Mapping Local and Global Liquid Phase Behavior in Living Cells Using Photo-Oligomerizable Seeds.

Liquid-liquid phase separation plays a key role in the assembly of diverse intracellular structures. However, the biophysical principles by which phase separation can be precisely localized within subregions of the cell are still largely unclear, particularly for low-abundance proteins. Here, we introduce an oligomerizing biomimetic system, "Corelets," and utilize its rapid and quantitative light-controlled tunability to map full intracellular phase diagrams, which dictate the concentrations at which phase separation occurs and the transition mechanism, in a protein sequence dependent manner. Surprisingly, both experiments and simulations show that while intracellular concentrations may be insufficient for global phase separation, sequestering protein ligands to slowly diffusing nucleation centers can move the cell into a different region of the phase diagram, resulting in localized phase separation. This diffusive capture mechanism liberates the cell from the constraints of global protein abundance and is likely exploited to pattern condensates associated with diverse biological processes. VIDEO ABSTRACT.

Electrifying HCOOH synthesis from CO2 building blocks over Cu-Bi nanorod arrays.

Precise electrochemical synthesis of commodity chemicals and fuels from CO2 building blocks provides a promising route to close the anthropogenic carbon cycle, in which renewable but intermittent electricity could be stored within the greenhouse gas molecules. Here, we report state-of-the-art CO2-to-HCOOH valorization performance over a multiscale optimized Cu-Bi cathodic architecture, delivering a formate Faradaic efficiency exceeding 95% within an aqueous electrolyzer, a C-basis HCOOH purity above 99.8% within a solid-state electrolyzer operated at 100 mA cm-2 for 200 h and an energy efficiency of 39.2%, as well as a tunable aqueous HCOOH concentration ranging from 2.7 to 92.1 wt%. Via a combined two-dimensional reaction phase diagram and finite element analysis, we highlight the role of local geometries of Cu and Bi in branching the adsorption strength for key intermediates like *COOH and *OCHO for CO2 reduction, while the crystal orbital Hamiltonian population analysis rationalizes the vital contribution from moderate binding strength of η2(O,O)-OCHO on Cu-doped Bi surface in promoting HCOOH electrosynthesis. The findings of this study not only shed light on the tuning knobs for precise CO2 valorization, but also provide a different research paradigm for advancing the activity and selectivity optimization in a broad range of electrosynthetic systems.

On the different regimes of stochastic gradient descent.

Modern deep networks are trained with stochastic gradient descent (SGD) whose key hyperparameters are the number of data considered at each step or batch size [Formula: see text], and the step size or learning rate [Formula: see text]. For small [Formula: see text] and large [Formula: see text], SGD corresponds to a stochastic evolution of the parameters, whose noise amplitude is governed by the "temperature" [Formula: see text]. Yet this description is observed to break down for sufficiently large batches [Formula: see text], or simplifies to gradient descent (GD) when the temperature is sufficiently small. Understanding where these cross-overs take place remains a central challenge. Here, we resolve these questions for a teacher-student perceptron classification model and show empirically that our key predictions still apply to deep networks. Specifically, we obtain a phase diagram in the [Formula: see text]-[Formula: see text] plane that separates three dynamical phases: i) a noise-dominated SGD governed by temperature, ii) a large-first-step-dominated SGD and iii) GD. These different phases also correspond to different regimes of generalization error. Remarkably, our analysis reveals that the batch size [Formula: see text] separating regimes (i) and (ii) scale with the size [Formula: see text] of the training set, with an exponent that characterizes the hardness of the classification problem.

Nematic phases and elastoresistivity from a multiorbital non-Fermi liquid.

We propose and study a two-orbital lattice extension of the Sachdev-Ye-Kitaev model in the large-N limit. The phase diagram of this model features a high-temperature isotropic non-Fermi liquid which undergoes first-order thermal transition into a nematic insulator or continuous thermal transition into a nematic metal phase, separated by a tunable tricritical point. These phases arise from spontaneous partial orbital polarization of the multiorbital non-Fermi liquid. We explore the spectral and transport properties of this model, including d.c. elastoresistivity, which exhibits a peak near nematic transition, as well as nonzero frequency elastoconductivity. Our work offers a useful perspective on nematic phases and transport in correlated multiorbital systems.

Mechanical theory of nonequilibrium coexistence and motility-induced phase separation.

Nonequilibrium phase transitions are routinely observed in both natural and synthetic systems. The ubiquity of these transitions highlights the conspicuous absence of a general theory of phase coexistence that is broadly applicable to both nonequilibrium and equilibrium systems. Here, we present a general mechanical theory for phase separation rooted in ideas explored nearly a half-century ago in the study of inhomogeneous fluids. The core idea is that the mechanical forces within the interface separating two coexisting phases uniquely determine coexistence criteria, regardless of whether a system is in equilibrium or not. We demonstrate the power and utility of this theory by applying it to active Brownian particles, predicting a quantitative phase diagram for motility-induced phase separation in both two and three dimensions. This formulation additionally allows for the prediction of novel interfacial phenomena, such as an increasing interface width while moving deeper into the two-phase region, a uniquely nonequilibrium effect confirmed by computer simulations. The self-consistent determination of bulk phase behavior and interfacial phenomena offered by this mechanical perspective provide a concrete path forward toward a general theory for nonequilibrium phase transitions.

Phenomenology and dynamics of competitive ecosystems beyond the niche-neutral regimes.

Structure, composition, and stability of ecological populations are shaped by the inter- and intraspecies interactions within their communities. It remains to be fully understood how the interplay of these interactions with other factors, such as immigration, controls the structure, the diversity, and the long-term stability of ecological systems in the presence of noise and fluctuations. We address this problem using a minimal model of interacting multispecies ecological communities that incorporates competition, immigration, and demographic noise. We find that a complete phase diagram exhibits rich behavior with multiple regimes that go beyond the classical "niche" and "neutral" regimes, extending and modifying the "rare biosphere" or "niche-like" dichotomy. In particular, we observe regimes that cannot be characterized as either niche or neutral where a multimodal species abundance distribution is observed. We characterize the transitions between the different regimes and show how these arise from the underlying kinetics of the species turnover, extinction, and invasion. Our model serves as a minimal null model of noisy competitive ecological systems, against which more complex models that include factors such as mutations and environmental noise can be compared.

Pure nematic quantum critical point accompanied by a superconducting dome.

SignificanceThe notion of the quantum critical point (QCP) is at the core of modern condensed matter physics. Near a QCP of the symmetry-breaking order, associated quantum-mechanical fluctuations are intensified, which can lead to unconventional superconductivity. Indeed, dome-shaped superconducting phases are often observed near the magnetic QCPs, which supports the spin fluctuation-driven superconductivity. However, the fundamental question remains as to whether a nonmagnetic QCP of electronic nematic order characterized by spontaneous rotational symmetry breaking can promote superconductivity in real materials. Here, we provide an experimental demonstration that a pure nematic QCP exists near the center of a superconducting dome in nonmagnetic FeSe[Formula: see text] Tex. This result evidences that nematic fluctuations enhanced around the nematic QCP can boost superconductivity.

Intercalating Architecture for the Design of Charge Density Wave in Metallic MA2Z4 Materials.

We present a novel approach to induce charge density waves (CDWs) in metallic MA2Z4 materials, resembling the behavior observed in transition metal dichalcogenides (TMDCs). This method leverages the intercalating architecture to maintain the same crystal field and Fermi surface topologies. Our investigation reveals that CDW instability in these materials arises from electron-phonon coupling (EPC) between the d band and longitudinal acoustic (LA) phonons, mirroring TMDC's behavior. By combining α-MA2Z4 with 1H-MX2 materials in a predictive CDW phase diagram using critical EPC constants, we demonstrate the feasibility of extending CDW across material families with comparable crystal fields and reveal the crucial role in CDW instability of the competition between ionic charge transfer and electron correlation. We further uncover a strain-induced Mott transition in ß2-NbGe2N4 monolayer featuring star-of-David patterns. This work highlights the potential of intercalating architecture to engineer CDW materials, expanding our understanding of CDW instability and correlation physics.

Biomimetic Capsid-Like Nanoshells Self-Assembled from Homopolypeptides.

The preparation of capsid-like nanoshells and the elucidation of their formation pathways are crucial for the application potential of capsid-like nanomaterials. In this study, we have prepared biomimetic capsid-like nanoshells (CLNs) through the solution self-assembly of poly (ß-phenethyl-L-aspartate) homopolypeptide (PPLA). The formation of CLNs is governed by an aggregation-fusion mechanism. Initially, PPLA molecules self-assemble into small spherical assemblies as subunits and the initial nuclei are formed through fusing some subunits. Subsequently, additional subunits rapidly fuse onto these nuclei, leading to the growth of full or partial CLNs during the growth phase. Moreover, the suitable condition benefiting CLNs formation is clarified by a morphological phase diagram based on the initial PPLA concentration against water content. Molecular-level measurements suggest that the molecular flexibility of PPLA is a key factor in the arrangement and fusion of subunits for the formation of CLNs. These findings offer new perspectives for a deeper understanding of the formation pathways of capsid-like nanoshells derived from synthetic polymers.

Phase Diagrams of Anthracene Derivatives in Pyridinium Ionic Liquids.

Crystal engineering for single crystallization of π-conjugated molecules has attracted much attention because of their electronic, photonic, and mechanical properties. However, reproducibility is a problem in conventional printing techniques because control of solvent evaporation is difficult. We investigated the phase diagrams of two anthracene derivatives in synthesized ionic liquids for non-volatile crystal engineering to determine the critical points for nucleation and crystal growth. Anthracene and 9,10-dibromoanthracene were used as representative π-conjugated molecules that form crystal structures with different packing types. Ionic liquids with an alkylpyridinium cation and bis(fluorosulfonyl)amide were good solvents for the anthracene derivatives from ca. 0 °C to 200 °C. The solubilities (critical points for crystal growth) of the anthracene derivatives in the ionic liquids reached the 100 mM level, which is similar to those in organic solvents. Ionic liquids with phenyl and octyl groups tended to show high-temperature dependence (a high dissolution entropy) with 9,10-dibromoanthracene. The precipitation temperature (critical point for crystal nucleation) at each 9,10-dibromoanthracene concentration was lower than the dissolution temperature. The differences between the dissolution and precipitation temperatures (supersaturated region) in the ionic liquids were greater than those in an organic solvent.

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.

Kinetic and Thermodynamic Interplay of Polymer-Mediated Liquid-Liquid Phase Separation for Poorly Water-Soluble Drugs.

Understanding the interplay between kinetics and thermodynamics of polymer-mediated liquid-liquid phase separation is crucial for designing and implementing an amorphous solid dispersion formulation strategy for poorly water-soluble drugs. This work investigates the phase behaviors of a poorly water-soluble model drug, celecoxib (CXB), in a supersaturated aqueous solution with and without polymeric additives (PVP, PVPVA, HPMCAS, and HPMCP). Drug-polymer-water ternary phase diagrams were also constructed to estimate the thermodynamic behaviors of the mixtures at room temperature. The liquid-liquid phase separation onset point for CXB was detected using an inline UV/vis spectrometer equipped with a fiber optic probe. Varying CXB concentrations were achieved using an accurate syringe pump throughout this study. The appearance of the transient nanodroplets was verified by cryo-EM and total internal reflection fluoresence microscopic techniques. The impacts of various factors, such as polymer composition, drug stock solution pumping rates, and the types of drug-polymer interactions, are tested against the onset points of the CXB liquid-liquid phase separation (LLPS). It was found that the types of drug-polymer interactions, i.e., hydrogen bonding and hydrophobic interactions, are vital to the position and shapes of LLPS in the supersaturation drug solution. A relation between the behaviors of LLPS and its location in the CXB-polymer-water ternary phase diagram was drawn from the findings.

Eutectic Resolves Lysolipid Paradox in Thermoresponsive Liposomes.

A better molecular understanding of the temperature-triggered drug release from lysolipid-based thermosensitive liposomes (LTSLs) is needed to overcome the recent setbacks in developing this important drug delivery system. Enhanced drug release was previously rationalized in terms of detergent-like effects of the lysolipid monostearyl lysophosphatidylcholine (MSPC), stabilizing local membrane defects upon LTSL lipid melting. This is highly surprising and here referred to as the 'lysolipid paradox,' because detergents usually induce the opposite effect─they cause leakage upon freezing, not melting. Here, we aim at better answers to (i) why lysolipid does not compromise drug retention upon storage of LTSLs in the gel phase, (ii) how lysolipids can enhance drug release from LTSLs upon lipid melting, and (iii) why LTSLs typically anneal after some time so that not all drug gets released. To this end, we studied the phase transitions of mixtures of dipalmitoylphosphatidylcholine (DPPC) and MSPC by a combination of differential scanning and pressure perturbation calorimetry and identified the phase structures with small- and wide-angle X-ray scattering (SAXS and WAXS). The key result is that LTSLs, which contain the standard amount of 10 mol % MSPC, are at a eutectic point when they release their cargo upon melting at about 41 °C. The eutectic present below 41 °C consists of a MSPC-depleted gel phase as well as small domains of a hydrocarbon chain interdigitated gel phase containing some 30 mol % MSPC. In these interdigitated domains, the lysolipid is stored safely without compromising membrane integrity. At the eutectic temperature, both the MSPC-depleted bilayer and interdigitated MSPC-rich domains melt at once to fluid bilayers, respectively. Intact, fluid membranes tolerate much less MSPC than interdigitated domains─where the latter have melted, the high local MSPC content causes transient pores. These pores allow for fast drug release. However, these pores disappear, and the membrane seals again as the MSPC distributes more evenly over the membrane so that its local concentration decreases below the pore-stabilizing threshold. We provide a pseudobinary phase diagram of the DPPC-MSPC system and structural and volumetric data for the interdigitated phase.

Dissolution Mechanisms of Amorphous Solid Dispersions: Application of Ternary Phase Diagrams To Explain Release Behavior.

The use of amorphous solid dispersions (ASDs) in commercial drug products has increased in recent years due to the large number of poorly soluble drugs in the pharmaceutical pipeline. However, the release behavior of ASDs is complex and remains not well understood. Often, the drug release from ASDs is rapid and complete at lower drug loadings (DLs) but becomes slow and incomplete at higher DLs. The DL where release becomes hindered is termed the limit of congruency (LoC). Currently, there are no approaches to predict the LoC. However, recent findings show that one potential cause leading to the LoC is a change in phase morphology after water-induced phase separation at the ASD/solution interface. In this study, the phase behavior of ASDs in contact with aqueous solutions was described thermodynamically by constructing experimental and computational ternary phase diagrams, and these were used to predict morphology changes and ultimately the LoC. Experimental ternary phase diagrams were obtained by equilibrating ASD/water mixtures over time. Computational ternary phase diagrams were obtained by Perturbed Chain Statistical Associating Fluid Theory (PC-SAFT). The morphology of the hydrophobic phase was studied with fluorescence confocal microscopy. It was demonstrated that critical point (plait point) composition approximately corresponded to the ASD DL, where the hydrophobic phase, formed during phase separation, became interconnected and hindered ASD release. This work provides mechanistic insights into the ASD release behavior and highlights the potential of in silico ASD design using phase diagrams.

Low-temperature cluster spin glass transition in the single-domain NiCr2O4nanoparticles.

NiCr2O4nanoparticles with average particle size ∼15 nm, a single-domain size maintains the bulk canted antiferromagnetic ground state, were synthesized by a microwave combustion method. The magnetic behavior was carefully investigated by static and dynamic magnetic susceptibility measurements. In addition to a spin-glass-like behavior below paramagnetic-ferrimagnetic transition atTC, the NiCr2O4nanoparticles demonstrate a low-temperature cluster spin glass transition below the spin canting transitionTS, which manifests itself as a magnetic anomaly peak around ∼12 K (at 100 Oe) in the zero-field cooled magnetization with a relatively stronger field dependence in a 'de Almeida-Thouless' line for spin glasses. The AC susceptibility analyses in different approaches demonstrate a larger relative peak temperature variation per frequency decade and a longer characteristic relaxation time in the order of 0.04 and 10-7s, against 0.01 and 10-9s for the high-temperature blocking, indicating the slow spin dynamics for the low-temperature cluster glassy phase. A field-temperature magnetic phase diagram is proposed for the single-domain NiCr2O4nanoparticles.

Rhodamine B for Probing the Effects of Modifications in Cetrimonium Bromide Counter-anions by Transition Metals on CTAB/Butanol/n-hexane/water Microemulsion.

Dye solubilization in microemulsion based on Cetyltrimethylammonium bromide (CTAB) and its modified forms (counter-anions based upon Zn2+, Cu2+ and Fe3+) is comparatively innovative and not explored in existing literature. Here, surfactant with modified counterions (SMCs) were used to study the effects of metal chlorides (ZnCl2, CuCl2 and FeCl3) modifications on the comparative solubilization of Rhodamine-B (RB) by Cetyltrimethylammonium bromide (CTAB) and its modified forms. The solubility of RB in different microemulsions were studied using UV-Visible spectroscopy and phase diagrams of CTAB with modified counter ions CTA+[ZnCl2.Br]- named as CZN-1, CTA+[CuCl2.Br]- named as CCU-1 and CTA+[FeCl3.Br]- named as CFE-1 based upon surfactant with modified counter ions (SMCs). Four different points in microemulsion region of phase diagram were selected with different percentage composition of Smix (surfactant and co-surfactant), oil and RB (taken as water component). The interaction of RB, CCU-1, CFE-1 and CZN-1 within microemulsion environment were studied using Fluorescence spectroscopy. Emission spectra of RB in CCU-1 and CFE-1 based microemulsion confirmed that RB formed complexes with Cu and Fe ions. It was also found that RB was less soluble in CTAB based microemulsion as compared to microemulsions based on SMCs. This novel research study will expose new path for future research work related to microemulsion.

Local thermodynamics govern formation and dissolution of Caenorhabditis elegans P granule condensates.

Membraneless compartments, also known as condensates, provide chemically distinct environments and thus spatially organize the cell. A well-studied example of condensates is P granules in the roundworm Caenorhabditis elegans that play an important role in the development of the germline. P granules are RNA-rich protein condensates that share the key properties of liquid droplets such as a spherical shape, the ability to fuse, and fast diffusion of their molecular components. An outstanding question is to what extent phase separation at thermodynamic equilibrium is appropriate to describe the formation of condensates in an active cellular environment. To address this question, we investigate the response of P granule condensates in living cells to temperature changes. We observe that P granules dissolve upon increasing the temperature and recondense upon lowering the temperature in a reversible manner. Strikingly, this temperature response can be captured by in vivo phase diagrams that are well described by a Flory-Huggins model at thermodynamic equilibrium. This finding is surprising due to active processes in a living cell. To address the impact of such active processes on intracellular phase separation, we discuss temperature heterogeneities. We show that, for typical estimates of the density of active processes, temperature represents a well-defined variable and that mesoscopic volume elements are at local thermodynamic equilibrium. Our findings provide strong evidence that P granule assembly and disassembly are governed by phase separation based on local thermal equilibria where the nonequilibrium nature of the cytoplasm is manifested on larger scales.

Optical conductivity and superconductivity in highly overdoped La2-x Ca x CuO4 thin films.

We have used atomic layer-by-layer oxide molecular beam epitaxy to grow epitaxial thin films of [Formula: see text] with x up to 0.5, greatly exceeding the solubility limit of Ca in bulk systems ([Formula: see text]). A comparison of the optical conductivity measured by spectroscopic ellipsometry to prior predictions from dynamical mean-field theory demonstrates that the hole concentration p is approximately equal to x. We find superconductivity with [Formula: see text] of 15 to 20 K up to the highest doping levels and attribute the unusual stability of superconductivity in [Formula: see text] to the nearly identical radii of La and Ca ions, which minimizes the impact of structural disorder. We conclude that careful disorder management can greatly extend the "superconducting dome" in the phase diagram of the cuprates.

Metastable-solid phase diagrams derived from polymorphic solidification kinetics.

Nonequilibrium processes during solidification can lead to kinetic stabilization of metastable crystal phases. A general framework for predicting the solidification conditions that lead to metastable-phase growth is developed and applied to a model face-centered cubic (fcc) metal that undergoes phase transitions to the body-centered cubic (bcc) as well as the hexagonal close-packed phases at high temperatures and pressures. Large-scale molecular dynamics simulations of ultrarapid freezing show that bcc nucleates and grows well outside of the region of its thermodynamic stability. An extensive study of crystal-liquid equilibria confirms that at any given pressure, there is a multitude of metastable solid phases that can coexist with the liquid phase. We define for every crystal phase, a solid cluster in liquid (SCL) basin, which contains all solid clusters of that phase coexisting with the liquid. A rigorous methodology is developed that allows for practical calculations of nucleation rates into arbitrary SCL basins from the undercooled melt. It is demonstrated that at large undercoolings, phase selections made during the nucleation stage can be undone by kinetic instabilities amid the growth stage. On these bases, a solidification-kinetic phase diagram is drawn for the model fcc system that delimits the conditions for macroscopic grains of metastable bcc phase to grow from the melt. We conclude with a study of unconventional interfacial kinetics at special interfaces, which can bring about heterogeneous multiphase crystal growth. A first-order interfacial phase transformation accompanied by a growth-mode transition is examined.

The ferroelectric photo ground state of SrTiO3: Cavity materials engineering.

Optical cavities confine light on a small region in space, which can result in a strong coupling of light with materials inside the cavity. This gives rise to new states where quantum fluctuations of light and matter can alter the properties of the material altogether. Here we demonstrate, based on first-principles calculations, that such light-matter coupling induces a change of the collective phase from quantum paraelectric to ferroelectric in the [Formula: see text] ground state, which has thus far only been achieved in out-of-equilibrium strongly excited conditions [X. Li et al., Science 364, 1079-1082 (2019) and T. F. Nova, A. S. Disa, M. Fechner, A. Cavalleri, Science 364, 1075-1079 (2019)]. This is a light-matter hybrid ground state which can only exist because of the coupling to the vacuum fluctuations of light, a photo ground state The phase transition is accompanied by changes in the crystal structure, showing that fundamental ground state properties of materials can be controlled via strong light-matter coupling. Such a control of quantum states enables the tailoring of materials properties or even the design of novel materials purely by exposing them to confined light.