[Objectives]This study aimed to optimize the chelation process for complex microelement iron supplement derived from pig blood by response surface methodology.[Methods]On the basis of single-factor test,p H value,conc...[Objectives]This study aimed to optimize the chelation process for complex microelement iron supplement derived from pig blood by response surface methodology.[Methods]On the basis of single-factor test,p H value,concentration of polypeptide solution and volume ratio of polypeptide solution to FeCl_2 solution were selected as influencing factors with Fe(II)chelation rate as the indicator for Box-Behnken central composite experimental design with three factors and three levels.The effects of three factors on the response value were analyzed by response surface methodology.[Results]The optimized chelation process for complex microelement iron supplement derived from pig blood by response surface methodology was as follows:pH 5.40,polypeptide solution concentration 2.27%,volume ratio of polypeptide solution to FeCl_2 solution 2.16∶1.Under this condition,the predictive Fe(II)chelation rate of iron supplement was 79.37%,while the actual value was 79.41%.[Conclusions]The optimized process may provide new thoughts for the development and utilization of complex microelement iron supplement derived from pig blood.展开更多
m^(6)A methylation is the most frequent modification of mRNA in eukaryotes and plays a crucial role in cancer progression by regulating biological functions.Insulin-like growth factor 2 mRNA-binding proteins(IGF2BP)ar...m^(6)A methylation is the most frequent modification of mRNA in eukaryotes and plays a crucial role in cancer progression by regulating biological functions.Insulin-like growth factor 2 mRNA-binding proteins(IGF2BP)are newly identified m^(6)A‘readers’.They belong to a family of RNA-binding proteins,which bind to the m^(6)A sites on different RNA sequences and stabilize them to promote cancer progression.In this review,we summarize the mechanisms by which different upstream factors regulate IGF2BP in cancer.The current literature analyzed here reveals that the IGF2BP family proteins promote cancer cell proliferation,survival,and chemoresistance,inhibit apoptosis,and are also associated with cancer glycolysis,angiogenesis,and the immune response in the tumor microenvironment.Therefore,with the discovery of their role as‘readers’of m^(6)A and the characteristic re-expression of IGF2BPs in cancers,it is important to elucidate their mechanism of action in the immunosuppressive tumor microenvironment.We also describe in detail the regulatory and interaction network of the IGF2BP family in downstream target RNAs and discuss their potential clinical applications as diagnostic and prognostic markers,as well as recent advances in IGF2BP biology and associated therapeutic value.展开更多
The intrinsic oncogenic mechanisms and properties of the tumor microenvironment(TME)have been extensively investigated.Primary features of the TME include metabolic reprogramming,hypoxia,chronic inflammation,and tumor...The intrinsic oncogenic mechanisms and properties of the tumor microenvironment(TME)have been extensively investigated.Primary features of the TME include metabolic reprogramming,hypoxia,chronic inflammation,and tumor immunosuppression.Previous studies suggest that senescence-associated secretory phenotypes that mediate intercellular information exchange play a role in the dynamic evolution of the TME.Specifically,hypoxic adaptation,metabolic dysregulation,and phenotypic shifts in immune cells regulated by cellular senescence synergistically contribute to the development of an immunosuppressive microenvironment and chronic inflammation,thereby promoting the progression of tumor events.This review provides a comprehensive summary of the processes by which cellular senescence regulates the dynamic evolution of the tumor-adapted TME,with focus on the complex mechanisms underlying the relationship between senescence and changes in the biological functions of tumor cells.The available findings suggest that components of the TME collectively contribute to the progression of tumor events.The potential applications and challenges of targeted cellular senescence-based and combination therapies in clinical settings are further discussed within the context of advancing cellular senescence-related research.展开更多
Prion diseases are fatal neurodegenerative diseases that can cause severe dementia.The misfolding and accumulation of the prion peptide (PrP)_(106–126) is crucial,and this process is closely relevant to biological me...Prion diseases are fatal neurodegenerative diseases that can cause severe dementia.The misfolding and accumulation of the prion peptide (PrP)_(106–126) is crucial,and this process is closely relevant to biological membranes.However,how PrP_(106–126)aggregation is affected by the molecular chirality of phospholipid membrane is unknown.Thus,in this study,a pair of L-and D-aspartic acid (Asp)-modified 1,2-dipalmitoyl-sn–glycero-3-phosphoethanolamine (DPPE) were synthesized to construct chiral liposomes.We discover that L-Asp-DPPE liposomes strongly inhibit the oligomerization and amyloidogenesis of PrP_(106–126),whether acting on monomers or oligomers,which rescues cytotoxicity induced by PrP_(106–126).By comparison,D-Asp-DPPE liposomes inhibit peptide oligomerization only at a high concentration and cannot prevent amyloidogenesis when acting on oligomers,which lead to pronounced cytotoxicity.Apoptosis experiment,dynamic change of intracellular Ca^(2+)(_(i)Ca^(2+)) and Ca^(2+)release from endoplasmic reticulum(ER),reactive oxygen species (ROS) production,adsorption dynamics and affinity tests,and fluorescent imaging clearly disclose that molecular chirality of the liposomes dominates conformational transition of PrP_(106–126)from random coil to β-sheet,binding and adsorption of the monomers and oligomers,and subsequent fibrillation process,resulting in distinct inhibition effect in Ca^(2+)overload and release,ROS production and cell apoptosis.This work is the first to report that interfacial molecular chirality is a potentially crucial influence on the fibrillation process of PrP_(106–126) and its cell responses,whereas the convergence of chiral amino acids and liposomes can be considered potential inhibitors in prion diseases.展开更多
Nature has selected,produced,and evolved numerous molecular architectural motifs over billions of years for particular bio-functions.During this process,molecular self-assembly plays a critically important role.Inspir...Nature has selected,produced,and evolved numerous molecular architectural motifs over billions of years for particular bio-functions.During this process,molecular self-assembly plays a critically important role.Inspired by these delicate assemblies,scientists devote themselves to developing various sophisticated complexes assembled by diverse and numerous structural motifs.By far,most of the examples focus on single-molecule self-assembly or co-assembly between two molecules,seldom works report the co-assembly among three building blocks due to the substantially increased complexity and decreased controllability.Here we report a novel three-component co-assembly among L-glutathione(L-GSH),AgNO_(3),and an aggregation-induced emission luminogen(AIEgen),namely triphenylamine-pyridinium(abbreviated to TPA-Py).TPA-Py,L-GSH,and Ag^(+)co-assemble into numerous long and ordered nanowires with left-handed helices,which show remarkable AIE properties that can be observed by naked eyes.This effect is only detected in this system,the replacement of TPA-Py with other AIEgens,L-GSH with other cysteine derivatives or anions,Ag^(+)with other metal ions,could not lead to the unique AIE effect,which endows this system with high specificity and controllability.This work provides new insight into the design of biomolecule recognition systems and discloses that ternary co-assembly could become a facile route to build sophisticated nanobiomaterials.展开更多
This study focuses on the transient liquid phase(TLP)bonding of DD5 single-crystal superalloy to Cr Co Nibased medium-entropy alloy(MEA)using a BNi-2 filler alloy.The microstructure and mechanical properties of the TL...This study focuses on the transient liquid phase(TLP)bonding of DD5 single-crystal superalloy to Cr Co Nibased medium-entropy alloy(MEA)using a BNi-2 filler alloy.The microstructure and mechanical properties of the TLP-bonded DD5/MEA joint were evaluated,and the microstructural evolution mechanism was investigated.The formation of the isothermal solidification zone(ISZ)depended on the diffusion of the melting-point depressants(Si and B elements)from the liquid filler into the DD5 and MEA substrates,as well as the dissolution of the substrates.Boron diffused along theγchannel of DD5 and reacted to form M_(5)B_(3)boride,herein referred to as the diffusion-affected zone(DAZ I).Similarly,the Cr_(5)B_(3)boride precipitated in the Ni-rich MEA matrix adjacent to the MEA substrate(i.e.,DAZ II).Additionally,a coherent orientation of[0]_(BCY)//[011]_(FCC)and(002)_(BCY)//(200)_(FCC)was detected between M_(5)B_(3)boride with a body-centered tetragonal(BCT)structure and the face-centered cubic(FCC)matrix.The performance of the joint was dominated by the properties of the bonding seam.As the bonding time increased from 20to 80 min,the athermal solidification zone(including eutectic microstructure)was gradually replaced by the ISZ exhibiting excellent plastic deformation capability,and the shear strength of the joint was improved.The maximum shear strength(752 MPa)was achieved when the eutectic-free joint was bonded at 1050℃ for 80 min.The fracture morphology revealed a mixture mode,indicating the initiation of cracks in the DAZ II,mainly propagating in the ISZ,and passing through the DAZ I.展开更多
Excited-state hydrogen bond strongly affects the intramolecular charge conversion process,which is very suitable for the design and development of high-performance fluorescent probes.However,as one of the most common ...Excited-state hydrogen bond strongly affects the intramolecular charge conversion process,which is very suitable for the design and development of high-performance fluorescent probes.However,as one of the most common solvents or additives used in sensing,the role of dimethyl sulfoxide(DMSO)in the system of the excited-state hydrogen bond is seldom explored.As the goal of this research,we investigated the sensing mechanism of a C0RM3-green fluorescent probe system for carbon monoxide releasing molecule(CORM-3)detection and tracking in vivo,through quantum chemistry calculations based on density-functional-theory(DFT)/time-dependent density-functional-theory(TDDFT)methods.Based on the analysis of the solvent effect of DMSO by the reduced density gradient function and IR spectroscopy,we provided a new strategy to explain the fluorescence mechanism.Subsequently,we verified the result through the potential energy curve of Phthalimide(PTI,the reduced product of C0RM3-green).The excited-state hydrogen bond between PTI and DMSO promotes radiation transition and leads to obvious difference in the photophysical properties of PTI and PTI-DMSO.展开更多
基金Supported by Youth Fund of National Natural Science Foundation of China(31801673)Talent Development Fund of Anhui Academy of Agricultural Sciences(17F1205)+2 种基金Youth Innovation Fund of President of Anhui Academy of Agricultural Sciences(17B1220)Team Building Project of Anhui Academy of Agricultural Sciences(18C1225)Youth Fund of Natural Science Foundation of Anhui Province(1808085QC94)
文摘[Objectives]This study aimed to optimize the chelation process for complex microelement iron supplement derived from pig blood by response surface methodology.[Methods]On the basis of single-factor test,p H value,concentration of polypeptide solution and volume ratio of polypeptide solution to FeCl_2 solution were selected as influencing factors with Fe(II)chelation rate as the indicator for Box-Behnken central composite experimental design with three factors and three levels.The effects of three factors on the response value were analyzed by response surface methodology.[Results]The optimized chelation process for complex microelement iron supplement derived from pig blood by response surface methodology was as follows:pH 5.40,polypeptide solution concentration 2.27%,volume ratio of polypeptide solution to FeCl_2 solution 2.16∶1.Under this condition,the predictive Fe(II)chelation rate of iron supplement was 79.37%,while the actual value was 79.41%.[Conclusions]The optimized process may provide new thoughts for the development and utilization of complex microelement iron supplement derived from pig blood.
基金supported by grants from the Liaoning Nature Science Foundationof China(No.2022JH2/101300042)The National Natural Science Foundation of China(No.82173194,81672877)+1 种基金the Key Research Project of Liaoning Provincial Department of Education of China(No.ZD2020004)2018 Youth Backbone Support Program of China Medical University(No.QGZ2018063).
文摘m^(6)A methylation is the most frequent modification of mRNA in eukaryotes and plays a crucial role in cancer progression by regulating biological functions.Insulin-like growth factor 2 mRNA-binding proteins(IGF2BP)are newly identified m^(6)A‘readers’.They belong to a family of RNA-binding proteins,which bind to the m^(6)A sites on different RNA sequences and stabilize them to promote cancer progression.In this review,we summarize the mechanisms by which different upstream factors regulate IGF2BP in cancer.The current literature analyzed here reveals that the IGF2BP family proteins promote cancer cell proliferation,survival,and chemoresistance,inhibit apoptosis,and are also associated with cancer glycolysis,angiogenesis,and the immune response in the tumor microenvironment.Therefore,with the discovery of their role as‘readers’of m^(6)A and the characteristic re-expression of IGF2BPs in cancers,it is important to elucidate their mechanism of action in the immunosuppressive tumor microenvironment.We also describe in detail the regulatory and interaction network of the IGF2BP family in downstream target RNAs and discuss their potential clinical applications as diagnostic and prognostic markers,as well as recent advances in IGF2BP biology and associated therapeutic value.
基金Grants from the Liaoning Nature Science Foundation of China,Grant/Award Number:2022JH2/101300042National Natural Science Foundation of China,Grant/Award Numbers:81672877,82173194。
文摘The intrinsic oncogenic mechanisms and properties of the tumor microenvironment(TME)have been extensively investigated.Primary features of the TME include metabolic reprogramming,hypoxia,chronic inflammation,and tumor immunosuppression.Previous studies suggest that senescence-associated secretory phenotypes that mediate intercellular information exchange play a role in the dynamic evolution of the TME.Specifically,hypoxic adaptation,metabolic dysregulation,and phenotypic shifts in immune cells regulated by cellular senescence synergistically contribute to the development of an immunosuppressive microenvironment and chronic inflammation,thereby promoting the progression of tumor events.This review provides a comprehensive summary of the processes by which cellular senescence regulates the dynamic evolution of the tumor-adapted TME,with focus on the complex mechanisms underlying the relationship between senescence and changes in the biological functions of tumor cells.The available findings suggest that components of the TME collectively contribute to the progression of tumor events.The potential applications and challenges of targeted cellular senescence-based and combination therapies in clinical settings are further discussed within the context of advancing cellular senescence-related research.
基金supported by the National Natural Science Foundation of China (Nos. 21775116 and 21922411)DICP Innovation Funding (Nos. DICP-RC201801 and DICP I202008)Liao Ning Revitalization Talents Program (No. XLYC1802109)。
文摘Prion diseases are fatal neurodegenerative diseases that can cause severe dementia.The misfolding and accumulation of the prion peptide (PrP)_(106–126) is crucial,and this process is closely relevant to biological membranes.However,how PrP_(106–126)aggregation is affected by the molecular chirality of phospholipid membrane is unknown.Thus,in this study,a pair of L-and D-aspartic acid (Asp)-modified 1,2-dipalmitoyl-sn–glycero-3-phosphoethanolamine (DPPE) were synthesized to construct chiral liposomes.We discover that L-Asp-DPPE liposomes strongly inhibit the oligomerization and amyloidogenesis of PrP_(106–126),whether acting on monomers or oligomers,which rescues cytotoxicity induced by PrP_(106–126).By comparison,D-Asp-DPPE liposomes inhibit peptide oligomerization only at a high concentration and cannot prevent amyloidogenesis when acting on oligomers,which lead to pronounced cytotoxicity.Apoptosis experiment,dynamic change of intracellular Ca^(2+)(_(i)Ca^(2+)) and Ca^(2+)release from endoplasmic reticulum(ER),reactive oxygen species (ROS) production,adsorption dynamics and affinity tests,and fluorescent imaging clearly disclose that molecular chirality of the liposomes dominates conformational transition of PrP_(106–126)from random coil to β-sheet,binding and adsorption of the monomers and oligomers,and subsequent fibrillation process,resulting in distinct inhibition effect in Ca^(2+)overload and release,ROS production and cell apoptosis.This work is the first to report that interfacial molecular chirality is a potentially crucial influence on the fibrillation process of PrP_(106–126) and its cell responses,whereas the convergence of chiral amino acids and liposomes can be considered potential inhibitors in prion diseases.
基金National Natural Science Foundation of China,Grant/Award Numbers:21501055,21922411,22174138DICP Innovation Funding,Grant/Award Numbers:RC201801,I202008Dalian Outstanding Young Scientific Talent,Grant/Award Number:2020RJ01。
文摘Nature has selected,produced,and evolved numerous molecular architectural motifs over billions of years for particular bio-functions.During this process,molecular self-assembly plays a critically important role.Inspired by these delicate assemblies,scientists devote themselves to developing various sophisticated complexes assembled by diverse and numerous structural motifs.By far,most of the examples focus on single-molecule self-assembly or co-assembly between two molecules,seldom works report the co-assembly among three building blocks due to the substantially increased complexity and decreased controllability.Here we report a novel three-component co-assembly among L-glutathione(L-GSH),AgNO_(3),and an aggregation-induced emission luminogen(AIEgen),namely triphenylamine-pyridinium(abbreviated to TPA-Py).TPA-Py,L-GSH,and Ag^(+)co-assemble into numerous long and ordered nanowires with left-handed helices,which show remarkable AIE properties that can be observed by naked eyes.This effect is only detected in this system,the replacement of TPA-Py with other AIEgens,L-GSH with other cysteine derivatives or anions,Ag^(+)with other metal ions,could not lead to the unique AIE effect,which endows this system with high specificity and controllability.This work provides new insight into the design of biomolecule recognition systems and discloses that ternary co-assembly could become a facile route to build sophisticated nanobiomaterials.
基金supported by the fund of Natural Science Basic Research Program of Shaanxi(Grant No.2020JQ-190)National Natural Science Foundations of China(Grant Nos.51975480,52075449,and U1737205)China Postdoctoral Science Foundation funded project(Grant Nos.2019TQ0263,and 2020M683560)。
文摘This study focuses on the transient liquid phase(TLP)bonding of DD5 single-crystal superalloy to Cr Co Nibased medium-entropy alloy(MEA)using a BNi-2 filler alloy.The microstructure and mechanical properties of the TLP-bonded DD5/MEA joint were evaluated,and the microstructural evolution mechanism was investigated.The formation of the isothermal solidification zone(ISZ)depended on the diffusion of the melting-point depressants(Si and B elements)from the liquid filler into the DD5 and MEA substrates,as well as the dissolution of the substrates.Boron diffused along theγchannel of DD5 and reacted to form M_(5)B_(3)boride,herein referred to as the diffusion-affected zone(DAZ I).Similarly,the Cr_(5)B_(3)boride precipitated in the Ni-rich MEA matrix adjacent to the MEA substrate(i.e.,DAZ II).Additionally,a coherent orientation of[0]_(BCY)//[011]_(FCC)and(002)_(BCY)//(200)_(FCC)was detected between M_(5)B_(3)boride with a body-centered tetragonal(BCT)structure and the face-centered cubic(FCC)matrix.The performance of the joint was dominated by the properties of the bonding seam.As the bonding time increased from 20to 80 min,the athermal solidification zone(including eutectic microstructure)was gradually replaced by the ISZ exhibiting excellent plastic deformation capability,and the shear strength of the joint was improved.The maximum shear strength(752 MPa)was achieved when the eutectic-free joint was bonded at 1050℃ for 80 min.The fracture morphology revealed a mixture mode,indicating the initiation of cracks in the DAZ II,mainly propagating in the ISZ,and passing through the DAZ I.
基金the National Natural Science Foundation of China(Nos.21775116 and 21922411)DICP Innovation Funding(No.DICP-RC201801)the Liaoning Revitalization Talents Program(No.XLVC1802109).
文摘Excited-state hydrogen bond strongly affects the intramolecular charge conversion process,which is very suitable for the design and development of high-performance fluorescent probes.However,as one of the most common solvents or additives used in sensing,the role of dimethyl sulfoxide(DMSO)in the system of the excited-state hydrogen bond is seldom explored.As the goal of this research,we investigated the sensing mechanism of a C0RM3-green fluorescent probe system for carbon monoxide releasing molecule(CORM-3)detection and tracking in vivo,through quantum chemistry calculations based on density-functional-theory(DFT)/time-dependent density-functional-theory(TDDFT)methods.Based on the analysis of the solvent effect of DMSO by the reduced density gradient function and IR spectroscopy,we provided a new strategy to explain the fluorescence mechanism.Subsequently,we verified the result through the potential energy curve of Phthalimide(PTI,the reduced product of C0RM3-green).The excited-state hydrogen bond between PTI and DMSO promotes radiation transition and leads to obvious difference in the photophysical properties of PTI and PTI-DMSO.
