In this work,the CuAl-LDO/c-CNTs catalyst was fabricated via in situ oriented assembly of layered-double hydroxides(LDHs)and citric acid-modified carbon nanotubes(c-CNTs)followed by annealing treatment,and evaluated i...In this work,the CuAl-LDO/c-CNTs catalyst was fabricated via in situ oriented assembly of layered-double hydroxides(LDHs)and citric acid-modified carbon nanotubes(c-CNTs)followed by annealing treatment,and evaluated in the selective catalytic oxidation(SCO)of NH_(3)to N_(2).The CuAl-LDO/c-CNTs catalyst presented better catalytic performance(98%NH_(3)conversion with nearly 90%N_(2)selectivity at 513 K)than other catalysts,such as CuAlO_(x)/CNTs,CuAlO_(x)/c-CNTs and CuAl-LDO/CNTs.Multiple characterizations were utilized to analyze the difference of physicochemical properties among four catalysts.XRD,TEM and XPS analyses manifested that CuO and Cu_(2)O nanoparticles dispersed well on the surface of the Cu Al-LDO/c-CNTs catalyst.Compared with other catalysts,larger specific surface area and better dispersion of CuAl-LDO/c-CNTs catalyst were conducive to the exposure of more active sites,thus improving the redox capacity of the active site and NH_(3)adsorption capacity.In-situ DRIFTS results revealed that the internal selective catalytic reduction(iSCR)mechanism was found over CuAl-LDO/c-CNTs catalyst.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
Ion exchange chromatography(IEC)is one of the essential methods to separate rare earth elements(REEs),which relies on the stationary phase.In this study,a novel aromatic sulfonic acid-modified silica stationary phase(...Ion exchange chromatography(IEC)is one of the essential methods to separate rare earth elements(REEs),which relies on the stationary phase.In this study,a novel aromatic sulfonic acid-modified silica stationary phase(SCX-Tol)was synthesized by grafting aromatic sulfonic acid groups onto silica surfaces using 2-(4-chlorosulfonylphenyl)ethyl trichlorosilane as the functionalizing agent in toluene.The successful modification was confirmed by scanning electron microscopy(SEM),elemental analysis,X-ray photoelectron spectroscopy(XPS),and Fourier transform infrared spectroscopy(FT-IR).The chromatographic performance of SCX-Tol was systematically evaluated and compared with two commercial ion-exchange columns.The results demonstrated the superior separation efficiency of SCX-Tol,particularly in the challenging separation of dysprosium(Dy)and yttrium(Y),which are traditionally difficult to resolve using chromatographic methods.The separation efficiency improved with an increasing density of sulfonic acid groups on the stationary phase surface.These findings indicate that SCX-Tol is a promising stationary phase for both the separation and quantification of REEs,off ering the potential applications in separating and detecting REEs.展开更多
A ultra-sensitive,highly specific,real-time polymerase chain reaction system based on mercaptoacetic acid-modified CdTe nanocrystals(mQDs)is reported.With the addition of 3 nm mQDs into the PCR reagent,the photolumine...A ultra-sensitive,highly specific,real-time polymerase chain reaction system based on mercaptoacetic acid-modified CdTe nanocrystals(mQDs)is reported.With the addition of 3 nm mQDs into the PCR reagent,the photoluminescent(PL)intensities of mQDs decreased gradually as the DNA templates and PCR cycles increased,in an approximate negative linear relation to the DNA concentration logarithm or cycles,the PL peaks exhibited red-shifts synchronously.Mg2+ions decreased the PL intensity of mQDs in a dose-dependent means,and Taq DNA polymerase enhanced the PL intensity of mQDs in a dose-dependent means.Real-time PCR based on mQDs showed an increased sensitivity at least 103 fold higher than that based on SYBR Green I.The specificity of PCR was enhanced in the PCR reagent with less than 1.33mg/mL mQDs.The potential mechanism is also discussed.This novel PCR system based on mQDs has great potential in applications such as ultra-sensitive specific DNA or RNA detection,dynamic molecular imaging,and photoelectric biosensors.展开更多
Zr-based metal-organic frameworks(MOFs)have been developed in recent years to treat heavy metals,e.g.hexavalent chromium Cr^(6+)pollution,which damages the surrounding ecosystem and threaten human health.This kind of ...Zr-based metal-organic frameworks(MOFs)have been developed in recent years to treat heavy metals,e.g.hexavalent chromium Cr^(6+)pollution,which damages the surrounding ecosystem and threaten human health.This kind of MOF is stable and convenient to prepare,but has the disadvantage of low adsorption capacity,limiting its wide application.To this end,a novel formic acid and amino modified MOFs were prepared,referred to as Form-UiO-66-NH_(2).Due to the modification of formic acid,its specific surface area,pore size,and crystal size were effectively expanded,and the adsorption capacity of Cr6+was significantly enhanced.Under optimal conditions,Form-UiO-66-NH_(2) exhibited an excellent adsorption capacity(338.98 mg/g),∼10 times higher than that reported for unmodified Zr-based MOFs and most other adsorbents.An in-depth study on the photoelectronic properties and pH confirmed that the adsorption mechanism of Form-UiO-66-NH2 to Cr^(6+)was electrostatic adsorption.After modification,the improvement of Cr^(6+)adsorption capacity by Form-UiO-66-NH_(2) was attributed to the expansion of its specific surface area and the increase in its surface charge.The present study revealed an important finding that Form-UiO-66-NH_(2) elucidated selective adsorption to Cr^(6+)in mixed wastewater containing toxic heavymetal ions and common nonmetallic water quality factors.This research provided a new acid and amino functionalization perspective for improving the adsorption capacity of Zr-based MOF adsorbents while simultaneously demonstrating their pertinence to target contaminant adsorption.展开更多
Acute liver injury(ALI)has an elevated fatality rate due to untimely and ineffective treatment.Although,schisandrin B(SchB)has been extensively used to treat diverse liver diseases,its therapeutic efficacy on ALI was ...Acute liver injury(ALI)has an elevated fatality rate due to untimely and ineffective treatment.Although,schisandrin B(SchB)has been extensively used to treat diverse liver diseases,its therapeutic efficacy on ALI was limited due to its high hydrophobicity.Palmitic acid-modified serum albumin(PSA)is not only an effective carrier for hydrophobic drugs,but also has a superb targeting effect via scavenger receptor-A(SR-A)on the M1 macrophages,which are potential therapeutic targets for ALI.Compared with the common macrophage-targeted delivery systems,PSA enables site-specific drug delivery to reduce off-target toxicity.Herein,we prepared SchB-PSA nanoparticles and further assessed their therapeutic effect on ALI.In vitro,compared with human serum albumin encapsulated SchB nanoparticles(SchB-HSA NPs),the SchB-PSA NPs exhibited more potent cytotoxicity on lipopolysaccharide(LPS)stimulated Raw264.7(LAR)cells,and LAR cells took up PSA NPs 8.79 times more than HSA NPs.As expected,the PSA NPs also accumulated more in the liver.Moreover,SchB-PSA NPs dramatically reduced the activation of NF-κB signaling,and significantly relieved inflammatory response and hepatic necrosis.Notably,the high dose of SchB-PSA NPs improved the survival rate in 72 h of ALI mice to 75%.Hence,SchB-PSA NPs are promising to treat ALI.展开更多
In order to study the chemical modification mechanism and rheological properties of polyphosphoric acid (PPA)-modified asphalt,asphalt modified with different PPA contents were characterized by four-component test,ato...In order to study the chemical modification mechanism and rheological properties of polyphosphoric acid (PPA)-modified asphalt,asphalt modified with different PPA contents were characterized by four-component test,atomic force microscopy (AFM) and Fourier transform infrared spectroscopy (FTIR).In the test,changes in asphalt chemical composition and colloidal structure were analyzed for different PPA contents,and infrared spectra were fitted with a Gaussian function.The reaction mechanism of PPA and matrix asphalt was also discussed.Based on dynamic shear rheometer (DSR) test and bending beam rheometer (BBR) test,rheological index G~*/sinδ and S/m were used to evaluate the modification effect of PPA on asphalt.The results show that,with an increase in PPA content,both large and small honeycomb structures increased in the three-dimensional topography seen in the atomic force microscope (AFM).In a certain space range,some of the micelles in the asphalt are connected each other to form interlocking skeleton structures,and locally form dense spatial network structures.The added PPA does not chemically react with the functional groups in the functional-group area of the infrared spectra (3 100-2 750 cm^(-1),1 800-1 330 cm^(-1)),and the structure is very stable.However,there is an obvious new absorption peak below 1 330 cm^(-1) in the fingerprint area,that is,the chemical reaction between PPA and the matrix asphalt generates a new compound,inorganic phosphate.Infrared spectra of PPA-modified asphalt with different contents were fitted by a Gaussian function,which makes up for the limitation that the absorption intensity information of each superimposed functional group cannot be obtained directly from the original infrared spectra.Results of this qualitative analysis were further verified by quantitative analysis.The addition of PPA can effectively improve the high and low-temperature performance of asphalt,and the lower the temperature is in the negative temperature zone,the more obvious the improvement is.When PPA content is more than 1%,the improvement of asphalt low-temperature performance is not obvious.展开更多
Aggregation represents a significant challenge for the long-term formulation stability of insulin therapeutics.The supramolecular PEGylation of insulin with conjugates of cucurbit[7]uril and polyethylene glycol(CB[7]-...Aggregation represents a significant challenge for the long-term formulation stability of insulin therapeutics.The supramolecular PEGylation of insulin with conjugates of cucurbit[7]uril and polyethylene glycol(CB[7]-PEG)has been shown to stabilize insulin formulations by reducing aggregation propensity.Yet prolonged in vivo duration of action,arising from sustained complex formation in the subcutaneous depot,limits the application scope for meal-time insulin uses and could increase hypoglycemic risk several hours after a meal.Supramolecular affinity of CB[7]in binding the B1-Phe residue on insulin is central to supramolecular PEGylation using this approach.Accordingly,here we synthesized N-terminal acid-modified insulin analogs to reduce CB[7]interaction affinity at physiological pH and reduce the duration of action by decreasing the subcutaneous depot effect of the formulation.These insulin analogs show weak to no interaction with CB[7]-PEG at physiological pH but demonstrate high formulation stability at reduced pH.Accordingly,N-terminal modified analogs have in vitro and in vivo bioactivity comparable to native insulin.Furthermore,in a rat model of diabetes,the acid-modified insulin formulated with CB[7]-PEG offers a reduced duration of action compared to native insulin formulated with CB[7]-PEG.This work extends the application of supramolecular PEGylation of insulin to achieve enhanced stability while reducing the risks arising from a subcutaneous depot effect prolonging in vivo duration of action.展开更多
Tooth presents an intriguing option as a bone graft due to its compositional similarity to bone.However,the deproteinized human demineralized tooth matrix(dpDTM),developed to overcome the limited availability of autol...Tooth presents an intriguing option as a bone graft due to its compositional similarity to bone.However,the deproteinized human demineralized tooth matrix(dpDTM),developed to overcome the limited availability of autologous tooth grafts,has suboptimal pore size and surface roughness.This study aimed to fabricate a surface-modified dpDTM using acid etching and collagen coating,followed by in vitro evaluation of physicochemical and biological properties.The dpDTM was modified into two protocols:Acid-modified dpDTM(A-dpDTM)and collagen-modified dpDTM(C-dpDTM).Results demonstrated that A-dpDTM and C-dpDTM had increased pore sizes and rougher surfaces compared to dpDTM.Collagen immobilization was evidenced by nitrogen presence exclusively in C-dpDTM.All groups had a Ca/P molar ratio of 1.67 and hydroxyapatite as the sole constituent,with 65-67%crystallinity.Degradation rates significantly increased to 30%and 20%for C-dpDTM and A-dpDTM,respectively,compared to 10%for dpDTM after 120 days.Cumulative collagen release of C-dpDTM on Day 30 was 45.16 mg/ml.Osteoblasts attachment and proliferation were enhanced on all scaffolds,especially C-dpDTM,which displayed the highest proliferation and differentiation rates.In conclusion,surface modified of dpDTM,including A-dpDTM and C-dpDTM,significantly enhances bioactivity by altering surface properties and promoting osteoblast activity,thereby demonstrating promise for bone regeneration applications.展开更多
Sepsis is a leading cause of death worldwide.This syndrome is commonly accompanied by overactivation of coagulation,excessive reactive oxygen species(ROS),and inflammatory cytokine storm.Notably,disseminated intravasc...Sepsis is a leading cause of death worldwide.This syndrome is commonly accompanied by overactivation of coagulation,excessive reactive oxygen species(ROS),and inflammatory cytokine storm.Notably,disseminated intravascular coagulation(DIC)accounts for around 40%of sepsis-associated deaths.However,anticoagulant therapy is still difficult for sepsis treatment because of the lethal bleeding side effects.Although the relationship between ROS and inflammatory cytokine storm has been described clearly,the pathogenic role of ROS in DIC,however,is still unclear,which renders novel therapeutic approaches hard to achieve bedside for inhibiting DIC.Herein,our new finding reveals that ROS greatly facilitates the entry of lipopolysaccharide(LPS)into the macrophage cytoplasm,which subsequently activates the caspase-11/gasdermin D pathway,and finally induces DIC through phosphatidylserine exposure.Based on this finding,novel gallic acid-modified Mo-based polyoxometalate dots(M-dots)with outstanding antioxidant activity are developed to provide ideal and efficient inhibition of DIC.As expected,M-dots are capable of markedly inhibiting sepsis-caused coagulation,organ injury,and death in sepsis.This therapeutic strategy,blocking the upstream pathway of coagulation rather than coagulation itself,can avoid the side effects of extensive bleeding caused by conventional anticoagulation therapy,and will provide a new avenue for the efficient treatment of sepsis.展开更多
基金supported by the National Natural Science Foundation of China(51978436,52000092,22272116)Fundamental Research Program of Shanxi Province(202103021224043)。
文摘In this work,the CuAl-LDO/c-CNTs catalyst was fabricated via in situ oriented assembly of layered-double hydroxides(LDHs)and citric acid-modified carbon nanotubes(c-CNTs)followed by annealing treatment,and evaluated in the selective catalytic oxidation(SCO)of NH_(3)to N_(2).The CuAl-LDO/c-CNTs catalyst presented better catalytic performance(98%NH_(3)conversion with nearly 90%N_(2)selectivity at 513 K)than other catalysts,such as CuAlO_(x)/CNTs,CuAlO_(x)/c-CNTs and CuAl-LDO/CNTs.Multiple characterizations were utilized to analyze the difference of physicochemical properties among four catalysts.XRD,TEM and XPS analyses manifested that CuO and Cu_(2)O nanoparticles dispersed well on the surface of the Cu Al-LDO/c-CNTs catalyst.Compared with other catalysts,larger specific surface area and better dispersion of CuAl-LDO/c-CNTs catalyst were conducive to the exposure of more active sites,thus improving the redox capacity of the active site and NH_(3)adsorption capacity.In-situ DRIFTS results revealed that the internal selective catalytic reduction(iSCR)mechanism was found over CuAl-LDO/c-CNTs catalyst.
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.
基金supported by the National Key Research and Development Program of China(2023YFF0722504)the National Natural Science Foundation of China(22474141 and 22374159)the Youth Innovation Promotion Association CAS(2021420)。
文摘Ion exchange chromatography(IEC)is one of the essential methods to separate rare earth elements(REEs),which relies on the stationary phase.In this study,a novel aromatic sulfonic acid-modified silica stationary phase(SCX-Tol)was synthesized by grafting aromatic sulfonic acid groups onto silica surfaces using 2-(4-chlorosulfonylphenyl)ethyl trichlorosilane as the functionalizing agent in toluene.The successful modification was confirmed by scanning electron microscopy(SEM),elemental analysis,X-ray photoelectron spectroscopy(XPS),and Fourier transform infrared spectroscopy(FT-IR).The chromatographic performance of SCX-Tol was systematically evaluated and compared with two commercial ion-exchange columns.The results demonstrated the superior separation efficiency of SCX-Tol,particularly in the challenging separation of dysprosium(Dy)and yttrium(Y),which are traditionally difficult to resolve using chromatographic methods.The separation efficiency improved with an increasing density of sulfonic acid groups on the stationary phase surface.These findings indicate that SCX-Tol is a promising stationary phase for both the separation and quantification of REEs,off ering the potential applications in separating and detecting REEs.
基金supported by the National Natural Science Foundation of China(No.20803040 and No.20471599)Chinese 973 Project(2010CB933901),863 Key Project(2007AA022004)+2 种基金New Century Excellent Talent of Ministry of Education of China(NCET-08-0350)Special Infection Diseases Key Project of China(2009ZX10004-311)Shanghai Science and Technology Fund(10XD1406100).
文摘A ultra-sensitive,highly specific,real-time polymerase chain reaction system based on mercaptoacetic acid-modified CdTe nanocrystals(mQDs)is reported.With the addition of 3 nm mQDs into the PCR reagent,the photoluminescent(PL)intensities of mQDs decreased gradually as the DNA templates and PCR cycles increased,in an approximate negative linear relation to the DNA concentration logarithm or cycles,the PL peaks exhibited red-shifts synchronously.Mg2+ions decreased the PL intensity of mQDs in a dose-dependent means,and Taq DNA polymerase enhanced the PL intensity of mQDs in a dose-dependent means.Real-time PCR based on mQDs showed an increased sensitivity at least 103 fold higher than that based on SYBR Green I.The specificity of PCR was enhanced in the PCR reagent with less than 1.33mg/mL mQDs.The potential mechanism is also discussed.This novel PCR system based on mQDs has great potential in applications such as ultra-sensitive specific DNA or RNA detection,dynamic molecular imaging,and photoelectric biosensors.
基金supported by the National Natural Science Foundation of China(Nos. 22076029, 21906029 and 21677040)the National Science and Technology planning Project, China(No. 2018-281)Guangzhou City Science and the Technology Plan Project, China(No. 201903010080)
文摘Zr-based metal-organic frameworks(MOFs)have been developed in recent years to treat heavy metals,e.g.hexavalent chromium Cr^(6+)pollution,which damages the surrounding ecosystem and threaten human health.This kind of MOF is stable and convenient to prepare,but has the disadvantage of low adsorption capacity,limiting its wide application.To this end,a novel formic acid and amino modified MOFs were prepared,referred to as Form-UiO-66-NH_(2).Due to the modification of formic acid,its specific surface area,pore size,and crystal size were effectively expanded,and the adsorption capacity of Cr6+was significantly enhanced.Under optimal conditions,Form-UiO-66-NH_(2) exhibited an excellent adsorption capacity(338.98 mg/g),∼10 times higher than that reported for unmodified Zr-based MOFs and most other adsorbents.An in-depth study on the photoelectronic properties and pH confirmed that the adsorption mechanism of Form-UiO-66-NH2 to Cr^(6+)was electrostatic adsorption.After modification,the improvement of Cr^(6+)adsorption capacity by Form-UiO-66-NH_(2) was attributed to the expansion of its specific surface area and the increase in its surface charge.The present study revealed an important finding that Form-UiO-66-NH_(2) elucidated selective adsorption to Cr^(6+)in mixed wastewater containing toxic heavymetal ions and common nonmetallic water quality factors.This research provided a new acid and amino functionalization perspective for improving the adsorption capacity of Zr-based MOF adsorbents while simultaneously demonstrating their pertinence to target contaminant adsorption.
基金This project is financially supported by grants from the National Natural Science Foundation of China(82173758 and 81872804)Sichuan major science and technology project on biotechnology and medicine(2018SZDZX0018).
文摘Acute liver injury(ALI)has an elevated fatality rate due to untimely and ineffective treatment.Although,schisandrin B(SchB)has been extensively used to treat diverse liver diseases,its therapeutic efficacy on ALI was limited due to its high hydrophobicity.Palmitic acid-modified serum albumin(PSA)is not only an effective carrier for hydrophobic drugs,but also has a superb targeting effect via scavenger receptor-A(SR-A)on the M1 macrophages,which are potential therapeutic targets for ALI.Compared with the common macrophage-targeted delivery systems,PSA enables site-specific drug delivery to reduce off-target toxicity.Herein,we prepared SchB-PSA nanoparticles and further assessed their therapeutic effect on ALI.In vitro,compared with human serum albumin encapsulated SchB nanoparticles(SchB-HSA NPs),the SchB-PSA NPs exhibited more potent cytotoxicity on lipopolysaccharide(LPS)stimulated Raw264.7(LAR)cells,and LAR cells took up PSA NPs 8.79 times more than HSA NPs.As expected,the PSA NPs also accumulated more in the liver.Moreover,SchB-PSA NPs dramatically reduced the activation of NF-κB signaling,and significantly relieved inflammatory response and hepatic necrosis.Notably,the high dose of SchB-PSA NPs improved the survival rate in 72 h of ALI mice to 75%.Hence,SchB-PSA NPs are promising to treat ALI.
基金Funded by National Natural Science Foundation of China(No.11962024)Inner Mongolia Transportation Technology Project(No.NJ-2014-9)Research Fund for the Doctoral Program of Higher Education of China(RFDP)(No.BS2020042)。
文摘In order to study the chemical modification mechanism and rheological properties of polyphosphoric acid (PPA)-modified asphalt,asphalt modified with different PPA contents were characterized by four-component test,atomic force microscopy (AFM) and Fourier transform infrared spectroscopy (FTIR).In the test,changes in asphalt chemical composition and colloidal structure were analyzed for different PPA contents,and infrared spectra were fitted with a Gaussian function.The reaction mechanism of PPA and matrix asphalt was also discussed.Based on dynamic shear rheometer (DSR) test and bending beam rheometer (BBR) test,rheological index G~*/sinδ and S/m were used to evaluate the modification effect of PPA on asphalt.The results show that,with an increase in PPA content,both large and small honeycomb structures increased in the three-dimensional topography seen in the atomic force microscope (AFM).In a certain space range,some of the micelles in the asphalt are connected each other to form interlocking skeleton structures,and locally form dense spatial network structures.The added PPA does not chemically react with the functional groups in the functional-group area of the infrared spectra (3 100-2 750 cm^(-1),1 800-1 330 cm^(-1)),and the structure is very stable.However,there is an obvious new absorption peak below 1 330 cm^(-1) in the fingerprint area,that is,the chemical reaction between PPA and the matrix asphalt generates a new compound,inorganic phosphate.Infrared spectra of PPA-modified asphalt with different contents were fitted by a Gaussian function,which makes up for the limitation that the absorption intensity information of each superimposed functional group cannot be obtained directly from the original infrared spectra.Results of this qualitative analysis were further verified by quantitative analysis.The addition of PPA can effectively improve the high and low-temperature performance of asphalt,and the lower the temperature is in the negative temperature zone,the more obvious the improvement is.When PPA content is more than 1%,the improvement of asphalt low-temperature performance is not obvious.
基金NIDDK(DK120430,DK121336,USA)to Danny Hung-Chieh ChouJDRF(5-CDA-2020-947-A-N,USA)to Matthew J.Webber。
文摘Aggregation represents a significant challenge for the long-term formulation stability of insulin therapeutics.The supramolecular PEGylation of insulin with conjugates of cucurbit[7]uril and polyethylene glycol(CB[7]-PEG)has been shown to stabilize insulin formulations by reducing aggregation propensity.Yet prolonged in vivo duration of action,arising from sustained complex formation in the subcutaneous depot,limits the application scope for meal-time insulin uses and could increase hypoglycemic risk several hours after a meal.Supramolecular affinity of CB[7]in binding the B1-Phe residue on insulin is central to supramolecular PEGylation using this approach.Accordingly,here we synthesized N-terminal acid-modified insulin analogs to reduce CB[7]interaction affinity at physiological pH and reduce the duration of action by decreasing the subcutaneous depot effect of the formulation.These insulin analogs show weak to no interaction with CB[7]-PEG at physiological pH but demonstrate high formulation stability at reduced pH.Accordingly,N-terminal modified analogs have in vitro and in vivo bioactivity comparable to native insulin.Furthermore,in a rat model of diabetes,the acid-modified insulin formulated with CB[7]-PEG offers a reduced duration of action compared to native insulin formulated with CB[7]-PEG.This work extends the application of supramolecular PEGylation of insulin to achieve enhanced stability while reducing the risks arising from a subcutaneous depot effect prolonging in vivo duration of action.
基金supported by National Science,Research and Innovation Fund(NSRF)and Prince of Songkla University(Ref.No.DEN6701281S)Cranio-Maxillofacial Hard Tissue Engineering Center,Faculty of Dentistry,Prince of Songkla University.
文摘Tooth presents an intriguing option as a bone graft due to its compositional similarity to bone.However,the deproteinized human demineralized tooth matrix(dpDTM),developed to overcome the limited availability of autologous tooth grafts,has suboptimal pore size and surface roughness.This study aimed to fabricate a surface-modified dpDTM using acid etching and collagen coating,followed by in vitro evaluation of physicochemical and biological properties.The dpDTM was modified into two protocols:Acid-modified dpDTM(A-dpDTM)and collagen-modified dpDTM(C-dpDTM).Results demonstrated that A-dpDTM and C-dpDTM had increased pore sizes and rougher surfaces compared to dpDTM.Collagen immobilization was evidenced by nitrogen presence exclusively in C-dpDTM.All groups had a Ca/P molar ratio of 1.67 and hydroxyapatite as the sole constituent,with 65-67%crystallinity.Degradation rates significantly increased to 30%and 20%for C-dpDTM and A-dpDTM,respectively,compared to 10%for dpDTM after 120 days.Cumulative collagen release of C-dpDTM on Day 30 was 45.16 mg/ml.Osteoblasts attachment and proliferation were enhanced on all scaffolds,especially C-dpDTM,which displayed the highest proliferation and differentiation rates.In conclusion,surface modified of dpDTM,including A-dpDTM and C-dpDTM,significantly enhances bioactivity by altering surface properties and promoting osteoblast activity,thereby demonstrating promise for bone regeneration applications.
基金supported by the National Natural Science Foundation of China(Nos.82373871,21974134,82072152,82270137,and 82370140)the Hunan Science Fund for Distinguished Young Scholar of China(Nos.2021JJ10067 and 2021JJ10072),the National Key Research and Development Program of China(No.2022YFC2304600)+2 种基金the Innovation-Driven Project of Central South University(No.202045005)the Hunan Provincial Natural Science Foundation of China(Nos.2022JJ30793 and 2021JJ31066)the Key Program of Ningxia Hui Autonomous Region Natural Science Foundation of China(No.2022JJ21059).
文摘Sepsis is a leading cause of death worldwide.This syndrome is commonly accompanied by overactivation of coagulation,excessive reactive oxygen species(ROS),and inflammatory cytokine storm.Notably,disseminated intravascular coagulation(DIC)accounts for around 40%of sepsis-associated deaths.However,anticoagulant therapy is still difficult for sepsis treatment because of the lethal bleeding side effects.Although the relationship between ROS and inflammatory cytokine storm has been described clearly,the pathogenic role of ROS in DIC,however,is still unclear,which renders novel therapeutic approaches hard to achieve bedside for inhibiting DIC.Herein,our new finding reveals that ROS greatly facilitates the entry of lipopolysaccharide(LPS)into the macrophage cytoplasm,which subsequently activates the caspase-11/gasdermin D pathway,and finally induces DIC through phosphatidylserine exposure.Based on this finding,novel gallic acid-modified Mo-based polyoxometalate dots(M-dots)with outstanding antioxidant activity are developed to provide ideal and efficient inhibition of DIC.As expected,M-dots are capable of markedly inhibiting sepsis-caused coagulation,organ injury,and death in sepsis.This therapeutic strategy,blocking the upstream pathway of coagulation rather than coagulation itself,can avoid the side effects of extensive bleeding caused by conventional anticoagulation therapy,and will provide a new avenue for the efficient treatment of sepsis.
