Metastable epialleles in humans.

First identified in isogenic mice, metastable epialleles (MEs) are loci where the extent of DNA methylation (DNAm) is variable between individuals but correlates across tissues derived from different germ layers within a given individual. This property, termed systemic interindividual variation (SIV), is attributed to stochastic methylation establishment before germ layer differentiation. Evidence suggests that some putative human MEs are sensitive to environmental exposures in early development. In this review we introduce key concepts pertaining to human MEs, describe methods used to identify MEs in humans, and review their genomic features. We also highlight studies linking DNAm at putative human MEs to early environmental exposures and postnatal (including disease) phenotypes.

How does a hyperuniform fluid freeze?

All phase transitions can be categorized into two different types: continuous and discontinuous phase transitions. Discontinuous phase transitions are normally accompanied with significant structural changes, and nearly all of them have the kinetic pathway of nucleation and growth, if the system does not suffer from glassy dynamics. Here, in a system of barrier-controlled reactive particles, we find that the discontinuous freezing transition of a nonequilibrium hyperuniform fluid into an absorbing state does not have the kinetic pathway of nucleation and growth, and the transition is triggered by long-wavelength fluctuations. The transition rate decreases with increasing the system size, which suggests that the metastable hyperuniform fluid could be kinetically stable in an infinitely large system. This challenges the common understanding of metastability in discontinuous phase transitions. Moreover, we find that the "metastable yet kinetically stable" hyperuniform fluid features a scaling in the structure factor [Formula: see text] in 2D, which is the third dynamic hyperuniform state in addition to the critical hyperuniform state with [Formula: see text] and the nonequilibrium hyperuniform fluid with [Formula: see text].

The dual role of martensitic transformation in fatigue crack growth.

Deformation-induced martensitic transformation (DIMT) has been used for designing high-performance alloys to prevent structural failure under static loads. Its effectiveness against fatigue, however, is unclear. This limits the application of DIMT for parts that are exposed to variable loads, although such scenarios are the rule and not the exception for structural failure. Here we reveal the dual role of DIMT in fatigue crack growth through in situ observations. Two antagonistic fatigue mechanisms mediated by DIMT are identified, namely, transformation-mediated crack arresting, which prevents crack growth, and transformation-mediated crack coalescence, which promotes crack growth. Both mechanisms are due to the hardness and brittleness of martensite as a transformation product, rather than to the actual transformation process itself. In fatigue crack growth, the prevalence of one mechanism over the other critically depends on the crack size and the mechanical stability of the parent austenite phase. Elucidating the two mechanisms and their interplay allows for the microstructure design and safe use of metastable alloys that experience fatigue loads. The findings also generally reveal how metastable alloy microstructures must be designed for materials to be fatigue-resistant.

Dynamic DNA Assembly by Programmable Hybridization Chain Reaction Mimicking Tubulin.

Dynamic biological structures involve the continual turnover of molecules within supramolecular assemblies such as tubulin. Inspired by dynamic biology self-organizing systems, we build an artificial dynamic structure based on DNA nanotechnology through a nonequilibrium chemical system. Herein, a metastable domain (MD), essentially a stem-loop structure, was introduced into DNA hairpins within hybridization chain reaction (HCR), thereby imparting dynamic activity to the DNA polymers. Hairpins with MD thermodynamically assemble to a high-energy polymer in the presence of trigger strands. The polymer can relax back to the stable unassembled state once the invader is added and finally relax to the activated hairpin by an anti-invader. Reversible assembly/disassembly of the HCR is achieved through invader/anti-invader cycles. We accomplished kinetic modulation, reversible conformational switching, cascading regulation, and enzyme activity control through the MD-HCR. We believe that the design of the MD-HCR could inspire the development of autonomous biological functions within artificial systems.

A Metastable Semiquinone Molecular Switch Modulated by Ascorbate/O2: a Study from a System Far-From-Equilibrium to Biological Assays in Mitochondria.

A molecular switch based on the metastable radical anion derived from a substituted heteroaryl quinone is described. Pyrrolil quinone thiocyanate (PQ 5) showed an interaction with the fluoride anion that was visible to the naked eye and quantified by UV/vis and 1H and 13C NMR. The metastable quinoid species formed by the interaction with F- ("ON" state) showed a molecular switching effect autocontrolled by the presence of ascorbate ("OFF" state) and back to the "ON" state by an autooxidation process, measured by visible and UV/vis spectroscopy. Due to its out-of-equilibrium properties and the exchange of matter and energy, a dissipative structural behaviour is proposed. Considering its similarity to the mechanism of coenzyme Q in oxidative phosphophorylation, PQ 5 was evaluated on Saccharomyces cerevisiae mitochondrial function for inhibition of complexes II, III and IV, reactive oxygen species (ROS) production, catalase activity and lipid peroxidation. The results showed that PQ 5 inhibited complex III activity as well as the activity of all electron transport chain (ETC) complexes. In addition, PQ 5 reduced ROS production and catalase activity in yeast. The results suggest that PQ 5 may have potential applications as a new microbicidal compound by inducing ETC dysfunction.

Mesoporous Metal Sponges Produced by Explosive Decomposition.

The formation of mesoporous gold sponges by explosive decomposition of 'knallgold' (also known as 'fulminating' gold) is studied. Proof-of-principle experiments are conducted and then the phenomena are further investigated using 'toy physics' molecular dynamics simulations. The simulations invoked various ratios of a volatile Lennard-Jones element G and a noble metal element N. In both experiment and simulation the morphology of the resulting sponge is found to depend on the stoichiometry of the starting material. As the mole fraction of G (χG) is increased from 0.5 to close to 1.0 in the simulations, the morphology of the sponges changes from closed to open, with a corresponding increase in the average mean curvature from 0 to +0.12 inverse Lennard-Jones length (L) units. The average Gaussian curvature of the simulated sponges is always negative, with the minimum value of 0.05 L-2 being found for χG ≈0.65. In broad agreement with experiment, sponge formation in the simulations is bounded by stoichiometry; no sponges form if χG is <0.52, for χG between 0.52 and 0.70 the sponge is characterized by vermicular cavities whereas classic bicontinuous fibrous sponges form for 0.70< χG < 0.85 and, finally, discrete particles result if χG >0.85.

Investigation of the Binary System of Proxyphylline Enantiomers: Structural Resolution and Phase Diagram Determination.

The solid-state landscape of proxyphylline (PXL), a chiral derivative of theophylline crystallizing as a racemic compound, was extensively investigated by means of thermal analyses and diffraction techniques. This study revealed the presence of five distinct polymorphic forms that were characterized: two polymorphs of the racemic mixture and three polymorphs of the pure enantiomer. The nature of each solid phase was confirmed by combining the different analytical techniques, revealing the presence of a thermodynamically stable racemic compound, RI (TFus= 134 °C), in equilibrium with the stable enantiopure crystal form, EI (TFus = 148.3 °C). Additionally, other crystal forms could be evidenced: a polymorph of the racemic compound, RII (TFus= 111.5 °C), as well as two metastable conglomerates, cEI and cEII, and two other polymorphs of the pure enantiomer, EII and EIII. The crystal structures of RI and EI are reported and discussed, highlighting the diversity of molecular conformations that can be adopted by the PXL molecule, which accounts for the versatility of the crystallization behaviors observed in this system. These findings enhance our understanding of the crystallization behavior of chiral pharmaceutical compounds and have implications for optimizing their crystallization processes in the pharmaceutical industry.

Insomnia disorder characterized by probabilistic metastable substates using blood-oxygenation-level-dependent (BOLD) phase signals.

PURPOSE: From a clinical point of view, how to force a transition from insomnia brain state to healthy brain state by external driven stimulation is of great interest. This needs to define brain state of insomnia disorder as metastable substates. The current study was to identify recurrent substates of insomnia disorder in terms of probability of occurrence, lifetime, and alternation profiles by using leading eigenvector dynamics analysis (LEiDA) method. METHODS: We enrolled 32 patients with insomnia disorder and 30 healthy subjects. We firstly obtained the BOLD phase coherence matrix from Hilbert transform of BOLD signals and then extracted all the leading eigenvectors from the BOLD phase coherence matrix for all subjects across all time points. Lastly, we clustered the leading eigenvectors using a k-means clustering algorithm to find the probabilistic metastable substates (PMS) and calculate the probability of occurrence and associated lifetime for substates. RESULTS: The resulting 3 clusters were optimal for brain state of insomnia disorder and healthy brain state, respectively. The occurred probabilities of the PMS were significantly different between the patients with insomnia disorder and healthy subjects, with 0.51 versus 0.44 for PMS-1 (p < 0.001), 0.25 versus 0.27 for PMS-2 (p = 0.051), and 0.24 versus 0.29 for PMS-3 (p < 0.001), as well as the lifetime (in TR) of 36.65 versus 33.15 for PMS-1 (p = 0.068), 14.36 versus 15.43 for PMS-2 (p = 0.117), and 14.80 versus 16.34 for PMS-3 (p = 0.042). The values of the diagonal of the transition matrix were much higher than the probabilities of switching states, indicating the metastable nature of substates. CONCLUSION: The resulted probabilistic metastable substates hint the characteristic brain dynamics of insomnia disorder. The results may lay a foundation to help determine how to force a transition from insomnia brain state to healthy brain state by external driven stimulation.

Lithium superoxide encapsulated in a benzoquinone anion matrix.

Lithium peroxide is the crucial storage material in lithium-air batteries. Understanding the redox properties of this salt is paramount toward improving the performance of this class of batteries. Lithium peroxide, upon exposure to p-benzoquinone (p-C6H4O2) vapor, develops a deep blue color. This blue powder can be formally described as [Li2O2][Formula: see text] [LiO2][Formula: see text] {Li[p-C6H4O2]}0.7, though spectroscopic characterization indicates a more nuanced structural speciation. Infrared, Raman, electron paramagnetic resonance, diffuse-reflectance ultraviolet-visible and X-ray absorption spectroscopy reveal that the lithium salt of the benzoquinone radical anion forms on the surface of the lithium peroxide, indicating the occurrence of electron and lithium ion transfer in the solid state. As a result, obligate lithium superoxide is formed and encapsulated in a shell of Li[p-C6H4O2] with a core of Li2O2 Lithium superoxide has been proposed as a critical intermediate in the charge/discharge cycle of Li-air batteries, but has yet to be isolated, owing to instability. The results reported herein provide a snapshot of lithium peroxide/superoxide chemistry in the solid state with redox mediation.

Structural relaxation and crystallization in supercooled water from 170 to 260 K.

The origin of water's anomalous properties has been debated for decades. Resolution of the problem is hindered by a lack of experimental data in a crucial region of temperatures, T, and pressures where supercooled water rapidly crystallizes-a region often referred to as "no man's land." A recently developed technique where water is heated and cooled at rates greater than 109 K/s now enables experiments in this region. Here, it is used to investigate the structural relaxation and crystallization of deeply supercooled water for 170 K < T < 260 K. Water's relaxation toward a new equilibrium structure depends on its initial structure with hyperquenched glassy water (HQW) typically relaxing more quickly than low-density amorphous solid water (LDA). For HQW and T > 230 K, simple exponential relaxation kinetics is observed. For HQW at lower temperatures, increasingly nonexponential relaxation is observed, which is consistent with the dynamics expected on a rough potential energy landscape. For LDA, approximately exponential relaxation is observed for T > 230 K and T < 200 K, with nonexponential relaxation only at intermediate temperatures. At all temperatures, water's structure can be reproduced by a linear combination of two, local structural motifs, and we show that a simple model accounts for the complex kinetics within this context. The relaxation time, τ rel , is always shorter than the crystallization time, τ xtal For HQW, the ratio, τ xtal /τ rel , goes through a minimum at ∼198 K where the ratio is about 60.

Nanosized and metastable molybdenum oxides as negative electrode materials for durable high-energy aqueous Li-ion batteries.

The development of inherently safe energy devices is a key challenge, and aqueous Li-ion batteries draw large attention for this purpose. Due to the narrow electrochemical stable potential window of aqueous electrolytes, the energy density and the selection of negative electrode materials are significantly limited. For achieving durable and high-energy aqueous Li-ion batteries, the development of negative electrode materials exhibiting a large capacity and low potential without triggering decomposition of water is crucial. Herein, a type of a negative electrode material (i.e., Li x Nb2/7Mo3/7O2) is proposed for high-energy aqueous Li-ion batteries. Li x Nb2/7Mo3/7O2 delivers a large capacity of ∼170 mA ⋅ h ⋅ g-1 with a low operating potential range of 1.9 to 2.8 versus Li/Li+ in 21 m lithium bis(trifluoromethanesulfonyl)amide (LiTFSA) aqueous electrolyte. A full cell consisting of Li1.05Mn1.95O4/Li9/7Nb2/7Mo3/7O2 presents high energy density of 107 W ⋅ h ⋅ kg-1 as the maximum value in 21 m LiTFSA aqueous electrolyte, and 73% in capacity retention is achieved after 2,000 cycles. Furthermore, hard X-ray photoelectron spectroscopy study reveals that a protective surface layer is formed at the surface of the negative electrode, by which the high-energy and durable aqueous batteries are realized with Li x Nb2/7Mo3/7O2 This work combines a high capacity with a safe negative electrode material through delivering the Mo-based oxide with unique nanosized and metastable characters.

Nascent fusion pore opening monitored at single-SNAREpin resolution.

Vesicle fusion with a target membrane is a key event in cellular trafficking and ensures cargo transport within the cell and between cells. The formation of a protein complex, called SNAREpin, provides the energy necessary for the fusion process. In a three-dimensional microfluidic chip, we monitored the fusion of small vesicles with a suspended asymmetric lipid bilayer. Adding ion channels into the vesicles, our setup allows the observation of a single fusion event by electrophysiology with 10-µs precision. Intriguingly, we identified that small transient fusion pores of discrete sizes reversibly opened with a characteristic lifetime of ∼350 ms. The distribution of their apparent diameters displayed two peaks, at 0.4 ± 0.1 nm and 0.8 ± 0.2 nm. Varying the number of SNAREpins, we demonstrated that the first peak corresponds to fusion pores induced by a single SNAREpin and the second peak is associated with pores involving two SNAREpins acting simultaneously. The pore size fluctuations provide a direct estimate of the energy landscape of the pore. By extrapolation, the energy landscape for three SNAREpins does not exhibit any thermally significant energy barrier, showing that pores larger than 1.5 nm are spontaneously produced by three or more SNAREpins acting simultaneously, and expand indefinitely. Our results quantitatively explain why one SNAREpin is sufficient to open a fusion pore and more than three SNAREpins are required for cargo release. Finally, they also explain why a machinery that synchronizes three SNAREpins, or more, is mandatory to ensure fast neurotransmitter release during synaptic transmission.

Coherent Phonon Manipulation via Electron-Phonon Interaction for Facilitated Relaxation of Metastable Centers in ZnO.

Methods that allow versatile manipulation of metastable centers in semiconductors are highly important owing to their potential for quantum information processing and computations. In this study, we demonstrate that the electron-phonon interaction enables phonon participation to promote relaxation of metastable centers in ZnO, which is known for its persistent photoconductivity (PPC) effect. Experimentally, we show that continuous infrared (IR) radiation (1064 nm, ∼30 mW/cm2) promotes longitudinal optical phonons via the Fröhlich interaction and increases the PPC relaxation rate by ∼4 folds. More importantly, we discover that coherent phonons activated by an ultrashort pulse IR laser of the same power increased the relaxation rate by ∼1200-fold, as confirmed by ultrafast transient spectroscopy to be correlated to the excitation of coherent acoustic phonons via the inverse piezoelectric effect. We expect this study to provide valuable guidance for the development of novel quantum and photoactive devices.

Molecular Serum Albumin Unmask Nanobio Properties of Molecular Graphenes in Shungite Carbon Nanoparticles.

Serum albumin is a popular macromolecule for studying the effect of proteins on the colloidal stability of nanoparticle (NP) dispersions, as well as the protein-nanoparticle interaction and protein corona formation. In this work, we analyze the specific conformation-dependent phase, redox, and fatty acid delivery properties of bovine albumin in the presence of shungite carbon (ShC) molecular graphenes stabilized in aqueous dispersions in the form of NPs in order to reveal the features of NP bioactivity. The formation of NP complexes with proteins (protein corona around NP) affects the transport properties of albumin for the delivery of fatty acids. Being acceptors of electrons and ligands, ShC NPs are capable of exhibiting both their own biological activity and significantly affecting conformational and phase transformations in protein systems.

Switching Lead for Tin in PbHfO3 : Noncubic Structure of SnHfO3.

The removal of lead from commercialized perovskite-oxide-based piezoceramics has been a recent major topic in materials research owing to legislation in many countries. In this regard, Sn(II)-perovskite oxides have garnered keen interest due to their predicted large spontaneous electric polarizations and isoelectronic nature for substitution of Pb(II) cations. However, they have not been considered synthesizable owing to their high metastability. Herein, the perovskite lead hafnate, i.e., PbHfO3 in space group Pbam, is shown to react with SnClF at a low temperature of 300 °C, and resulting in the first complete Sn(II)-for-Pb(II) substitution, i.e. SnHfO3 . During this topotactic transformation, a high purity and crystallinity is conserved with Pbam symmetry, as confirmed by X-ray and electron diffraction, elemental analysis, and 119 Sn Mössbauer spectroscopy. In situ diffraction shows SnHfO3 also possesses reversible phase transformations and is potentially polar between ≈130-200 °C. This so-called 'de-leadification' is thus shown to represent a highly useful strategy to fully remove lead from perovskite-oxide-based piezoceramics and opening the door to new explorations of polar and antipolar Sn(II)-oxide materials.

Electrocatalytic Oxygen Reduction Using Metastable Zirconium Suboxide.

Strategies for discovery of high-performance electrocatalysts are important to advance clean energy technologies. Metastable phases such as low temperature or interfacial structures that are difficult to access in bulk may offer such catalytically active surfaces. We report here that the suboxide Zr3O, which is formed at Zr-ZrO2 interfaces but does not appear in the experimental Zr-O phase diagram exhibits outstanding oxygen reduction reaction (ORR) performance surpassing that of benchmark Pt/C and most transition metal-based catalysts. Addition of Fe3C nanoparticles to give a Zr-Zr3O-Fe3C/NC catalyst (NC=nitrogen-doped carbon) gives a half-wave potential (E1/2) of 0.914 V, outperforming Pt/C and showing only a 3 mV decrease after 20,000 electrochemical cycles. A zinc-air battery (ZAB) using this cathode material has a high power density of 241.1 mW cm-2 and remains stable for over 50 days of continuous cycling, demonstrating potential for practical applications. Zr3O demonstrates that interfacial or other phases that are difficult to stabilize may offer new directions for the discovery of high-performance electrocatalysts.

Emerging two dimensional metastable-phase oxides: insights and prospects in synthesis and catalysis.

Since the discovery of graphene, the development of new two-dimensional (2D) materials has received considerable interest. Recently, as a newly emerging member of the 2D family, 2D metastable-phase oxides that combine the unique advantages of metal oxides, 2D structures, and metastable-phase materials have shown enormous potential in various catalytic reactions. In this review, the potential of various 2D materials to form a metastable-phase is predicted. The advantages of 2D metastable-phase oxides for advanced applications, reliable methods of synthesizing 2D metastable-phase oxides, and the application of these oxides in different catalytic reactions are presented. Finally, the challenges associated with 2D metastable-phase oxides and future perspectives are discussed.

Metastable Supramolecular Assembly of Simple Monomers Enabled by Confinement: Towards Aqueous Phase Room Temperature Phosphorescence.

The application of supramolecular assembly (SA) with room temperature phosphorescence (RTP) in aqueous phase has the potential to revolutionize numerous fields. However, using simple molecules with crystalline RTP to construct SA with aqueous phase RTP is hardly possible from the standpoint of forces. The reason lies in that the transition from crystal to SA involves a structure transformation from highly stable to more dynamic state, leading to increased non-radiative deactivation pathways and silent RTP signal. Here, with the benefit of the confinement from the layered double hydroxide (LDH), various simple molecules (benzene derivatives) can successfully form metastable SA with aqueous phase RTP. The maximum of RTP lifetime and efficiency can reach 654.87 ms and 5.02%, respectively. Mechanistic studies reveal the LDH energy trap can strengthen the intermolecular interaction, providing the prerequisite for the existence of metastable SA and appearance of aqueous phase RTP. The universality of this strategy will usher exploration into other multifunctional monomer, facilitating the development of SAs with aqueous phase RTP.

Temperature-dependent structural transition following X-ray-induced metal center reduction in oxidized cytochrome c oxidase.

Cytochrome c oxidase (CcO) is the terminal enzyme in the electron transfer chain in the inner membrane of mitochondria. It contains four metal redox centers, two of which, CuB and heme a3, form the binuclear center (BNC), where dioxygen is reduced to water. Crystal structures of CcO in various forms have been reported, from which ligand-binding states of the BNC and conformations of the protein matrix surrounding it have been deduced to elucidate the mechanism by which the oxygen reduction chemistry is coupled to proton translocation. However, metal centers in proteins can be susceptible to X-ray-induced radiation damage, raising questions about the reliability of conclusions drawn from these studies. Here, we used microspectroscopy-coupled X-ray crystallography to interrogate how the structural integrity of bovine CcO in the fully oxidized state (O) is modulated by synchrotron radiation. Spectroscopic data showed that, upon X-ray exposure, O was converted to a hybrid O∗ state where all the four metal centers were reduced, but the protein matrix was trapped in the genuine O conformation and the ligands in the BNC remained intact. Annealing the O∗ crystal above the glass transition temperature induced relaxation of the O∗ structure to a new R∗ structure, wherein the protein matrix converted to the fully reduced R conformation with the exception of helix X, which partly remained in the O conformation because of incomplete dissociation of the ligands from the BNC. We conclude from these data that reevaluation of reported CcO structures obtained with synchrotron light sources is merited.

Kinetic-Modulated Crystal Phase of Ru for Hydrogen Oxidation.

Crystal-phase-engineering provides a powerful strategy for regulating the catalytic performance yet remains great challenge. Herein, the kinetic-modulated crystal-phase-control of Ru nanosheet assemblies (Ru NAs) is demonstrated by simply altering the concentration of citric acid (CA). Detailed experimental results reveal that high concentration of CA retards the growth kinetics and thus leads to the formation of metastable face-centered cubic (fcc) Ru NAs, while low concentration of CA results in the fast growth kinetics and the preferential formation of Ru NAs with stable hexagonal close packed (hcp) phase. Moreover, Ru NAs with different phases are used as catalyst for hydrogen oxidation reaction (HOR) to evaluate the effects of crystal phase on catalytic performance. Impressively, Ru NAs with fcc phase display a mass activity of 2.75 A mgRu -1 at 50 mV, which is much higher than those of Ru NAs with fcc/hcp (1.02 A mgRu -1 ) and hcp (0.74 A mgRu -1 ) phases. Theoretical calculations show that fcc Ru NAs display weaker adsorption toward * H and lower energy barrier toward the rate-determining step (RDS) during HOR. This work provides a facile strategy for regulating the crystal phase of Ru nanocrystals, which may attract rapid interests of researchers in materials, chemistry, and catalysis.