The treatment of fungi with DNA methyltransferase(DNMT)and/or histone deacetylase(HDAC)inhibitors is a promising way to activate secondary metabolite biosynthetic pathways that are dormant under normal conditions.In t...The treatment of fungi with DNA methyltransferase(DNMT)and/or histone deacetylase(HDAC)inhibitors is a promising way to activate secondary metabolite biosynthetic pathways that are dormant under normal conditions.In this study,we included an HDAC inhibitor,suberoylanilide hydroxamic acid(SBHA),in the culture medium of endophytic fungi isolated from the medicinal plant Datura stramonium L.The production of two compounds was induced in the culture supplemented with SBHA,and their structures were determined to be the fusaric acid derivatives 5-butyl-6-oxo-1,6-dihydropyridine-2-carboxylic acid and 5-(but-9-enyl)-6-oxo-1,6-dihydropyridine-2-carboxylic acid.The result confirmed that the use of chemical epigenetic modifiers is an effective technique for promoting the expression of silent biosynthetic pathways to produce unique secondary metabolites.展开更多
The recent discovery of cancer cell plasticity,i.e.their ability to reprogram into cancer stem cells(CSCs)either naturally or under chemotherapy and/or radiotherapy,has changed,once again,the way we consider cancer tr...The recent discovery of cancer cell plasticity,i.e.their ability to reprogram into cancer stem cells(CSCs)either naturally or under chemotherapy and/or radiotherapy,has changed,once again,the way we consider cancer treatment.If cancer stemness is a reversible epigenetic state rather than a genetic identity,opportunities will arise for therapeutic strategies that remodel epigenetic landscapes of CSCs.However,the systematic use of DNA methyltransferase and histone deacetylase inhibitors,alone or in combination,in advanced solid tumors including colorectal cancers,regardless of their molecular subtypes,does not seem to be the best strategy.In this review,we first summarize the knowledge researchers have gathered on the epigenetic signatures of CSCs with the difficulty of isolating rare populations of cells.We raise questions about the relevant use of currently available epigenetic inhibitors(epidrugs)while the expression of numerous cancer stem cell markers are often repressed by epigenetic mechanisms.These markers include the three cluster of differentiation CD133,CD44 and CD166 that have been extensively used for the isolation of colon CSCs.and.Finally,we describe current treatment strategies using epidrugs,and we hypothesize that,using correlation tools comparing associations of relevant CSC markers with chromatin modifier expression,we could identify better candidates for epienzyme targeting.展开更多
The article is focused on the influence of inorganic salts on the adsorption of cationically modified starch to fibers. Results show that low concentrations of inorganic salts usually affect the process of adsorption ...The article is focused on the influence of inorganic salts on the adsorption of cationically modified starch to fibers. Results show that low concentrations of inorganic salts usually affect the process of adsorption in a positive way. Adsorption efficiency at higher concentrations, however, depends on the type of inorganic salts as well as the sequence of adding inorganic salts and starch to paper suspension.展开更多
In this investigation,attempts are made to examine the effects of soil-structure interaction on the deflection modification factor of multistory buildings and to clarify the role of deformable soil on this factor.A co...In this investigation,attempts are made to examine the effects of soil-structure interaction on the deflection modification factor of multistory buildings and to clarify the role of deformable soil on this factor.A comprehensive study is conducted to investigate the effect of inertial interaction on displacement demand ratios in soil-structure systems with different structural characteristics and various non-dimensional parameters,using a simplified interacting model.A two-step regression analysis of the nonlinear,dynamic computer simulation results obtained,leads to a reliable and accurate formula for predicting deflection modification factors that incorporate foundation flexibility.The results illustrate that the application of deflection modification factors derived from fixed-base structures can lead to unsafe evaluation of the structures on soft soil.The proposed formula provides a useful tool for design engineers to incorporate the effect of soil-structure interaction into the evaluation of structural deformations.展开更多
In order to look for the best proportion of β-tricalcium phosphate（β-TCP）and poly（lactideco-glycolide）（PLGA）we fabricated porous composites β-TCP/PLGA scaffold using freeze-drying method.Morphologicalcharacte...In order to look for the best proportion of β-tricalcium phosphate（β-TCP）and poly（lactideco-glycolide）（PLGA）we fabricated porous composites β-TCP/PLGA scaffold using freeze-drying method.Morphologicalcharacterization using scanning electron microscopy showed that the interconnected pore distribution was even and there was no significant difference with the increase of PLGA content.Moreover,the porosity,compressive strength and degradation in vitro were characterized.The fabricated scaffolds with increased PLGA in the composites β-TCP/PLGA scaffolds willget stronger mechanicalproperty and better appearance,furthermore,get suitable environment for cells.According to the evaluation indexes for the tissue engineering scaffold,the group of scaffold（β-TCP/PLGA=6：4）was selected to evaluate the induced celladhesion and proliferative ability of the scaffolds.Then as transplant embed into the bone criticaldefect sites on rats femur.The repairing processes of bone defect sites were characterized by X-ray analysis within 12 weeks.X-ray analysis showed that the bone defect sites alldisplayed the formation of callus obviously,In summary,our data suggest that the scaffold（β-TCP/PLGA=6：4）has a promising clinicalfuture in regeneration of bone criticaldefects.展开更多
Poly（urea-formaldehyde）（UF） microcapsules with epoxy resin E-51 as core material used as self-healing materials were prepared by interfacial polymerization method. The surface of UF microcapsules was modifi ed by ...Poly（urea-formaldehyde）（UF） microcapsules with epoxy resin E-51 as core material used as self-healing materials were prepared by interfacial polymerization method. The surface of UF microcapsules was modifi ed by γ-（2,3-epoxypropoxy） propytrimethoxysilane（KH-560）. The interfacial interactions between UF microcapsules and KH-560 were studied by Fourier transform infrared spectroscopy（FTIR） and X-ray photoelectron spectrometric analysis（XPS） of microcapsules. The surface topography of microcapsules was characterized by scanning electron microscopy（SEM）. The thermal stability and mechanical properties were evaluated. FTIR and XPS results showed that there were physical and chemical combinations between the silicon coupling agent and the microcapsules surface. The thermal stability and mechanical property analysis showed that the addition of KH-560 could greatly improve the thermal stability, tensile property and elastic property. SEM results indicated that the addition of KH-560 could improve the bonding between the surface of microcapsules and resin matrix and improve the ability of self-healing.展开更多
Diffuse midline glioma(DMG),H3K27-altered,is lethal pediatric-type,high-grade,localized to the midline region of the central nervous system.Effective treatment guidelines are absent,and clinical trials are preferred f...Diffuse midline glioma(DMG),H3K27-altered,is lethal pediatric-type,high-grade,localized to the midline region of the central nervous system.Effective treatment guidelines are absent,and clinical trials are preferred for primary or recur-rent DMG patients.Recently,epigenetic agent-based immunotherapy has exhibited promising therapeutic effects in the clinical setting.However,the underlying mechanisms remain a mystery.The rare DMG tumor samples from biopsy or resection largely impede basic research,by using patient-derived tumor cells which better recapitulate the parental tu-mor’s heterogeneity compared to established cell lines.As an epigenetic reprogramming disease,DMG exhibits a global loss of H3K27 trimethylation(H3K27me3)and a gain of H3K27 acetylation(H3K27ac).Analysis of multiple epige-netic marks is fundamentally necessary.However,traditional techniques cannot allow ultra-low input and high-throughput.Herein we have developed a new method called high-throughput in situ tagged immunoprecipitation sequencing(HiTIP-seq),which uses an integrated superhydrophobic microwell array technology(InSMART).We were able to perform 100 parallel assays from as few as 100 cells per microwell on a single chip.We applied the tech-nology to profile epigenetic alterations of three-dimensional(3D)cell cultures derived from DMG patients.Our HiTIP-seq integrated with RNA sequencing(RNA-seq)analysis revealed that the combination of epigenetic agents(panobino-stat and tazemetostat),reprogrammed histone modifications and drove transcriptome changes.Among them,Wnt inhibitory factor 1(WIF1)has a gain of H3K27ac and a loss of H3K27me3,which leads to the upregulated expression.Altogether,HiTIP-seq is a versatile method for high-throughput analysis of histone modifications,suitable for both DMG research and studying rare 3D models.展开更多
In order to improve the substrate diffusion properties and stability of an immobilized enzyme alginate microgels modified with TiO2 nanoparticles were employed as the enzyme immobilizing support.Ionotropic gelation wa...In order to improve the substrate diffusion properties and stability of an immobilized enzyme alginate microgels modified with TiO2 nanoparticles were employed as the enzyme immobilizing support.Ionotropic gelation was applied for the preparation of hybrid gels while Ca2＋ Ce3＋ Ni2＋Cu2＋and Fe3＋were employed as the crosslinkers.Papain was selected as the model enzyme. UV-Vis spectroscopy was employed to investigate the activity of papain to evaluate kinetics and stability.Analysis results show that the highest affinity the lowest Michaelis-Menten constant Km =11.0 mg/mL and the highest stability are obtained when using Cu2＋as the crosslinker.The effect of the mass ratio of TiO2 to papain on the stability and leakage of papain is also investigated and the results show that 10∶1 TiO2∶papain is optimal because the proper use of TiO2 can reduce enzyme leakage and ensure enzyme stability.Preparing Cu/alginate/TiO2 hybrid gels via ionotropic gelation can provide a satisfactory diffusion capability and enzyme stability.展开更多
Applying conventional analytical methods,the following results have been found:the satura-tion value of acid--modified multifunction copolyest fibre( acid-modified polyester fibre)is1.74,then this kind of fibre is goo...Applying conventional analytical methods,the following results have been found:the satura-tion value of acid--modified multifunction copolyest fibre( acid-modified polyester fibre)is1.74,then this kind of fibre is good for being dyed medium and light colours with cationicdyes;its level of erystalization is lower than of PET fibre;the third monomer(SIPM)con-tent in the fibre will be reduced by about 8% by the "alkali treatment"in dyeing and finishingprocess:through measuring and analysing the dye-up-take curves of time and temperature ofdyeing the fibre with cationic dyes,we indicate the key factors in dyeing are the 100℃ dyeingtemperature and the time for heat preservation;moveover,adding sodium sulphate will help leveldyeing but lower the dye-uptake.展开更多
基金This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education,Culture,Sports,Science and Technology,Japan.
文摘The treatment of fungi with DNA methyltransferase(DNMT)and/or histone deacetylase(HDAC)inhibitors is a promising way to activate secondary metabolite biosynthetic pathways that are dormant under normal conditions.In this study,we included an HDAC inhibitor,suberoylanilide hydroxamic acid(SBHA),in the culture medium of endophytic fungi isolated from the medicinal plant Datura stramonium L.The production of two compounds was induced in the culture supplemented with SBHA,and their structures were determined to be the fusaric acid derivatives 5-butyl-6-oxo-1,6-dihydropyridine-2-carboxylic acid and 5-(but-9-enyl)-6-oxo-1,6-dihydropyridine-2-carboxylic acid.The result confirmed that the use of chemical epigenetic modifiers is an effective technique for promoting the expression of silent biosynthetic pathways to produce unique secondary metabolites.
基金Supported by"Institut National de la Sante et de la Recherche Médicale"(Inserm)"Centre National de la Recherche Scientifique"(CNRS)"la Ligue Nationale contre le Cancer"(Committees 59,60 and 62)
文摘The recent discovery of cancer cell plasticity,i.e.their ability to reprogram into cancer stem cells(CSCs)either naturally or under chemotherapy and/or radiotherapy,has changed,once again,the way we consider cancer treatment.If cancer stemness is a reversible epigenetic state rather than a genetic identity,opportunities will arise for therapeutic strategies that remodel epigenetic landscapes of CSCs.However,the systematic use of DNA methyltransferase and histone deacetylase inhibitors,alone or in combination,in advanced solid tumors including colorectal cancers,regardless of their molecular subtypes,does not seem to be the best strategy.In this review,we first summarize the knowledge researchers have gathered on the epigenetic signatures of CSCs with the difficulty of isolating rare populations of cells.We raise questions about the relevant use of currently available epigenetic inhibitors(epidrugs)while the expression of numerous cancer stem cell markers are often repressed by epigenetic mechanisms.These markers include the three cluster of differentiation CD133,CD44 and CD166 that have been extensively used for the isolation of colon CSCs.and.Finally,we describe current treatment strategies using epidrugs,and we hypothesize that,using correlation tools comparing associations of relevant CSC markers with chromatin modifier expression,we could identify better candidates for epienzyme targeting.
文摘The article is focused on the influence of inorganic salts on the adsorption of cationically modified starch to fibers. Results show that low concentrations of inorganic salts usually affect the process of adsorption in a positive way. Adsorption efficiency at higher concentrations, however, depends on the type of inorganic salts as well as the sequence of adding inorganic salts and starch to paper suspension.
文摘In this investigation,attempts are made to examine the effects of soil-structure interaction on the deflection modification factor of multistory buildings and to clarify the role of deformable soil on this factor.A comprehensive study is conducted to investigate the effect of inertial interaction on displacement demand ratios in soil-structure systems with different structural characteristics and various non-dimensional parameters,using a simplified interacting model.A two-step regression analysis of the nonlinear,dynamic computer simulation results obtained,leads to a reliable and accurate formula for predicting deflection modification factors that incorporate foundation flexibility.The results illustrate that the application of deflection modification factors derived from fixed-base structures can lead to unsafe evaluation of the structures on soft soil.The proposed formula provides a useful tool for design engineers to incorporate the effect of soil-structure interaction into the evaluation of structural deformations.
基金Funded by the National Natural Science Foundation of China(No.81201386)the China Postdoctoral Science Foundation(No.20100470110)
文摘In order to look for the best proportion of β-tricalcium phosphate（β-TCP）and poly（lactideco-glycolide）（PLGA）we fabricated porous composites β-TCP/PLGA scaffold using freeze-drying method.Morphologicalcharacterization using scanning electron microscopy showed that the interconnected pore distribution was even and there was no significant difference with the increase of PLGA content.Moreover,the porosity,compressive strength and degradation in vitro were characterized.The fabricated scaffolds with increased PLGA in the composites β-TCP/PLGA scaffolds willget stronger mechanicalproperty and better appearance,furthermore,get suitable environment for cells.According to the evaluation indexes for the tissue engineering scaffold,the group of scaffold（β-TCP/PLGA=6：4）was selected to evaluate the induced celladhesion and proliferative ability of the scaffolds.Then as transplant embed into the bone criticaldefect sites on rats femur.The repairing processes of bone defect sites were characterized by X-ray analysis within 12 weeks.X-ray analysis showed that the bone defect sites alldisplayed the formation of callus obviously,In summary,our data suggest that the scaffold（β-TCP/PLGA=6：4）has a promising clinicalfuture in regeneration of bone criticaldefects.
基金Funded by the Science and Technology Planning Project of Guangdong Province,China(2013B010404045)the National Natural Science Foundation of China(No.21106022)the Educational Commission of Guangdong Province,China(Yq2013100)
文摘Poly（urea-formaldehyde）（UF） microcapsules with epoxy resin E-51 as core material used as self-healing materials were prepared by interfacial polymerization method. The surface of UF microcapsules was modifi ed by γ-（2,3-epoxypropoxy） propytrimethoxysilane（KH-560）. The interfacial interactions between UF microcapsules and KH-560 were studied by Fourier transform infrared spectroscopy（FTIR） and X-ray photoelectron spectrometric analysis（XPS） of microcapsules. The surface topography of microcapsules was characterized by scanning electron microscopy（SEM）. The thermal stability and mechanical properties were evaluated. FTIR and XPS results showed that there were physical and chemical combinations between the silicon coupling agent and the microcapsules surface. The thermal stability and mechanical property analysis showed that the addition of KH-560 could greatly improve the thermal stability, tensile property and elastic property. SEM results indicated that the addition of KH-560 could improve the bonding between the surface of microcapsules and resin matrix and improve the ability of self-healing.
基金supported by grants from the National Science Foundation of China(No.22127804)the National Natural Science Foundation of China(No.81771931 and 31971325)+1 种基金Institute of Biomedicine,the Tsinghua-Peking Joint Center for Life Sciences,and the Clinical Medicine Development Fund of Tsinghua University(No.10001020510)the National Key Research and Development Program of China(No.2016YFC0900200).
文摘Diffuse midline glioma(DMG),H3K27-altered,is lethal pediatric-type,high-grade,localized to the midline region of the central nervous system.Effective treatment guidelines are absent,and clinical trials are preferred for primary or recur-rent DMG patients.Recently,epigenetic agent-based immunotherapy has exhibited promising therapeutic effects in the clinical setting.However,the underlying mechanisms remain a mystery.The rare DMG tumor samples from biopsy or resection largely impede basic research,by using patient-derived tumor cells which better recapitulate the parental tu-mor’s heterogeneity compared to established cell lines.As an epigenetic reprogramming disease,DMG exhibits a global loss of H3K27 trimethylation(H3K27me3)and a gain of H3K27 acetylation(H3K27ac).Analysis of multiple epige-netic marks is fundamentally necessary.However,traditional techniques cannot allow ultra-low input and high-throughput.Herein we have developed a new method called high-throughput in situ tagged immunoprecipitation sequencing(HiTIP-seq),which uses an integrated superhydrophobic microwell array technology(InSMART).We were able to perform 100 parallel assays from as few as 100 cells per microwell on a single chip.We applied the tech-nology to profile epigenetic alterations of three-dimensional(3D)cell cultures derived from DMG patients.Our HiTIP-seq integrated with RNA sequencing(RNA-seq)analysis revealed that the combination of epigenetic agents(panobino-stat and tazemetostat),reprogrammed histone modifications and drove transcriptome changes.Among them,Wnt inhibitory factor 1(WIF1)has a gain of H3K27ac and a loss of H3K27me3,which leads to the upregulated expression.Altogether,HiTIP-seq is a versatile method for high-throughput analysis of histone modifications,suitable for both DMG research and studying rare 3D models.
基金The National Natural Science Foundation of China(No.21005016)the Foundation of Educational Commission of Jiangsu Province(No.JHB2011-2)
文摘In order to improve the substrate diffusion properties and stability of an immobilized enzyme alginate microgels modified with TiO2 nanoparticles were employed as the enzyme immobilizing support.Ionotropic gelation was applied for the preparation of hybrid gels while Ca2＋ Ce3＋ Ni2＋Cu2＋and Fe3＋were employed as the crosslinkers.Papain was selected as the model enzyme. UV-Vis spectroscopy was employed to investigate the activity of papain to evaluate kinetics and stability.Analysis results show that the highest affinity the lowest Michaelis-Menten constant Km =11.0 mg/mL and the highest stability are obtained when using Cu2＋as the crosslinker.The effect of the mass ratio of TiO2 to papain on the stability and leakage of papain is also investigated and the results show that 10∶1 TiO2∶papain is optimal because the proper use of TiO2 can reduce enzyme leakage and ensure enzyme stability.Preparing Cu/alginate/TiO2 hybrid gels via ionotropic gelation can provide a satisfactory diffusion capability and enzyme stability.
文摘Applying conventional analytical methods,the following results have been found:the satura-tion value of acid--modified multifunction copolyest fibre( acid-modified polyester fibre)is1.74,then this kind of fibre is good for being dyed medium and light colours with cationicdyes;its level of erystalization is lower than of PET fibre;the third monomer(SIPM)con-tent in the fibre will be reduced by about 8% by the "alkali treatment"in dyeing and finishingprocess:through measuring and analysing the dye-up-take curves of time and temperature ofdyeing the fibre with cationic dyes,we indicate the key factors in dyeing are the 100℃ dyeingtemperature and the time for heat preservation;moveover,adding sodium sulphate will help leveldyeing but lower the dye-uptake.
