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Iron phosphide (FeP) nanoparticles have excellent properties such as fast charge transfer kinetics, high electrical conductivity, and high stability, making them a promising catalyst for hydrogen evolution reaction (HER). A challenge to the wide use of iron phosphide nanomaterials for this application is the available synthesis protocols that limit control over the resulting crystalline phase of the product. In this study, we report a method for synthesizing FeP through a solution-based process. Here, we use iron oxyhydroxide (β-FeOOH) as a cost-effective, environmentally friendly, and air-stable source of iron, along with tri- n -octylphosphine (TOP) as the phosphorus source and solvent. FeP is formed in a nanobundle morphology in the solution phase reaction at a temperature of 320 °C. The materials were characterized by pXRD and transmission electron microscopy (TEM). The optimization parameters evaluated to produce the phosphorus-rich FeP phase included the reaction rate, time, amount of TOP, and reaction temperature. Mixtures of Fe 2 P and FeP phases were obtained at shorter reaction times and slow heating rates (4.5 °C /min), while longer reaction times and faster heating rates (18.8 °C/min) favored the formation of phosphorus-rich FeP. Overall, the reaction lever that consistently yielded FeP as the predominant crystalline phase was a fast heat rate., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Antigen-specific T cells are central to the adaptive immune response against T. cruzi infection and underpin the efficacy of on-going vaccine strategies. In this context, the present study focuses on T-cell assays that define the parasite-specificity on the basis of upregulation of TCR stimulation-induced surface markers. For this purpose, we tested different dual marker combinations (OX40, CD25, CD40L, CD137, CD69, PD-L1, CD11a, CD49d, HLA-DR, CD38) to reliably identify activated CD4 + and CD8 + T-cell populations from PBMCs of chronic Chagas disease (CCD) patients after 12 or 24 h of stimulation with T. cruzi lysate. Results demonstrated that activation-induced markers (AIM) assays combining the expression of OX40, CD25, CD40L, CD137, CD69 and/or PD-L1 surface markers are efficient at detecting T. cruzi-specific CD4 + T cells in CCD patients, in comparison to non-infected donors, after both stimulation times. For CD8 + T cells, only PD-L1/OX40 after 24 h of antigen exposure resulted to be useful to track a parasite-specific response. We also demonstrated that the agnostic activation is mediated by different T. cruzi strains, such as Dm28c, CL Brener or Sylvio. Additionally, we successfully used this approach to identify the phenotype of activated T lymphocytes based on the expression of CD45RA and CCR7. Overall, our results show that different combinations of AIM markers represent an effective and simple tool for the detection of T. cruzi-specific CD4 + and CD8 + T cells., (© 2022 John Wiley & Sons Ltd.)

Viral fusion is a critical step in the entry pathway of enveloped viruses and remains a viable target for antiviral exploration. The current approaches for studying fusion mechanisms include ensemble fusion assays, high-resolution cryo-TEM, and single-molecule fluorescence-based methods. While these methods have provided invaluable insights into the dynamic events underlying fusion processes, they come with their own limitations. These often include extensive data and image analysis in addition to experimental time and technical requirements. This work proposes the use of the spin-spin T2 relaxation technique as a sensitive bioanalytical method for the rapid quantification of interactions between viral fusion proteins and lipids in real time. In this study, new liposome-coated iron oxide nanosensors (LIONs), which mimic as magnetic-labeled host membranes, are reported to detect minute interactions occurring between the membrane and influenza's fusion glycoprotein, hemagglutinin (HA). The influenza fusion protein's interaction with the LION membrane is detected by measuring changes in the sensitive spin-spin T2 magnetic relaxation time using a bench-top NMR instrument. More data is gleaned from including the fluorescent dye DiI into the LION membrane. In addition, the effects of environmental factors on protein-lipid interaction that affect fusion such as pH, time of incubation, trypsin, and cholesterol were also examined. Furthermore, the efficacy and sensitivity of the spin-spin T2 relaxation assay in quantifying similar protein/lipid interactions with more native configurations of HA were demonstrated using virus-like particles (VLPs). Shorter domains derived from HA were used to start a reductionist path to identify the parts of HA responsible for the NMR changes observed. Finally, the known fusion inhibitor Arbidol was employed in our spin-spin T2 relaxation-based fusion assay to demonstrate the application of LIONs in real-time monitoring of this aspect of fusion for evaluation of potential fusion inhibitors.

Nanowires and nanorods of magnetite (Fe 3 O 4 ) are of interest due to their varied biological applications but most importantly for their use as magnetic resonance imaging contrast agents. One-dimensional (1D) structures of magnetite, however, are more challenging to synthesize because the surface energy favors the formation of isotropic structures. Synthetic protocols can be dichotomous, producing either the 1D structure or the magnetite phase but not both. Here, superparamagnetic Fe 3 O 4 nanorods were prepared in solution by the reduction of iron oxy-hydroxide (β-FeOOH) nanoneedles with hydrazine (N 2 H 4 ). The amount of hydrazine and the reaction time affected the phase and morphology of the resulting iron oxide nanoparticles. One-dimensional nanostructures of Fe 3 O 4 could be produced consistently from various aspect ratios of β-FeOOH nanoneedles, although the length of the template was not retained. Fe 3 O 4 nanorods were characterized by transmission electron microscopy, X-ray powder diffraction, X-ray photoelectron spectroscopy, and SQUID magnetometry., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

We report a solution-based synthetic method to produce shape-tunable iron pyrite (FeS 2 ) nanocrystals using iron oxy-hydroxide (β-FeOOH) as a precursor and their application for selective reduction of functionalized nitroarenes to aniline derivatives with formic acid-triethylamine (HCOOH-Et 3 N) as a hydrogen donor system., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

Gold nanorods (GNRs) have received broad attention due to their tunable surface plasmonic resonance modes, which make them an attractive candidate for biomedical applications in drug and gene delivery, biological imaging, and cancer treatment. In this study, we highlight the interactions of four different aspect ratios (ARs), 2.6, 3.2, 5.4 and 11.5, of GNRs with HeLa cells with respect to cellular uptake and cellular viability while also considering the effects of other parameters such as the surface stabilizer, supernatant, and serum proteins present in the medium. From this work, it was determined that the cell viability depended on the chemical composition of the supernatant, especially the amount of excess surfactant, hexadecyltrimethylammonium bromide (CTAB), used for the synthesis of GNRs; thus, the effect of aspect ratio of GNRs on endocytosis could not be directly discerned. For example, when exposed to GNRs of aspect ratio 11.5, HeLa cells showed higher cellular uptake compared to the shorter aspect ratios and a lower cytotoxicity simply because of the lower concentration of CTAB used during the synthesis, and a gentler purification method, such as sedimentation, also appeared to be a factor. Overall, the synthesis protocols, functionalization, purification processes, and the stability of GNRs in media have a major effect on cellular uptake and viability. Our results suggest that perhaps AR does play a role in endocytosis although an overall trend could not be unequivocally established, and sedimentation, contact time, and internalization kinetics need to be probed further using more biocompatible ligands in future studies.

Micropillar patterns were fabricated and used to study cell adhesion, morphology, and function. Micropillars were produced in poly(2-hydroxyethyl methacrylate (HEMA)/ N , N -(dimethylaminoethyl)methacrylate (DMAEMA)/tetraethylene glycol dimethacrylate (TEGDMA)) hydrogels using soft lithography, had dimensions of 1 μm diameter, and were either 2.05 or 4.91 μm tall. The patterned hydrogel substrates increased adhesion and induced the formation of cellular aggregates. Digital micrographs were used to quantify aggregate size and number. Differentiation of hMSCs toward adipocytes and chondrocytes was performed using the respective complete culture and differentiation medium for 2 weeks. Cells were stained for Oil red O, Alcian blue, and Type II collagen. Hydrogel substrates supported the differentiation of hMSCs to adipocytes and chondrocytes. The taller micropillar patterns supported the attachment and growth of larger aggregates and were more amenable to aid chondrogenic differentiation.

Chagas disease is a lifelong pathology resulting from Trypanosoma cruzi infection. It represents one of the most frequent causes of heart failure and sudden death in Latin America. Herein, we provide evidence that aerobic glycolytic pathway activation in monocytes drives nitric oxide (NO) production, triggering tyrosine nitration (TN) on CD8+ T cells and dysfunction in patients with chronic Chagas disease. Monocytes from patients exhibited a higher frequency of hypoxia-inducible factor 1α and increased expression of its target genes/proteins. Nonclassical monocytes are expanded in patients' peripheral blood and represent an important source of NO. Monocytes entail CD8+ T cell surface nitration because both the frequency of nonclassical monocytes and that of NO-producing monocytes positively correlated with the percentage of TN+ lymphocytes. Inhibition of glycolysis in in vitro-infected peripheral blood mononuclear cells decreased the inflammatory properties of monocytes/macrophages, diminishing the frequency of IL-1β- and NO-producing cells. In agreement, glycolysis inhibition reduced the percentage of TN+CD8+ T cells, improving their functionality. Altogether, these results clearly show that glycolysis governs oxidative stress on monocytes and modulates monocyte-T cell interplay in human chronic Chagas disease. Understanding the pathological immune mechanisms that sustain an inflammatory environment in human pathology is key to designing improved therapies.

Trypanosoma cruzi, the aetiological agent of Chagas disease, has a highly efficient detoxification system to deal with the oxidative burst imposed by its host. One of the antioxidant enzymes involved is the cytosolic tryparedoxin peroxidase (c-TXNPx), which catalyses the reduction to hydrogen peroxide, small-chain organic hydroperoxides and peroxynitrite. This enzyme is present in all parasite stages, and its overexpression renders parasites more resistant to the oxidative defences of macrophages, favouring parasite survival. This work addressed the study of the specific humoral and cellular immune response triggered by c-TXNPx in human natural infection. Thus, sera and peripheral blood mononuclear cells (PBMC) were collected from chronically infected asymptomatic and cardiac patients, and non-infected individuals. Results showed that levels of IgG antibodies against c-TXNPx were low in sera from individuals across all groups. B-cell epitope prediction limited immunogenicity to a few, small regions on the c-TXNPx sequence. At a cellular level, PBMC from asymptomatic and cardiac patients proliferated and secreted interferon-γ after c-TXNPx stimulation, compared with mock control. However, only proliferation was higher in asymptomatic patients compared with cardiac and non-infected individuals. Furthermore, asymptomatic patients showed an enhanced frequency of CD19 + CD69 + cells upon exposure to c-TXNPx. Overall, our results show that c-TXNPx fails to induce a strong immune response in natural infection, being measurable only in those patients without any clinical symptoms. The low impact of c-TXNPx in the human immune response could be strategic for parasite survival, as it keeps this crucial antioxidant enzyme activity safe from the mechanisms of adaptive immune response., (© 2018 John Wiley & Sons Ltd.)

Trypanosoma cruzi is a genetically heterogeneous group of organisms that cause Chagas disease. It has been long suspected that the clinical outcome of the disease and response to therapeutic agents are, at least in part, related to the genetic characteristics of the parasite. Herein, we sought to validate the significance of the genotype of T. cruzi isolates recovered from patients with different clinical forms of Chagas disease living in Argentina on their biological behaviour and susceptibility to drugs. Genotype identification of the newly established isolates confirmed the reported predominance of TcV, with a minor frequency of TcI. Epimastigote sensitivity assays demonstrated marked dissimilar responses to benznidazole, nifurtimox, pentamidine and dihydroartemisinin in vitro. Two TcV isolates exhibiting divergent response to benznidazole in epimastigote assays were further tested for the expression of anti-oxidant proteins. Benznidazole-resistant BOL-FC10A epimastigotes had decreased expression of Old Yellow Enzyme and cytosolic superoxide dismutase, and overexpression of mitochondrial superoxide dismutase and tryparedoxin- 1, compared to benznidazole-susceptible AR-SE23C parasites. Drug sensitivity assays on intracellular amastigotes and trypomastigotes reproduced the higher susceptibility of AR-SE23C over BOL-FC10A parasites to benznidazole observed in epimastigotes assays. However, the susceptibility/resistance profile of amastigotes and trypomastigotes to nifurtimox, pentamidine and dihydroartemisinin varied markedly with respect to that of epimastigotes. C3H/He mice infected with AR-SE23C trypomastigotes had higher levels of parasitemia and mortality rate during the acute phase of infection compared to mice infected with BOL-FC10A trypomastigotes. Treatment of infected mice with benznidazole or nifurtimox was efficient to reduce patent parasitemia induced by either isolate. Nevertheless, qPCR performed at 70 dpi revealed parasite DNA in the blood of mice infected with AR-SE23C but not in BOL-FC10A infected mice. These results demonstrate high level of intra-type diversity which may represent an important obstacle for the testing of chemotherapeutic agents., Competing Interests: The authors have declared that no competing interests exist.

In this study, we report a unique strategy that utilizes ZnO and ZnS microparticles and rods as fire-retardant materials when coated onto cotton fabrics. ZnO and ZnO/ZnS microparticles or rods were grown or adsorbed to the surface of cotton fibers. Properties such as heat release rate, total smoke release, and mass loss rate of the materials were tested using a cone calorimeter. ZnO and ZnO/ZnS rods were able to reduce the heat release rate and total smoke release from 118 kW/m 2 and 18.3 m 2 /m 2 to about 70.0 kW/m 2 and 6.00 m 2 /m 2 , respectively. The maximum average rate of heat emission and fire growth rate index, which is used to evaluate the fire spread rate, the size of the fire, and the propensity of fire development, were improved with these coatings and indicate that there are potential applications of these materials as fire retardants., Competing Interests: The authors declare no competing financial interest.

Monocyte transendothelial migration is a multi-step process critical for the initiation and development of atherosclerosis. The chemokine monocyte chemoattractant protein-1 (MCP-1) is overexpressed during atheroma and its concentration gradients in the extracellular matrix (ECM) is critical for the transendothelial recruitment of monocytes. Based on prior observations, we hypothesize that both free and bound gradients of MCP-1 within the ECM are involved in directing monocyte migration. The interaction between a three-dimensional (3D), cell-free, collagen matrix and MCP-1; and its effect on monocyte migration was measured in this study. Our results showed such an interaction existed between MCP-1 and collagen, as 26% of the total MCP-1 added to the collagen matrix was bound to the matrix after extensive washes. We also characterized the collagen-MCP-1 interaction using biophysical techniques. The treatment of the collagen matrix with MCP-1 lead to increased monocyte migration, and this phenotype was abrogated by treating the matrix with an anti-MCP-1 antibody. Thus, our results indicate a binding interaction between MCP-1 and the collagen matrix, which could elicit a haptotactic effect on monocyte migration. A better understanding of such mechanisms controlling monocyte migration will help identify target cytokines and lead to the development of better anti-inflammatory therapeutic strategies., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The efficient extraction of (bio)molecules from fluid mixtures is vital for applications ranging from target characterization in (bio)chemistry to environmental analysis and biomedical diagnostics. Inspired by biological processes that seamlessly synchronize the capture, transport and release of biomolecules, we designed a robust chemomechanical sorting system capable of the concerted catch and release of target biomolecules from a solution mixture. The hybrid system is composed of target-specific, reversible binding sites attached to microscopic fins embedded in a responsive hydrogel that moves the cargo between two chemically distinct environments. To demonstrate the utility of the system, we focus on the effective separation of thrombin by synchronizing the pH-dependent binding strength of a thrombin-specific aptamer with volume changes of the pH-responsive hydrogel in a biphasic microfluidic regime, and show a non-destructive separation that has a quantitative sorting efficiency, as well as the system's stability and amenability to multiple solution recycling.

Numerous abnormalities of the peripheral blood T cell compartment have been reported in human chronic Trypanosoma cruzi infection and related to prolonged antigenic stimulation by persisting parasites. Herein, we measured circulating lymphocytes of various phenotypes based on the differential expression of CD19, CD4, CD27, CD10, IgD, IgM, IgG and CD138 in a total of 48 T. cruzi-infected individuals and 24 healthy controls. Infected individuals had decreased frequencies of CD19+CD27+ cells, which positively correlated with the frequencies of CD4+CD27+ cells. The contraction of CD19+CD27+ cells was comprised of IgG+IgD-, IgM+IgD- and isotype switched IgM-IgD- memory B cells, CD19+CD10+CD27+ B cell precursors and terminally differentiated CD19+CD27+CD138+ plasma cells. Conversely, infected individuals had increased proportions of CD19+IgG+CD27-IgD- memory and CD19+IgM+CD27-IgD+ transitional/naïve B cells. These observations prompted us to assess soluble CD27, a molecule generated by the cleavage of membrane-bound CD27 and used to monitor systemic immune activation. Elevated levels of serum soluble CD27 were observed in infected individuals with Chagas cardiomyopathy, indicating its potentiality as an immunological marker for disease progression in endemic areas. In conclusion, our results demonstrate that chronic T. cruzi infection alters the distribution of various peripheral blood B cell subsets, probably related to the CD4+ T cell deregulation process provoked by the parasite in humans.

Nanobiomaterials are introducing new capabilities to coordinate cell selection, growth, morphology, and differentiation. Herein, we report that tuning the geometry of ordered arrays of nanopillars (NP) elicits specialized morphologies in adherent cells. Systematic analysis of the effects of the NP radius, height, and spacing reveals that stem cells assume either flattened, polarized, or stellate morphologies in direct response to interpillar spacing. Notably, on NPs of pitch near a critical spacing (d(crit) ≈ 2 μm for C3H10T1/2 cells), cells exhibit rounding of the cell body, pronounced polarization, and extension of narrow axon-like cell projections aligned with the square lattice of the NP array and extending hundreds of micrometers. Furthermore, increasing the NPs' aspect ratio from 12:1 to 50:1 to produce NPs with a corresponding reduction in the NP bending stiffness of 2 orders of magnitude amplified the cellular response and resulted in a previously unseen degree of cell polarization and alignment. The rapid morphological transformation is reproducible on surfaces that maintain key parameters of the NP geometry and spacing, is influenced by the cell seeding density, and persists for different stem cell lines and primary mesenchymal stem cells. The demonstrated ability to support various morphogenetic trends in stem cells by simply tuning the geometry of the NP substrates provides a stepping-stone for the future design of scaffolds where cellular morphology and alignment are crucial.

During the in-situ order-disorder transition of intermetallic L1(2)-type Au(3)Fe(1-x) nanocrystals, structural information has been retrieved from their electron diffraction patterns based on the Pawley refinement that is unrelated to the electron kinematical or dynamical scattering nature as well as the Rietveld refinement using a kinematical approximation. At room temperature, it was found that the nanocrystals contain approximately x=40% vacancies at the Fe site. Based on in-situ heating this phase displayed an irreversible order-disorder transition, with the transition temperature between 553 and 593 K. A sudden increase in lattice parameter was detected during the first heating from the ordered phase, while the second heating of the disordered phase showed only a linear relationship with temperature. From the lattice parameter measurement of the disordered phase, the coefficient of thermal expansion was estimated as 1.462 × 10(-5)K(-1). The long-range order parameter S was determined by the refined site occupancies, as well as the integrated intensities of the superlattice (100) and fundamental (220) reflections using the Pawley and Rietveld refinements during the order-disorder transition. Considering the dynamical scattering effect, Blackman two-beam approximation theory was applied to corrected S, which slightly attenuated after the correction. A comparison of the electron diffraction with X-ray diffraction data was made. It was demonstrated that elemental and structural information could be retrieved through quantitative electron diffraction studies of the nanomaterials. Since the Pawley refinement algorithm does not include the electron scattering event, it is especially useful to refine the electron diffraction data regardless of the sample thickness., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Alloys and intermetallic compounds of Au with the 3d transition metals Fe, Co, and Ni are nonequilibrium phases that have many useful potential applications as catalytic, magnetic, optic, and multifunctional magneto-optic materials. However, the atomically ordered Au-M (M = Fe, Co, Ni) intermetallics are particularly elusive from a synthetic standpoint. Here we report the low-temperature solution synthesis of the L12 (Cu3Au-type) intermetallic compounds Au3Fe, Au3Co, and Au3Ni using n-butyllithium as a reducing agent. Reaction pathway studies for the Au3Co system indicate that Au nucleates first, followed by Co incorporation to form the intermetallic. The nonequilibrium intermetallic nanocrystals have been characterized by powder XRD, TEM, EDS, selected area electron diffraction, and nanobeam electron diffraction, which collectively confirm the compositions and superlattice structures.

Context: Point-of-care testing glucose meters are strongly recommended in the management of diabetes and are increasingly being used for making therapeutically important decisions. Thus, it is essential that their results correlate well with those of laboratory analyzers., Objectives: To test the reliability of point-of-care testing glucose meters., Design: Two studies were performed: (1), an in-house study comparing accuracy of point-of-care testing glucose meters with a reference analyzer using fresh whole blood specimens (2), a real-time comparison of (a) 2 successive glucose meter readings and (b) glucose meter reading to central laboratory analyzer reading., Setting: (1), Seven glucose meters from 4 manufacturers were compared with the Yellow Springs YSI 2300 blood glucose analyzer using whole blood without preservative. (2), (a) Whole blood samples were read within 5 minutes of each other using Accu-Chek meters and (b) between a glucose meter and a Hitachi laboratory analyzer., Results: (1) Within the Accu-Chek group of glucose meters, fresh, preservative-free whole blood samples showed the lowest bias. (2) At the hypoglycemic level, successive glucose meter readings agreed well, but there was considerable disagreement between glucose meter and central laboratory values. Because laboratory analyzers are of proven accuracy, they are used as the reference. In the glucose meter-central laboratory analyzer correlation, for both hypoglycemic and hyperglycemic values, readings in which the differences were greater than 10% occurred more than 61% of the time. In the hypoglycemic range, differences greater than 20% occurred 57% of the time., Conclusions: One should scrutinize point-of-care testing glucose meter readings at the hypoglycemic and hyperglycemic levels and whenever possible to corroborate these clinical results with central laboratory analyzers.

Hollow metal nanospheres are of interest for a variety of academic and technological applications, including drug delivery, catalysis, plasmonics, and lightweight structural composites. Despite recent advances in synthesizing metal nanostructures with controlled morphologies, there are very few reports of hollow bimetallic nanospheres, although such systems promise to offer advantages over single-metal systems. Here, were report a one-pot synthetic strategy for accessing hollow CoPt nanospheres with a Co-Pt alloy structure. The approach utilizes an in situ Co template and exploits galvanic displacement reactions to selectively dissolve the Co core while depositing a Pt shell. The combination of reducing conditions and a polymer stabilizer appears to allow the Co and Pt to co-reduce and form a Co-Pt fcc alloy phase with a morphology that is templated by the sacrificial Co core. The hollow CoPt nanospheres, which show magnetic hysteresis at low temperatures, are thermally stable up to 300 degrees C. The approach, which adds to a growing toolbox of reactions that yield morphologically controlled magnetic CoPt and FePt nanomaterials, is likely to be general for a variety of alloy systems.

Intermetallic compounds and alloys are traditionally synthesized by heating mixtures of metal powders to high temperatures for long periods of time. A low-temperature solution-based alternative has been developed, and this strategy exploits the enhanced reactivity of nanoparticles and the nanometer diffusion distances afforded by binary nanocomposite precursors. Prereduced metal nanoparticles are combined in known ratios, and they form nanomodulated composites that rapidly transform into intermetallics and alloys upon heating at low temperatures. The approach is general in terms of accessible compositions, structures, and morphologies. Multiple compounds in the same binary system can be readily accessed; e.g., AuCu, AuCu3, Au3Cu, and the AuCu-II superlattice are all accessible in the Au-Cu system. This concept can be extended to other binary systems, including the intermetallics FePt3, CoPt, CuPt, and Cu3Pt and the alloys Ag-Pt, Au-Pd, and Ni-Pt. The ternary intermetallic Ag2Pd3S can also be rapidly synthesized at low temperatures from a nanocomposite precursor comprised of Ag2S and Pd nanoparticles. Using this low-temperature solution-based approach, a variety of morphologically diverse nanomaterials are accessible: surface-confined thin films (planar and nonplanar supports), free-standing monoliths, nanomesh materials, inverse opals, and dense gram-scale nanocrystalline powders of intermetallic AuCu. Importantly, the multimetallic materials synthesized using this approach are functional, yielding a room-temperature Fe-Pt ferromagnet, a superconducting sample of Ag2Pd3S (Tc = 1.10 K), and a AuPd4 alloy that selectively catalyzes the formation of H2O2 from H2 and O2. Such flexibility in the synthesis and processing of functional intermetallic and alloy materials is unprecedented.