Hearing loss is one of the most prevalent sensory disorders affecting the human nervous system.Liquid–liquid phase separation(LLPS)is a physiological process that facilitates the reversible and dynamic assembly of bi...Hearing loss is one of the most prevalent sensory disorders affecting the human nervous system.Liquid–liquid phase separation(LLPS)is a physiological process that facilitates the reversible and dynamic assembly of biomolecular condensates.Increasing evidence suggests that LLPS plays a significant role in the pathogenesis of hereditary hearing loss.Nevertheless,there is a conspicuous lack of systematic investigations exploring the impact of LLPS abnormalities on the etiology of hereditary hearing loss.In this review,we examine the mechanisms by which dysfunctions in LLPS contribute to hereditary hearing loss,specifically focusing on its effects on mechanoelectrical transduction in hair bundles,transcriptional regulation,post-transcriptional modifications,the actin cytoskeleton,ion homeostasis within the inner ear,and energy and redox homeostasis.Furthermore,we evaluate the considerable potential of targeting LLPS as a therapeutic approach for hearing loss and propose innovative perspectives on LLPS that may guide future research initiatives in the field of auditory disorders.展开更多
Intracellular liquid-liquid phase separation(LLPS)represents a pivotal biological process for the formation of cellular compartments,which involves the formation of droplet-like condensates through the hydrophobic and...Intracellular liquid-liquid phase separation(LLPS)represents a pivotal biological process for the formation of cellular compartments,which involves the formation of droplet-like condensates through the hydrophobic and hydrophilic interactions of biomolecules.LLPS plays a crucial role in normal cellular physiological activities,and it is also intimately linked to the pathological mechanisms of various diseases.This review summarizes the significant role of LLPS in regulating transcriptional mechanisms within the nucleus,with a focus on the mechanisms by which LLPS modulates gene transcription.Additionally,we highlight the roles of key proteins involved in LLPS,such as FOXK1,BRD4,Tau protein,and HDAC6,in the context of disease.We delve into the relationships between LLPS and diseases such as chronic kidney disease,atherosclerosis,Alzheimer’s disease,and triple-negative breast cancer,revealing the regulatory mechanisms of LLPS in disease onset and progression.Furthermore,we discuss the potential of pharmacological interventions targeting LLPS as novel therapeutic approaches,encompassing strategies such as gene therapy,traditional Chinese medicine monomers,and small-molecule inhibitors.In the future,a deeper understanding of the LLPS mechanism will continue to propel its application in disease prevention and treatment,providing robust support for the development of novel therapeutic strategies.展开更多
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 c...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.展开更多
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 ...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.展开更多
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 c...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.展开更多
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. Th...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.展开更多
Based on that the poly（acrylonitrile-co-maleic acid） （PANCMA）/DMSO/nonsolvent system agreed with the empirical linearized cloud point （LCP） relation, thermodynamics and kinetics of liquid-liquid phase separation...Based on that the poly（acrylonitrile-co-maleic acid） （PANCMA）/DMSO/nonsolvent system agreed with the empirical linearized cloud point （LCP） relation, thermodynamics and kinetics of liquid-liquid phase separation behavior of this system were investigated through coagulation value and phase diagram. It was found that adding solvent to the coagulation bath decreased the coagulation power and diffusion exchange rate of solvent and nonsolvent, and the system became more stable thermodynamically. On the other hand, the system with poly（vinyl alcohol） （PVA） as additive was thermodynamically less stable than that with poly （vinylpyrrolidone） （PVP） and/or not. In addition, the polymer solution system at higher temperature became thermodynamically more stable and had a higher nonsolvent tolerance. Moreover, higher temperature heightened the diffusion exchange rate of solvent and nonsolvent and accelerated phase separation. It is indicated that phase diagram and coagulation value offered some useful and necessary thermodynamic and kinetic information to establish optimal conditions and guide practical membrane fabrication in the results.展开更多
Most cancers are currently incurable,partly due to abnormal post-translational modifications(PTMs).In this study,we initially used multiple myeloma(MM)as a working model and found that SUMOylation activating enzyme su...Most cancers are currently incurable,partly due to abnormal post-translational modifications(PTMs).In this study,we initially used multiple myeloma(MM)as a working model and found that SUMOylation activating enzyme subunit 1(SAE1)promotes the malignancy of MM.Through proteome microarray analysis,SAE1 was identified as a potential target for bioactive colcemid or its derivative colchicine.Elevated levels of SAE1 were associated with poor clinical survival and increased MM proliferation in vitro and in vivo.Additionally,SAE1 directly SUMOylated and upregulated the total protein expression of p27,leading to LLPS-mediated nuclear export of p27.Our study also demonstrated the involvement of SAE1 in other types of cancer cells,and provided the first monomer crystal structure of SAE1 and its key binding model with colchicine.Colchicine also showed promising results in the Patient-Derived Tumor Xenograft(PDX)model.Furthermore,a controlled clinical trial with 56 MM patients demonstrated the clinical efficacy of colchicine.Our findings reveal a novel mechanism by which tumor cells evade p27-induced cellular growth arrest through p27 SUMOylation-mediated nuclear export.SAE1 may serve as a promising therapeutic target,and colchicine may be a potential treatment option for multiple types of cancer in clinical settings.展开更多
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,...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.展开更多
Identification of environmental stress sensors is one of the most important research topics in plant abiotic stress research.Traditional strategies to identify stress sensors or early signaling components based on the...Identification of environmental stress sensors is one of the most important research topics in plant abiotic stress research.Traditional strategies to identify stress sensors or early signaling components based on the cell membrane as a primary site of sensing and calcium signal as a second messenger have had only limited successes.Therefore,the current theoretical framework underlying stress sensing in plants should be reconsidered and additional mechanisms need to be introduced.Recently,accumulating evidence has emerged to suggest that liquid-liquid phase separation(LLPS)is a major mechanism for environmental stress sensing and response in plants.In this review,we briefly introduce LLPS regarding its concept,compositions,and dynamics,and then summarize recent progress of LLPS research in plants,emphasizing the contribution of LLPS to the sensing of various environmental stresses,such as dehydration,osmotic stress,and low and high temperatures.Finally,we propose strategies to identify key proteins that sense and respond to environmental stimuli on the basis of LLPS,and discuss the research directions of LLPS in plant abiotic stress responses and its potential application in enhancing stress tolerance in crops.展开更多
Biomolecular aggregation within cellular environments via liquid-liquid phase separation(LLPS)spontaneously forms droplet-like structures,which play pivotal roles in diverse biological processes.These structures are c...Biomolecular aggregation within cellular environments via liquid-liquid phase separation(LLPS)spontaneously forms droplet-like structures,which play pivotal roles in diverse biological processes.These structures are closely associated with a range of diseases,including neurodegenerative disorders,cancer and infectious diseases,highlighting the significance of understanding LLPS mechanisms for elucidating disease pathogenesis,and exploring potential therapeutic interventions.In this review,we delineate recent advancements in LLPS research,emphasizing its pathological relevance,therapeutic considerations,and the pivotal role of bioinformatic tools and databases in facilitating LLPS investigations.Additionally,we undertook a comprehensive analysis of bioinformatic resources dedicated to LLPS research in order to elucidate their functionality and applicability.By providing comprehensive insights into current LLPS-related bioinformatics resources,this review highlights its implications for human health and disease.展开更多
The research,fabrication and development of piezoelectric nanofibrous materials offer effective solutions to the challenges related to energy consumption and non-renewable resources.However,enhancing their electrical ...The research,fabrication and development of piezoelectric nanofibrous materials offer effective solutions to the challenges related to energy consumption and non-renewable resources.However,enhancing their electrical output still remains a significant challenge.Here,a strategy of inducing constrained phase separation on single nanofibers via shear force was proposed.Employing electrospinning technology,a polyacrylonitrile/polyvinylidene difluoride(PAN/PVDF)nanofibrous membrane was fabricated in one step,which enabled simultaneous piezoelectric and triboelectric conversion within a single-layer membrane.Each nanofiber contained independent components of PAN and PVDF and exhibited a rough surface.The abundant frictional contact points formed between these heterogeneous components contributed to an enhanced endogenous triboelectric output,showcasing an excellent synergistic effect of piezoelectric and triboelectric response in the nanofibrous membrane.Additionally,the component mass ratio influenced the microstructure,piezoelectric conformation and piezoelectric performance of the PAN/PVDF nanofibrous membranes.Through comprehensive performance comparison,the optimal mass ratio of PAN to PVDF was determined to be 9∶1.The piezoelectric devices made of the optimal PAN/PVDF nanofibrous membranes with rough nanofiber surfaces generated an output voltage of 20 V,which was about 1.8 times that of the smooth one at the same component mass ratio.The strategy of constrained phase separation on the surface of individual nanofibers provides a new approach to enhance the output performance of single-layer piezoelectric nanofibrous materials.展开更多
TiAl alloys with the(α2+γ)lamellar structure are highly valued for their excellent high-temperature strength and creep resistance.Understanding the formation mechanism of the lamellar structure is crucial for tuning...TiAl alloys with the(α2+γ)lamellar structure are highly valued for their excellent high-temperature strength and creep resistance.Understanding the formation mechanism of the lamellar structure is crucial for tuning the microstructure and properties.This work investigates the formation of lamellar structure in Ti-48AI-7Nb-2.5V-1Cr alloy,revealing the presence of hcp-based long-period superstructure(hcp-LPS)as a metastable phase during lamellar formation.The identification of hcp-LPS demonstrates that the necessary solute enrichment for the formation ofγlamellae occurs on the hexagonalαmatrix,implying that phase separation ofα→Al-richαlamellae+Al-depletedαlamellae is the first step of lamellar formation.Once phase separation is completed,all subsequent phase transitions occur within the Al-richαlamellae.Additionally,the formation of twin lamellae is further discussed.The formation of the twin lamellae occurs sequentially.Pre-existing lamella promotes the formation of later lamella by inducing so-lute enrichment in its surrounding region,and then the successive slip of Shockley partial dislocations with opposite Burgers vectors ensures special stacking of later lamellae.These findings not only con-tribute to the fundamental understanding of spinodal mechanisms in hexagonal crystals,but also provide novel insights into the formation of twin lamellae.展开更多
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 molecu...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.展开更多
Ribosome is an intracellular ribonucleoprotein particle that serves as the site of protein biosynthesis.Ribosomal dysfunction caused by mutations in genes encoding ribosomal proteins(RPs)and ribosome biogenesis factor...Ribosome is an intracellular ribonucleoprotein particle that serves as the site of protein biosynthesis.Ribosomal dysfunction caused by mutations in genes encoding ribosomal proteins(RPs)and ribosome biogenesis factors(RBFs)can lead to a spectrum of diseases,collectively known as ribosomopathy.Phase separation is a thermodynamic process that produces multiple phases from a homogeneous mixture.The formation of membraneless organelles and intracellular structures,including ribosomes and nucleoli,cannot occur without the involvement of phase separation.Here,ribosome structure,biogenesis,and their relationship with ribosomopathy are systematically reviewed.The tissue specificity of ribosomopathy and the role of phase separation in ribosomopathy are particularly discussed,which may offer some clues for understanding the mechanisms of ribosomopathy.Then,some new ideas for the prevention,diagnosis,and treatment of ribosomopathy are provided.展开更多
Understanding the liquid-liquid phase separation(LLPS)of immunoglobulin G(IgG)is crucial,as it profoundly influences IgG’s biological activity and stability.In this study,we employed coarse-grained molecular dynamics...Understanding the liquid-liquid phase separation(LLPS)of immunoglobulin G(IgG)is crucial,as it profoundly influences IgG’s biological activity and stability.In this study,we employed coarse-grained molecular dynamics simulations to systematically investigate the phase separation behavior of IgG.We first constructed two types of IgG models:all-pair IgG model and partial-pair IgG model,and compared the coexistence curve from our simulations with experimental data.Our results showed that the partial-pair IgG model aligns better with the experimental critical temperature and critical density.Using this model,we then calculated the temperature-dependent variations of IgG’s radius of gyration,surface tension,viscosity,etc.More importantly,we demonstrated that variations in the interaction strengths among IgG molecules significantly influence their phase separation behavior.Specifically,a higher standard deviation of interaction strength at different temperatures is found to lead to more stable phase-separated states.Furthermore,we observed that the introduction of repulsive polymers and strongly attractive polymers consistently enhances IgG phase separation,while weakly attractive polymers exhibit a dual regulatory effect on the phase separation.Overall,this study provides valuable insights into the mechanisms governing IgG phase behavior,with potential implications for optimizing biopharmaceutical products.展开更多
Chiral active matter exhibits a variety of collective behaviors,including phase separation,which is governed by the rule of“like chiralities attract,while opposite chiralities repel”.In this work,we investigate the ...Chiral active matter exhibits a variety of collective behaviors,including phase separation,which is governed by the rule of“like chiralities attract,while opposite chiralities repel”.In this work,we investigate the chiral demixing strategy of double-chiral partial mixture with inter-chiral frustration.We find that the inter-chiral frustration can significantly enhance the chiral demixing of active particles with different chiralities,both during the transient and in the steady state,not only accelerating the progress,but also improving the degree of phase separation.This phenomenon is reminiscent of the phase separation of binary mixtures in condensed matter physics,where the inter-chiral frustration can play a crucial role in the formation of the phase-separated states.We construct the phase diagram of the system and discuss the critical frustration for the enhancement of chiral demixing.Our work presents the first systematic investigation of inter-chiral frustration in self-propelled chiral active matter,filling a critical gap in the field.展开更多
Long-chain polyamides(LCPAs)are a class of bio-based polymers that can bridge conventional polyolefins and polycondensates.In this work,taking the advantage of the amphiphilic nature of polyamide 1012(PA1012),membrane...Long-chain polyamides(LCPAs)are a class of bio-based polymers that can bridge conventional polyolefins and polycondensates.In this work,taking the advantage of the amphiphilic nature of polyamide 1012(PA1012),membranes were prepared by using a non-conventional phase separation approach,namely,mixed‘non-solvents’evaporation induced phase separation(MNEIPS).PA1012 can be dissolved in a mixture of polar and non-polar solvents,both of which are non-solvents of PA1012.During the sequential evaporation of the two solvents,the phase separation of PA1012 occurred,inducing the formation of porous structures.We investigated the process of membrane formation in detail,with a specific focus on the liquid-liquid and liquid-solid phase transitions involved.Moreover,we studied the influence of critical factors,such as polymer concentration and mixed-solvent ratio,on the morphologies and properties of PA1012 membranes.This study provides new insights into the development of porous materials based on long-chain polycondensates.展开更多
For chromatographic separation,the reasonable modulation of stationary phases is the key factor to achieve high separation performance.We proposed that developing MOF stationary phases through precisely modulating the...For chromatographic separation,the reasonable modulation of stationary phases is the key factor to achieve high separation performance.We proposed that developing MOF stationary phases through precisely modulating the thermodynamic interactions between MOFs and analytes is conducive to improving the separation resolution.MIL-125,MIL-125-NH_(2),MIL-143-BTB,and MIL-143-TATB were developed as stationary phases with the careful modulation of organic ligands.MIL-125-NH_(2)and MIL-143-TATB coated columns exhibited much better separation performance than their counterparts,MIL-125 and MIL-143-BTB,respectively.The investigation of the separation mechanism indicated that thermodynamic interaction,rather than kinetic diffusion,was responsible for the separation improvement.MIL-125-NH_(2)and MIL-143-TATB provided stronger and distinguishable interactions with targets than corresponding MIL-125 and MIL-143-BTB,respectively,resulting in enhanced separation performance.This work demonstrates a guide to improving the separation performance of MOF stationary phases by increasing the thermodynamic interactions between MOFs and analytes.展开更多
Phosphorus(P)is crucial for crop growth.However,in waters,P is considered as contaminant due to its role in causing eutrophication and algae blooms.Therefore,recovering P from wastewater is essential for sustainable P...Phosphorus(P)is crucial for crop growth.However,in waters,P is considered as contaminant due to its role in causing eutrophication and algae blooms.Therefore,recovering P from wastewater is essential for sustainable P management.This study investigated the removal of P from aqueous solutions using bioinspired poly(ethylenimine)-poly(acrylamideco-acrylic acid)(PEI-PAMcoAA)coacervates.In detail,we investigated various parameters affecting P removal,including the ratio of PEI to PAMcoAA(ranging from 1:2 to 3:1,stoichiometry ratio of NH_(2) to COOH),pH(5.0-8.0)of P-containing solutions,initial P concentration(0.05-5 mmol/L),and the addition of calcium(Ca,0.1-5 mmol/L).We found that increasing the PEI:PAMcoAA ratio from1:2 to 3:1 significantly enhanced P removal efficiency,increasing from 47.21%to 95.44%.Under neutral pH conditions without calcium(Ca),PEI-PAMcoAA coacervates demonstrated optimal P removal capabilities(achieving an efficiency of 77.96%)through electrostatic adsorption.In contrast,the addition of Ca under alkaline conditions markedly improved P removal efficiency,increasing it from 64.16%to 82.42%.Detailed analyses of P within the coacervates indicated that Ca facilitates P precipitation and provides additional binding sites.These findings demonstrated that PEI-(Ca)-PAMcoAA coacervates show promise for efficiently removing P,particularly at low P concentrations.After the Premoval,the immobilized P can potentially be reused directly,as P able to be released from the reacted products.Therefore,the reacted coacervates could serve as a non-toxic fertilizer.Given its simplicity,high efficiency,and environmental friendliness,P removal based on bioinspired coacervates represents a low-hanging fruit in the pursuit of sustainable P management.展开更多
基金supported by the National Natural Science Foundation of China(82430035)the Foundation for Innovative Research Groups of Hubei Province(2023AFA038)+1 种基金the National Key Research and Development Program of China(2021YFF0702303,2024YFC2511101,and 2023YFE0203200)the Fundamental Research Funds for the Central Universities(2024BRA019).
文摘Hearing loss is one of the most prevalent sensory disorders affecting the human nervous system.Liquid–liquid phase separation(LLPS)is a physiological process that facilitates the reversible and dynamic assembly of biomolecular condensates.Increasing evidence suggests that LLPS plays a significant role in the pathogenesis of hereditary hearing loss.Nevertheless,there is a conspicuous lack of systematic investigations exploring the impact of LLPS abnormalities on the etiology of hereditary hearing loss.In this review,we examine the mechanisms by which dysfunctions in LLPS contribute to hereditary hearing loss,specifically focusing on its effects on mechanoelectrical transduction in hair bundles,transcriptional regulation,post-transcriptional modifications,the actin cytoskeleton,ion homeostasis within the inner ear,and energy and redox homeostasis.Furthermore,we evaluate the considerable potential of targeting LLPS as a therapeutic approach for hearing loss and propose innovative perspectives on LLPS that may guide future research initiatives in the field of auditory disorders.
基金supported by the Hebei Natural Science Foundation(Grant No.H2022110019).Peer review。
文摘Intracellular liquid-liquid phase separation(LLPS)represents a pivotal biological process for the formation of cellular compartments,which involves the formation of droplet-like condensates through the hydrophobic and hydrophilic interactions of biomolecules.LLPS plays a crucial role in normal cellular physiological activities,and it is also intimately linked to the pathological mechanisms of various diseases.This review summarizes the significant role of LLPS in regulating transcriptional mechanisms within the nucleus,with a focus on the mechanisms by which LLPS modulates gene transcription.Additionally,we highlight the roles of key proteins involved in LLPS,such as FOXK1,BRD4,Tau protein,and HDAC6,in the context of disease.We delve into the relationships between LLPS and diseases such as chronic kidney disease,atherosclerosis,Alzheimer’s disease,and triple-negative breast cancer,revealing the regulatory mechanisms of LLPS in disease onset and progression.Furthermore,we discuss the potential of pharmacological interventions targeting LLPS as novel therapeutic approaches,encompassing strategies such as gene therapy,traditional Chinese medicine monomers,and small-molecule inhibitors.In the future,a deeper understanding of the LLPS mechanism will continue to propel its application in disease prevention and treatment,providing robust support for the development of novel therapeutic strategies.
基金financially supported by the National Natural Science Foundation of China (Nos. 22072159 and 22172007)the Fundamental Research Funds for the Central Universities(No. buctrc202015)
文摘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.
基金This work was financially supported by the National Natural Science Foundation of China(Nos.21973041,21674047,21474051 and 21734005)the Program for Changjiang Scholars and Innovative Research Team in University(PCSIRT)the Fundamental Research Funds for the Central Universities.
文摘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.
文摘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.
基金Project(50171055) supported by the National Natural Science Foundation of China Project(2004E108) supported by Shaanxi Natural Science Foundation, China+1 种基金 Project(03JK132) supported by Shaanxi Education Bureau Foundation, China Project(200208) supported by the Doctorate Creation Foundation of Northwestern Polytechnical University
文摘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.
基金Acknowledgements： The financial supports of the National Research Fund of Fundamental Key Projects （2007CB936403） and the National Natural Science Foundation of China （20571077） are gratefully acknowledged.
文摘Based on that the poly（acrylonitrile-co-maleic acid） （PANCMA）/DMSO/nonsolvent system agreed with the empirical linearized cloud point （LCP） relation, thermodynamics and kinetics of liquid-liquid phase separation behavior of this system were investigated through coagulation value and phase diagram. It was found that adding solvent to the coagulation bath decreased the coagulation power and diffusion exchange rate of solvent and nonsolvent, and the system became more stable thermodynamically. On the other hand, the system with poly（vinyl alcohol） （PVA） as additive was thermodynamically less stable than that with poly （vinylpyrrolidone） （PVP） and/or not. In addition, the polymer solution system at higher temperature became thermodynamically more stable and had a higher nonsolvent tolerance. Moreover, higher temperature heightened the diffusion exchange rate of solvent and nonsolvent and accelerated phase separation. It is indicated that phase diagram and coagulation value offered some useful and necessary thermodynamic and kinetic information to establish optimal conditions and guide practical membrane fabrication in the results.
基金supported by National Natural Science Foundation of China(82341230 to Ye Yang)Basic Research Plan(Natural Science Foundation)in“Climbing”Program of Jiangsu Province(BK20240003 to Ye Yang,China)+1 种基金Science and Technology Development Plan Project of Jiangsu Provincial Administration of Traditional Chinese Medicine(ZD202203 to Chunyan Gu,China)a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(Traditional Chinese Medicine,Integration of Chinese and Western Medicine)(China).
文摘Most cancers are currently incurable,partly due to abnormal post-translational modifications(PTMs).In this study,we initially used multiple myeloma(MM)as a working model and found that SUMOylation activating enzyme subunit 1(SAE1)promotes the malignancy of MM.Through proteome microarray analysis,SAE1 was identified as a potential target for bioactive colcemid or its derivative colchicine.Elevated levels of SAE1 were associated with poor clinical survival and increased MM proliferation in vitro and in vivo.Additionally,SAE1 directly SUMOylated and upregulated the total protein expression of p27,leading to LLPS-mediated nuclear export of p27.Our study also demonstrated the involvement of SAE1 in other types of cancer cells,and provided the first monomer crystal structure of SAE1 and its key binding model with colchicine.Colchicine also showed promising results in the Patient-Derived Tumor Xenograft(PDX)model.Furthermore,a controlled clinical trial with 56 MM patients demonstrated the clinical efficacy of colchicine.Our findings reveal a novel mechanism by which tumor cells evade p27-induced cellular growth arrest through p27 SUMOylation-mediated nuclear export.SAE1 may serve as a promising therapeutic target,and colchicine may be a potential treatment option for multiple types of cancer in clinical settings.
基金supported by the National Science Fund for Distinguished Young Scholars of China(grant no.22025207)National Natural Science Foundation of China(grant nos.22172172 and 22232006)+3 种基金Youth Innovation Promotion Association of CAS(grant no.2022049)China Scholarship Council(CSC,grant no.202104910187)IPE Project for Frontier Basic Research(grant no.QYJC-2022-011)Natural Science Foundation of Hebei Province(grant nos.B2020103036 and B2020103025).
文摘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.
基金supported by the National Natural Science Foundation of China(Grant No.32270283 and 32070295)the Science and Technology Commission of Shanghai Municipality(Grant no.22ZR1469600).
文摘Identification of environmental stress sensors is one of the most important research topics in plant abiotic stress research.Traditional strategies to identify stress sensors or early signaling components based on the cell membrane as a primary site of sensing and calcium signal as a second messenger have had only limited successes.Therefore,the current theoretical framework underlying stress sensing in plants should be reconsidered and additional mechanisms need to be introduced.Recently,accumulating evidence has emerged to suggest that liquid-liquid phase separation(LLPS)is a major mechanism for environmental stress sensing and response in plants.In this review,we briefly introduce LLPS regarding its concept,compositions,and dynamics,and then summarize recent progress of LLPS research in plants,emphasizing the contribution of LLPS to the sensing of various environmental stresses,such as dehydration,osmotic stress,and low and high temperatures.Finally,we propose strategies to identify key proteins that sense and respond to environmental stimuli on the basis of LLPS,and discuss the research directions of LLPS in plant abiotic stress responses and its potential application in enhancing stress tolerance in crops.
基金funded by grants from the Natural Science Foundation of Guangdong Province,China(No.2023A1515010148)the Postdoctoral Fellowship Program of CPSF(No.GZC20241143)+2 种基金the China Postdoctoral Science Foundation(No.2024M752202)the National Natural Youth Science Foundation of China(No.32100927)the National Natural Science Foundation of China(No.81970481).
文摘Biomolecular aggregation within cellular environments via liquid-liquid phase separation(LLPS)spontaneously forms droplet-like structures,which play pivotal roles in diverse biological processes.These structures are closely associated with a range of diseases,including neurodegenerative disorders,cancer and infectious diseases,highlighting the significance of understanding LLPS mechanisms for elucidating disease pathogenesis,and exploring potential therapeutic interventions.In this review,we delineate recent advancements in LLPS research,emphasizing its pathological relevance,therapeutic considerations,and the pivotal role of bioinformatic tools and databases in facilitating LLPS investigations.Additionally,we undertook a comprehensive analysis of bioinformatic resources dedicated to LLPS research in order to elucidate their functionality and applicability.By providing comprehensive insights into current LLPS-related bioinformatics resources,this review highlights its implications for human health and disease.
基金National Natural Science Foundation of China(No.52373281)National Energy-Saving and Low-Carbon Materials Production and Application Demonstration Platform Program,China(No.TC220H06N)。
文摘The research,fabrication and development of piezoelectric nanofibrous materials offer effective solutions to the challenges related to energy consumption and non-renewable resources.However,enhancing their electrical output still remains a significant challenge.Here,a strategy of inducing constrained phase separation on single nanofibers via shear force was proposed.Employing electrospinning technology,a polyacrylonitrile/polyvinylidene difluoride(PAN/PVDF)nanofibrous membrane was fabricated in one step,which enabled simultaneous piezoelectric and triboelectric conversion within a single-layer membrane.Each nanofiber contained independent components of PAN and PVDF and exhibited a rough surface.The abundant frictional contact points formed between these heterogeneous components contributed to an enhanced endogenous triboelectric output,showcasing an excellent synergistic effect of piezoelectric and triboelectric response in the nanofibrous membrane.Additionally,the component mass ratio influenced the microstructure,piezoelectric conformation and piezoelectric performance of the PAN/PVDF nanofibrous membranes.Through comprehensive performance comparison,the optimal mass ratio of PAN to PVDF was determined to be 9∶1.The piezoelectric devices made of the optimal PAN/PVDF nanofibrous membranes with rough nanofiber surfaces generated an output voltage of 20 V,which was about 1.8 times that of the smooth one at the same component mass ratio.The strategy of constrained phase separation on the surface of individual nanofibers provides a new approach to enhance the output performance of single-layer piezoelectric nanofibrous materials.
基金supported by the National Science and Technology Major Project of China(No.J2019-VI-0011-0125)ND Basic Research Funds of China(No.G2022WD)Shaanxi Province Innovation Capability Support Program(No.2023-CX-TD-47).
文摘TiAl alloys with the(α2+γ)lamellar structure are highly valued for their excellent high-temperature strength and creep resistance.Understanding the formation mechanism of the lamellar structure is crucial for tuning the microstructure and properties.This work investigates the formation of lamellar structure in Ti-48AI-7Nb-2.5V-1Cr alloy,revealing the presence of hcp-based long-period superstructure(hcp-LPS)as a metastable phase during lamellar formation.The identification of hcp-LPS demonstrates that the necessary solute enrichment for the formation ofγlamellae occurs on the hexagonalαmatrix,implying that phase separation ofα→Al-richαlamellae+Al-depletedαlamellae is the first step of lamellar formation.Once phase separation is completed,all subsequent phase transitions occur within the Al-richαlamellae.Additionally,the formation of twin lamellae is further discussed.The formation of the twin lamellae occurs sequentially.Pre-existing lamella promotes the formation of later lamella by inducing so-lute enrichment in its surrounding region,and then the successive slip of Shockley partial dislocations with opposite Burgers vectors ensures special stacking of later lamellae.These findings not only con-tribute to the fundamental understanding of spinodal mechanisms in hexagonal crystals,but also provide novel insights into the formation of twin lamellae.
基金supported by grants from the Beijing Municipal Science and Technology Committee (Z181100001318003)the National Natural Science Foundation of China (31421002, 31561143001,31630048, and 31790403)+17 种基金the National Natural Science Foundation of China (91853113 and 31872716)the National Natural Science Foundation of China (11672317)the National Natural Science Foundation of China (31871394 and 31670730)supported by grants from the National Natural Science Foundation of China (31420103916 and 31991192)the Ministry of Science and Technology of China (2017YFA0503401)supported by grants from the Ministry of Science and Technology of China (2019YFA0707000)supported by grants from the Ministry of Science and Technology of China (2019YFA0508401)the Strategic Priority Research Program of the Chinese Academy of Sciences (CAS) (XDB19000000)the Key Research Program of Frontier Sciences, CAS (QYZDY-SSW-SMC006)supported by funds from the Ministry of Science and Technology of China and the National Natural Science Foundation of China (2017YFA0506600 and 31871309)supported by funds from the Ministry of Science and Technology of China and the National Natural Science Foundation of China (2019YFA0508403 and 31871443)supported by grants from the Ministry of Science and Technology of China (2016YFA0501902)the Science and Technology Commission of Shanghai Municipality (18JC1420500)the Shanghai Municipal Science and Technology Major Project (2019SHZDZX02)the Shanghai Municipal Science and Technology Major Project (2018SHZDZX01)CAS (XDB19020102)supported by grants from RGC of Hong Kong (AoE-M09-12 and C6004-17G)National Key R&D Program of China (2016YFA0501903 and 2019YFA0508402)。
文摘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.
基金supported by the National Natural Science Foundation of China(Nos.82071097 and 82370906)the Shanghai Pujiang Program(No.2020PJD026)+1 种基金the Key Laboratory of Oral Biomedical Research of Zhejiang Province Foundation(No.2021M007)the Research Project of Shanghai Municipal Health Commission(No.20234Z0006),China.
文摘Ribosome is an intracellular ribonucleoprotein particle that serves as the site of protein biosynthesis.Ribosomal dysfunction caused by mutations in genes encoding ribosomal proteins(RPs)and ribosome biogenesis factors(RBFs)can lead to a spectrum of diseases,collectively known as ribosomopathy.Phase separation is a thermodynamic process that produces multiple phases from a homogeneous mixture.The formation of membraneless organelles and intracellular structures,including ribosomes and nucleoli,cannot occur without the involvement of phase separation.Here,ribosome structure,biogenesis,and their relationship with ribosomopathy are systematically reviewed.The tissue specificity of ribosomopathy and the role of phase separation in ribosomopathy are particularly discussed,which may offer some clues for understanding the mechanisms of ribosomopathy.Then,some new ideas for the prevention,diagnosis,and treatment of ribosomopathy are provided.
基金supported by the National Natural Science Foundation of China(Grant Nos.12222506,12347102,and 12174184).
文摘Understanding the liquid-liquid phase separation(LLPS)of immunoglobulin G(IgG)is crucial,as it profoundly influences IgG’s biological activity and stability.In this study,we employed coarse-grained molecular dynamics simulations to systematically investigate the phase separation behavior of IgG.We first constructed two types of IgG models:all-pair IgG model and partial-pair IgG model,and compared the coexistence curve from our simulations with experimental data.Our results showed that the partial-pair IgG model aligns better with the experimental critical temperature and critical density.Using this model,we then calculated the temperature-dependent variations of IgG’s radius of gyration,surface tension,viscosity,etc.More importantly,we demonstrated that variations in the interaction strengths among IgG molecules significantly influence their phase separation behavior.Specifically,a higher standard deviation of interaction strength at different temperatures is found to lead to more stable phase-separated states.Furthermore,we observed that the introduction of repulsive polymers and strongly attractive polymers consistently enhances IgG phase separation,while weakly attractive polymers exhibit a dual regulatory effect on the phase separation.Overall,this study provides valuable insights into the mechanisms governing IgG phase behavior,with potential implications for optimizing biopharmaceutical products.
基金supported by the National Natural Science Foun-dation of China(Grant Nos.12375031 and 11875135)China National University Student Innovation and Entrepreneurship(Grant No.202410385040)Fujian University Alliance of Physics Discipline Training Program of Innovation for Under-graduates Development Program,China.
文摘Chiral active matter exhibits a variety of collective behaviors,including phase separation,which is governed by the rule of“like chiralities attract,while opposite chiralities repel”.In this work,we investigate the chiral demixing strategy of double-chiral partial mixture with inter-chiral frustration.We find that the inter-chiral frustration can significantly enhance the chiral demixing of active particles with different chiralities,both during the transient and in the steady state,not only accelerating the progress,but also improving the degree of phase separation.This phenomenon is reminiscent of the phase separation of binary mixtures in condensed matter physics,where the inter-chiral frustration can play a crucial role in the formation of the phase-separated states.We construct the phase diagram of the system and discuss the critical frustration for the enhancement of chiral demixing.Our work presents the first systematic investigation of inter-chiral frustration in self-propelled chiral active matter,filling a critical gap in the field.
基金supported by the Fundamental Research Funds for the Central Universities(No.2023ZYGXZR107)the TCL Science and Technology Innovation Fund。
文摘Long-chain polyamides(LCPAs)are a class of bio-based polymers that can bridge conventional polyolefins and polycondensates.In this work,taking the advantage of the amphiphilic nature of polyamide 1012(PA1012),membranes were prepared by using a non-conventional phase separation approach,namely,mixed‘non-solvents’evaporation induced phase separation(MNEIPS).PA1012 can be dissolved in a mixture of polar and non-polar solvents,both of which are non-solvents of PA1012.During the sequential evaporation of the two solvents,the phase separation of PA1012 occurred,inducing the formation of porous structures.We investigated the process of membrane formation in detail,with a specific focus on the liquid-liquid and liquid-solid phase transitions involved.Moreover,we studied the influence of critical factors,such as polymer concentration and mixed-solvent ratio,on the morphologies and properties of PA1012 membranes.This study provides new insights into the development of porous materials based on long-chain polycondensates.
基金supported by the National Natural Science Foundation of China(Nos.22174067,22204078,22374077,and 22474059)the Natural Science Foundation of Jiangsu Province of China(No.BK20220370)+2 种基金Jiangsu Provincial Department of Education(No.22KJB150009)Jiangsu Association for Science and Technology(No.TJ-2023-076)the Priority Academic Program Development of Jiangsu Higher Education Institutions。
文摘For chromatographic separation,the reasonable modulation of stationary phases is the key factor to achieve high separation performance.We proposed that developing MOF stationary phases through precisely modulating the thermodynamic interactions between MOFs and analytes is conducive to improving the separation resolution.MIL-125,MIL-125-NH_(2),MIL-143-BTB,and MIL-143-TATB were developed as stationary phases with the careful modulation of organic ligands.MIL-125-NH_(2)and MIL-143-TATB coated columns exhibited much better separation performance than their counterparts,MIL-125 and MIL-143-BTB,respectively.The investigation of the separation mechanism indicated that thermodynamic interaction,rather than kinetic diffusion,was responsible for the separation improvement.MIL-125-NH_(2)and MIL-143-TATB provided stronger and distinguishable interactions with targets than corresponding MIL-125 and MIL-143-BTB,respectively,resulting in enhanced separation performance.This work demonstrates a guide to improving the separation performance of MOF stationary phases by increasing the thermodynamic interactions between MOFs and analytes.
基金supported by the National Key Research and Development Program of China(Nos.2023YFD1900602 and 2023YFD1900605)the Fundamental Research Funds for the Central Universities(No.SWU-KR24036)the Visiting Training Funds for Teachers from Ordinary Undergraduate Colleges and Universities in Shandong Province.
文摘Phosphorus(P)is crucial for crop growth.However,in waters,P is considered as contaminant due to its role in causing eutrophication and algae blooms.Therefore,recovering P from wastewater is essential for sustainable P management.This study investigated the removal of P from aqueous solutions using bioinspired poly(ethylenimine)-poly(acrylamideco-acrylic acid)(PEI-PAMcoAA)coacervates.In detail,we investigated various parameters affecting P removal,including the ratio of PEI to PAMcoAA(ranging from 1:2 to 3:1,stoichiometry ratio of NH_(2) to COOH),pH(5.0-8.0)of P-containing solutions,initial P concentration(0.05-5 mmol/L),and the addition of calcium(Ca,0.1-5 mmol/L).We found that increasing the PEI:PAMcoAA ratio from1:2 to 3:1 significantly enhanced P removal efficiency,increasing from 47.21%to 95.44%.Under neutral pH conditions without calcium(Ca),PEI-PAMcoAA coacervates demonstrated optimal P removal capabilities(achieving an efficiency of 77.96%)through electrostatic adsorption.In contrast,the addition of Ca under alkaline conditions markedly improved P removal efficiency,increasing it from 64.16%to 82.42%.Detailed analyses of P within the coacervates indicated that Ca facilitates P precipitation and provides additional binding sites.These findings demonstrated that PEI-(Ca)-PAMcoAA coacervates show promise for efficiently removing P,particularly at low P concentrations.After the Premoval,the immobilized P can potentially be reused directly,as P able to be released from the reacted products.Therefore,the reacted coacervates could serve as a non-toxic fertilizer.Given its simplicity,high efficiency,and environmental friendliness,P removal based on bioinspired coacervates represents a low-hanging fruit in the pursuit of sustainable P management.
