The dynamics of biomolecules span across a wide range of timescales,reflecting the complexity of free energy landscapes of biomolecules.Among these,the microsecond-tomillisecond(μs-ms)timescale dynamics are particula...The dynamics of biomolecules span across a wide range of timescales,reflecting the complexity of free energy landscapes of biomolecules.Among these,the microsecond-tomillisecond(μs-ms)timescale dynamics are particularly significant,offering detailed insights into the kinetic,thermodynamic,and structural aspects of biological function.Many critical biological processes,including enzyme catalysis,protein folding,ligand binding,and allosteric regulation,operate within this timescale.Nuclear magnetic resonance(NMR)spectroscopy is a powerful technique for probing molecular dynamics in this time window,commonly used NMR methods for investigatingμs-ms timescale dynamics include Carr-Purcell-Meiboom-Gill(CPMG)relaxation dispersion,chemical exchange saturation transfer(CEST),and rotating-frame longitudinal relaxation dispersion(R_(1ρ)relaxation dispersion).This review provides a brief ove rview of the fundamental principles and some recent advances of these methods,highlighting their interrelationships and applications in elucidating biomolecular dynamics.展开更多
Global climate change seriously threatens food security.To address this challenge,breeders have achieved remarkable results using multiple breeding strategies and technologies.In recent years,the application of biomol...Global climate change seriously threatens food security.To address this challenge,breeders have achieved remarkable results using multiple breeding strategies and technologies.In recent years,the application of biomolecular condensates to crop improvement has remained in its early stages.Nevertheless,growing evidence indicates their crucial roles in regulating crop development and stress adaptation.This review synthesizes recent advances in understanding biomolecular condensate functions across key plant developmental phases and their regulatory roles in abiotic and biotic stress responses.The regulatory mechanisms associated with these condensates primarily encompass transcriptional regulation,RNA processing and metabolism,translational control,and membrane organelle biogenesis,collectively establishing a solid theoretical foundation for agricultural molecular breeding.In the final section,we discuss the potential applications and challenges of biomolecular condensates in crop improvement.展开更多
Cytoscape is one of the most popular platforms for biomolecular networks research. However Cytoscape cannot display biomolecular names according to their accession identifiers in different databases. A plugin named Ai...Cytoscape is one of the most popular platforms for biomolecular networks research. However Cytoscape cannot display biomolecular names according to their accession identifiers in different databases. A plugin named Ai2NU is designed and implemented in this paper. It can make biomolecular names displayed automatically in biomolecular networks graphs in Cytoscape by constructing a local dictionary. It is convenient for researchers to recognize biomolecules and enhance the research efficiency.展开更多
Accurate characterization of the interactions between biomolecules not only provides fundamental insights into cellular processes but also paves the way for drug discovery and development. With recent increases in thr...Accurate characterization of the interactions between biomolecules not only provides fundamental insights into cellular processes but also paves the way for drug discovery and development. With recent increases in throughput and sensitivity, biophysical technologies have become prominent tools for studying biomolecular interactions. Biophysical techniques that can reduce costs, shorten detection time, simplify the complexity of the system under analysis, and simultaneously provide high-quality data content are particularly favored. Here, we summarize the qualitative and quantitative analysis of biomolecular interactions using Micro Scale Thermophoresis(MST), as well as extend the application of MST functions to explore thermodynamics, enzyme kinetics and protein folding-unfolding processes. MST has emerged as a simple and powerful biophysical approach for identifying and quantifying binding events based on the movement of molecules along microscopic temperature gradients. The advantages of MST over other competitive biophysical techniques include freedom from immobilization, rapid analysis times, lower sample consumption, and the ability to analyze binding affinities in cell lysates. This article discusses the instrumental setups, principles, experimental workflows, and examples of MST application in practice.展开更多
We successfully conduct the label-free and real-time detection of the interactions between epoxy groups and rabbit IgG and 5＇ CTT CAG GTC ATG AGC CTG AT 3＇ oligonucleotide, and between the hybridization of 5＇ CTT C...We successfully conduct the label-free and real-time detection of the interactions between epoxy groups and rabbit IgG and 5＇ CTT CAG GTC ATG AGC CTG AT 3＇ oligonucleotide, and between the hybridization of 5＇ CTT CAG GTC ATG AGC CTG AT 3＇ and its complementary 3＇ GAA GTC CAC TAC TCG GAC TA 5＇ oligonucleotide, by the oblique-incidence reflectivity difference （OI-RD） method. The dynamic curves of OI-RD signals, corresponding to the kinetic processes of biomolecular combination or hybridization, are acquired. In our case, the combination of epoxy groups with rabbit IgG and 5＇ CTT CAC CTC ATG AGC CTG AT 3＇ oligonucleotide need almost one and a half hours and about two hundred seconds, respectively; and the hybridization of the two oligonucleotides needs about five hundred seconds. The experimental results show that the OI-RD is a promising method for the real-time and label-free detection of biomolecular interactions.展开更多
Objective: To investigate biomolecular alteration of sesamol on human lung adenocarcinoma(SK-LU-1) cells compared with cisplatin using Fourier transform infrared microscopy(FTIR). Methods: Cytotoxicity of sesamol was ...Objective: To investigate biomolecular alteration of sesamol on human lung adenocarcinoma(SK-LU-1) cells compared with cisplatin using Fourier transform infrared microscopy(FTIR). Methods: Cytotoxicity of sesamol was investigated against SK-LU-1 cells by using neutral red. DNA fragmentation and the cell cycle analysis were determined by agarose gel electrophoresis and flow cytometry, respectively. The FTIR microscopy technique was applied to explore the changes in cellular biochemical compositions in cells treated with sesamol that the biochemical and biological assays cannot cover. The alkylating property was determined by 4-(4-nitrobenzyl)pyridine assay. Results: Sesamol and cisplatin exerted an antiproliferative effect at 48 h with respective IC50 values of 2.7 and 0.07 m M. Both induced apoptosis by causing DNA damage and accumulation of cell populations at sub-G1. FTIR microscopy and Principle Component Analysis clearly discriminated the sesamol-and cisplatin-treated cells from the untreated cells or control. A significant increase of total lipid content was found in cisplatin-treated cells. Conformational changes in the proteins secondary structure from the β-helix to the β-sheet were found in both sesamol-and cisplatin-treated cells, as well as significant reductions in relative DNA content of both compared to the control were observed, suggesting DNA damage. A shift in the peak position of DNA region provides insight on the DNA interactions. Conclusions: The non-alkylating effect of sesamol based on the nitrobenzyl pyridine assay delineates the non-covalent binding mode of sesamol on DNA. Hydrogen bonding is the binding mode of sesamol on DNA, while for cisplatin it was covalent and hydrogen bonding.展开更多
In practical applications of dynamic DNA nanotechnology,a biomolecular controller is required for maintaining the operation of the molecular actuator at a desired condition based on the information from molecular sens...In practical applications of dynamic DNA nanotechnology,a biomolecular controller is required for maintaining the operation of the molecular actuator at a desired condition based on the information from molecular sensors.By making use of the DNA strand displacement mechanism as a"programming language"in the controller design,a biomolecular PI controller has been proposed.However,this PI control system has been verified only at the simulation level,and a theoretical regulation analysis is still required.Accordingly,in this study,we perform a rigorous regulation analysis of the biomolecular PI control system.Specifically,we theoretically prove that the output signal approaches the target level at a quasi-steady state.To this end,we apply the concept of finite-time regulation property to the biomolecular PI control system.展开更多
With the development of biomolecular modeling and simulation,especially implicit solvent modeling,higher requirements are set for the stability,efficiency and mesh quality of molecular mesh generation software.In this...With the development of biomolecular modeling and simulation,especially implicit solvent modeling,higher requirements are set for the stability,efficiency and mesh quality of molecular mesh generation software.In this review,we summarize the recent works in biomolecular mesh generation and molecular visualization.First,we introduce various definitions of molecular surface and corresponding meshing software.Second,as the mesh quality significantly influences biomolecular simulation,we investigate some remeshing methods in the fields of computer graphics and molecular modeling.Then,we show the application of biomolecular mesh in the boundary element method(BEM)and the finite element method(FEM).Finally,to conveniently visualize the numerical results based on the mesh,we present two types of molecular visualization systems.展开更多
Plants have developed intricate mechanisms for rapid and efficient stress perception and adaptation in response to environmental stressors.Recent research highlights the emerging role of biomolecular condensates in mo...Plants have developed intricate mechanisms for rapid and efficient stress perception and adaptation in response to environmental stressors.Recent research highlights the emerging role of biomolecular condensates in modulating plant stress perception and response.These condensates function through numerous mechanisms to regulate cellular processes such as transcription,translation,RNA meta-bolism,and signaling pathways under stress conditions.In this review,we provide an overview of cur-rent knowledge on stress-responsive biomolecular condensates in plants,including well-defined con-densates such as stress granules,processing bodies,and the nucleolus,as well as more recently discovered plant-specific condensates.By briefly referring to findings from yeast and animal studies,we discuss mechanisms by which plant condensates perceive stress signals and elicit cellular re-sponses.Finally,we provide insights for future investigations on stress-responsive condensates in plants.Understanding how condensates act as stress sensors and regulators will pave the way for potential applications in improving plant resilience through targeted genetic or biotechnological interventions.展开更多
Due to the stimulated emission amplification,lasers with excellent characteristics,including the high energy density,ultra-narrow spectral linewidth,and high directionality,are extremely favorable for sensing,detectio...Due to the stimulated emission amplification,lasers with excellent characteristics,including the high energy density,ultra-narrow spectral linewidth,and high directionality,are extremely favorable for sensing,detection,and imaging.Bringing these merits into the micro/nano scale,micro/nano lasers with miniaturized device sizes further enable outstanding spatial and temporal confinement,greatly boosting the light-matter interaction and bridging the size mismatch between light and biomolecules.Thanks to these advantages,micro/nano lasers have drawn widespread attention and opened new opportunities for a variety of biomedical and biochemical applications.In this paper,we review recent developments in biomolecular sensing and cellular analysis based on micro/nano lasers.We first describe the fundamental building blocks of micro/nano lasers,with discussions on gain material considerations,cavity structures,and pumping.We then review recent applications using micro/nano lasers as biosensors and bioprobes,including biomolecule(mainly proteins and DNAs)sensing,wavelength-multiplexed cell labeling/tracking/probing,and high-resolution cellular/tissue bioimaging.Finally,an outlook of the challenges and potential developments of micro/nano lasers for biological sensing and clinical applications is provided.展开更多
Cells orchestrate their processes through complex interactions,precisely organizing biomolecules in space and time.Recent discoveries have highlighted the crucial role of biomolecular condensates—membrane-less assemb...Cells orchestrate their processes through complex interactions,precisely organizing biomolecules in space and time.Recent discoveries have highlighted the crucial role of biomolecular condensates—membrane-less assemblies formed through the condensation of proteins,nucleic acids,and other molecules—in driving efficient and dynamic cellular processes.These condensates are integral to various physiological functions,such as gene expression and intracellular signal transduction,enabling rapid and finely tuned cellular responses.Their ability to regulate cellular signaling pathways is particularly significant,as it requires a careful balance between flexibility and precision.Disruption of this balance can lead to pathological conditions,including neurodegenerative diseases,cancer,and viral infections.Consequently,biomolecular condensates have emerged as promising therapeutic targets,with the potential to offer novel approaches to disease treatment.In this review,we present the recent insights into the regulatory mechanisms by which biomolecular condensates influence intracellular signaling pathways,their roles in health and disease,and potential strategies for modulating condensate dynamics as a therapeutic approach.Understanding these emerging principles may provide valuable directions for developing effective treatments targeting the aberrant behavior of biomolecular condensates in various diseases.展开更多
Dear Editor,In the accompanying Comment,Bratchenko et al.raised two concerns about the spectral data analysis pipeline employed for the Surface-enhanced Raman scattering and Artificial Intelligence for Cancer Screenin...Dear Editor,In the accompanying Comment,Bratchenko et al.raised two concerns about the spectral data analysis pipeline employed for the Surface-enhanced Raman scattering and Artificial Intelligence for Cancer Screening(SERS-AICS)technique in our original paper:(1)inappropriate accuracy presentation and(2)the use of a single data split for model evaluation.As a promising technique for molecular fingerprinting,SERS-basedearlycancerdetection approaches using biofluids and liquid biopsy are typically evaluated base stricty on theiracuray and elaility.展开更多
Biomolecular motors have been extensively studied as efficient molecular machines in detection systems owing to their unique signal conversion mechanisms and high energy conversion efficiencies.The application of thes...Biomolecular motors have been extensively studied as efficient molecular machines in detection systems owing to their unique signal conversion mechanisms and high energy conversion efficiencies.The application of these motors in the detection of pathogenic microorganisms is particularly promising.Through reasonable design and optimization,biomolecular motors can enable precise and efficient detection,enhancing clinical diagnostics.This paper reviews recent advances in detection systems utilizing various biomolecular motors,including kinesin,dynein,myosin,DNA polymerase,F_(o)F_(1)-ATPase,and flagellar motors.Detection mechanisms involving these motors are also introduced.Furthermore,the review covers recent progress in detecting antigens,antibodies,bacteria,and small molecules using biomolecular motors.Finally,the challenges and future prospects of biomolecular motor-based detection systems for pathogenic microorganisms are discussed,highlighting their potential as rapid and efficient tools for applications in food safety and medicine.展开更多
This commentary underscores the importance and implications of the study“Biomolecular condensates with complex architectures via controlled nucleation,”led by Jan C.M.van Hest and Tuomas P.J.Knowles,published in Nat...This commentary underscores the importance and implications of the study“Biomolecular condensates with complex architectures via controlled nucleation,”led by Jan C.M.van Hest and Tuomas P.J.Knowles,published in Nature Chemical Engineering.The research team developed a novel system to investigate the structure of biological condensates using quaternized amylose,carboxymethylated amylose,and single-stranded DNA.They successfully created multiphase droplets with distinct dense phases and demonstrated that droplet architecture can be controlled through temperature and salt concentration adjustments.This study offers valuable insights into the formation and function of membraneless organelles in cells and suggests promising applications for designing biomimetic materials and therapeutic strategies.展开更多
Stress granules are membraneless organelles that serve as a protective cellular response to external stressors by sequestering non-translating messenger RNAs(mRNAs)and regulating protein synthesis.Stress granules form...Stress granules are membraneless organelles that serve as a protective cellular response to external stressors by sequestering non-translating messenger RNAs(mRNAs)and regulating protein synthesis.Stress granules formation mechanism is conserved across species,from yeast to mammals,and they play a critical role in minimizing cellular damage during stress.Composed of heterogeneous ribonucleoprotein complexes,stress granules are enriched not only in mRNAs but also in noncoding RNAs and various proteins,including translation initiation factors and RNA-binding proteins.Genetic mutations affecting stress granule assembly and disassembly can lead to abnormal stress granule accumulation,contributing to the progression of several diseases.Recent research indicates that stress granule dynamics are pivotal in determining their physiological and pathological functions,with acute stress granule formation offering protection and chronic stress granule accumulation being detrimental.This review focuses on the multifaceted roles of stress granules under diverse physiological conditions,such as regulation of mRNA transport,mRNA translation,apoptosis,germ cell development,phase separation processes that govern stress granule formation,and their emerging implications in pathophysiological scenarios,such as viral infections,cancer,neurodevelopmental disorders,neurodegeneration,and neuronal trauma.展开更多
Cells adhesion is very important for many physiological processes. Using advanced Raman microspectroscopic technique, we selected T Leukemia cells (Jurkat) as the materials and obtained simultaneously conformation inf...Cells adhesion is very important for many physiological processes. Using advanced Raman microspectroscopic technique, we selected T Leukemia cells (Jurkat) as the materials and obtained simultaneously conformation information of various biomolecules inside the whole living cells. By comparing the Raman microspectroscopic spectra of single and adhesive cancer cells, we found for the first time that when cells adhered, the conformation of the biomolecules (DNA, protein, carbohydrates and lipids) inside the cells had different changes: (i) the backbone of double-stranded DNA maintained orderly B-form or modified B-form conformation, whereas the groups of its deoxyribose and bases were modified; (ii) the conformational changes of the main chain and the side chain in the protein were obviously variant. The lines intensity belonging to α-helix andβ-sheet decreased, while that ofβ-turn increased. Tyrosine and tryptophane residues of the protein changed from "buried state" to "exposed state"; the lines intensity of its sulfhydryl group also increased; the conformation of its disulfide bond changed from two kinds to three kinds. These facts suggest that the cells adhesion causes changes in H-bonds organization of the main chain and environment of the side chain in the protein; (iii) the groups of the carbohydrates were also modified simultaneously; (iv) the conformation of the lipids bilayers of the membranes changed obviously; the order parameter for lateral interaction between chains decreased gradually with the increase of number of the adhesive cells. So cells adhesion resulted in an increase in fluidity of the membrane and ion permeability on the membrane.展开更多
We present a general framework for a higher-order spline level-set （HLS） method and apply this to biomolecule surfaces construction. Starting from a first order energy functional, we obtain a general level set formu...We present a general framework for a higher-order spline level-set （HLS） method and apply this to biomolecule surfaces construction. Starting from a first order energy functional, we obtain a general level set formulation of geometric partial differential equation, and provide an efficient approach to solving this partial differential equation using a C2 spline basis. We also present a fast cubic spline interpolation algorithm based on convolution and the Z-transform, which exploits the local relationship of interpolatory cubic spline coefficients with respect to given function data values. One example of our HLS method is demonstrated their individual atomic coordinates which is the construction of biomolecule and solvated radii as prerequisites. surfaces （an implicit solvation interface） with展开更多
The cyclic guanosine monophosphate (GMP)–adenosine monophosphate (AMP) synthetase (cGAS)–stimulator of interferon genes(STING) pathway, comprising the DNA sensor cGAS, the second messenger cyclic GMP–AMP (cGAMP), a...The cyclic guanosine monophosphate (GMP)–adenosine monophosphate (AMP) synthetase (cGAS)–stimulator of interferon genes(STING) pathway, comprising the DNA sensor cGAS, the second messenger cyclic GMP–AMP (cGAMP), and the endoplasmicreticulum (ER) adaptor protein STING, detects cytoplasmic double-stranded DNA (dsDNA) to trigger type I-interferon responses forhost defense against pathogens. Previous studies defined a model for the allosteric activation of cGAS by DNA-binding, but recentwork reveals other layers of mechanisms to regulate cGAS activation such as the phase condensation and metal ions, especially thediscovery of Mn^(2+) as a cGAS activator. Activation of the 23-cGAMP sensor STING requires translocating from the ER to the Golgiapparatus. The sulfated glycosaminoglycans at the Golgi are found to be the second STING ligand promoting STING oligomerizationand activation in addition to 23-cGAMP, while surpassed levels of 23-cGAMP induce ER-located STING to form a highly organizedER membranous condensate named STING phase-separator to restrain STING activation. Here, we summarize recent advances in theregulation of cGAS–STING activation and their implications in physiological or pathological conditions, particularly focusing on theemerging complexity of the regulation.展开更多
With the great advancement of experimental tools,a tremendous amount of biomolecular data has been generated and accumulated in various databases.The high dimensionality,structural complexity,the nonlinearity,and enta...With the great advancement of experimental tools,a tremendous amount of biomolecular data has been generated and accumulated in various databases.The high dimensionality,structural complexity,the nonlinearity,and entanglements of biomolecular data,ranging from DNA knots,RNA secondary structures,protein folding configurations,chromosomes,DNA origami,molecular assembly,to others at the macromolecular level,pose a severe challenge in their analysis and characterization.In the past few decades,mathematical concepts,models,algorithms,and tools from algebraic topology,combinatorial topology,computational topology,and topological data analysis,have demonstrated great power and begun to play an essential role in tackling the biomolecular data challenge.In this work,we introduce biomolecular topology,which concerns the topological problems and models originated from the biomolecular systems.More specifically,the biomolecular topology encompasses topological structures,properties and relations that are emerged from biomolecular structures,dynamics,interactions,and functions.We discuss the various types of biomolecular topology from structures(of proteins,DNAs,and RNAs),protein folding,and protein assembly.A brief discussion of databanks(and databases),theoretical models,and computational algorithms,is presented.Further,we systematically review related topological models,including graphs,simplicial complexes,persistent homology,persistent Laplacians,de Rham-Hodge theory,Yau-Hausdorff distance,and the topology-based machine learning models.展开更多
Biomolecular condensates or membraneless organelles(MLOs)formed by liquid-liquid phase separation(LLPS)divide intracellular spaces into discrete compartments for specific functions.Dysregulation of LLPS or aberrant ph...Biomolecular condensates or membraneless organelles(MLOs)formed by liquid-liquid phase separation(LLPS)divide intracellular spaces into discrete compartments for specific functions.Dysregulation of LLPS or aberrant phase transition that disturbs the formation or material states of MLOs is closely correlated with neurodegeneration,tumorigenesis,and many other pathological processes.Herein,we summarize the recent progress in development of methods to monitor phase separation and we discuss the biogenesis and function of MLOs formed through phase separation.We then present emerging proof-of-concept examples regarding the disruption of phase separation homeostasis in a diverse array of clinical conditions including neurodegenerative disorders,hearing loss,cancers,and immunological diseases.Finally,we describe the emerging discovery of chemical modulators of phase separation.展开更多
基金financially supported by funds from the Natural Science Foundation of Beijing Municipality(Grant Number 7232251)the National Natural Science Foundation of China(Grant Number 22474006)。
文摘The dynamics of biomolecules span across a wide range of timescales,reflecting the complexity of free energy landscapes of biomolecules.Among these,the microsecond-tomillisecond(μs-ms)timescale dynamics are particularly significant,offering detailed insights into the kinetic,thermodynamic,and structural aspects of biological function.Many critical biological processes,including enzyme catalysis,protein folding,ligand binding,and allosteric regulation,operate within this timescale.Nuclear magnetic resonance(NMR)spectroscopy is a powerful technique for probing molecular dynamics in this time window,commonly used NMR methods for investigatingμs-ms timescale dynamics include Carr-Purcell-Meiboom-Gill(CPMG)relaxation dispersion,chemical exchange saturation transfer(CEST),and rotating-frame longitudinal relaxation dispersion(R_(1ρ)relaxation dispersion).This review provides a brief ove rview of the fundamental principles and some recent advances of these methods,highlighting their interrelationships and applications in elucidating biomolecular dynamics.
基金supported by the Shanghai Agricultural Science and Technology Innovation Project(B2024003)the Innovation Program of Shanghai Municipal Education Commission(2023ZKZD05)the Shanghai Oriental Talent(Rural Revitalization)Top Talent Project(T2023102).
文摘Global climate change seriously threatens food security.To address this challenge,breeders have achieved remarkable results using multiple breeding strategies and technologies.In recent years,the application of biomolecular condensates to crop improvement has remained in its early stages.Nevertheless,growing evidence indicates their crucial roles in regulating crop development and stress adaptation.This review synthesizes recent advances in understanding biomolecular condensate functions across key plant developmental phases and their regulatory roles in abiotic and biotic stress responses.The regulatory mechanisms associated with these condensates primarily encompass transcriptional regulation,RNA processing and metabolism,translational control,and membrane organelle biogenesis,collectively establishing a solid theoretical foundation for agricultural molecular breeding.In the final section,we discuss the potential applications and challenges of biomolecular condensates in crop improvement.
基金Project supported by the Shanghai Leading Academic Discipline Project(Grnat No.J50103)the Ph D Programs Foundation of Ministry of Education of China(Grant No.20080280007)+1 种基金the Innovation Program of Municipal Education Commission of Shanghai Municipality(Grant No.11Y203)the Innovation Foundation of Shanghai University
文摘Cytoscape is one of the most popular platforms for biomolecular networks research. However Cytoscape cannot display biomolecular names according to their accession identifiers in different databases. A plugin named Ai2NU is designed and implemented in this paper. It can make biomolecular names displayed automatically in biomolecular networks graphs in Cytoscape by constructing a local dictionary. It is convenient for researchers to recognize biomolecules and enhance the research efficiency.
基金This work was supported by State Key Laboratory of Natural and Biomimetic Drugs,Peking University。
文摘Accurate characterization of the interactions between biomolecules not only provides fundamental insights into cellular processes but also paves the way for drug discovery and development. With recent increases in throughput and sensitivity, biophysical technologies have become prominent tools for studying biomolecular interactions. Biophysical techniques that can reduce costs, shorten detection time, simplify the complexity of the system under analysis, and simultaneously provide high-quality data content are particularly favored. Here, we summarize the qualitative and quantitative analysis of biomolecular interactions using Micro Scale Thermophoresis(MST), as well as extend the application of MST functions to explore thermodynamics, enzyme kinetics and protein folding-unfolding processes. MST has emerged as a simple and powerful biophysical approach for identifying and quantifying binding events based on the movement of molecules along microscopic temperature gradients. The advantages of MST over other competitive biophysical techniques include freedom from immobilization, rapid analysis times, lower sample consumption, and the ability to analyze binding affinities in cell lysates. This article discusses the instrumental setups, principles, experimental workflows, and examples of MST application in practice.
基金Project supported by the National Basic Research Program in China(Grant No.2007CB935700)
文摘We successfully conduct the label-free and real-time detection of the interactions between epoxy groups and rabbit IgG and 5＇ CTT CAG GTC ATG AGC CTG AT 3＇ oligonucleotide, and between the hybridization of 5＇ CTT CAG GTC ATG AGC CTG AT 3＇ and its complementary 3＇ GAA GTC CAC TAC TCG GAC TA 5＇ oligonucleotide, by the oblique-incidence reflectivity difference （OI-RD） method. The dynamic curves of OI-RD signals, corresponding to the kinetic processes of biomolecular combination or hybridization, are acquired. In our case, the combination of epoxy groups with rabbit IgG and 5＇ CTT CAC CTC ATG AGC CTG AT 3＇ oligonucleotide need almost one and a half hours and about two hundred seconds, respectively; and the hybridization of the two oligonucleotides needs about five hundred seconds. The experimental results show that the OI-RD is a promising method for the real-time and label-free detection of biomolecular interactions.
基金supported by the Higher Education Research Promotion and National Research University Project of Thailand,Office of the Higher Education Commission,through the Food and Functional Food Research Cluster and Research and Development of Herbal Nutraceutics Subcluster of Khon Kaen University(FC 3.1.13 PhD and NRU 541057)
文摘Objective: To investigate biomolecular alteration of sesamol on human lung adenocarcinoma(SK-LU-1) cells compared with cisplatin using Fourier transform infrared microscopy(FTIR). Methods: Cytotoxicity of sesamol was investigated against SK-LU-1 cells by using neutral red. DNA fragmentation and the cell cycle analysis were determined by agarose gel electrophoresis and flow cytometry, respectively. The FTIR microscopy technique was applied to explore the changes in cellular biochemical compositions in cells treated with sesamol that the biochemical and biological assays cannot cover. The alkylating property was determined by 4-(4-nitrobenzyl)pyridine assay. Results: Sesamol and cisplatin exerted an antiproliferative effect at 48 h with respective IC50 values of 2.7 and 0.07 m M. Both induced apoptosis by causing DNA damage and accumulation of cell populations at sub-G1. FTIR microscopy and Principle Component Analysis clearly discriminated the sesamol-and cisplatin-treated cells from the untreated cells or control. A significant increase of total lipid content was found in cisplatin-treated cells. Conformational changes in the proteins secondary structure from the β-helix to the β-sheet were found in both sesamol-and cisplatin-treated cells, as well as significant reductions in relative DNA content of both compared to the control were observed, suggesting DNA damage. A shift in the peak position of DNA region provides insight on the DNA interactions. Conclusions: The non-alkylating effect of sesamol based on the nitrobenzyl pyridine assay delineates the non-covalent binding mode of sesamol on DNA. Hydrogen bonding is the binding mode of sesamol on DNA, while for cisplatin it was covalent and hydrogen bonding.
文摘In practical applications of dynamic DNA nanotechnology,a biomolecular controller is required for maintaining the operation of the molecular actuator at a desired condition based on the information from molecular sensors.By making use of the DNA strand displacement mechanism as a"programming language"in the controller design,a biomolecular PI controller has been proposed.However,this PI control system has been verified only at the simulation level,and a theoretical regulation analysis is still required.Accordingly,in this study,we perform a rigorous regulation analysis of the biomolecular PI control system.Specifically,we theoretically prove that the output signal approaches the target level at a quasi-steady state.To this end,we apply the concept of finite-time regulation property to the biomolecular PI control system.
基金supported by the Science Challenge Program under Grant TZ2016003by the National Key Research and Development Program of Ministry of Science and Technology under Grant 2016YFB0201304the National Natural Science Foundation of China(61772523,21573274,11771435,and 61620106003).
文摘With the development of biomolecular modeling and simulation,especially implicit solvent modeling,higher requirements are set for the stability,efficiency and mesh quality of molecular mesh generation software.In this review,we summarize the recent works in biomolecular mesh generation and molecular visualization.First,we introduce various definitions of molecular surface and corresponding meshing software.Second,as the mesh quality significantly influences biomolecular simulation,we investigate some remeshing methods in the fields of computer graphics and molecular modeling.Then,we show the application of biomolecular mesh in the boundary element method(BEM)and the finite element method(FEM).Finally,to conveniently visualize the numerical results based on the mesh,we present two types of molecular visualization systems.
基金the National Key Research and Development Program of China(2024YFA1308100)Ministry of Science and Technology of China(2022YFA1303400)the National Natural Science Foundation of China(32450060)to X.F.
文摘Plants have developed intricate mechanisms for rapid and efficient stress perception and adaptation in response to environmental stressors.Recent research highlights the emerging role of biomolecular condensates in modulating plant stress perception and response.These condensates function through numerous mechanisms to regulate cellular processes such as transcription,translation,RNA meta-bolism,and signaling pathways under stress conditions.In this review,we provide an overview of cur-rent knowledge on stress-responsive biomolecular condensates in plants,including well-defined con-densates such as stress granules,processing bodies,and the nucleolus,as well as more recently discovered plant-specific condensates.By briefly referring to findings from yeast and animal studies,we discuss mechanisms by which plant condensates perceive stress signals and elicit cellular re-sponses.Finally,we provide insights for future investigations on stress-responsive condensates in plants.Understanding how condensates act as stress sensors and regulators will pave the way for potential applications in improving plant resilience through targeted genetic or biotechnological interventions.
基金supported by the National Natural Science Foundation of China(Nos.62005031 and 62005032)National Foreign Experts Program(No.DL2023165003L)Innovation Support Plan for Returned Overseas Scholars(No.cx2021058)to Xiaoqin WU and Yipei WANG,and the Richard A.Auhll Endowed Professorship to Xudong FAN.
文摘Due to the stimulated emission amplification,lasers with excellent characteristics,including the high energy density,ultra-narrow spectral linewidth,and high directionality,are extremely favorable for sensing,detection,and imaging.Bringing these merits into the micro/nano scale,micro/nano lasers with miniaturized device sizes further enable outstanding spatial and temporal confinement,greatly boosting the light-matter interaction and bridging the size mismatch between light and biomolecules.Thanks to these advantages,micro/nano lasers have drawn widespread attention and opened new opportunities for a variety of biomedical and biochemical applications.In this paper,we review recent developments in biomolecular sensing and cellular analysis based on micro/nano lasers.We first describe the fundamental building blocks of micro/nano lasers,with discussions on gain material considerations,cavity structures,and pumping.We then review recent applications using micro/nano lasers as biosensors and bioprobes,including biomolecule(mainly proteins and DNAs)sensing,wavelength-multiplexed cell labeling/tracking/probing,and high-resolution cellular/tissue bioimaging.Finally,an outlook of the challenges and potential developments of micro/nano lasers for biological sensing and clinical applications is provided.
基金supported by the National Research Foundation of Korea(NRF)grants NRF-2022R1A4A3024551 and RS-2024-00457141(to W.K.)the Bio&Medical Technology Development Program grant NRF-2022M3A9J3073020(to B.C.)funded by the Ministry of Science,ICT&Future Planning.Figures 1,3,4,5,6,7,8,9,10,and 11 were created using BioRender(http://biorender.com/).
文摘Cells orchestrate their processes through complex interactions,precisely organizing biomolecules in space and time.Recent discoveries have highlighted the crucial role of biomolecular condensates—membrane-less assemblies formed through the condensation of proteins,nucleic acids,and other molecules—in driving efficient and dynamic cellular processes.These condensates are integral to various physiological functions,such as gene expression and intracellular signal transduction,enabling rapid and finely tuned cellular responses.Their ability to regulate cellular signaling pathways is particularly significant,as it requires a careful balance between flexibility and precision.Disruption of this balance can lead to pathological conditions,including neurodegenerative diseases,cancer,and viral infections.Consequently,biomolecular condensates have emerged as promising therapeutic targets,with the potential to offer novel approaches to disease treatment.In this review,we present the recent insights into the regulatory mechanisms by which biomolecular condensates influence intracellular signaling pathways,their roles in health and disease,and potential strategies for modulating condensate dynamics as a therapeutic approach.Understanding these emerging principles may provide valuable directions for developing effective treatments targeting the aberrant behavior of biomolecular condensates in various diseases.
文摘Dear Editor,In the accompanying Comment,Bratchenko et al.raised two concerns about the spectral data analysis pipeline employed for the Surface-enhanced Raman scattering and Artificial Intelligence for Cancer Screening(SERS-AICS)technique in our original paper:(1)inappropriate accuracy presentation and(2)the use of a single data split for model evaluation.As a promising technique for molecular fingerprinting,SERS-basedearlycancerdetection approaches using biofluids and liquid biopsy are typically evaluated base stricty on theiracuray and elaility.
基金supported by the National Natural Science Foundation of China(Grant number 22078297)Natural Science Foundation of Zhejiang Province(Grant number LTGC23H200002)+1 种基金Science and Technology Plan Project of Taizhou(Grant number 23ywa37)Special Research Fund of Hospital Pharmacy of Zhejiang Pharmaceutical Association(Grant number 2020ZYY46).
文摘Biomolecular motors have been extensively studied as efficient molecular machines in detection systems owing to their unique signal conversion mechanisms and high energy conversion efficiencies.The application of these motors in the detection of pathogenic microorganisms is particularly promising.Through reasonable design and optimization,biomolecular motors can enable precise and efficient detection,enhancing clinical diagnostics.This paper reviews recent advances in detection systems utilizing various biomolecular motors,including kinesin,dynein,myosin,DNA polymerase,F_(o)F_(1)-ATPase,and flagellar motors.Detection mechanisms involving these motors are also introduced.Furthermore,the review covers recent progress in detecting antigens,antibodies,bacteria,and small molecules using biomolecular motors.Finally,the challenges and future prospects of biomolecular motor-based detection systems for pathogenic microorganisms are discussed,highlighting their potential as rapid and efficient tools for applications in food safety and medicine.
基金supported by the National Key Research and Development Program of China(2020YFA0908200)and the National Natural Science Foundation of China(32271383).
文摘This commentary underscores the importance and implications of the study“Biomolecular condensates with complex architectures via controlled nucleation,”led by Jan C.M.van Hest and Tuomas P.J.Knowles,published in Nature Chemical Engineering.The research team developed a novel system to investigate the structure of biological condensates using quaternized amylose,carboxymethylated amylose,and single-stranded DNA.They successfully created multiphase droplets with distinct dense phases and demonstrated that droplet architecture can be controlled through temperature and salt concentration adjustments.This study offers valuable insights into the formation and function of membraneless organelles in cells and suggests promising applications for designing biomimetic materials and therapeutic strategies.
基金supported by a grant from the Merkin Peripheral Neuropathy and Nerve Regeneration Center(to PKS)the Rutgers University Startup Fund(to PKS).
文摘Stress granules are membraneless organelles that serve as a protective cellular response to external stressors by sequestering non-translating messenger RNAs(mRNAs)and regulating protein synthesis.Stress granules formation mechanism is conserved across species,from yeast to mammals,and they play a critical role in minimizing cellular damage during stress.Composed of heterogeneous ribonucleoprotein complexes,stress granules are enriched not only in mRNAs but also in noncoding RNAs and various proteins,including translation initiation factors and RNA-binding proteins.Genetic mutations affecting stress granule assembly and disassembly can lead to abnormal stress granule accumulation,contributing to the progression of several diseases.Recent research indicates that stress granule dynamics are pivotal in determining their physiological and pathological functions,with acute stress granule formation offering protection and chronic stress granule accumulation being detrimental.This review focuses on the multifaceted roles of stress granules under diverse physiological conditions,such as regulation of mRNA transport,mRNA translation,apoptosis,germ cell development,phase separation processes that govern stress granule formation,and their emerging implications in pathophysiological scenarios,such as viral infections,cancer,neurodevelopmental disorders,neurodegeneration,and neuronal trauma.
文摘Cells adhesion is very important for many physiological processes. Using advanced Raman microspectroscopic technique, we selected T Leukemia cells (Jurkat) as the materials and obtained simultaneously conformation information of various biomolecules inside the whole living cells. By comparing the Raman microspectroscopic spectra of single and adhesive cancer cells, we found for the first time that when cells adhered, the conformation of the biomolecules (DNA, protein, carbohydrates and lipids) inside the cells had different changes: (i) the backbone of double-stranded DNA maintained orderly B-form or modified B-form conformation, whereas the groups of its deoxyribose and bases were modified; (ii) the conformational changes of the main chain and the side chain in the protein were obviously variant. The lines intensity belonging to α-helix andβ-sheet decreased, while that ofβ-turn increased. Tyrosine and tryptophane residues of the protein changed from "buried state" to "exposed state"; the lines intensity of its sulfhydryl group also increased; the conformation of its disulfide bond changed from two kinds to three kinds. These facts suggest that the cells adhesion causes changes in H-bonds organization of the main chain and environment of the side chain in the protein; (iii) the groups of the carbohydrates were also modified simultaneously; (iv) the conformation of the lipids bilayers of the membranes changed obviously; the order parameter for lateral interaction between chains decreased gradually with the increase of number of the adhesive cells. So cells adhesion resulted in an increase in fluidity of the membrane and ion permeability on the membrane.
基金Bajaj is supported in part by NSF of USA under Grant No. CNS-0540033NIH under Grant Nos. P20-RR020647, R01- EB00487, R01-GM074258, R01-GM07308.+2 种基金Xu and Zhang are supported by the National Natural Science Foundation of China under Grant No. 60773165the National Basic Research 973 Program of China under Grant No. 2004CB318000. Zhang is also supported by Beijing Educational Committee Foundation under Grant No. KM200811232009.
文摘We present a general framework for a higher-order spline level-set （HLS） method and apply this to biomolecule surfaces construction. Starting from a first order energy functional, we obtain a general level set formulation of geometric partial differential equation, and provide an efficient approach to solving this partial differential equation using a C2 spline basis. We also present a fast cubic spline interpolation algorithm based on convolution and the Z-transform, which exploits the local relationship of interpolatory cubic spline coefficients with respect to given function data values. One example of our HLS method is demonstrated their individual atomic coordinates which is the construction of biomolecule and solvated radii as prerequisites. surfaces （an implicit solvation interface） with
基金The work is supported by the National Natural Science Foundation of China(31830022 and 81621001)the Chinese Ministry of Science and Technology(2019YFA0508500 and 2020YFA0707800)China Postdoctoral Science Foundation(2021M700242).
文摘The cyclic guanosine monophosphate (GMP)–adenosine monophosphate (AMP) synthetase (cGAS)–stimulator of interferon genes(STING) pathway, comprising the DNA sensor cGAS, the second messenger cyclic GMP–AMP (cGAMP), and the endoplasmicreticulum (ER) adaptor protein STING, detects cytoplasmic double-stranded DNA (dsDNA) to trigger type I-interferon responses forhost defense against pathogens. Previous studies defined a model for the allosteric activation of cGAS by DNA-binding, but recentwork reveals other layers of mechanisms to regulate cGAS activation such as the phase condensation and metal ions, especially thediscovery of Mn^(2+) as a cGAS activator. Activation of the 23-cGAMP sensor STING requires translocating from the ER to the Golgiapparatus. The sulfated glycosaminoglycans at the Golgi are found to be the second STING ligand promoting STING oligomerizationand activation in addition to 23-cGAMP, while surpassed levels of 23-cGAMP induce ER-located STING to form a highly organizedER membranous condensate named STING phase-separator to restrain STING activation. Here, we summarize recent advances in theregulation of cGAS–STING activation and their implications in physiological or pathological conditions, particularly focusing on theemerging complexity of the regulation.
基金supported by Nanyang Technological University Startup Grant M4081842Singapore Ministry of Education Academic Research fund Tier 1 RG109/19,MOE-T2EP20120-0013 and MOE-T2EP20220-0010+10 种基金supported by NIH grant GM126189NSF grants DMS-2052983,DMS-1761320,and IIS-1900473supported by Natural Science Foundation of China(NSFC)grant(11971144)Highlevel Scientific Research Foundation of Hebei Provincethe Start-up Research Fund from Yanqi Lake Beijing Institute of Mathematical Sciences and Applicationssupported by Tianjin Natural Science Foundation(Grant No.19JCYBJC30200)supported by National Natural Science Foundation of China(NSFC)grant(12171275)Tsinghua University Spring Breeze Fund(2020Z99CFY044)Tsinghua University Start-up FundTsinghua University Education Foundation fund(042202008)National Center for Theoretical Sciences(NCTS)for providing an excellent research environment while part of this research was done。
文摘With the great advancement of experimental tools,a tremendous amount of biomolecular data has been generated and accumulated in various databases.The high dimensionality,structural complexity,the nonlinearity,and entanglements of biomolecular data,ranging from DNA knots,RNA secondary structures,protein folding configurations,chromosomes,DNA origami,molecular assembly,to others at the macromolecular level,pose a severe challenge in their analysis and characterization.In the past few decades,mathematical concepts,models,algorithms,and tools from algebraic topology,combinatorial topology,computational topology,and topological data analysis,have demonstrated great power and begun to play an essential role in tackling the biomolecular data challenge.In this work,we introduce biomolecular topology,which concerns the topological problems and models originated from the biomolecular systems.More specifically,the biomolecular topology encompasses topological structures,properties and relations that are emerged from biomolecular structures,dynamics,interactions,and functions.We discuss the various types of biomolecular topology from structures(of proteins,DNAs,and RNAs),protein folding,and protein assembly.A brief discussion of databanks(and databases),theoretical models,and computational algorithms,is presented.Further,we systematically review related topological models,including graphs,simplicial complexes,persistent homology,persistent Laplacians,de Rham-Hodge theory,Yau-Hausdorff distance,and the topology-based machine learning models.
基金supported by grants from the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB0480000)the National Key Research and Development Program of China(2022YFA1103800,2022YFA1303100,2023YFE0210100)+10 种基金the National Natural Science Foundation of China(22337005,22377119,32025010,32241002,32270812,32270920,32325016,32350024,32261160376,82150003,82188101,82325016,92157202,92254301,T2325003)STI2030-Major Projects(2021ZD0202501)the Science and Technology Commission of Shanghai Municipality(2019SHZDZX02,20490712600)the Key Research Program CAS(ZDBS-ZRKJZ-TLC003)International Cooperation Program CAS(154144KYSB20200006)CAS Project for Young Scientists in Basic Research(YSBR-075)Guangdong Province Science and Technology Program(2023B1111050005,2023B1212060050)Natural Science Foundation of Anhui Province(2108085J12)Center for Advanced Interdisciplinary Science and Biomedicine of IHM(QYPY20220008)Shenzhen Talent Program(KQTD20210811090115021)Guangdong Innovative and Entrepreneurial Research Team Program(2021ZT09Y104)。
文摘Biomolecular condensates or membraneless organelles(MLOs)formed by liquid-liquid phase separation(LLPS)divide intracellular spaces into discrete compartments for specific functions.Dysregulation of LLPS or aberrant phase transition that disturbs the formation or material states of MLOs is closely correlated with neurodegeneration,tumorigenesis,and many other pathological processes.Herein,we summarize the recent progress in development of methods to monitor phase separation and we discuss the biogenesis and function of MLOs formed through phase separation.We then present emerging proof-of-concept examples regarding the disruption of phase separation homeostasis in a diverse array of clinical conditions including neurodegenerative disorders,hearing loss,cancers,and immunological diseases.Finally,we describe the emerging discovery of chemical modulators of phase separation.
