Biocompatible amphiphilic nanoparticles(NPs)with tunable particle morphology and surface property are important for their applications as functional materials.However,previously developed methods to prepare amphiphili...Biocompatible amphiphilic nanoparticles(NPs)with tunable particle morphology and surface property are important for their applications as functional materials.However,previously developed methods to prepare amphiphilic NPs generally involve several steps,especially an additional step for surface modification,greatly hindering their largescale production and widespread applications.Here,a versatile one-step strategy is developed to prepare biocompatible amphiphilic dimer NPs with tunable particle morphology and surface property.The amphiphilic dimer NPs,which consist of a hydrophobic shellac bulb and a hydrophilic poly(lactic acid)(PLA)bulb with PLA-poly(ethylene glycol)(PEG)on the bulb surface,are prepared in a single step by controlled co-precipitation and self-assembly.Amphiphilic PLA-PEG/shellac dimer NPs demonstrate excellent tunability in particle morphology,thus showing good performances in controlling the interfacial curvature and emulsion type.In addition,temperatureresponsive PLA-poly(N-isopropyl acrylamide)(PNIPAM)/shellac dimer NPs are prepared following the same method and emulsions stabilized by them show temperature-triggered response.The applications of PLA-PEG-folic acid(FA)/shellac dimer NPs for drug delivery have also been demonstrated,which show a very good performance.The strategy of preparing the dimer NPs is green,scalable,facile and versatile,which provides a good platform for the design of dimer NPs with tunable particle morphology and surface property for diverse applications.展开更多
Interparticle frictional interactions are ubiquitous in colloidal systems,exerting a profound influence on their structural and physical attributes.In this study,we employed Brownian dynamics simulations to explore th...Interparticle frictional interactions are ubiquitous in colloidal systems,exerting a profound influence on their structural and physical attributes.In this study,we employed Brownian dynamics simulations to explore the non-equilibrium dynamics in colloidal systems,focusing particularly on the role of tangential friction and its influence on the macroscopic physical properties of colloids.We found that the disruption of instantaneous time-reversal symmetry by tangential frictional interactions can trigger the self-assembly of colloidal systems into intricate network configurations,and these novel structures exhibit unique depletion force and rheological properties that set them apart from traditional colloidal gel systems.These findings not only help deepen our comprehension of the self-assembly phenomena in non-equilibrium colloidal systems but also offer fresh insights for the development of colloidal materials with tailored characteristics.展开更多
We quantify the mean potential energy of a passive colloidal particle harmonically confined in a bacterial solution using optical traps.We find that the average potential energy of the passive particle depends on the ...We quantify the mean potential energy of a passive colloidal particle harmonically confined in a bacterial solution using optical traps.We find that the average potential energy of the passive particle depends on the trap stiffness,in contrast to the equilibrium case where energy partition is independent of the external constraints.The constraint dependence of the mean potential energy originates from the fact that the persistent collisions between the passive particle and the active bacteria are influenced by the particle relaxation dynamics.Our experimental results are consistent with the Brownian dynamics simulations,and confirm the recent theoretical prediction.展开更多
With the advantages of better mimicking the specificity of natural tissues,three-dimensional(3D)cell culture plays a major role in drug development,toxicity testing,and tissue engineering.However,existing scaffolds or...With the advantages of better mimicking the specificity of natural tissues,three-dimensional(3D)cell culture plays a major role in drug development,toxicity testing,and tissue engineering.However,existing scaffolds or microcarriers for 3D cell culture are often limited in size and show suboptimal performance in simulating the vascular complexes of living organisms.Therefore,we present a novel hierarchically inverse opal porous scaffold made via a simple microfluidic approach for promoting 3D cell co-culture techniques.The designed scaffold is constructed using a combined concept involving an emulsion droplet template and inert polymer polymerization.This work demonstrates that the resultant scaffolds ensure a sufficient supply of nutrients during cell culture,so as to achieve large-volume cell culture.In addition,by serially planting different cells in the scaffold,a 3D co-culture system of endothelial-cellencapsulated hepatocytes can be developed for constructing certain functional tissues.It is also demonstrated that the use of the proposed scaffold for a co-culture system helps hepatocytes to maintain specific in vivo functions.These hierarchically inverse opal scaffolds lay the foundation for 3D cell culture and even the construction of biomimetic tissues.展开更多
Various behaviors of cancer cells are strongly influenced by their interaction with extracellular matrices(ECM).We investigate how this interaction may be influenced if the cancer cells’ability of secreting matrix me...Various behaviors of cancer cells are strongly influenced by their interaction with extracellular matrices(ECM).We investigate how this interaction may be influenced if the cancer cells’ability of secreting matrix metalloproteinases(MMPs)to degrade ECM is inhibited by adding the MMP inhibitor.We useMDA-MB-231-GFP cells as model cells and use matrigel to mimic ECM.It is found that the added MMP inhibitor significantly reduces the migration speed of cancer cells covered by matrigel but has little influence on the migration persistence and shape factor of the cells and that with the MMP inhibitor added the presence of matrigel on the top has no influence on the migration speed of the cells but increases the cells’shape factor and migration persistence.展开更多
Compartmentation via filamentation has recently emerged as a novel mechanism for metabolic regulation. In order to identify filamentforming metabolic enzymes systematically, we performed a genome-wide screening of all...Compartmentation via filamentation has recently emerged as a novel mechanism for metabolic regulation. In order to identify filamentforming metabolic enzymes systematically, we performed a genome-wide screening of all strains available from an open reading frameGFP collection in Saccharomyces cerevisiae. We discovered nine novel filament-forming proteins and also confirmed those identified previously. From the 4159 strains, we found 23 proteins, mostly metabolic enzymes, which are capable of forming filaments in vivo. In silico protein-protein interaction analysis suggests that these filament-forming proteins can be clustered into several groups, including translational initiation machinery and glucose and nitrogen metabolic pathways. Using glutamine-utilising enzymes as examples, we found that the culture conditions affect the occurrence and length of the metabolic filaments. Furthermore, we found that two CTP synthases（Ura7p and Ura8p） and two asparagine synthetases（Asn1p and Asn2p） form filaments both in the cytoplasm and in the nucleus.Live imaging analyses suggest that metabolic filaments undergo sub-diffusion. Taken together, our genome-wide screening identifies additional filament-forming proteins in S. cerevisiae and suggests that filamentation of metabolic enzymes is more general than currently appreciated.展开更多
Two-dimensional(2D)melting is a fundamental research topic in condensed matter physics,which can also provide guidance on fabricating new functional materials.Nevertheless,our understanding of 2D melting is still far ...Two-dimensional(2D)melting is a fundamental research topic in condensed matter physics,which can also provide guidance on fabricating new functional materials.Nevertheless,our understanding of 2D melting is still far from being complete due to existence of possible complicate transition mechanisms and absence of effective analysis methods.Here,using Monte Carlo simulations,we investigate 2D melting of 60°rhombs which melt from two different surface-fullycoverable crystals,a complex hexagonal crystal(cHX)whose primitive cell contains three rhombs,and a simple rhombic crystal(RB)whose primitive cell contains one rhomb.The melting of both crystals shows a sequence of solid,hexatic in molecular orientation(Hmo),and isotropic phases which obey the Berezinskii-Kosterlitz-Thouless-Halperin-Nelson-Young(BKTHNY)theory.However,local polymorphic configuration(LPC)based analysis reveals different melting mechanisms:the cHX-Hmotransition is driven by the proliferation of point-like defects during which defect-associated LPCs are generated sequentially,whereas the RB-Hmotransition is driven by line defects where defect-associated LPCs are generated simultaneously.These differences result in the observed different solid-Hmotransition points which areφA=0.812 for the cHX-HmoandφA=0.828 for the RB-Hmo.Our work will shed light on the initial-crystal-dependence of 2D melting behavior.展开更多
We employ multiple order parameters to analyze the local structure of liquid water obtained from all-atom simulations,and accordingly identify three types of molecules in water. In addition to the well-known low-densi...We employ multiple order parameters to analyze the local structure of liquid water obtained from all-atom simulations,and accordingly identify three types of molecules in water. In addition to the well-known low-density-liquid and highdensity-liquid molecules, the newly identified third type possesses an ultra-high density and over-coordinated H-bonds.The existence of this third type decreases the probability of transition of high-density-liquid molecules to low-densityliquid molecules and increases the probability of the reverse one.展开更多
Impacts of microenvironments on cell migration have been reported in various interaction modes.A rapid tumor metastasis occurs along topological interfaces in vivo,such as the interface between the blood vessels and n...Impacts of microenvironments on cell migration have been reported in various interaction modes.A rapid tumor metastasis occurs along topological interfaces in vivo,such as the interface between the blood vessels and nerves.In this work,we culture MDA-MB231 cells at dish-liquid,dish-hydrogel,and hydrogel-liquid interfaces,respectively,to study how these different interfaces influence cell dynamics and morphology.Our results show that the migration mode of cells changes from an amoeboid motion to a mesenchymal motion but their speed do not change obviously if the interface changes from hydrogel-liquid to dish-liquid.In contrast,the migration mode of cells at a dish-hydrogel interface maintains as a mesenchymal motion,whereas their speed increases significantly.展开更多
Thermophoresis and diffusiophoresis respectively refer to the directed drift of suspended particles in solutions with external thermal and chemical gradients, which have been widely used in the manipulation of mesosco...Thermophoresis and diffusiophoresis respectively refer to the directed drift of suspended particles in solutions with external thermal and chemical gradients, which have been widely used in the manipulation of mesoscopic particles. We here study a phoretic-like motion of a passive colloidal particle immersed in inhomogeneous active baths, where the thermal and chemical gradients are replaced separately by activity and concentration gradients of the active particles. By performing simulations, we show that the passive colloidal particle experiences phoretic-like forces that originate from its interactions with the inhomogeneous active fluid, and thus drifts along the gradient field, leading to an accumulation. The results are similar to the traditional phoretic effects occurring in passive colloidal suspensions, implying that the concepts of thermophoresis and diffusiophoresis could be generalized into active baths.展开更多
We use single-molecule FRET and newly-developed D-loop techniques to investigate strand displacement activity of Klenow fragment(exo-)of DNA polymerase I in DNA sequences rich in guanine and cytosine(GC)bases.We find ...We use single-molecule FRET and newly-developed D-loop techniques to investigate strand displacement activity of Klenow fragment(exo-)of DNA polymerase I in DNA sequences rich in guanine and cytosine(GC)bases.We find that there exist in the FRET traces numerous ascending jumps,which are induced by the backsliding of Klenow fragment on DNA chains.Our measurements show that the probability of backsliding is closely related to the GC-richness and d NTP concentration:increasing the GC-richness leads to an increase in the backsliding probability,and increasing the d NTP concentration however leads to a decrease in the backsliding probability.These results provide a new insight into the mechanism of DNA polymerase I.展开更多
Micro-droplets of soft matter solutions have different morphologies upon drying,and can become wrinkled,buckled or cavitated particles.We investigate the morphology evolution of a drying soft matter droplet in this wo...Micro-droplets of soft matter solutions have different morphologies upon drying,and can become wrinkled,buckled or cavitated particles.We investigate the morphology evolution of a drying soft matter droplet in this work:at the early stage of drying,wrinkling or cavitation instability can occur in the droplet,depending on the comparison between the critical wrinkling and cavitation pressure;at a later stage of drying,no wrinkles will appear if cavitation happens first,while cavitation can still occur if wrinkling happens first.A three-dimensional phase diagram in the space of elastic length,gel layer thickness and weight loss is provided to illustrate the drying pathways of a soft matter droplet.This diagram can help guide future fabrications of micro-particles with desired morphologies.展开更多
We develop a minimal phenomenological model to describe the auxetic response recently observed in liquid crystal elastomers, and further determine by theoretical calculation the critical condition required for the aux...We develop a minimal phenomenological model to describe the auxetic response recently observed in liquid crystal elastomers, and further determine by theoretical calculation the critical condition required for the auxetic response to occur.展开更多
Topological edge flow and dissipationless odd viscosity are two remarkable features of chiral active fluids composed of active spinners.These features can significantly influence the dynamics of suspended passive part...Topological edge flow and dissipationless odd viscosity are two remarkable features of chiral active fluids composed of active spinners.These features can significantly influence the dynamics of suspended passive particles and the interactions between the particles.By computer simulations,we investigate the transport phenomenon of anisotropic passive objects and the self-assembly behavior of passive spherical particles in the active spinner fluid.It is found that in confined systems,nonspherical passive objects can stably cling to boundary walls and are unidirectionally and robustly transported by edge flow of spinners.Furthermore,in an unconfined system,passive spherical particles are able to form stable clusters that spontaneously and unidirectionally rotate as a whole.In these phenomena,strong particle-wall and interparticle effective attractions play a vital role,which originate from spinner-mediated depletion-like interactions and can be largely enhanced by odd viscosity of spinner fluids.Our results thus provide new insight into the robust transport of cargoes and the nonequilibrium self-assembly of passive intruders.展开更多
Breast cancer is the most prevalent form of cancer among women,with a staggering 2.3 million new cases and 680,000deaths reported annually in recent years.The high mortality rate is primarily attributed to metastasis,...Breast cancer is the most prevalent form of cancer among women,with a staggering 2.3 million new cases and 680,000deaths reported annually in recent years.The high mortality rate is primarily attributed to metastasis,as most fatalities arise from secondary growths in organs such as the bone,liver,lung,and brain rather than the primary tumor[1].Cancer cells possess invasive migratory capabilities that enable them to spread to secondary organs via the bloodstream or lymphatic system.Effective treatment strategies prioritize understanding the entire tumor ecosystem to holistically address the complexity of this disease[2].展开更多
Due to the breaking of time-reversal and parity symmetries and the presence of non-conservative microscopic interactions,active spinner fluids and solids respectively exhibit nondissipative odd viscosity and nonstorag...Due to the breaking of time-reversal and parity symmetries and the presence of non-conservative microscopic interactions,active spinner fluids and solids respectively exhibit nondissipative odd viscosity and nonstorage odd elasticity,engendering phenomena unattainable in traditional passive or active systems.Here,we study the effects of odd viscosity and elasticity on phase behaviors of active spinner systems.We find the spinner fluid under a simple shear experiences an anisotropic gas-liquid phase separation driven by the odd-viscosity stress.This phase separation exhibits equilibrium-like behavior,with both binodal-like and spinodal curves and critical point.However,the formed dense liquid phase is unstable,since the odd elasticity instantly takes over the odd viscosity to condense the liquid into a solid-like phase.The unusual phase behavior essentially arises from the competition between thermal fluctuations and the odd response-induced effective attraction.Our results demonstrate that the cooperation of odd viscosity and elasticity can lead to exotic phase behavior,revealing their fundamental roles in phase transition.展开更多
Magnetic resonance imaging(MRI)is a critical tool in medical diagnostics,yet conventional MRI contrast agents(CAs)are often limited by their small-molecule nature,resulting in rapid clearance and low relaxivity.This s...Magnetic resonance imaging(MRI)is a critical tool in medical diagnostics,yet conventional MRI contrast agents(CAs)are often limited by their small-molecule nature,resulting in rapid clearance and low relaxivity.This study presents a chiral strategy for developing high-performance polymeric gadoliniumbased CAs,PAA-EOB-GdA and PAA-EOB-GdB,tailored for enhanced vascular and tumor imaging.Notably,PAA-EOB-GdA,a chiral Gd-DOTA derivative integrated with sodium poly(acrylic acid)(PAA),benefits from the optimized water exchange rate of chiral Gd(Ⅲ)complex and the polymer effect of PAA,exhibiting exceptionally high relaxivity(r1=37.87 mM^(-1) s^(-1),11.9-fold of clinical Gd-DOTA)and showed remarkable imaging efficacy in magnetic resonance angiography(MRA)with low-dose administration(0.05 mmol kg^(-1))and an extended imaging duration.Its performance in tumor imaging was also impressive,maintaining superior enhancement values compared to Gd-DOTA.These characteristics feature PAA-EOB-GdA as a promising candidate for clinical diagnosis in both vascular and tumor imaging applications.展开更多
Organ-on-a-chip(OoC)has emerged as a revolutionary technique in recent decades,capable of replicating essential aspects of physiological and pathophysiological processes of human organs in vitro.Serving as an effectiv...Organ-on-a-chip(OoC)has emerged as a revolutionary technique in recent decades,capable of replicating essential aspects of physiological and pathophysiological processes of human organs in vitro.Serving as an effective tissue culture method for creating digital twins,OoCs show significant promise and have found applications in disease modelling,drug screening,and tissue engineering.However,there has been a lack of emphasis on the fundamental design principles of OoCs in existing literature,a crucial aspect that cannot be overlooked,especially for beginners venturing into the realm of OoCs.Therefore,this paper endeavors to provide a comprehensive overview by delving into the historical development of OoCs,outlining the characteristics of their scaffolds,presenting design strategies for both conceptualisation and fabrication processes,and offering a detailed description of design mechanisms and guidelines based on recent research publications.Furthermore,it explores future prospects and challenges within the OoC domain.Serving as a foundational guide for those new to OoC exploration,this paper aims to furnish a thorough introduction to the fabrication and design strategies employed in OoCs.展开更多
The intrinsic pressure framework,which treats self-propelling force as an external force,provides a convenient and consistent description of mechanical equilibrium in active matter.However,direct experimental evidence...The intrinsic pressure framework,which treats self-propelling force as an external force,provides a convenient and consistent description of mechanical equilibrium in active matter.However,direct experimental evidence is still lacking.To validate this framework,here we employ a programmable robotic platform,where a single light-controlled wheeled robot travels in an activity landscape.Our experiments quantitatively demonstrate that the intrinsic pressure difference across the activity interface is balanced by the emerged polarization force.This result unambiguously confirms the theoretical predictions,thus validating the intrinsic pressure framework and laying the experimental foundation for the intrinsic pressure-based mechanical description of dry active matter.展开更多
Microcapsules are versatile delivery vehicles and widely used in various areas.Generally,microcapsules with solid shells lack selective permeation and only exhibit a simple release mode.Here,we use ultrathin-shell wat...Microcapsules are versatile delivery vehicles and widely used in various areas.Generally,microcapsules with solid shells lack selective permeation and only exhibit a simple release mode.Here,we use ultrathin-shell water-in-oil-in-water double emulsions as templates and design porous ultrathin-shell microcapsules for selective permeation and multiple stimuli-triggered release.After preparation of double emulsions by microfluidic devices,negatively charged shellac nanoparticles dispersed in the inner water core electrostatically complex with positively charged telechelicα,ω-diamino functionalized polydimethylsiloxane polymers dissolved in the middle oil shell at the water/oil interface,thus forming a porous shell of shellac nanoparticles cross-linked by telechelic polymers.Subsequently,the double emulsions become porous microcapsules upon evaporation of the middle oil phase.The porous ultrathin-shell microcapsules exhibit excellent properties,including tunable size,selective permeation and stimuli-triggered release.Small molecules or particles can diffuse across the shell,while large molecules or particles are encapsulated in the core,and release of the encapsulated cargos can be triggered by osmotic shock or a pH change.Due to their unique performance,porous ultrathin-shell microcapsules present promising platforms for various applications,such as drug delivery.展开更多
基金supported by National Natural Science Foundation of China(No.22278352)National Key Research and Development Program of China(No.2021YFC3001100)+3 种基金Longyan City Science and Technology Plan Project(No.2020LYF17043)Longyan City Science and Technology Plan Project(No.2020LYF17042)ARC Discovery Project(No.DP200101238)and NHMRC Investigator Grant(No.APP2008698)supported by the Harvard Materials Research Science and Engineering Center(No.DMR2011754)。
文摘Biocompatible amphiphilic nanoparticles(NPs)with tunable particle morphology and surface property are important for their applications as functional materials.However,previously developed methods to prepare amphiphilic NPs generally involve several steps,especially an additional step for surface modification,greatly hindering their largescale production and widespread applications.Here,a versatile one-step strategy is developed to prepare biocompatible amphiphilic dimer NPs with tunable particle morphology and surface property.The amphiphilic dimer NPs,which consist of a hydrophobic shellac bulb and a hydrophilic poly(lactic acid)(PLA)bulb with PLA-poly(ethylene glycol)(PEG)on the bulb surface,are prepared in a single step by controlled co-precipitation and self-assembly.Amphiphilic PLA-PEG/shellac dimer NPs demonstrate excellent tunability in particle morphology,thus showing good performances in controlling the interfacial curvature and emulsion type.In addition,temperatureresponsive PLA-poly(N-isopropyl acrylamide)(PNIPAM)/shellac dimer NPs are prepared following the same method and emulsions stabilized by them show temperature-triggered response.The applications of PLA-PEG-folic acid(FA)/shellac dimer NPs for drug delivery have also been demonstrated,which show a very good performance.The strategy of preparing the dimer NPs is green,scalable,facile and versatile,which provides a good platform for the design of dimer NPs with tunable particle morphology and surface property for diverse applications.
基金the support of the National Natural Science Foundation of China(Grant Nos.12274448,12325405,and 12174390)the National Key R&D Program of China(Grant No.2022YFF0503504)。
文摘Interparticle frictional interactions are ubiquitous in colloidal systems,exerting a profound influence on their structural and physical attributes.In this study,we employed Brownian dynamics simulations to explore the non-equilibrium dynamics in colloidal systems,focusing particularly on the role of tangential friction and its influence on the macroscopic physical properties of colloids.We found that the disruption of instantaneous time-reversal symmetry by tangential frictional interactions can trigger the self-assembly of colloidal systems into intricate network configurations,and these novel structures exhibit unique depletion force and rheological properties that set them apart from traditional colloidal gel systems.These findings not only help deepen our comprehension of the self-assembly phenomena in non-equilibrium colloidal systems but also offer fresh insights for the development of colloidal materials with tailored characteristics.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.11874397,11674365,11774393,and 11774394).
文摘We quantify the mean potential energy of a passive colloidal particle harmonically confined in a bacterial solution using optical traps.We find that the average potential energy of the passive particle depends on the trap stiffness,in contrast to the equilibrium case where energy partition is independent of the external constraints.The constraint dependence of the mean potential energy originates from the fact that the persistent collisions between the passive particle and the active bacteria are influenced by the particle relaxation dynamics.Our experimental results are consistent with the Brownian dynamics simulations,and confirm the recent theoretical prediction.
基金the National Key Research and Development Program of China(2020YFA0908200)the National Natural Science Foundation of China(52073060,32101159,and 61927805)+1 种基金the Shenzhen Fundamental Research Program(JCYJ20190813152616459)the Wenzhou Institute,University of Chinese Academy of Sciences(WIUCAS)’startup fund(WIUCASQD2019007).
文摘With the advantages of better mimicking the specificity of natural tissues,three-dimensional(3D)cell culture plays a major role in drug development,toxicity testing,and tissue engineering.However,existing scaffolds or microcarriers for 3D cell culture are often limited in size and show suboptimal performance in simulating the vascular complexes of living organisms.Therefore,we present a novel hierarchically inverse opal porous scaffold made via a simple microfluidic approach for promoting 3D cell co-culture techniques.The designed scaffold is constructed using a combined concept involving an emulsion droplet template and inert polymer polymerization.This work demonstrates that the resultant scaffolds ensure a sufficient supply of nutrients during cell culture,so as to achieve large-volume cell culture.In addition,by serially planting different cells in the scaffold,a 3D co-culture system of endothelial-cellencapsulated hepatocytes can be developed for constructing certain functional tissues.It is also demonstrated that the use of the proposed scaffold for a co-culture system helps hepatocytes to maintain specific in vivo functions.These hierarchically inverse opal scaffolds lay the foundation for 3D cell culture and even the construction of biomimetic tissues.
基金National Natural Science Foundation of China(Grant No.11774394)the Key Research Program of Frontier Sciences of Chinese Academy of Sciences(Grant No.QYZDB-SSW-SYS003)the K.C.Wong Education Foundation.
文摘Various behaviors of cancer cells are strongly influenced by their interaction with extracellular matrices(ECM).We investigate how this interaction may be influenced if the cancer cells’ability of secreting matrix metalloproteinases(MMPs)to degrade ECM is inhibited by adding the MMP inhibitor.We useMDA-MB-231-GFP cells as model cells and use matrigel to mimic ECM.It is found that the added MMP inhibitor significantly reduces the migration speed of cancer cells covered by matrigel but has little influence on the migration persistence and shape factor of the cells and that with the MMP inhibitor added the presence of matrigel on the top has no influence on the migration speed of the cells but increases the cells’shape factor and migration persistence.
基金supported by the UK Medical Research Council (to J.L.L.), China Scholarship Council-University of Oxford Scholarship (to Q.J.S), Chinese Scholarship Council Studentship (to Y.H.), Malaysia Government Scholarship (to H.K.), the National Natural Science Foundation of China (No. 11304372) (to H.L., F. Y and P.Y.W.) and anonymous donation (to J.L.L.)
文摘Compartmentation via filamentation has recently emerged as a novel mechanism for metabolic regulation. In order to identify filamentforming metabolic enzymes systematically, we performed a genome-wide screening of all strains available from an open reading frameGFP collection in Saccharomyces cerevisiae. We discovered nine novel filament-forming proteins and also confirmed those identified previously. From the 4159 strains, we found 23 proteins, mostly metabolic enzymes, which are capable of forming filaments in vivo. In silico protein-protein interaction analysis suggests that these filament-forming proteins can be clustered into several groups, including translational initiation machinery and glucose and nitrogen metabolic pathways. Using glutamine-utilising enzymes as examples, we found that the culture conditions affect the occurrence and length of the metabolic filaments. Furthermore, we found that two CTP synthases（Ura7p and Ura8p） and two asparagine synthetases（Asn1p and Asn2p） form filaments both in the cytoplasm and in the nucleus.Live imaging analyses suggest that metabolic filaments undergo sub-diffusion. Taken together, our genome-wide screening identifies additional filament-forming proteins in S. cerevisiae and suggests that filamentation of metabolic enzymes is more general than currently appreciated.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.11874277,21621004,12104453,and 12090054)the Strategic Priority Research Program of Chinese Academy of Sciences(Grant No.XDB33030300)
文摘Two-dimensional(2D)melting is a fundamental research topic in condensed matter physics,which can also provide guidance on fabricating new functional materials.Nevertheless,our understanding of 2D melting is still far from being complete due to existence of possible complicate transition mechanisms and absence of effective analysis methods.Here,using Monte Carlo simulations,we investigate 2D melting of 60°rhombs which melt from two different surface-fullycoverable crystals,a complex hexagonal crystal(cHX)whose primitive cell contains three rhombs,and a simple rhombic crystal(RB)whose primitive cell contains one rhomb.The melting of both crystals shows a sequence of solid,hexatic in molecular orientation(Hmo),and isotropic phases which obey the Berezinskii-Kosterlitz-Thouless-Halperin-Nelson-Young(BKTHNY)theory.However,local polymorphic configuration(LPC)based analysis reveals different melting mechanisms:the cHX-Hmotransition is driven by the proliferation of point-like defects during which defect-associated LPCs are generated sequentially,whereas the RB-Hmotransition is driven by line defects where defect-associated LPCs are generated simultaneously.These differences result in the observed different solid-Hmotransition points which areφA=0.812 for the cHX-HmoandφA=0.828 for the RB-Hmo.Our work will shed light on the initial-crystal-dependence of 2D melting behavior.
基金Project supported by the Key Research Program of Frontier Sciences of the Chinese Academy of Sciences(Grant No.QYZDB-SSW-SYS003)the National Natural Science Foundation of China(Grant Nos.11574310 and 11774394)
文摘We employ multiple order parameters to analyze the local structure of liquid water obtained from all-atom simulations,and accordingly identify three types of molecules in water. In addition to the well-known low-density-liquid and highdensity-liquid molecules, the newly identified third type possesses an ultra-high density and over-coordinated H-bonds.The existence of this third type decreases the probability of transition of high-density-liquid molecules to low-densityliquid molecules and increases the probability of the reverse one.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.11774394 and 11704404)the Chinese Academy of Sciences(CAS),and the Key Research Program of Frontier Sciences of CAS(Grant No.QYZDB-SSW-SYS003).
文摘Impacts of microenvironments on cell migration have been reported in various interaction modes.A rapid tumor metastasis occurs along topological interfaces in vivo,such as the interface between the blood vessels and nerves.In this work,we culture MDA-MB231 cells at dish-liquid,dish-hydrogel,and hydrogel-liquid interfaces,respectively,to study how these different interfaces influence cell dynamics and morphology.Our results show that the migration mode of cells changes from an amoeboid motion to a mesenchymal motion but their speed do not change obviously if the interface changes from hydrogel-liquid to dish-liquid.In contrast,the migration mode of cells at a dish-hydrogel interface maintains as a mesenchymal motion,whereas their speed increases significantly.
基金Project supported by the National Natural Science Foundation of China (Grant No. 11874397)the Strategic Priority Research Program of the Chinese Academy of Sciences (Grant No. XDB33000000)。
文摘Thermophoresis and diffusiophoresis respectively refer to the directed drift of suspended particles in solutions with external thermal and chemical gradients, which have been widely used in the manipulation of mesoscopic particles. We here study a phoretic-like motion of a passive colloidal particle immersed in inhomogeneous active baths, where the thermal and chemical gradients are replaced separately by activity and concentration gradients of the active particles. By performing simulations, we show that the passive colloidal particle experiences phoretic-like forces that originate from its interactions with the inhomogeneous active fluid, and thus drifts along the gradient field, leading to an accumulation. The results are similar to the traditional phoretic effects occurring in passive colloidal suspensions, implying that the concepts of thermophoresis and diffusiophoresis could be generalized into active baths.
基金Project supported by the National Natural Science Foundation of China(Grant No.12090051)the CAS Key Research Program of Frontier Sciences(Grant Nos.QYZDJSSW-SYS014 and ZDBS-LY-SLH015)the Youth Innovation Promotion Association of CAS(Grant No.2017015)。
文摘We use single-molecule FRET and newly-developed D-loop techniques to investigate strand displacement activity of Klenow fragment(exo-)of DNA polymerase I in DNA sequences rich in guanine and cytosine(GC)bases.We find that there exist in the FRET traces numerous ascending jumps,which are induced by the backsliding of Klenow fragment on DNA chains.Our measurements show that the probability of backsliding is closely related to the GC-richness and d NTP concentration:increasing the GC-richness leads to an increase in the backsliding probability,and increasing the d NTP concentration however leads to a decrease in the backsliding probability.These results provide a new insight into the mechanism of DNA polymerase I.
基金supports from Chinese Academy of Sciences(No.XDA17010504 and No.XDPB15)the National Natural Science Foundation of China(No.12047503)+1 种基金the support of the National Natural Science Foundation of China(Grant No.11774394)the Key Research Program of Frontier Sciences of Chinese Academy of Sciences(Grant No.QYZDB-SSW-SYS003)
文摘Micro-droplets of soft matter solutions have different morphologies upon drying,and can become wrinkled,buckled or cavitated particles.We investigate the morphology evolution of a drying soft matter droplet in this work:at the early stage of drying,wrinkling or cavitation instability can occur in the droplet,depending on the comparison between the critical wrinkling and cavitation pressure;at a later stage of drying,no wrinkles will appear if cavitation happens first,while cavitation can still occur if wrinkling happens first.A three-dimensional phase diagram in the space of elastic length,gel layer thickness and weight loss is provided to illustrate the drying pathways of a soft matter droplet.This diagram can help guide future fabrications of micro-particles with desired morphologies.
基金Project supported by the National Natural Science Foundation of China (Grant No. 22193032)。
文摘We develop a minimal phenomenological model to describe the auxetic response recently observed in liquid crystal elastomers, and further determine by theoretical calculation the critical condition required for the auxetic response to occur.
基金Supported by the National Natural Science Foundation of China(Grant Nos.11874397,11774393,11774394,and 11974044)the Strategic Priority Research Program of Chinese Academy of Sciences(Grant No.XDB33030300)。
文摘Topological edge flow and dissipationless odd viscosity are two remarkable features of chiral active fluids composed of active spinners.These features can significantly influence the dynamics of suspended passive particles and the interactions between the particles.By computer simulations,we investigate the transport phenomenon of anisotropic passive objects and the self-assembly behavior of passive spherical particles in the active spinner fluid.It is found that in confined systems,nonspherical passive objects can stably cling to boundary walls and are unidirectionally and robustly transported by edge flow of spinners.Furthermore,in an unconfined system,passive spherical particles are able to form stable clusters that spontaneously and unidirectionally rotate as a whole.In these phenomena,strong particle-wall and interparticle effective attractions play a vital role,which originate from spinner-mediated depletion-like interactions and can be largely enhanced by odd viscosity of spinner fluids.Our results thus provide new insight into the robust transport of cargoes and the nonequilibrium self-assembly of passive intruders.
基金supported by the National Natural Science Foundation of China(12325405 and 22307098)the National Key Research and Development Program of China(2022YFA1405002)the Strategic Priority Research Program of Chinese Academy of Sciences(XDB33000000)。
文摘Breast cancer is the most prevalent form of cancer among women,with a staggering 2.3 million new cases and 680,000deaths reported annually in recent years.The high mortality rate is primarily attributed to metastasis,as most fatalities arise from secondary growths in organs such as the bone,liver,lung,and brain rather than the primary tumor[1].Cancer cells possess invasive migratory capabilities that enable them to spread to secondary organs via the bloodstream or lymphatic system.Effective treatment strategies prioritize understanding the entire tumor ecosystem to holistically address the complexity of this disease[2].
基金the support of the National Natural Science Foundation of China(Nos.T2325027,12274448,12325405,and 12174390)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB33000000).
文摘Due to the breaking of time-reversal and parity symmetries and the presence of non-conservative microscopic interactions,active spinner fluids and solids respectively exhibit nondissipative odd viscosity and nonstorage odd elasticity,engendering phenomena unattainable in traditional passive or active systems.Here,we study the effects of odd viscosity and elasticity on phase behaviors of active spinner systems.We find the spinner fluid under a simple shear experiences an anisotropic gas-liquid phase separation driven by the odd-viscosity stress.This phase separation exhibits equilibrium-like behavior,with both binodal-like and spinodal curves and critical point.However,the formed dense liquid phase is unstable,since the odd elasticity instantly takes over the odd viscosity to condense the liquid into a solid-like phase.The unusual phase behavior essentially arises from the competition between thermal fluctuations and the odd response-induced effective attraction.Our results demonstrate that the cooperation of odd viscosity and elasticity can lead to exotic phase behavior,revealing their fundamental roles in phase transition.
基金financially supported by the National Natural Science Foundation of China(Grants 22075281 and 22105201)Zhejiang Provincial Natural Science of Foundation of China(Grant LZ21B010001)+3 种基金The Scientific Research Fund of Hunan Provincial Education Department(Grant 24B0456)the Natural Science Foundation of Hunan Province(Grant 2025JJ50125)University of Chinese Academy of Science(Grant WIUCASQD2020008)Wenzhou high-level innovation team(Development and Application Team of Functional Liver Cancer-on-a-Chip).
文摘Magnetic resonance imaging(MRI)is a critical tool in medical diagnostics,yet conventional MRI contrast agents(CAs)are often limited by their small-molecule nature,resulting in rapid clearance and low relaxivity.This study presents a chiral strategy for developing high-performance polymeric gadoliniumbased CAs,PAA-EOB-GdA and PAA-EOB-GdB,tailored for enhanced vascular and tumor imaging.Notably,PAA-EOB-GdA,a chiral Gd-DOTA derivative integrated with sodium poly(acrylic acid)(PAA),benefits from the optimized water exchange rate of chiral Gd(Ⅲ)complex and the polymer effect of PAA,exhibiting exceptionally high relaxivity(r1=37.87 mM^(-1) s^(-1),11.9-fold of clinical Gd-DOTA)and showed remarkable imaging efficacy in magnetic resonance angiography(MRA)with low-dose administration(0.05 mmol kg^(-1))and an extended imaging duration.Its performance in tumor imaging was also impressive,maintaining superior enhancement values compared to Gd-DOTA.These characteristics feature PAA-EOB-GdA as a promising candidate for clinical diagnosis in both vascular and tumor imaging applications.
基金supported by the National Key Research and Development Program of China(No.2022YFA1405002)the National Natural Science Foundation of China(Nos.12325405,T2221001,32400074)Seed Funding of the First Affiliated Hospital,Zhejiang University School of Medicine(No.BQD2319).
文摘Organ-on-a-chip(OoC)has emerged as a revolutionary technique in recent decades,capable of replicating essential aspects of physiological and pathophysiological processes of human organs in vitro.Serving as an effective tissue culture method for creating digital twins,OoCs show significant promise and have found applications in disease modelling,drug screening,and tissue engineering.However,there has been a lack of emphasis on the fundamental design principles of OoCs in existing literature,a crucial aspect that cannot be overlooked,especially for beginners venturing into the realm of OoCs.Therefore,this paper endeavors to provide a comprehensive overview by delving into the historical development of OoCs,outlining the characteristics of their scaffolds,presenting design strategies for both conceptualisation and fabrication processes,and offering a detailed description of design mechanisms and guidelines based on recent research publications.Furthermore,it explores future prospects and challenges within the OoC domain.Serving as a foundational guide for those new to OoC exploration,this paper aims to furnish a thorough introduction to the fabrication and design strategies employed in OoCs.
基金supported by the National Natural Science Foundation of China (Grant Nos.T2325027,12274448,T2350007,12404239,12174041,12325405,12090054,and T2221001)the National Key R&D Program of China (Grant No.2022YFF0503504)。
文摘The intrinsic pressure framework,which treats self-propelling force as an external force,provides a convenient and consistent description of mechanical equilibrium in active matter.However,direct experimental evidence is still lacking.To validate this framework,here we employ a programmable robotic platform,where a single light-controlled wheeled robot travels in an activity landscape.Our experiments quantitatively demonstrate that the intrinsic pressure difference across the activity interface is balanced by the emerged polarization force.This result unambiguously confirms the theoretical predictions,thus validating the intrinsic pressure framework and laying the experimental foundation for the intrinsic pressure-based mechanical description of dry active matter.
基金This work is supported by National Key Research and Development Programof China(Grant Nos.YS2021YFC3000089,2020YFA0908200)Zhejiang Provincial Natural Science Foundation of China(Grant No.Y20B060027)+2 种基金National Natural Science Foundation of China(Grant No.21878258)ARC Discovery Project(Grant Nos.DP200101238,DP210103079)NHMRC Investigator Grant APP2008698.
文摘Microcapsules are versatile delivery vehicles and widely used in various areas.Generally,microcapsules with solid shells lack selective permeation and only exhibit a simple release mode.Here,we use ultrathin-shell water-in-oil-in-water double emulsions as templates and design porous ultrathin-shell microcapsules for selective permeation and multiple stimuli-triggered release.After preparation of double emulsions by microfluidic devices,negatively charged shellac nanoparticles dispersed in the inner water core electrostatically complex with positively charged telechelicα,ω-diamino functionalized polydimethylsiloxane polymers dissolved in the middle oil shell at the water/oil interface,thus forming a porous shell of shellac nanoparticles cross-linked by telechelic polymers.Subsequently,the double emulsions become porous microcapsules upon evaporation of the middle oil phase.The porous ultrathin-shell microcapsules exhibit excellent properties,including tunable size,selective permeation and stimuli-triggered release.Small molecules or particles can diffuse across the shell,while large molecules or particles are encapsulated in the core,and release of the encapsulated cargos can be triggered by osmotic shock or a pH change.Due to their unique performance,porous ultrathin-shell microcapsules present promising platforms for various applications,such as drug delivery.
