Three-dimensional liquid metal-based neuro-interfaces for human hippocampal organoids.

Human hippocampal organoids (hHOs) derived from human induced pluripotent stem cells (hiPSCs) have emerged as promising models for investigating neurodegenerative disorders, such as schizophrenia and Alzheimer's disease. However, obtaining the electrical information of these free-floating organoids in a noninvasive manner remains a challenge using commercial multi-electrode arrays (MEAs). The three-dimensional (3D) MEAs developed recently acquired only a few neural signals due to limited channel numbers. Here, we report a hippocampal cyborg organoid (cyb-organoid) platform coupling a liquid metal-polymer conductor (MPC)-based mesh neuro-interface with hHOs. The mesh MPC (mMPC) integrates 128-channel multielectrode arrays distributed on a small surface area (~2*2 mm). Stretchability (up to 500%) and flexibility of the mMPC enable its attachment to hHOs. Furthermore, we show that under Wnt3a and SHH activator induction, hHOs produce HOPX+ and PAX6+ progenitors and ZBTB20+PROX1+ dentate gyrus (DG) granule neurons. The transcriptomic signatures of hHOs reveal high similarity to the developing human hippocampus. We successfully detect neural activities from hHOs via the mMPC from this cyb-organoid. Compared with traditional planar devices, our non-invasive coupling offers an adaptor for recording neural signals from 3D models.

Emerging Topics in Metal Complexes: Pharmacological Activity.

This Special Issue (SI), "Emerging Topics in Metal Complexes: Pharmacological Activity", includes reports updating our knowledge on metals with multidirectional biological properties and metal-containing compounds/complexes for their potential therapeutic applications, with a focus on strategies improving their pharmacological features [...].

Comparing nitric acid treatment and microwave digestion for efficiency of metal extraction from bioprocess samples.

Metal ions may act as enzyme cofactors and influence the kinetics of biochemical reactions that may also influence the biological production of therapeutic proteins and quality attributes such as glycosylation. Because sample preparation is a significant step in the reliable analysis of metals, we compared two sample preparation procedures for metal analysis of bioreactor culture media samples by ICP-MS: (i) samples were diluted in 2 % nitric acid (treatment with nitric acid, TNA); and (ii) samples were mixed with equal volume of 5 % nitric acid and closed vessel digestion was performed in a microwave (closed vessel digestion, CVD). In the comparison of extraction efficiencies between TNA and CVD procedures, CVD showed better extraction for Ca and Cu among bulk metals (∼30 %) and for Ni among the trace metals (∼65 %) for the bioreactor broth supernatant samples. For the cell pellet samples, the CVD procedure was found to be better for extraction of Fe (∼65 % more) among bulk metals, Zn (∼20 % more) among minor metals and Co (∼60 % more) and Ni (∼45 % more) among trace metals. Differences between the two procedures were less than 10 % and TNA was better for all other metals quantified from both supernatant samples and cell pellet samples. The current study helps bring more clarity to the methodology on comprehensive metal analysis to monitor and maintain trace metal content for biologics production.

Carbonic Anhydrases: Different Active Sites, Same Metal Selectivity Rules.

Carbonic anhydrases are mononuclear metalloenzymes catalyzing the reversible hydration of carbon dioxide in organisms belonging to all three domains of life. Although the mechanism of the catalytic reaction is similar, different families of carbonic anhydrases do not have a common ancestor nor do they exhibit significant resemblance in the amino acid sequence or the structure and composition of the metal-binding sites. Little is known about the physical principles determining the metal affinity and selectivity of the catalytic centers, and how well the native metal is protected from being dislodged by other metal species from the local environment. Here, we endeavor to shed light on these issues by studying (via a combination of density functional theory calculations and polarizable continuum model computations) the thermodynamic outcome of the competition between the native metal cation and its noncognate competitor in various metal-binding sites. Typical representatives of the competing cations from the cellular environments of the respective classes of carbonic anhydrases are considered. The calculations reveal how the Gibbs energy of the metal competition changes when varying the metal type, structure, composition, and solvent exposure of the active center. Physical principles governing metal competition in different carbonic anhydrase metal-binding sites are delineated.

Exploiting Principal Component Analysis (PCA) to reveal temperature, buffer and metal ions' role in neuromelanin (NM) synthesis by dopamine (DA) oxidative polymerization.

Neuromelanin (NM) plays a well-established role in neurological disorders pathogenesis; the mechanism of action is still discussed and the investigations in this field are limited by NM's complex and heterogeneous composition, insolubility, and low availability from human brains. An alternative can be offered by synthetic NM obtained from dopamine (DA) oxidative polymerization; however, a deep knowledge of the influence of both physicochemical parameters (T, pH, ionic strength) and other compounds in the reaction media (buffer, metal ions, other catecholamines) on DA oxidation process and, consequently, on synthetic NM features is mandatory to develop reliable NM preparation methodologies. To partially fulfill this aim, the present work focuses on defining the role of temperature, buffer and metal ions on both DA oxidation rate and DA oligomer size. DA oxidation in the specific conditions is monitored by UV-Vis spectroscopy and Principal Component Analysis (PCA) is run either on the raw spectra to model the background absorption increase, related to small DA oligomers formation, or on their first derivative to rationalize DA consumption. After having studied three case studies, 3-Way PCA is applied to directly evaluate the effect of temperature and buffer type on DA oxidation in the presence of different metal ions. Despite the proof-of-concept nature of the work and the number of compounds still to be included in the investigation, the preliminary results and the possibility to further expand the chemometric approach represent an interesting contribution to the field of in vitro simulation of NM synthesis.

Biostimulation of sulfate reduction for in-situ metal(loid) precipitation at an industrial site in Flanders, Belgium.

A 30-month pilot study was conducted to evaluate the potential of in-situ metal(loid) removal through biostimulation of sulfate-reducing processes. The study took place at an industrial site in Flanders, Belgium, known for metal(loid) contamination in soil and groundwater. Biostimulation involved two incorporations of an organic substrate (emulsified vegetable oil) as electron donor and potassium bicarbonate to raise the pH of the groundwater by 1-1.5 units. The study focused on the most impacted permeable fine sand aquifer (8-9 m below groundwater level) confined by layers of non-permeable clay. The fine sands exhibited initially oxic conditions (50-200 mV), an acidic pH of 4.5 and sulfate concentrations ranging from 600 to 800 mg/L. At the central monitoring well, anoxic conditions (-200 to -400 mV) and a pH of 5.9 established shortly after the second substrate and reagent injection. Over the course of 12 months, there was a significant decrease in the concentration of arsenic (from 2500 to 12 µg/L), nickel (from 360 to <2 µg/L), zinc (from 78,000 to <2 µg/L), and sulfate (from 930 to 450 mg/L). Low levels of metal(loid)s were still present after 34 months (end of study). Mineralogical analysis indicated that the precipitates formed were amorphous in nature. Evidence for biologically driven metal(loid) precipitation was provided by compound specific stable isotope analysis of sulfate. In addition, changes in microbial populations were assessed using next-generation sequencing, revealing stimulation of native sulfate-reducing bacteria. These results highlight the potential of biostimulation for long-term in situ metal(loid) plume treatment/containment.

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.

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.

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.

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.

Designing process and analysis of a new SOI-MESFET structure with enhanced DC and RF characteristics for high-frequency and high-power applications.

This research introduces a new designing process and analysis of an innovative Silicon-on-Insulator Metal-Semiconductor Field-Effect (SOI MESFET) structure that demonstrates improved DC and RF characteristics. The design incorporates several modifications to control and reduce the electric field concentration within the channel. These modifications include relocating the transistor channel to sub-regions near the source and drain, adjusting the position of the gate electrode closer to the source, introducing an aluminum layer beneath the channel, and integrating an oxide layer adjacent to the gate. The results show that the AlOx-MESFET configuration exhibits a remarkable increase of 128% in breakdown voltage and 156% in peak power. Furthermore, due to enhanced conductivity and a significant reduction in gate-drain capacitance, there is a notable improvement of 53% in the cut-off frequency and a 28% increase in the maximum oscillation frequency. Additionally, the current gain experiences a boost of 15%. The improved breakdown voltage and peak power make it suitable for applications requiring robust performance under high voltage and power conditions. The increased maximum oscillation frequency and cut-off frequency make it ideal for high-frequency applications where fast signal processing is crucial. Moreover, the enhanced current gain ensures efficient amplification of signals. The introduced SOI MESFET structure with its modifications offers significant improvements in various performance metrics. It provides high oscillation frequency, better breakdown voltage and good cut-off frequency, and current gain compared to the traditional designs. These enhancements make it a highly desirable choice for applications that demand high-frequency and high-power capabilities.

Development of new materials for electrothermal metals using data driven and machine learning.

After adopting a combined approach of data-driven methods and machine learning, the prediction of material performance and the optimization of composition design can significantly reduce the development time of materials at a lower cost. In this research, we employed four machine learning algorithms, including linear regression, ridge regression, support vector regression, and backpropagation neural networks, to develop predictive models for the electrical performance data of titanium alloys. Our focus was on two key objectives: resistivity and the temperature coefficient of resistance (TCR). Subsequently, leveraging the results of feature selection, we conducted an analysis to discern the impact of alloying elements on these two electrical properties.The prediction results indicate that for the resistivity data prediction task, the radial basis function kernel-based support vector machine model performs the best, with a correlation coefficient above 0.995 and a percentage error within 2%, demonstrating high predictive capability. For the TCR data prediction task, the best-performing model is a backpropagation neural network with two hidden layers, also with a correlation coefficient above 0.995 and a percentage error within 3%, demonstrating good generalization ability. The feature selection results using random forest and Xgboost indicate that Al and Zr have a significant positive effect on resistivity, while Al, Zr, and V have a significant negative effect on TCR. The conclusion of the composition optimization design suggests that to achieve both high resistivity and TCR, it is recommended to set the Al content in the range of 1.5% to 2% and the Zr content in the range of 2.5% to 3%.

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.

The Impact of Inorganic Systems and Photoactive Metal Compounds on Cytochrome P450 Enzymes and Metabolism: From Induction to Inhibition.

While cytochrome P450 (CYP; P450) enzymes are commonly associated with the metabolism of organic xenobiotics and drugs or the biosynthesis of organic signaling molecules, they are also impacted by a variety of inorganic species. Metallic nanoparticles, clusters, ions, and complexes can alter CYP expression, modify enzyme interactions with reductase partners, and serve as direct inhibitors. This commonly overlooked topic is reviewed here, with an emphasis on understanding the structural and physiochemical basis for these interactions. Intriguingly, while both organometallic and coordination compounds can act as potent CYP inhibitors, there is little evidence for the metabolism of inorganic compounds by CYPs, suggesting a potential alternative approach to evading issues associated with rapid modification and elimination of medically useful compounds.

Structural characteristics of alpha-fetoprotein, including N-glycosylation, metal ion and fatty acid binding sites.

Alpha-fetoprotein (AFP), a serum glycoprotein, is expressed during embryonic development and the pathogenesis of liver cancer. It serves as a clinical tumor marker, function as a carcinogen, immune suppressor, and transport vehicle; but the detailed AFP structural information has not yet been reported. In this study, we used single-particle cryo-electron microscopy(cryo-EM) to analyze the structure of the recombinant AFP obtained a 3.31 Å cryo-EM structure and built an atomic model of AFP. We observed and identified certain structural features of AFP, including N-glycosylation at Asn251, four natural fatty acids bound to distinct domains, and the coordination of metal ions by residues His22, His264, His268, and Asp280. Furthermore, we compared the structural similarities and differences between AFP and human serum albumin. The elucidation of AFP's structural characteristics not only contributes to a deeper understanding of its functional mechanisms, but also provides a structural basis for developing AFP-based drug vehicles.

Human T-Cell Responses to Metallic Ion-Doped Bioactive Glasses.

Biomaterials are extensively used as replacements for damaged tissue with bioactive glasses standing out as bone substitutes for their intrinsic osteogenic properties. However, biomaterial implantation has the following risks: the development of implant-associated infections and adverse immune responses. Thus, incorporating metallic ions with known antimicrobial properties can prevent infection, but should also modulate the immune response. Therefore, we selected silver, copper and tellurium as doping for bioactive glasses and evaluated the immunophenotype and cytokine profile of human T-cells cultured on top of these discs. Results showed that silver significantly decreased cell viability, copper increased the T helper (Th)-1 cell percentage while decreasing that of Th17, while tellurium did not affect either cell viability or immune response, as evaluated via multiparametric flow cytometry. Multiplex cytokines assay showed that IL-5 levels were decreased in the copper-doped discs, compared with its undoped control, while IL-10 tended to be lower in the doped glass, compared with the control (plastic) while undoped condition showed lower expression of IL-13 and increased MCP-1 and MIP-1ß secretion. Overall, we hypothesized that the Th1/Th17 shift, and specific cytokine expression indicated that T-cells might cross-activate other cell types, potentially macrophages and eosinophils, in response to the scaffolds.

Diverse crystalline protein scaffolds through metal-dependent polymorphism.

As protein crystals are increasingly finding diverse applications as scaffolds, controlled crystal polymorphism presents a facile strategy to form crystalline assemblies with controllable porosity with minimal to no protein engineering. Polymorphs of consensus tetratricopeptide repeat proteins with varying porosity were obtained through co-crystallization with metal salts, exploiting the innate metal ion geometric requirements. A single structurally exposed negative amino acid cluster was responsible for metal coordination, despite the abundance of negatively charged residues. Density functional theory calculations showed that while most of the crystals were the most thermodynamically stable assemblies, some were kinetically trapped states. Thus, crystalline porosity diversity is achieved and controlled with metal coordination, opening a new scope in the application of proteins as biocompatible protein-metal-organic frameworks (POFs). In addition, metal-dependent polymorphic crystals allow direct comparison of metal coordination preferences.

An overview on the key advantages and limitations of batch and dynamic modes of biosorption of metal ions.

Water purification using adsorption is a crucial process for maintaining human life and preserving the environment. Batch and dynamic adsorption modes are two types of water purification processes that are commonly used in various countries due to their simplicity and feasibility on an industrial scale. However, it is important to understand the advantages and limitations of these two adsorption modes in industrial applications. Also, the possibility of using batch mode in industrial scale was scrutinized, along with the necessity of using dynamic mode in such applications. In addition, the reasons for the necessity of performing batch adsorption studies before starting the treatment on an industrial scale were mentioned and discussed. In fact, this review article attempts to throw light on these subjects by comparing the biosorption efficiency of some metals on utilized biosorbents, using both batch and fixed-bed (column) adsorption modes. The comparison is based on the effectiveness of the two processes and the mechanisms involved in the treatment. Parameters such as biosorption capacity, percentage removal, and isotherm models for both batch and column (fixed bed) studies are compared. The article also explains thermodynamic and kinetic models for batch adsorption and discusses breakthrough evaluations in adsorptive column systems. The review highlights the benefits of using convenient batch-wise biosorption in lab-scale studies and the key advantages of column biosorption in industrial applications.