Most existing blockchain schemes are based on the design concept“openness and transparency”to realize data security,which usually require transaction data to be presented in the form of plaintext.However,it inevitab...Most existing blockchain schemes are based on the design concept“openness and transparency”to realize data security,which usually require transaction data to be presented in the form of plaintext.However,it inevitably brings the issues with respect to data privacy and operating performance.In this paper,we proposed a novel blockchain scheme called Cipherchain,which can process and maintain transaction data in the form of ciphertext while the characteristics of immutability and auditability are guaranteed.Specifically in our scheme,transactions can be encrypted locally based on a searchable encryption scheme called multi-user public key encryption with conjunctive keyword search(mPECK),and can be accessed by multiple specific participants after appended to the globally consistent distributed ledger.By introducing execution-consensus-update paradigm of transaction flow,Cipherchain cannot only make it possible for transaction data to exist in the form of ciphertext,but also guarantee the overall system performance not greatly affected by cryptographic operations and other local execution work.In addition,Cipherchain is a promising scheme to realize the technology combination of“blockchain+cloud computing”and“permissioned blockchain+public blockchain”.展开更多
Antisense oligonucleotide(ASO)for anti-apoptosis is emerging as a highly promising therapeutic agents for ischemic stroke with complex pathological environment.However,its therapeutic efficacy is seriously limited by ...Antisense oligonucleotide(ASO)for anti-apoptosis is emerging as a highly promising therapeutic agents for ischemic stroke with complex pathological environment.However,its therapeutic efficacy is seriously limited by a number of challenges including inefficient internalization,low blood-brain barrier(BBB)penetration,poor stability,and potential toxicity of the carrier.Herein,a carrier-free programmed spherical nucleic acid nanostructure is developed for effective ischemic stroke therapy via integrating multifunctional modules into one DNA structure.By co-encoding caspase-3-ASO and transferrin receptor(TfR)aptamer into circle template,the spherical nucleic acid nanostructure(TD)was obtained via self-assembly.The experimental results demonstrated that the developed TD displayed efficient BBB penetration capability(6.4 times)and satisfactory caspase-3 silence effect(2.3 times)due to the dense DNA packaging in TD.Taken together,our study demonstrated that the carrier-free programmed spherical nucleic acid nanostructure could significantly improve the therapeutic efficacy of ischemic stroke and was a promising therapeutic tool for various brain damage-related diseases.展开更多
Dear Editor,Economic and population growth increasingly consume resources from the environment and present a major challenge regarding the management of waste.The demand for insects as a resource is increasing,as they...Dear Editor,Economic and population growth increasingly consume resources from the environment and present a major challenge regarding the management of waste.The demand for insects as a resource is increasing,as they have the potential to aid in waste recycling and alleviate shortages of natural resources(Ojha et al.,2020).The black soldier fly(BSE,Hermetia illucens L.)is a species native to tropical and subtropical parts of the Americas.展开更多
5-Aminolevulinic acid(5-ALA)has been approved for clinical photodynamic therapy(PDT)due to its negligible photosensitive toxicity.However,the curative effect of 5-ALA is restricted by intracellular biotransformation i...5-Aminolevulinic acid(5-ALA)has been approved for clinical photodynamic therapy(PDT)due to its negligible photosensitive toxicity.However,the curative effect of 5-ALA is restricted by intracellular biotransformation inactivation of 5-ALA and potential DNA repair of tumor cells.Inspired by the crucial function of iron ions in 5-ALA transformation and DNA repair,a liposomal nanomedicine(MFLs@5-ALA/DFO)with intracellular iron ion regulation property was developed for boosting the PDT of 5-ALA,which was prepared by co-encapsulating 5-ALA and DFO(deferoxamine,a special iron chelator)into the membrane fusion liposomes(MFLs).MFLs@5-ALA/DFO showed an improved pharmaceutical behavior and rapidly fused with tumor cell membrane for 5-ALA and DFO co-delivery.MFLs@5-ALA/DFO could efficiently reduce iron ion,thus blocking the biotransformation of photosensitive protoporphyrin IX(Pp IX)to heme,realizing significant accumulation of photosensitivity.Meanwhile,the activity of DNA repair enzyme was also inhibited with the reduction of iron ion,resulting in the aggravated DNA damage in tumor cells.Our findings showed MFLs@5-ALA/DFO had potential to be applied for enhanced PDT of 5-ALA.展开更多
Inspired by the adaptation of cells to the surrounding environment,the combination of cell membrane and nanomaterials has gradually become a new type of biomimetic nanocomposite.The construction of endogenous membrane...Inspired by the adaptation of cells to the surrounding environment,the combination of cell membrane and nanomaterials has gradually become a new type of biomimetic nanocomposite.The construction of endogenous membrane biomimetic nanocarriers(EMBNs)not only retains the structure of membrane surface protein,but also has the properties of nanoparticles(NPs),also provides the ability of natural interaction between nanomaterials and organisms,thus overcoming the severe challenges faced by traditional nanodelivery systems in clinical application.In this paper,the construction methods of EMBNs are reviewed,focusing on a simple method to prepare membrane proteins.Secondly,EMBNs were classified according a variety of cell membranes.Finally,the unique advantages of EMBNs in nanomedicine are introduced,including improving biocompatibility,homologous targeting ability,prolonging blood circulation time and immune escape abilty.In nanomedicine,such as targeted delivery,phototherapy,immunotherapy and tumor imaging,multifaceted biological interfaces through membrane masking provide a new approach for the development of multifunctional NPs.展开更多
Oligonucleotide drugs have been used widely as therapeutic agents for gene therapy,while their instability in biological media and inefficiency for intracellular delivery remain major hurdles for practical in vivo app...Oligonucleotide drugs have been used widely as therapeutic agents for gene therapy,while their instability in biological media and inefficiency for intracellular delivery remain major hurdles for practical in vivo applications.Herein,we report a circular Y-shaped aptamer–DNAzyme conjugate(cYAD)for highly efficient in vivo gene silencing via RNA cleavage,which can been employed in various disease treatments,including cancer,inflammation,as well as viral infections.Systematic studies revealed that cyclization of the DNA structure could improve the stability of oligonucleotide drugs in vivo.Besides,the bivalent aptamer motifs provided a specific and enhanced tumor cell targeting ability for accumulation and retention of the oligonucleotide drugs at the tumor site.As a proof of concept,a widely applicable Na+-dependent fluorescent sensor,NaA43 DNAzyme,was used to inhibit MET gene expression in mice tumor model tissues,which exhibited highly efficient gene silencing performance in vivo,which confirmed our findings with cYAD.This strategy provides a novel approach for the construction of oligonucleotide drugs for practical therapeutic applications.展开更多
基金This work is supported by the NSFC(Grant Nos.61671087,61962009,61003287)the Fok Ying Tong Education Foundation(Grant No.131067)+4 种基金the Major Scientific and Technological Special Project of Guizhou Province(Grant No.20183001)the Foundation of State Key Laboratory of Public Big Data(Grant No.2018BDKFJJ018)CCF-Tencent Open Fund WeBank Special Funding(CCF-WebankRAGR20180104)the High-quality and Cutting-edge Disciplines Construction Project for Universities in Beijing(Internet Information,Communication University of China)the Fundamental Research Funds for the Central Universities,and the Fundamental Research Funds for the Central Universities No.2019XD-A02.
文摘Most existing blockchain schemes are based on the design concept“openness and transparency”to realize data security,which usually require transaction data to be presented in the form of plaintext.However,it inevitably brings the issues with respect to data privacy and operating performance.In this paper,we proposed a novel blockchain scheme called Cipherchain,which can process and maintain transaction data in the form of ciphertext while the characteristics of immutability and auditability are guaranteed.Specifically in our scheme,transactions can be encrypted locally based on a searchable encryption scheme called multi-user public key encryption with conjunctive keyword search(mPECK),and can be accessed by multiple specific participants after appended to the globally consistent distributed ledger.By introducing execution-consensus-update paradigm of transaction flow,Cipherchain cannot only make it possible for transaction data to exist in the form of ciphertext,but also guarantee the overall system performance not greatly affected by cryptographic operations and other local execution work.In addition,Cipherchain is a promising scheme to realize the technology combination of“blockchain+cloud computing”and“permissioned blockchain+public blockchain”.
基金This work was funded by the National Natural Science Foundation of China(Nos.82073395 and 319009919)Postdoctoral Science Foundation of China(Nos.2020TQ0288).
文摘Antisense oligonucleotide(ASO)for anti-apoptosis is emerging as a highly promising therapeutic agents for ischemic stroke with complex pathological environment.However,its therapeutic efficacy is seriously limited by a number of challenges including inefficient internalization,low blood-brain barrier(BBB)penetration,poor stability,and potential toxicity of the carrier.Herein,a carrier-free programmed spherical nucleic acid nanostructure is developed for effective ischemic stroke therapy via integrating multifunctional modules into one DNA structure.By co-encoding caspase-3-ASO and transferrin receptor(TfR)aptamer into circle template,the spherical nucleic acid nanostructure(TD)was obtained via self-assembly.The experimental results demonstrated that the developed TD displayed efficient BBB penetration capability(6.4 times)and satisfactory caspase-3 silence effect(2.3 times)due to the dense DNA packaging in TD.Taken together,our study demonstrated that the carrier-free programmed spherical nucleic acid nanostructure could significantly improve the therapeutic efficacy of ischemic stroke and was a promising therapeutic tool for various brain damage-related diseases.
基金funded by projects under the National Natural Science Foundation of China(nos.32021001)the China Postdoctoral Science Foundation(nos.2022M723142)the Chinese Academy of Sciences(nos.XDPB16).
文摘Dear Editor,Economic and population growth increasingly consume resources from the environment and present a major challenge regarding the management of waste.The demand for insects as a resource is increasing,as they have the potential to aid in waste recycling and alleviate shortages of natural resources(Ojha et al.,2020).The black soldier fly(BSE,Hermetia illucens L.)is a species native to tropical and subtropical parts of the Americas.
基金supported by the National Natural Science Foundation of China(Nos.82073395,21904119 and 319009919)Innovation Talent Support Program of Henan Province(No.19HASTIT006,China)+1 种基金Key Scientific Research Projects,Education Department of Henan Province(No.20A350009,China)Key scientific research projects,Science and Technology Department of Henan Province(No.192102310147,China)。
文摘5-Aminolevulinic acid(5-ALA)has been approved for clinical photodynamic therapy(PDT)due to its negligible photosensitive toxicity.However,the curative effect of 5-ALA is restricted by intracellular biotransformation inactivation of 5-ALA and potential DNA repair of tumor cells.Inspired by the crucial function of iron ions in 5-ALA transformation and DNA repair,a liposomal nanomedicine(MFLs@5-ALA/DFO)with intracellular iron ion regulation property was developed for boosting the PDT of 5-ALA,which was prepared by co-encapsulating 5-ALA and DFO(deferoxamine,a special iron chelator)into the membrane fusion liposomes(MFLs).MFLs@5-ALA/DFO showed an improved pharmaceutical behavior and rapidly fused with tumor cell membrane for 5-ALA and DFO co-delivery.MFLs@5-ALA/DFO could efficiently reduce iron ion,thus blocking the biotransformation of photosensitive protoporphyrin IX(Pp IX)to heme,realizing significant accumulation of photosensitivity.Meanwhile,the activity of DNA repair enzyme was also inhibited with the reduction of iron ion,resulting in the aggravated DNA damage in tumor cells.Our findings showed MFLs@5-ALA/DFO had potential to be applied for enhanced PDT of 5-ALA.
基金This work was supported by the Development Plan of Youth Innovation Team in Colleges and Universities of Shandong Province(2020KJC003).
文摘Inspired by the adaptation of cells to the surrounding environment,the combination of cell membrane and nanomaterials has gradually become a new type of biomimetic nanocomposite.The construction of endogenous membrane biomimetic nanocarriers(EMBNs)not only retains the structure of membrane surface protein,but also has the properties of nanoparticles(NPs),also provides the ability of natural interaction between nanomaterials and organisms,thus overcoming the severe challenges faced by traditional nanodelivery systems in clinical application.In this paper,the construction methods of EMBNs are reviewed,focusing on a simple method to prepare membrane proteins.Secondly,EMBNs were classified according a variety of cell membranes.Finally,the unique advantages of EMBNs in nanomedicine are introduced,including improving biocompatibility,homologous targeting ability,prolonging blood circulation time and immune escape abilty.In nanomedicine,such as targeted delivery,phototherapy,immunotherapy and tumor imaging,multifaceted biological interfaces through membrane masking provide a new approach for the development of multifunctional NPs.
基金supported by grants from the National Natural Science Foundation of China(nos.81601597,21904119,319009919,21621003,and U1704178)Innovation Talent Support Program of Henan Province(no.19HASTIT006)+2 种基金Key Scientific Research Projects(Education Department of Henan Province,nos.17A350003 and 20A350009)Key Scientific Research Projects(Science and Technology Department of Henan Province,no.192102310147)Postdoctoral Science Foundation of China(nos.2018T110745 and 2017M622380).
文摘Oligonucleotide drugs have been used widely as therapeutic agents for gene therapy,while their instability in biological media and inefficiency for intracellular delivery remain major hurdles for practical in vivo applications.Herein,we report a circular Y-shaped aptamer–DNAzyme conjugate(cYAD)for highly efficient in vivo gene silencing via RNA cleavage,which can been employed in various disease treatments,including cancer,inflammation,as well as viral infections.Systematic studies revealed that cyclization of the DNA structure could improve the stability of oligonucleotide drugs in vivo.Besides,the bivalent aptamer motifs provided a specific and enhanced tumor cell targeting ability for accumulation and retention of the oligonucleotide drugs at the tumor site.As a proof of concept,a widely applicable Na+-dependent fluorescent sensor,NaA43 DNAzyme,was used to inhibit MET gene expression in mice tumor model tissues,which exhibited highly efficient gene silencing performance in vivo,which confirmed our findings with cYAD.This strategy provides a novel approach for the construction of oligonucleotide drugs for practical therapeutic applications.
