS AND METHODS: A total of 66 samples with 22 samples in each group. Three groups including 3D-printed surgical guide with metal sleeve (Group A), without metal sleeve (Group B), an carbon fiber reinforced without metal sleeve (Group C) were included in the study. All samples were evaluated before sequential drilling and after sequential drilling using Vision Measuring Machine. The data were tabulated and statistically evaluated. RESULTS: The data obtained were statistically analyzed with one-way analysis of variance and posthoc test. The data obtained for wear observed in the samples showed that the wear was highest in Group B with a mean of 0.5036 ± 0.1118 and the least was observed in Group A with a mean of 0.0228 ± 0.0154 and Group C was almost similar to Group A with mean of 0.0710 ± 0.0381. The results showed there was a significant difference between Group B with Group A and C, respectively (P < 0.05). The results showed that there was no significant difference regarding the wear observed between Groups A and C (P > 0.05). CONCLUSION: The wear observed in the guide with a metal sleeve and carbon fiber reinforced without a metal sleeve was almost similar. The carbon fiber-reinforced guide showed better tolerance to guide drill equivalent to metal sleeve. Thus, carbon fiber nanoparticles reinforced in 3D printing resin have shown improved strength and can be used as a good replacement for a metal sleeve for an accurate placement of the implant.

The adaptability, distribution, ecological function and restoration application of biological soil crusts on metal tailings: A critical review.

A large amount of metal tailings causes many environmental issues. Thus, the techniques for their ecological restoration have garnered extensive attention. However, they are still in the exploratory stage. Biological soil crusts (BSCs) are a coherent layer comprising photoautotrophic organisms, heterotrophic organisms and soil particles. They are crucial in global terrestrial ecosystems and play an equal importance in metal tailings. We summarized the existing knowledge on BSCs growing on metal tailings. The main photosynthetic organisms (cyanobacteria, eukaryotic algae, lichens, and mosses) of BSCs exhibit a high heavy metal(loid) (HM) tolerance. BSCs also have a strong adaptability to other adverse conditions in tailings, such as poor structure, acidification, and infertility. The literature about tailing BSCs has been rapidly increasing, particularly after 2022. The extensive literature confirms that the BSCs distributed on metal tailings, including all major types of metal tailings in different climatic regisions, are common. BSCs perform various ecological functions in tailings, including HM stress reduction, soil structure improvement, soil nutrient increase, biogeochemical cycle enhancement, and microbial community restoration. They interact and accelerate revegetation of tailings (at least in the temperate zone) and soil formation. Restoring tailings by accelerating/inducing BSC formation (e.g., resource augmentation and inoculation) has also attracted attention and achieved small-scale on-site application. However, some knowledge gaps still exist. The potential areas for further research include the relation between BSCs and HMs, large-scale quantification of tailing BSCs, application of emerging biological techniques, controlled laboratory experiments, and other restoration applications.

Associations of metals and metal mixtures with glucose homeostasis: A combined bibliometric and epidemiological study.

This study employs a combination of bibliometric and epidemiological methodologies to investigate the relationship between metal exposure and glucose homeostasis. The bibliometric analysis quantitatively assessed this field, focusing on study design, predominant metals, analytical techniques, and citation trends. Furthermore, we analyzed cross-sectional data from Beijing, examining the associations between 14 blood metals and 6 glucose homeostasis markers using generalized linear models (GLM). Key metals were identified using LASSO-PIPs criteria, and Bayesian kernel machine regression (BKMR) was applied to assess metal mixtures, introducing an "Overall Positive/Negative Effect" concept for deeper analysis. Our findings reveal an increasing research interest, particularly in selenium, zinc, cadmium, lead, and manganese. Urine (27.6%), serum (19.0%), and whole blood (19.0%) were the primary sample types, with cross-sectional studies (49.5%) as the dominant design. Epidemiologically, significant associations were found between 9 metals-cobalt, copper, lithium, manganese, nickel, lead, selenium, vanadium, zinc-and glucose homeostasis. Notably, positive-metal mixtures exhibited a significant overall positive effect on insulin levels, and notable interactions involving nickel were identified. These finding not only map the knowledge landscape of research in this domain but also introduces a novel perspective on the analysis strategies for metal mixtures.

Detection and recognition of metal surface corrosion based on CBG-YOLOv5s.

The automatic detection of the degree of surface corrosion on metal structures is of significant importance for assessing structural damage and safety. To effectively identify the corrosion status on the surface of coastal metal facilities, this study proposed a CBG-YOLOv5s model for metal surface corrosion detection, based on the YOLOv5s model. Firstly, we integrated the Convolutional Block Attention Module (CBAM) into the C3 module and developed the C3CBAM module. This module effectively enhanced the channel and spatial attention capabilities of the feature map, thereby improving the feature representation. Second, we introduced a multi-scale feature fusion concept in the feature fusion part of the model and added a small target detection layer to improve small target detection. Finally, we designed a lighter C3Ghost module, which reduced the number of parameters and the computational load of the model, thereby improving the running speed of the model. In addition, to verify the effectiveness of our method, we constructed a dataset containing 6000 typical images of metal surface corrosion and conducted extensive experiments on this dataset. The results showed that compared to the YOLOv5s model and several other commonly used object detection models, our method achieved superior performance in terms of detection accuracy and speed.

Toxic metals and pediatric clinical immune dysfunction: A systematic review of the epidemiological evidence.

BACKGROUND: Children are at high risk for exposure to toxic metals and are vulnerable to their effects. Significant research has been conducted evaluating the role of these metals on immune dysfunction, characterized by biologic and clinical outcomes. However, there are inconsistencies in these studies. The objective of the present review is to critically evaluate the existing literature on the association between toxic metals (lead, mercury, arsenic, and cadmium) and pediatric immune dysfunction. METHODS: Seven databases (PubMed (NLM), Embase (Elsevier), CINAHL (Ebsco), Web of Science (Clarivate Analytics), ProQuest Public Health Database, and ProQuest Environmental Science Collection) were searched following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in February 2024. Rayaan software identified duplicates and screened by title and abstract in a blinded and independent review process. The remaining full texts were reviewed for content and summarized. Exclusions during the title, abstract, and full-text reviews included: 1) not original research, 2) not epidemiology, 3) did not include toxic metals, 4) did not examine an immune health outcome, or 5) not pediatric (>18 years). This systematic review protocol followed the PRISMA guidelines. Rayaan was used to screen records using title and abstract by two blinded and independent reviewers. This process was repeated for full-text article screening selection. RESULTS: The search criteria produced 7906 search results; 2456 duplicate articles were removed across search engines. In the final review, 79 studies were included which evaluated the association between toxic metals and outcomes indicative of pediatric immune dysregulation. CONCLUSIONS: The existing literature suggests an association between toxic metals and pediatric immune dysregulation. Given the imminent threat of infectious diseases demonstrated by the recent COVID-19 epidemic in addition to increases in allergic disease, understanding how ubiquitous exposure to these metals in early life can impact immune response, infection risk, and vaccine response is imperative.

Towards an optimal design of a functionally graded porous uncemented acetabular component using genetic algorithm.

Generation of polyethylene wear debris and peri­prosthetic bone resorption have been identified as potential causes of acetabular component loosening in Total Hip Arthroplasty. This study was aimed at optimization of a functionally graded porous acetabular component to minimize peri­prosthetic bone resorption and polyethylene liner wear. Porosity levels (porosity values at acetabular rim, and dome) and functional gradation exponents (radial and polar) were considered as the design parameters. The relationship between porosity and elastic properties were obtained from numerical homogenization. The multi-objective optimization was carried out using a non-dominated sorting genetic algorithm integrated with finite element analysis of the hemipelvises subject to various loading conditions of common daily activities. The optimal functionally graded porous designs (OFGPs -1, -2, -3, -4, -5) exhibited less strain-shielding in cancellous bone compared to solid metal-backing. Maximum bone-implant interfacial micromotions (63-68 µm) for OFGPs were found to be close to that of solid metal-backing (66 µm), which might facilitate bone ingrowth. However, OFGPs exhibited an increase in volumetric wear (3-10 %) compared to solid metal-backing. The objective functions were found to be more sensitive to changes in polar gradation exponent than radial gradation exponent, based on the Sobol' method. Considering the common failure mechanisms, OFGP-1, having highly porous acetabular rim and less porous dome, appears to be a better alternative to the solid metal-backing.