Traditional electrospray ionization tandem mass spectrometry(ESI-MS^(n))has been a powerful tool in diverse research areas,however,it faces great limitations in the study of protein-small molecule interactions.In this...Traditional electrospray ionization tandem mass spectrometry(ESI-MS^(n))has been a powerful tool in diverse research areas,however,it faces great limitations in the study of protein-small molecule interactions.In this article,the state-of-the-art temperature-controlled electrospray ionization tandem mass spectrometry(TC-ESI-MS^(n))is applied to investigate interactions between ubiquitin and two flavonol molecules,respectively.The combination of collision-induced dissociation(CID)and MS solution-melting experiments facilitates the understanding of flavonol-protein interactions in a new dimension across varying temperature ranges.While structural changes of proteins disturbed by small molecules are unseen in ESI-MS^(n),TC-ESI-MS^(n)allows a simultaneous assessment of the stability of the complex in both gas and liquid phases under various temperature conditions,meanwhile investigating the impact on the protein’s structure and tracking changes in thermodynamic data,and the characteristics of structural intermediates.展开更多
OBJECTIVE:To explore if Hewei Jiangni granule(和胃降逆颗粒,HWJNG)could regulate esophageal hypersensitivity via stromal interaction molecule 1(STIM1)/transient receptor potential vanilloid subfamily member 1(TRPV1)pat...OBJECTIVE:To explore if Hewei Jiangni granule(和胃降逆颗粒,HWJNG)could regulate esophageal hypersensitivity via stromal interaction molecule 1(STIM1)/transient receptor potential vanilloid subfamily member 1(TRPV1)pathway.METHODS:Qualitative analysis of HWJNG was analysis by high performance of liquid and gas chromatography.In vivo,animal model of non-erosive reflux disease(NERD)was established by fructose intake and restraint stress.HWJNG and Omeprazole were administered by gavage to the drug intervention group.Reflux and visceral hypersensitivity were analyzed by pathological changes,PH value test,mechanical paw withdrawal threshold,thermal withdrawal latency and mast cells(MCs)degranulation.In vitro,substance P(SP)-induced P815 cells and dorsal root ganglion(DRG)cells were cocultured.Expression in both mice and cells of STIM1,TRPV1,and esophageal visceral hypersensitivity-related gastrointestinal neurochemicals were validated by enzyme linked immunosorbent assays,quantitative realtime polymerase chain reaction(qRT-PCR)and Western blot.Moreover,overexpression and small interfering RNA against STIM1 were utilized to verify of the role of HWJNG in DRG cells.RESULTS:HWJNG significantly suppressed intercellular space widening,injury of mitochondrial,MCs degranulation,mechanical allodynia and heat neuropathic sensory and increased pH value of esophageal mucosa in NERD mice.HWJNG inhibited expression of visceral hypersensitivityrelated gastrointestinal neurochemicals in esophageal mucosa and activated P815 cells,and expression of the STIM1,TRPV1 and related neurotransmitters in DRG and DRG cells.STIM1 siRNA and HWJNG both reduced P815 cells adhesion to DRGs cells and Ca2+flow into the cytoplasmic space of DRG cells.Furthermore,HWJNG could reversed STIM1 overexpression induced upregulation of TRPV1.CONCLUSION:HWJNG suppressed intercellular space widening in NERD mice,stabilized MCs and restored neuronal hyperexcitability by regulating visceral hypersensitivity via STIM1/TRPV1 pathway.展开更多
Molecular recognition of bioreceptors and enzymes relies on orthogonal interactions with small molecules within their cavity. To date, Chinese scientists have developed three types of strategies for introducing active...Molecular recognition of bioreceptors and enzymes relies on orthogonal interactions with small molecules within their cavity. To date, Chinese scientists have developed three types of strategies for introducing active sites inside the cavity of macrocyclic arenes to better mimic molecular recognition of bioreceptors and enzymes.The editorial aims to enlighten scientists in this field when they develop novel macrocycles for molecular recognition, supramolecular assembly, and applications.展开更多
Multi-agent model is well-known to suit design of complex systems. This paradigm allows describing autonomous entities to interact together directly or through their environment. It is specially adapted to design 3D s...Multi-agent model is well-known to suit design of complex systems. This paradigm allows describing autonomous entities to interact together directly or through their environment. It is specially adapted to design 3D simulations taking into account spatial constraints on agents. In this work, we have designed a multi-agent model which adds a feature to the classical representation of agent: a body, encapsulating a physical model of the agent. We have applied this model to lipids and proteins belonging to the inner mitochondrial membrane, a biological membrane. Information provided by atomic structures is available through international databases and has been used to design a shape-based grain model for the agent body. We selected a model with three grains per molecule in which each grain is characterized by a type determining how they interact together and consequently the agent behaviors. Lipids and two kinds of protein structures have been described within this model allowing us to simulate their organization in membranes.展开更多
A novel capillary electrophoresis method coupled with on-line microdialysis using an attachable electrode has been developed to study the interaction of macromolecule with small molecule. The binding constants of bovi...A novel capillary electrophoresis method coupled with on-line microdialysis using an attachable electrode has been developed to study the interaction of macromolecule with small molecule. The binding constants of bovine serum album (BSA) with D,L-tryptophan (Trp), sulfamethoxazole (SMZ) with trypsin and chymotrypsin were determined. These values are 2.3 x 10(4)L/mol for BSA-L-Trp; 1.77 x 10(3) L/mol for BSA-D-Trp in pH 7.4, 50 mmol/ L phosphate; 1.4 x 10(4) L/mol for SMZ- trypsin and 6.0 x 10(3) L/mol for SMZ-chymotrypsin in pH 6.5, 25 mmol/L Tris buffer. The proposed method has merits of speed, low sample consumption and readily available to be performed in desired physiological conditions.展开更多
The dynamics of the scattering processes of diatomic molecules from metal surfaces has been studied with different theoretical approaches. Modified LEPS (London-Eyring-Polanyi-Sato) potential surfaces for several diat...The dynamics of the scattering processes of diatomic molecules from metal surfaces has been studied with different theoretical approaches. Modified LEPS (London-Eyring-Polanyi-Sato) potential surfaces for several diatomie molecule-surface systems have been constructed and examined for the dynamic study. The surfaces are treated as rigid but corrugated. The potential parameters are adjusted to produce reliable potential hypersurfaces. Molecular dissociation, diffraction, adsorption and consequent desorption in the scattering processes have been observed through quasiclassieal trajectory calculations. The significance of the effective corrugation of the potential surfaces has been evaluated in calculating the dissociation and adsorption probabilities. Vibration-rotation-translation energy transfer in the inelastic scattering is investigated to understand the mechanism of selective adsorptions mediated through vibrational or rotational degrees of freedom. We have carried out quantum mechanical calculations to obtain the rotational and vibrational transition probabilities. Relative importance of rotational and vibrational transitions for each adsorbed state with respect to incidence energy has been carefully examined to determine the dominant factor which causes the adsorbed state. The results show that vibration mediation is an essential factor to the selective adsorption especially in the ease of higher incidence energies.展开更多
Two possible complexes formed by the interaction of CH_3OH and H_2CO,one hydrogen-bonded (Ⅰ)and one donor-acceptor complex(Ⅱ),have been reported in the previous paper.Based on the ab initio 6-31G basis set calculati...Two possible complexes formed by the interaction of CH_3OH and H_2CO,one hydrogen-bonded (Ⅰ)and one donor-acceptor complex(Ⅱ),have been reported in the previous paper.Based on the ab initio 6-31G basis set calculations,the properties of the charge density for the complexeshave been analyzed using the theory of atoms in molecules.The nature of the complex formation has been discussed in terms of the properties of the charge density distributions.展开更多
The activation of Ca2+ entry through store-operated channels by agonists that deplete Ca2+ from the endoplasmic reticulum (ER) is a ubiquitous signaling mechanism, the molecular basis of which has remained elusive for...The activation of Ca2+ entry through store-operated channels by agonists that deplete Ca2+ from the endoplasmic reticulum (ER) is a ubiquitous signaling mechanism, the molecular basis of which has remained elusive for the past two decades. Store-operated Ca2+-release-activated Ca2+ (CRAC) channels constitute the sole pathway for Ca2+ entry following antigen-receptor engagement. In a set of breakthrough studies over the past two years, stromal interaction molecule 1 (STIM1, the ER Ca2+ sensor) and Orai1 (a pore-forming subunit of the CRAC channel) have been identified. Here we review these recent studies and the insights they provide into the mechanism of store-operated Ca2+ channels (SOCCs).展开更多
Hepatitis B virus X(HBx)protein plays a pivotal role in the development of hepatitis B virus(HBV)-associated hepatocellular carcinoma.Although regulation of cytosolic calcium is essential for HBV replication and is me...Hepatitis B virus X(HBx)protein plays a pivotal role in the development of hepatitis B virus(HBV)-associated hepatocellular carcinoma.Although regulation of cytosolic calcium is essential for HBV replication and is mediated by HBx protein,the mechanism of HBx protein regulating intracellular calcium level remains poorly understood.The present study examined whether HBx protein elevated the intracellular calcium through interacting with storeoperated calcium entry(SOCE)components,Orai1 and stromal interaction molecule 1,and then identified the targets of HBx protein,with an attempt to understand the mechanism of HBx protein upsetting intracellular calcium homeostasis.By employing co-immunoprecipitation and GST-pull-down assay,we found that Orai1 protein interacted with HBx protein,and the C-terminus of Orai1 was implicated in the interaction.Confocal microscopy also revealed that HBx protein could co-localize with full-length Orai1 protein in HEK293 cells.Moreover,live cell calcium imaging exhibited that HBx protein elevated intracellular calcium,possibly by binding to SOCE components.Our results suggest that HBx protein binds to STIM1-Orai1 complexes to positively regulate the activity of plasma membrane store-operated calcium channels.展开更多
During drought,plant functions at multi-levels(i.e.,tissue,.cellular and molecular)are adjustable with the change of water condition,which is known as drought resistance.Various biological,chemical and physical mechan...During drought,plant functions at multi-levels(i.e.,tissue,.cellular and molecular)are adjustable with the change of water condition,which is known as drought resistance.Various biological,chemical and physical mechanisms have been found in plant drought resistance,among which the role of physical cues(especially mechanics)has attracted significantly increasing attention.Recent studies have shown that mechanics is one of the fundamental factors that control the responses and self-adaptation from tissue to molecular levels in plant when the external conditions changes.In the review,we examine how the factor of mechanics acts on the multi-level plant functions under drought stress,including water transport,tissue deformation,cell growth,cell movements,molecules interaction and signal pathway.展开更多
The interaction between a probing tip and an adsorbed molecule can significantly impact the molecular chemical structure and even induce its motion on the surface.In this study,the tip-induced bond weakening,tilting,a...The interaction between a probing tip and an adsorbed molecule can significantly impact the molecular chemical structure and even induce its motion on the surface.In this study,the tip-induced bond weakening,tilting,and hopping processes of a single molecule were investigated by sub-nanometre resolved tip-enhanced Raman spectroscopy(TERS).We used single carbon monoxide(CO)molecules adsorbed on the Cu(100)surface as a model system for the investigation.The vibrational frequency of the C−O stretching mode is always redshifted as the tip approaches,revealing the weakening of the C−O bond owing to tip−molecule interactions.Further analyses of both the vibrational Stark effect and TERS imaging patterns suggest a delicate tilting phenomenon of the adsorbed CO molecule on Cu(100),which eventually leads to lateral hopping of the molecule.While a tilting orientation is found toward the hollow site along the[110]direction of the Cu(100)surface,the hopping event is more likely to proceed via the bridge site to the nearest Cu neighbour along the[100]or[010]direction.Our results provide deep insights into the microscopic mechanisms of tip−molecule interactions and tip-induced molecular motions on surfaces at the single-bond level.展开更多
Nine low-lying electronic states of the AsP molecule, including ∑＋, ∏, and A symmetries with singlet, triplet, and quintet spin multiplicities, are studied using multi-reference configuration interaction method. Th...Nine low-lying electronic states of the AsP molecule, including ∑＋, ∏, and A symmetries with singlet, triplet, and quintet spin multiplicities, are studied using multi-reference configuration interaction method. The potential energy curves and the spectroscopic constants of these nine states are determined, and compared with the experimental observed data as well as other theoretical works available at present. Three quintet states are reported for the first time. Furthermore, the analytical potential energy functions of these states are fitted using Murrell-Sorbie function and least sauare fitting method.展开更多
基金supports by the National Natural Science Foundation of China(No.22174037)the Joint Funds of the Hunan Provincial Natural Science Foundation of China(No.2023JJ50255)+1 种基金Changsha Science and Technology Project(No.Z202269490128)National Key Research and Development Program of China(No.2023YFF0613400)are appreciated.
文摘Traditional electrospray ionization tandem mass spectrometry(ESI-MS^(n))has been a powerful tool in diverse research areas,however,it faces great limitations in the study of protein-small molecule interactions.In this article,the state-of-the-art temperature-controlled electrospray ionization tandem mass spectrometry(TC-ESI-MS^(n))is applied to investigate interactions between ubiquitin and two flavonol molecules,respectively.The combination of collision-induced dissociation(CID)and MS solution-melting experiments facilitates the understanding of flavonol-protein interactions in a new dimension across varying temperature ranges.While structural changes of proteins disturbed by small molecules are unseen in ESI-MS^(n),TC-ESI-MS^(n)allows a simultaneous assessment of the stability of the complex in both gas and liquid phases under various temperature conditions,meanwhile investigating the impact on the protein’s structure and tracking changes in thermodynamic data,and the characteristics of structural intermediates.
基金National Natural Science Foundation of China:Study on the Molecular Mechanism of the Regulation of Crypt Goblet Cell Pyroptosis and Exocytosis to Repair Ulcerative Colitis Mucus Barrier by the Method of Clearing and Opening the Xuanfu from the Perspective of"Xuanfu-Crypt"(No.82305143),and National Natural Science Foundation of China:Exploring the Molecular Mechanism of"Hewei Jiangni Fang"Intervention in Non-erosive Reflux Disease Esophageal Hypersensitivity from the Perspective of Mas-related Gene X2/Stromal Interaction Molecule 1/Cell Adhesion Molecule 1 Pathway Regulation of Mast Cell/Dorsal Root Ganglion Communication based on the"Xinkai-Kujiang"Method(No.82374401)。
文摘OBJECTIVE:To explore if Hewei Jiangni granule(和胃降逆颗粒,HWJNG)could regulate esophageal hypersensitivity via stromal interaction molecule 1(STIM1)/transient receptor potential vanilloid subfamily member 1(TRPV1)pathway.METHODS:Qualitative analysis of HWJNG was analysis by high performance of liquid and gas chromatography.In vivo,animal model of non-erosive reflux disease(NERD)was established by fructose intake and restraint stress.HWJNG and Omeprazole were administered by gavage to the drug intervention group.Reflux and visceral hypersensitivity were analyzed by pathological changes,PH value test,mechanical paw withdrawal threshold,thermal withdrawal latency and mast cells(MCs)degranulation.In vitro,substance P(SP)-induced P815 cells and dorsal root ganglion(DRG)cells were cocultured.Expression in both mice and cells of STIM1,TRPV1,and esophageal visceral hypersensitivity-related gastrointestinal neurochemicals were validated by enzyme linked immunosorbent assays,quantitative realtime polymerase chain reaction(qRT-PCR)and Western blot.Moreover,overexpression and small interfering RNA against STIM1 were utilized to verify of the role of HWJNG in DRG cells.RESULTS:HWJNG significantly suppressed intercellular space widening,injury of mitochondrial,MCs degranulation,mechanical allodynia and heat neuropathic sensory and increased pH value of esophageal mucosa in NERD mice.HWJNG inhibited expression of visceral hypersensitivityrelated gastrointestinal neurochemicals in esophageal mucosa and activated P815 cells,and expression of the STIM1,TRPV1 and related neurotransmitters in DRG and DRG cells.STIM1 siRNA and HWJNG both reduced P815 cells adhesion to DRGs cells and Ca2+flow into the cytoplasmic space of DRG cells.Furthermore,HWJNG could reversed STIM1 overexpression induced upregulation of TRPV1.CONCLUSION:HWJNG suppressed intercellular space widening in NERD mice,stabilized MCs and restored neuronal hyperexcitability by regulating visceral hypersensitivity via STIM1/TRPV1 pathway.
文摘Molecular recognition of bioreceptors and enzymes relies on orthogonal interactions with small molecules within their cavity. To date, Chinese scientists have developed three types of strategies for introducing active sites inside the cavity of macrocyclic arenes to better mimic molecular recognition of bioreceptors and enzymes.The editorial aims to enlighten scientists in this field when they develop novel macrocycles for molecular recognition, supramolecular assembly, and applications.
文摘Multi-agent model is well-known to suit design of complex systems. This paradigm allows describing autonomous entities to interact together directly or through their environment. It is specially adapted to design 3D simulations taking into account spatial constraints on agents. In this work, we have designed a multi-agent model which adds a feature to the classical representation of agent: a body, encapsulating a physical model of the agent. We have applied this model to lipids and proteins belonging to the inner mitochondrial membrane, a biological membrane. Information provided by atomic structures is available through international databases and has been used to design a shape-based grain model for the agent body. We selected a model with three grains per molecule in which each grain is characterized by a type determining how they interact together and consequently the agent behaviors. Lipids and two kinds of protein structures have been described within this model allowing us to simulate their organization in membranes.
文摘A novel capillary electrophoresis method coupled with on-line microdialysis using an attachable electrode has been developed to study the interaction of macromolecule with small molecule. The binding constants of bovine serum album (BSA) with D,L-tryptophan (Trp), sulfamethoxazole (SMZ) with trypsin and chymotrypsin were determined. These values are 2.3 x 10(4)L/mol for BSA-L-Trp; 1.77 x 10(3) L/mol for BSA-D-Trp in pH 7.4, 50 mmol/ L phosphate; 1.4 x 10(4) L/mol for SMZ- trypsin and 6.0 x 10(3) L/mol for SMZ-chymotrypsin in pH 6.5, 25 mmol/L Tris buffer. The proposed method has merits of speed, low sample consumption and readily available to be performed in desired physiological conditions.
基金The projcct supportcd by National Natural Science Foundation of China
文摘The dynamics of the scattering processes of diatomic molecules from metal surfaces has been studied with different theoretical approaches. Modified LEPS (London-Eyring-Polanyi-Sato) potential surfaces for several diatomie molecule-surface systems have been constructed and examined for the dynamic study. The surfaces are treated as rigid but corrugated. The potential parameters are adjusted to produce reliable potential hypersurfaces. Molecular dissociation, diffraction, adsorption and consequent desorption in the scattering processes have been observed through quasiclassieal trajectory calculations. The significance of the effective corrugation of the potential surfaces has been evaluated in calculating the dissociation and adsorption probabilities. Vibration-rotation-translation energy transfer in the inelastic scattering is investigated to understand the mechanism of selective adsorptions mediated through vibrational or rotational degrees of freedom. We have carried out quantum mechanical calculations to obtain the rotational and vibrational transition probabilities. Relative importance of rotational and vibrational transitions for each adsorbed state with respect to incidence energy has been carefully examined to determine the dominant factor which causes the adsorbed state. The results show that vibration mediation is an essential factor to the selective adsorption especially in the ease of higher incidence energies.
基金Projeet supported by the National Natural Science Foundation of China.
文摘Two possible complexes formed by the interaction of CH_3OH and H_2CO,one hydrogen-bonded (Ⅰ)and one donor-acceptor complex(Ⅱ),have been reported in the previous paper.Based on the ab initio 6-31G basis set calculations,the properties of the charge density for the complexeshave been analyzed using the theory of atoms in molecules.The nature of the complex formation has been discussed in terms of the properties of the charge density distributions.
文摘The activation of Ca2+ entry through store-operated channels by agonists that deplete Ca2+ from the endoplasmic reticulum (ER) is a ubiquitous signaling mechanism, the molecular basis of which has remained elusive for the past two decades. Store-operated Ca2+-release-activated Ca2+ (CRAC) channels constitute the sole pathway for Ca2+ entry following antigen-receptor engagement. In a set of breakthrough studies over the past two years, stromal interaction molecule 1 (STIM1, the ER Ca2+ sensor) and Orai1 (a pore-forming subunit of the CRAC channel) have been identified. Here we review these recent studies and the insights they provide into the mechanism of store-operated Ca2+ channels (SOCCs).
基金supported by grants from the National Natural Science Foundation of China(No.81001063)the Fundamental Research Funds for the Central Universities(No.2015QN150)
文摘Hepatitis B virus X(HBx)protein plays a pivotal role in the development of hepatitis B virus(HBV)-associated hepatocellular carcinoma.Although regulation of cytosolic calcium is essential for HBV replication and is mediated by HBx protein,the mechanism of HBx protein regulating intracellular calcium level remains poorly understood.The present study examined whether HBx protein elevated the intracellular calcium through interacting with storeoperated calcium entry(SOCE)components,Orai1 and stromal interaction molecule 1,and then identified the targets of HBx protein,with an attempt to understand the mechanism of HBx protein upsetting intracellular calcium homeostasis.By employing co-immunoprecipitation and GST-pull-down assay,we found that Orai1 protein interacted with HBx protein,and the C-terminus of Orai1 was implicated in the interaction.Confocal microscopy also revealed that HBx protein could co-localize with full-length Orai1 protein in HEK293 cells.Moreover,live cell calcium imaging exhibited that HBx protein elevated intracellular calcium,possibly by binding to SOCE components.Our results suggest that HBx protein binds to STIM1-Orai1 complexes to positively regulate the activity of plasma membrane store-operated calcium channels.
基金the National Natural Science Foundation of China(Grants 11532009,11972280,11972185,11902155,and 11902245)the Natural Science Foundation of Jiangsu Province(Grant BK20190382)+3 种基金the foundation of"Jiangsu Provincial Key Laboratory of Bionic Functional Materials"the Foundation for the Priority Academic Program Development of Jiangsu Higher Education Institutionsthe Open Fund of the State Key Laboratory of MechanicsControl of Mechanical Structures of China(Grants MCMS-I-0219K01 and MCMS-E-0219K02).
文摘During drought,plant functions at multi-levels(i.e.,tissue,.cellular and molecular)are adjustable with the change of water condition,which is known as drought resistance.Various biological,chemical and physical mechanisms have been found in plant drought resistance,among which the role of physical cues(especially mechanics)has attracted significantly increasing attention.Recent studies have shown that mechanics is one of the fundamental factors that control the responses and self-adaptation from tissue to molecular levels in plant when the external conditions changes.In the review,we examine how the factor of mechanics acts on the multi-level plant functions under drought stress,including water transport,tissue deformation,cell growth,cell movements,molecules interaction and signal pathway.
基金supported by the National Key R&D Program of China(Grant Nos.2021YFA1500500 and 2016YFA0200600)National Natural Science Foundation of China(Grant No.21790352)+2 种基金Strategic Priority Research Program of the Chinese Academy of Sciences(Grant No.XDB36000000)the Anhui Initiative in Quantum Information Technologies(Grant No.AHY090000)support from the China National Postdoctoral Program for Innovative Talents(No.BX2021282).
文摘The interaction between a probing tip and an adsorbed molecule can significantly impact the molecular chemical structure and even induce its motion on the surface.In this study,the tip-induced bond weakening,tilting,and hopping processes of a single molecule were investigated by sub-nanometre resolved tip-enhanced Raman spectroscopy(TERS).We used single carbon monoxide(CO)molecules adsorbed on the Cu(100)surface as a model system for the investigation.The vibrational frequency of the C−O stretching mode is always redshifted as the tip approaches,revealing the weakening of the C−O bond owing to tip−molecule interactions.Further analyses of both the vibrational Stark effect and TERS imaging patterns suggest a delicate tilting phenomenon of the adsorbed CO molecule on Cu(100),which eventually leads to lateral hopping of the molecule.While a tilting orientation is found toward the hollow site along the[110]direction of the Cu(100)surface,the hopping event is more likely to proceed via the bridge site to the nearest Cu neighbour along the[100]or[010]direction.Our results provide deep insights into the microscopic mechanisms of tip−molecule interactions and tip-induced molecular motions on surfaces at the single-bond level.
基金the National Natural Sci-ence Foundation of China under Grant No.10674114.
文摘Nine low-lying electronic states of the AsP molecule, including ∑＋, ∏, and A symmetries with singlet, triplet, and quintet spin multiplicities, are studied using multi-reference configuration interaction method. The potential energy curves and the spectroscopic constants of these nine states are determined, and compared with the experimental observed data as well as other theoretical works available at present. Three quintet states are reported for the first time. Furthermore, the analytical potential energy functions of these states are fitted using Murrell-Sorbie function and least sauare fitting method.
