Numerical simulation of the Liquid-liquid phase separation and microstructure evolution of Al-In immiscible alloys during cooling

A numerical model has been developed to describe the microstructural evolution of Al In immiscible alloys through the miscibility gap. The model considers the common action of nucleation, diffusible growth, Brownian collision and motion collision between the second phase droplets. The simulation results are dynamically visualized and show that the volume fraction, distribution and size of the second phase droplets satisfactorily agree with the experimental results. So the model can be used to predict the microstructural evolution of Al In immiscible alloys during the cooling process.

Liquid-liquid phase separation in highly undercooled Ni-Pb hypermonotectic alloys

Liquid-liquid phase separation in the undercooled Ni-20%Pb(mole fraction, the same below if not mentioned) hypermonotectic melts was investigated by the observation of the water-quenched structure and DTA analysis. The results indicate that the number of spherical cells in the water-quenched microstructure increases with dropping temperature, and the cells gather and grow up obviously. The spherical cell origins from L1 phase separated from homogeneous melt, and is the product of monotectic reaction. Both results of the water-quenched structures and DTA analysis prove that liquid phase separation still occurs in the highly undercooled Ni-Pb hypermonotectic alloy melts, and liquid phase separation in the immiscible gap can not be fully inhibited by high undercooling and rapid solidification.

Multistep Desolvation as a Fundamental Principle Governing Peptide Self-Assembly Through Liquid-Liquid Phase Separation

Biomolecular self-assembly based on peptides and proteins is a general phenomenon encountered in natural and synthetic systems.Liquid–liquid phase separation(LLPS)is intimately involved in biomolecular self-assembly,yet the key factors at a molecular scale activating or modulating such a process remain largely elusive.Herein,we discovered in our experiments that multistep desolvation is fundamental to the formation and evolution of peptide-rich droplets:The first step was partial desolvation of peptides to form peptide clusters,and the second step was selective desolvation of hydrophobic groups within clusters to trigger LLPS and the formation of peptiderich droplets,followed by complete desolvation of droplets,initiating the nucleation of peptide selfassembly.Manipulation of the degree of desolvation at different stages was an effective strategy to control the self-assembly pathways and polymorphisms.This study sheds light on the molecular origin of LLPS-mediated self-assembly distinct from classical one-step self-assembly and paves the way for the precise control of supramolecular self-assembly.

Long-term functional maintenance of primary hepatocytes in vitro using macroporous hydrogels engineered through liquid-liquid phase separation

Preserving the functionality of hepatocytes in vitro poses a significant challenge in liver tissue engineering and bioartificial liver,as these cells rapidly lose their metabolic and functional characteristics after isolation.Inspired by the macroporous structures found in native liver tissues,here we develop synthetic hydrogel scaffolds that closely mimic the liver’s structural organization through the phase separation between polyethylene glycol(PEG)and polysaccharides.Our hydrogels exhibit interconnected macroporous structures and appropriate mechanical properties,providing an optimal microenvironment conducive to hepatocyte adhesion and the formation of sizable aggregates.Compared to two-dimensional hepatocyte cultures,enhanced functionalities of hepatocytes cultured in our macroporous hydrogels were observed for 14 days,as evidenced by quantitative reverse-transcription–polymerase chain reactions(qRT-PCR),immunofluorescence,and enzyme linked immunosorbent assay(ELISA)analyses.Protein sequencing data further confirmed the establishment of cell–cell interactions among hepatocytes when cultured in our hydrogels.Notably,these hepatocytes maintained a protein expression lineage that closely resembled freshly isolated hepatocytes,particularly in the Notch and tumor necrosis factor(TNF)signaling pathways.These results suggest that the macroporous hydrogels are attractive scaffolds for liver tissue engineering.

Self-assembly of Amphiphilic Diblock Copolymers Induced by Liquid-Liquid Phase Separation

The liquid-liquid phase separation(LLPS)widely exists in biology,synthetic chemistry,crystallization kinetics and other fields,and it is very important to realize the related functions.The research on the competition between LLPS and micellization/vesiculation has made considerable progress.However,the way to effectively control the formation paths from homogeneous state to aggregates has not been completely solved,which is vital to determine its structure and properties and even its future functions.Here we describe the phenomenon of LLPS and its effect on the dynamic process of self-assembly of amphiphilic diblock copolymers(BCPs).Starting from the establishment of phase diagram,we explore the existence conditions of LLPS state,the internal morphology and external size of large droplets,and its significant implications to the dynamic path of vesicle formation.Vesicles formed via LLPS have larger sized outer dimensions and inner cavities,and contain more solvents during certain stages.The detailed research of LLPS and its self-assembly simulation has contributed to completing its theoretical basis and practical applications in the future in various fields.

Numerical Simulation Study of Oil-Water Emulsion Separation in an Ultrasonic Field:Effect of Coupling between Acoustic and Flow Field Parameters

In this study,the separation and coalescence of oil-in-water emulsions are explored in an ultrasonic field using the lattice Boltzmann method.By simulating the propagation of ultrasonic waves,this study focuses on examining the effects of acoustic wave frequency,the ratio of oil to water components,and the aspect ratio of the boundary on the emulsification and separation processes of oil-water mixtures.The following conclusions are drawn.①Frequency affects the speed of oil droplet separation,leading to an increase in droplet size over time.Larger droplets are found near the source,while smaller droplets are distributed throughout the wave web.②As the boundary aspect ratio increases,the emulsification efficiency of the droplets weakens,and the system takes longer to stabilize.③Emulsions with a higher component of oil can better resist acoustic waves.④At the same acoustic frequency,longer wavelength ultrasonic fields promote the formation of uniformly distributed,smaller oil droplets,which is beneficial to the storage of emulsions.These numerical simulation results offer insights for optimizing conditions for oil-in-water separation and serve as a numerical reference for the study of oil-in-water emulsion separation in ultrasonic environments.

Recent progress in ternary mixed matrix membranes for CO_(2) separation

Mixed matrix membranes(MMMs)could combine the advantages of both polymeric membranes and porousfillers,making them an effective alternative to conventional polymer membranes.However,interfacial incompatibility issues,such as the presence of interfacial voids,hardening of polymer chains,and blockage of micropores by polymers between common MMMsfillers and the polymer matrix,currently limit the gas sep-aration performance of MMMs.Ternary phase MMMs(consisting of afiller,an additive,and a matrix)made by adding a third compound,usually functionalized additives,can overcome the structural problems of binary phase MMMs and positively impact membrane separation performance.This review introduces the structure and fabrication processes for ternary MMMs,categorizes various nanofillers and the third component,and summarizes and analyzes in detail the CO_(2) separation performance of newly developed ternary MMMs based on both rubbery and glassy polymers.Based on this separation data,the challenges of ternary MMMs are also discussed.Finally,future directions for ternary MMMs are proposed.

Regulating FUS Liquid-Liquid Phase Separation via Specific Metal Recognition

Liquid-liquid phase separation(LLPS)or biomolecular condensation that leads to formation of membraneless organelles plays a critical role in many biochemical processes.Mechanism study of regulating LLPS is therefore central to the understanding of protein aggregation and disease-relevant process.We report a fused in sarcoma protein(FUS)-derived low complexity(LC)sequence that undergoes LLPS in the presence of metal ions.The LC protein was constructed by fusing a hexhistidine-tag to the N-terminal low complexity domain(the residues 1–165 in QGSY-rich segment)of FUS.Spontaneous condensation of the intrinsic disordered protein into coacervate droplets was observed in the presence of metal ions that chelate oligohistidine moieties to form protein matrix.We demonstrate the key role of metal ion-histidine coordination in governing LLPS behaviours and the fluidity of biomolecular condensates.By taking advantage of competitive binding using chelators,we show the possibility of regulating dynamic behaviors of disease-relevant protein droplets,and developing a potential approach towards controllable biological encapsulation/release.

Recent applications and chiral separation development based on stationary phases in open tubular capillary electrochromatography(2019–2022)

Capillary electrochromatography(CEC)plays a significant role in chiral separation via the double separation principle,partition coefficient difference between the two phases,and electroosmotic flow-driven separation.Given the distinct properties of the inner wall stationary phase(SP),the separation ability of each SP differs from one another.Particularly,it provides large room for promising applications of open tubular capillary electrochromatography(OT-CEC).We divided the OT-CEC SPs developed over the past four years into six types:ionic liquids,nanoparticle materials,microporous materials,biomaterials,non-nanopolymers,and others,to mainly introduce their characteristics in chiral drug separation.There also added a few classic SPs that occurred within ten years as supplements to enrich the features of each SP.Additionally,we discuss their applications in metabolomics,food,cosmetics,environment,and biology as analytes in addition to chiral drugs.OT-CEC plays an increasingly significant role in chiral separation and may promote the development of capillary electrophoresis(CE)combined with other instruments in recent years,such as CE with mass spectrometry(CE/MS)and CE with ultraviolet light detector(CE/UV).

Binary fluids in mesoporous materials: Phase separation studied by NMR relaxation and diffusion

Relaxation and diffusion measurements were carried out on single and binary liquids filling the pore space of controlled porous glass Vycor with an average pore size of about 4 nm.The dispersion of the longitudinal relaxation time Tr is discussed as a means to identify liquid-surface interaction based on existing models developed for metal-free glass surfaces.In addition,the change of T1 and T2 with respect to their bulk values is discussed,in particular T2 serves as a probe for the strength of molecular interactions.As the native glass surface is polar and contains a large amount of hydroxyl groups,a pronounced interaction of polar and protic adsorbate liquids is expected;however,the T dispersion,and the corresponding reduction of T2,are also observed for non-polar liquids such as alkanes and cyclohexane.Deuterated liquids are employed for simplifying data analysis in binary systems,but also for separating the respective contributions of intra-and intermolecular interactions to the overall relaxation rate.Despite the lack of paramagnetic impurities in the glass material,H and 2H relaxation dispersions of equivalent molecules are frequently found to differ from each other,suggesting intermolecular relaxation mechanisms for the'H nuclei.The variation of the T dispersion when comparing single and binary systems gives clear evidence for the preferential adsorption of one of the two liquids,suggesting complete phase separation in several cases.Measurement of the apparent tortuosity by self-diffusion experiments supports the concept of a local variation of sample composition within the porespace.

Liquid-liquid phase separation in biology: mechanisms,physiological functions and human diseases

Cells are compartmentalized by numerous membrane-enclosed organelles and membraneless compartments to ensure that a wide variety of cellular activities occur in a spatially and temporally controlled manner. The molecular mechanisms underlying the dynamics of membrane-bound organelles, such as their fusion and fission, vesicle-mediated trafficking and membrane contactmediated inter-organelle interactions, have been extensively characterized. However, the molecular details of the assembly and functions of membraneless compartments remain elusive. Mounting evidence has emerged recently that a large number of membraneless compartments, collectively called biomacromolecular condensates, are assembled via liquid-liquid phase separation(LLPS). Phase-separated condensates participate in various biological activities, including higher-order chromatin organization,gene expression, triage of misfolded or unwanted proteins for autophagic degradation, assembly of signaling clusters and actin-and microtubule-based cytoskeletal networks, asymmetric segregations of cell fate determinants and formation of pre-and post-synaptic density signaling assemblies. Biomacromolecular condensates can transition into different material states such as gel-like structures and solid aggregates. The material properties of condensates are crucial for fulfilment of their distinct functions, such as biochemical reaction centers, signaling hubs and supporting architectures. Cells have evolved multiple mechanisms to ensure that biomacromolecular condensates are assembled and disassembled in a tightly controlled manner. Aberrant phase separation and transition are causatively associated with a variety of human diseases such as neurodegenerative diseases and cancers. This review summarizes recent major progress in elucidating the roles of LLPS in various biological pathways and diseases.

Liquid-liquid phase separation of Arabidopsis transcriptional repressor VRN1

With the support by the National Natural Science Foundation of China and the Ministry of Science and Technology and China,the research team led by Prof.Lai LuHua(来鲁华)at BNLMS,College of Chemistry and Molecular Engineering,Peking-Tsinghua Center for Life Sciences,and Center for Quantitative Biology,Peking University recently reported that Arabidopsis transcriptional repressor VRN1undergoes liquid-liquid phase separation with DNA in Angew Chem Int Ed(2019,58:4858—4862).This research uncovers the mechanism of DNA induced VRN1phase separation and provides novel insight of phase separation mediated transcriptional repression.Zhou HuaBin,agraduate student from Lai's group,is the first author of this paper.

Getting in phase: DNA damage repair mechanisms and liquid-liquid phase separation of the plant-specific histone methyltransferase MtSUVR2

Liquid-liquid phase separation(LLPS)has become a widely accepted mechanism forthedynamic compartmentalization of different cellular components into membraneless organelles or other cellular bodies.LLPS occurs when the concentration of a protein,nucleic acid,or other molecule reaches a saturation concentration and its partition into high-and low-concentration phases is energetically favorable.

Microfluidic production of liposomes through liquid-liquid phase separation in ternary droplets

Liposomes,the self-assembled phospholipid vesicles,have been extensively used in various fields such as artificial cells,drug delivery systems,biosensors and cosmetics.However,current microfluidic routes to liposomes mostly rely on water-in-oil-in-water double emulsion droplets as templates,and require complex fabrication of microfluidic devices,and tedious manipulation of multiphase fluids.Here we present a simple microfluidic approach to preparing monodisperse liposomes from oil-in-water droplets.For demonstration,we used butyl acetate-water-ethanol ternary mixtures as inner phase and an aqueous solution of surfactants as outer phase to make oil-in-water droplets,which can evolve into water-in-oil-in-water double emulsion droplets by liquid-liquid phase separation of ternary mixtures.Subsequently,the resultant water-in-oil-in-water droplets underwent a dewetting transition to form separated monodisperse liposomes and residual oil droplets,with the assistance of surfactants.The method is simple,does not require complex microfluidic devices and tedious manipulation,and provides a new platform for controllable preparation of liposomes.

Liquid-liquid phase separation in tumor biology

Liquid–liquid phase separation(LLPS)is a novel principle for explaining the precise spatial and temporal regulation in living cells.LLPS compartmentalizes proteins and nucleic acids into micron-scale,liquid-like,membraneless bodies with specific functions,which were recently termed biomolecular condensates.Biomolecular condensates are executors underlying the intracellular spatiotemporal coordination of various biological activities,including chromatin organization,genomic stability,DNA damage response and repair,transcription,and signal transduction.Dysregulation of these cellular processes is a key event in the initiation and/or evolution of cancer,and emerging evidence has linked the formation and regulation of LLPS to malignant transformations in tumor biology.In this review,we comprehensively summarize the detailed mechanisms of biomolecular condensate formation and biophysical function and review the recent major advances toward elucidating the multiple mechanisms involved in cancer cell pathology driven by aberrant LLPS.In addition,we discuss the therapeutic perspectives of LLPS in cancer research and the most recently developed drug candidates targeting LLPS modulation that can be used to combat tumorigenesis.

Role and therapeutic potential of liquid-liquid phase separation in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a late-onset neurodegenerative disease selectively affecting motor neurons, leading to pro-gressive paralysis. Although most cases are sporadic,-10% are familial. Similar proteins are found in aggregates in sporadicand familial ALS, and over the last decade, research has been focused on the underlying nature of this common pathology.Notably, TDP-43 inclusions are found in almost all ALS patients, while Fus inclusions have been reported in some familial ALSpatients. Both TDP-43 and FUS possess ‘low-complexity domains' (LCDs) and are considered as ‘intrinsically disordered proteins',which form liquid droplets in vitro due to the weak interactions caused by the LCDs. Dysfunctional ‘liquid-lquid phase separa-tion'(LLPS) emerged as a new mechanism linking AlS-related proteins to pathogenesis. Here, we review the current state ofknowledge on ALS-related gene products associated with a proteinopathy and discuss their status as lLPS proteins. n addition,we highlight the therapeutic potential of targeting LLPS for treating ALS.

RNA 5-methylcytosine regulates YBX2-dependent liquid-liquid phase separation

5-Methylcytosine(m^(5)C)is one of the most prevalent internal modifications of messenger RNA(mRNA)in higher eukaryotes.Here we report that Y box protein 2(YBX2)serves as a novel mammalian m^(5)C binding protein to undergo liquid-liquid phase separation(LLPS)both in vivo and in vitro,and this YBX2-dependent LLPS is enhanced by m^(5)C marked RNA.Furthermore,the crystal structure assay revealed that W100,as a distinct m^(5)C binding site of YBX2,is critical in mediating YBX2 phase separation.Our study resolved the relationship between RNA m^(5)C and phase separation,providing a clue for a new regulatory layer of epigenetics.

Magnetically induced phase separation in the fcc phase and thermodynamic calculations of phase equilibria of the Co-Cr system

Two-phase equilibria between the ferromagnetic fcc and the paramagnetic fcc phase from 800 ℃ to 900 ℃ in the Co-rich region have been detected by the diffusion couple technique. Two phase separation region of the fcc has been confirmed along the Curie temperature.The phase equilibria including the present results and the thermodynamic data of the Co-Cr system reported in the literature were analyzed on the basis of the thermodynamic evaluation. A set of thermodynamic values for the liquid, fcc, hcp, bcc, sigma phases was obtained. The calculated phase equilibria were in good agreement with most of the experimental data.

METASTABLE PHASE SEPARATION OF Fe_(50)Cu_(50) HYPOPERITECTIC ALLOY UNDER SPACE SIMULATION CONDITIONS

1.IntroductionRecentlytherehasbeenangrowinginterestinthesolidificationofperitecticsystems[1--4]tespeciallythosesystemslikeFe-CuandCu-Co,whichexhibitdefinitethermodynamictendencytowardsliquidimmiscibilityuponundercoolingduetothenearlyflatliquiduscurve...