Temozolomide(TMZ)is considered as a standard-of-care DNA alkylating agent for treating glioblastoma multiforme.Despite being a highly potent molecule,TMZ poses several limitations,including short half-life,rapid metab...Temozolomide(TMZ)is considered as a standard-of-care DNA alkylating agent for treating glioblastoma multiforme.Despite being a highly potent molecule,TMZ poses several limitations,including short half-life,rapid metabolism,low brain bioavailability and dosedependent toxicities.Attempts have been made to improve the delivery of TMZ that mainly exhibited nominal therapeutic outcomes.In the current study,we have conjugated TMZ to mPEG-b-P(CB-{g-COOH})copolymer to obtain mPEG-b-P(CB-{g-COOH;g-TMZn})that demonstrated improvement in stability and efficacy.Further,a hybrid TMZ nanoconjugate formulation was developed using mPEG-b-P(CB-{g-COOH;g-TMZ_(40)})and mPEG-polylactic acid(mPEG-PLA)showed an average size of 105.7 nm with narrow PDI of<0.2 and TMZ loading of 21.6%.Stability was assessed under physiological conditions wherein TMZ was found to be stable with a half-life of∼194 h compared to 1.8 h for free TMZ.The Hybrid TMZ nanoconjugates showed improved intracellular uptake and reduced IC_(50)values in C6 and U87MG glioma cells.Furthermore,they exhibited better in vivo therapeutic outcome,i.e.,reduced brain weight,hemispherical width ratio and improved survival rate in C6-cell induced orthotropic glioma model in Sprague Dawley rats compared to the free TMZtreated and positive control animals.Histopathological evaluation also revealed reduced cell infiltration in the lungs and reduced toxicity in major organs.Overall,the hybrid nanoconjugates of TMZ significantly improved its stability and efficacy in the GBM model,thereby opening newer avenues for treatment.展开更多
Objective:To investigate the relation between fruit seeds,plants residuals and appendicitis. Methods:Among cases that underwent appendectomy,the appendicitis cases having fruit seeds and undigested plant residuals in ...Objective:To investigate the relation between fruit seeds,plants residuals and appendicitis. Methods:Among cases that underwent appendectomy,the appendicitis cases having fruit seeds and undigested plant residuals in their etiology were examined retrospectively.Also, histopathological features,age,sex,and parameters of morbidity and mortality were used. Results:Fruit seed was found in one case(0.05%) with presence of pus in appendix lumen, undigested plant residuals in 7 cases(0.35%).It was determined that there were appendix inflammation in 2 of the plant residuals cases,while there were obstruction and lymphoid hyperplasia in the appendix lumen of 5 cases.No mortality was observed.Conclusions:The ratio of acute appendicitis caused by plants is minimal among all appendectomised patients, but avoidence of eating undigested fruit seeds and chewing plants well may help to prevent appendicitis.展开更多
Brucellosis,caused by Brucella,is one of the most common zoonosis.However,there is still no vaccine for human use.Although some live attenuated vaccines have been approved for animals,the protection effect is not idea...Brucellosis,caused by Brucella,is one of the most common zoonosis.However,there is still no vaccine for human use.Although some live attenuated vaccines have been approved for animals,the protection effect is not ideal.In this study,we developed a dual-antigen nanoconjugate vaccine containing both polysaccharide and protein antigens against Brucella.First,the antigenic polysaccharide was covalently coupled to the outer membrane protein Omp19 using protein glycan coupling technology,and then it was successfully loaded on a nano-carrier through the SpyTag/SpyCatcher system.After confirming the efficient immune activation and safety performance of the dual-antigen nanoconjugate vaccine,the potent serum antibody response against the two antigens and remarkable protective effect in non-lethal and lethal Brucella infection models were further demonstrated through different routes of administration.These results indicated that the dual-antigen nanoconjugate vaccine enhanced both T helper 1 cell(Th1)and Th2 immune responses and protected mice from Brucella infection.Furthermore,we found that this protective effect was maintained for at least 18 weeks.To our knowledge,this is the first Brucella vaccine bearing diverse antigens,including a protein and polysaccharide,on a single nanoparticle.Thus,we also present an attractive technology for co-delivery of different types of antigens using a strategy applicable to other vaccines against infectious diseases.展开更多
Conjugate vaccines represent one of the most effective means for controlling the occurrence of bacterial diseases.Although nanotechnology has been greatly applied in the field of vaccines,it is seldom used for conjuga...Conjugate vaccines represent one of the most effective means for controlling the occurrence of bacterial diseases.Although nanotechnology has been greatly applied in the field of vaccines,it is seldom used for conjugate vaccine research because it is very difficult to connect polysaccharides and nanocarriers.In this work,an orthogonal and modular biosynthesis method was used to produce nanoconjugate vaccines using the SpyTag/SpyCatcher system.When SpyTag/SpyCatcher system is combined with protein glycosylation technology,bacterial O-polysaccharide obtained from Shigela flexneri 2a can be conjugated onto the surfaces of different virus-like particles(VLPs)in a biocompatible and controlled manner.After confirming the excellent lymph node targeting and humoral immune activation abilities,these nanoconjugate vaccines further induced efficient prophylactic effects against infection in a mouse model.These results demonstrated that natural polysaccharide antigens can be easily connected to VLPs to prepare highly efficient nanoconjugate vaccines.To the best of the researchers1 knowledge,this is the first time VLP-based nanoconjugate vaccines are produced efficiently,and this strategy could be applied to develop various pathogenic nanoconjugate vaccines.展开更多
Edge-functionalization of graphene is emerging as a powerful chemical method for the construction ofπ-delocalized highlyplanar graphene nanoconjugates that are not accessible through surface-supported syntheses.Herei...Edge-functionalization of graphene is emerging as a powerful chemical method for the construction ofπ-delocalized highlyplanar graphene nanoconjugates that are not accessible through surface-supported syntheses.Herein,a graphene-porphyrin nanoconjugate via a robust pyrazine(pz)linkage has been obtained by condensing 2,3-diamino-5,10,15,20-tetraphenylporphyrin(DA-TPP)with ortho-quinone(o-quinone)moieties at edge sites of graphene oxide(GO).The as-prepared GO-pz-TPP exhibits an intense absorption extending from 375 to 900 nm and a high quenching yield(98%)of fluorescence,indicating a strong electronic coupling effect between GO and TPP units.GO-pz-TPP displays strong nonlinear optical(NLO)absorption and giant NLO coefficients with 800 and 1,030 nm fs laser,in sharp contrast to traditional graphene-porphyrin nanohybrids only NLO-active towards ns laser.Such a dramatic NLO performance towards femtosecond pulsed laser has not been achieved in any carbonchromophores nanohybridized materials to date.This work validates theπ-extended edge-functionalization strategy as a means to tune the NLO properties of graphene,thereby providing a new paradigm for the assembly of versatile optoelectronic materials.展开更多
Electron-donating porphyrins(Por),electron-accepting phthalocyanines(Pcs),and reduced graphene oxide(RGO)were integrated into a multicomponent nanoconjugate(Por-RGO-Pc).The donor-π-acceptor nanoconjugate Por-RGO-Pc w...Electron-donating porphyrins(Por),electron-accepting phthalocyanines(Pcs),and reduced graphene oxide(RGO)were integrated into a multicomponent nanoconjugate(Por-RGO-Pc).The donor-π-acceptor nanoconjugate Por-RGO-Pc was characterized using Fourier transform infrared spectroscopy(FTIR),transmission electron microscopy(TEM),scanning electron microscopy(SEM),atomic force microscopy(AFM),and ultraviolet-visible(UV-Vis)spectroscopy.Photoinduced cascading electron/charge transfer from Por to RGO and from RGO to Pc was established from fluorescence,electrochemical,and femtosecond transient absorption(fs-TA)spectroscopy studies.The increased distance between the electron donors and acceptors of the Por-RGO-Pc nanoconjugate compared to the parent materials and the intermediate RGO-Pc results in longlived charge separation,and an enhancement in nonlinear optical(NLO)absorption(a large NLO coefficient of about 827.44 cm/GW)towards nanosecond laser irradiation at 532 nm.展开更多
基金support to DC through a research grant (BT/PR22123/NNT/28/1120/2016)support through DST-INSPIRE fellowship to PS (DST/INSPIRE Fellowship/2018/IF180652)
文摘Temozolomide(TMZ)is considered as a standard-of-care DNA alkylating agent for treating glioblastoma multiforme.Despite being a highly potent molecule,TMZ poses several limitations,including short half-life,rapid metabolism,low brain bioavailability and dosedependent toxicities.Attempts have been made to improve the delivery of TMZ that mainly exhibited nominal therapeutic outcomes.In the current study,we have conjugated TMZ to mPEG-b-P(CB-{g-COOH})copolymer to obtain mPEG-b-P(CB-{g-COOH;g-TMZn})that demonstrated improvement in stability and efficacy.Further,a hybrid TMZ nanoconjugate formulation was developed using mPEG-b-P(CB-{g-COOH;g-TMZ_(40)})and mPEG-polylactic acid(mPEG-PLA)showed an average size of 105.7 nm with narrow PDI of<0.2 and TMZ loading of 21.6%.Stability was assessed under physiological conditions wherein TMZ was found to be stable with a half-life of∼194 h compared to 1.8 h for free TMZ.The Hybrid TMZ nanoconjugates showed improved intracellular uptake and reduced IC_(50)values in C6 and U87MG glioma cells.Furthermore,they exhibited better in vivo therapeutic outcome,i.e.,reduced brain weight,hemispherical width ratio and improved survival rate in C6-cell induced orthotropic glioma model in Sprague Dawley rats compared to the free TMZtreated and positive control animals.Histopathological evaluation also revealed reduced cell infiltration in the lungs and reduced toxicity in major organs.Overall,the hybrid nanoconjugates of TMZ significantly improved its stability and efficacy in the GBM model,thereby opening newer avenues for treatment.
基金Supported by the Department of Biotechnology.Government of India
文摘Objective:To investigate the relation between fruit seeds,plants residuals and appendicitis. Methods:Among cases that underwent appendectomy,the appendicitis cases having fruit seeds and undigested plant residuals in their etiology were examined retrospectively.Also, histopathological features,age,sex,and parameters of morbidity and mortality were used. Results:Fruit seed was found in one case(0.05%) with presence of pus in appendix lumen, undigested plant residuals in 7 cases(0.35%).It was determined that there were appendix inflammation in 2 of the plant residuals cases,while there were obstruction and lymphoid hyperplasia in the appendix lumen of 5 cases.No mortality was observed.Conclusions:The ratio of acute appendicitis caused by plants is minimal among all appendectomised patients, but avoidence of eating undigested fruit seeds and chewing plants well may help to prevent appendicitis.
基金supported by the National Key Research and Development Program of China(2021YFC2102100)the National Natural Science Foundation of China(U20A20361,32271507,81930122,and 82171819)the Beijing Postdoctoral Research Foundation(2021-ZZ-035)。
文摘Brucellosis,caused by Brucella,is one of the most common zoonosis.However,there is still no vaccine for human use.Although some live attenuated vaccines have been approved for animals,the protection effect is not ideal.In this study,we developed a dual-antigen nanoconjugate vaccine containing both polysaccharide and protein antigens against Brucella.First,the antigenic polysaccharide was covalently coupled to the outer membrane protein Omp19 using protein glycan coupling technology,and then it was successfully loaded on a nano-carrier through the SpyTag/SpyCatcher system.After confirming the efficient immune activation and safety performance of the dual-antigen nanoconjugate vaccine,the potent serum antibody response against the two antigens and remarkable protective effect in non-lethal and lethal Brucella infection models were further demonstrated through different routes of administration.These results indicated that the dual-antigen nanoconjugate vaccine enhanced both T helper 1 cell(Th1)and Th2 immune responses and protected mice from Brucella infection.Furthermore,we found that this protective effect was maintained for at least 18 weeks.To our knowledge,this is the first Brucella vaccine bearing diverse antigens,including a protein and polysaccharide,on a single nanoparticle.Thus,we also present an attractive technology for co-delivery of different types of antigens using a strategy applicable to other vaccines against infectious diseases.
基金supported by the National Natural Science Foundation of China(Nos.81930122 and U20A20361)the National Key Research and Development Project of China(No.2021YFC2102101).
文摘Conjugate vaccines represent one of the most effective means for controlling the occurrence of bacterial diseases.Although nanotechnology has been greatly applied in the field of vaccines,it is seldom used for conjugate vaccine research because it is very difficult to connect polysaccharides and nanocarriers.In this work,an orthogonal and modular biosynthesis method was used to produce nanoconjugate vaccines using the SpyTag/SpyCatcher system.When SpyTag/SpyCatcher system is combined with protein glycosylation technology,bacterial O-polysaccharide obtained from Shigela flexneri 2a can be conjugated onto the surfaces of different virus-like particles(VLPs)in a biocompatible and controlled manner.After confirming the excellent lymph node targeting and humoral immune activation abilities,these nanoconjugate vaccines further induced efficient prophylactic effects against infection in a mouse model.These results demonstrated that natural polysaccharide antigens can be easily connected to VLPs to prepare highly efficient nanoconjugate vaccines.To the best of the researchers1 knowledge,this is the first time VLP-based nanoconjugate vaccines are produced efficiently,and this strategy could be applied to develop various pathogenic nanoconjugate vaccines.
基金the National Natural Science Foundation of China(No.51432006)the Ministry of Science and Technology of China for the International Science Linkages Program(No.2011DFG52970)+2 种基金the Ministry of Education of China for the Changjiang Innovation Research Team(No.IRT14R23)the Ministry of Education and the State Administration of Foreign Experts Affairs for the 111 Project(No.B13025)the Innovation Program of Shanghai Municipal Education Commission are gratefully acknowledged.M.G.H thanks the Australian Research Council(No.DP170100411)for support.
文摘Edge-functionalization of graphene is emerging as a powerful chemical method for the construction ofπ-delocalized highlyplanar graphene nanoconjugates that are not accessible through surface-supported syntheses.Herein,a graphene-porphyrin nanoconjugate via a robust pyrazine(pz)linkage has been obtained by condensing 2,3-diamino-5,10,15,20-tetraphenylporphyrin(DA-TPP)with ortho-quinone(o-quinone)moieties at edge sites of graphene oxide(GO).The as-prepared GO-pz-TPP exhibits an intense absorption extending from 375 to 900 nm and a high quenching yield(98%)of fluorescence,indicating a strong electronic coupling effect between GO and TPP units.GO-pz-TPP displays strong nonlinear optical(NLO)absorption and giant NLO coefficients with 800 and 1,030 nm fs laser,in sharp contrast to traditional graphene-porphyrin nanohybrids only NLO-active towards ns laser.Such a dramatic NLO performance towards femtosecond pulsed laser has not been achieved in any carbonchromophores nanohybridized materials to date.This work validates theπ-extended edge-functionalization strategy as a means to tune the NLO properties of graphene,thereby providing a new paradigm for the assembly of versatile optoelectronic materials.
基金Financial support from the National Natural Science Foundation of China(No.51432006)the Ministry of Science and Technology of China for the International Science Linkages Program(No.2011DFG52970)+2 种基金the Ministry of Education of China for the Changjiang Innovation Research Team(No.IRT14R23)the Ministry of Education and the State Administration of Foreign Experts Affairs for the 111 Project(No.B13025)the Innovation Program of Shanghai Municipal Education Commission are gratefully acknowledged.M.G.H thanks the Australian Research Council(No.DP170100411)for support.
文摘Electron-donating porphyrins(Por),electron-accepting phthalocyanines(Pcs),and reduced graphene oxide(RGO)were integrated into a multicomponent nanoconjugate(Por-RGO-Pc).The donor-π-acceptor nanoconjugate Por-RGO-Pc was characterized using Fourier transform infrared spectroscopy(FTIR),transmission electron microscopy(TEM),scanning electron microscopy(SEM),atomic force microscopy(AFM),and ultraviolet-visible(UV-Vis)spectroscopy.Photoinduced cascading electron/charge transfer from Por to RGO and from RGO to Pc was established from fluorescence,electrochemical,and femtosecond transient absorption(fs-TA)spectroscopy studies.The increased distance between the electron donors and acceptors of the Por-RGO-Pc nanoconjugate compared to the parent materials and the intermediate RGO-Pc results in longlived charge separation,and an enhancement in nonlinear optical(NLO)absorption(a large NLO coefficient of about 827.44 cm/GW)towards nanosecond laser irradiation at 532 nm.
