Suspension cells play a crucial role in many biological processes. However, compared to adherent cells, it is particularly challenging to introduce exogenous genes into suspension cells to regulate their biological fu...Suspension cells play a crucial role in many biological processes. However, compared to adherent cells, it is particularly challenging to introduce exogenous genes into suspension cells to regulate their biological functions with non-viral gene vectors, mainly due to the low cellular uptake and endosomal escape of polyplexes. Herein, to improve the interactions of polyplexes with cellular membranes, we design and synthesize highly branched poly(β-amino ester)(HPAE) via an “A2 + B4 + C2” Michael addition strategy.Results show that branching significantly increases DNA condensation of HPAE, cellular uptake and endosomal escape of HPAE/DNA polyplexes. In mast cells(MCs), HPAE exhibits up to 80-fold higher gene transfection efficiency compared to the corresponding linear poly(β-amino ester)(LPAE) and the leading commercial gene transfection reagents PEI25k, jetPEI, and Lipofectamine 3000, without causing obvious cytotoxicity. Our study establishes a reliable non-viral platform for efficient gene transfection of suspension cells.展开更多
Highly branched poly(β-amino ester)s(HPAEs) have shown their great promise in gene delivery. However, their broad molecular weight distribution(MWD) poses an additional challenge to the mechanistic understanding of t...Highly branched poly(β-amino ester)s(HPAEs) have shown their great promise in gene delivery. However, their broad molecular weight distribution(MWD) poses an additional challenge to the mechanistic understanding of the influence of molecular weight(MW) on their gene transfection activity. Using a stepwise precipitation strategy, HPAEs were fractionated. It is shown that MW has a significant effect on the transfection activity and cytotoxicity of HPAEs. The intermediate MW mediates higher transfection efficiency while maintaining high cell viability. Mechanistic studies show that the intermediate MW confers stronger DNA binding affinity to HPAEs, leading to the formulation of polyplexes with a relatively smaller size and more positive zeta potential. This study not only suggests a simple strategy to fractionate HPAEs with narrow MWD but also provides new insights into understanding the structure-property relationship, which would facilitate the clinical translation of HPAEs in gene therapy.展开更多
Smart grid enhances the intelligence of the traditional power grid,which allows sharing varied data such as consumer,production,or energy with service consumers.Due to the untrustworthy networks,there exist potential ...Smart grid enhances the intelligence of the traditional power grid,which allows sharing varied data such as consumer,production,or energy with service consumers.Due to the untrustworthy networks,there exist potential security threats(e.g.,unauthorized access and modification,malicious data theft)hindering the development of smart grid.While several access control schemes have been proposed for smart grid to achieve sensitive data protection and fine-grained identity management,most of them cannot satisfy the requirements of decentralizing smart grid environment and suffer from key escrow problems.In addition,some existing solutions cannot achieve dynamic user management for lacking the privilege revocation mechanism.In this paper,we propose a decentralizing access control system with user revocation to relieve the above problems.We design a new multiple-authority attribute-based encryption(MABE)scheme to keep data confidentiality and adapt decentralizing smart grid applications.We also compare our proposal with the similar solution from both security and performance.The comparing results show that our access control system can achieve a trade-off among confidentiality,authentication,distribution and efficiency in smart grid.展开更多
The triboelectric nanogenerator(TENG)is a new mechanical energy harvesting technology in which the typical viscoelastic material polydimethylsiloxane(PDMS)is widely used.Micro-/nano-textures are often fabricated on th...The triboelectric nanogenerator(TENG)is a new mechanical energy harvesting technology in which the typical viscoelastic material polydimethylsiloxane(PDMS)is widely used.Micro-/nano-textures are often fabricated on the PDMS surface to enhance the electrical performance of TENG.As the contact region decreases to micro/nano scale,the adhesive forces become dominant.However,there is still a lack of contact mechanics model considering both material viscoelasticity and the adhesive forces to guide the surface texture design.In this paper,the explicit data-fitting formulas based on the fractional derivative Zener model are firstly derived to identify the viscoelastic constitutive parameters,which can not only avoid the influence of the initial contact point,but also ensure the accurate conversion between the creep compliance and the relaxation modulus function.Then a viscoelastic-adhesive contact model based on the fitted constitutive parameters is established,and the numerical algorithms such as bi-conjugate stabilized(Bi-CGSTAB)method and fast Fourier transform(FFT)technique are employed to analyze the effects of material viscoelasticity and texture sizes on the contact and electrical performance.It is shown that,compared with results from the elastic-adhesive contact model,the contact area ratio based on the viscoelastic-adhesive contact model is significantly larger,which is much closer to the experimental results.Among the selected sizes of pyramid texture,the higher electrical performance can be obtained from the textures with a smaller pitch and a larger width under the heavier applied load.This study can provide a theoretical reference for the design of viscoelastic surface texture of TENG.展开更多
Periodontitis is recognized as the major cause of tooth loss in adults, posing an adverse impact on systemic health. In periodontitis, excessive production of reactive oxygen species (ROS) at the inflamed site culmina...Periodontitis is recognized as the major cause of tooth loss in adults, posing an adverse impact on systemic health. In periodontitis, excessive production of reactive oxygen species (ROS) at the inflamed site culminates in periodontal destruction. In this study, a novel ROS-responsive drug delivery system based on polydopamine (PDA) functionalized mesoporous silica nanoparticles was developed for delivering minocycline hydrochloride (MH) to treat periodontitis. The outer PDA layer and the inner MH of the nanoparticles acted as ROS scavengers and anti-inflammatory agents, respectively. Under the synergistic action of PDA and MH, macrophages were polarized from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype. The in vitro experiments provided convincing evidence that PDA could scavenge ROS effectively, and the expression of pro-inflammatory cytokines was attenuated and the secretion of anti-inflammatory cytokines was enhanced through M1 to M2 polarization of macrophages with the cooperation of MH. In addition, the results obtained from the periodontitis rat models demonstrated that the synergetic effect of PDA and MH prevented alveolar bone loss without causing any adverse effect. Taken together, the results from the present investigation provide a new strategy to remodel the inflammatory microenvironment by inducing the polarization of macrophages from M1 toward M2 state for the treatment of periodontitis.展开更多
基金funded by National Natural Science Foundation of China (NSFC, No. 51903202)the Innovation Capability Support Program of Shaanxi (No. 2022TD-48)the Key R&D Program of Shaanxi Province (No. 2020GXLH-Y-016)。
文摘Suspension cells play a crucial role in many biological processes. However, compared to adherent cells, it is particularly challenging to introduce exogenous genes into suspension cells to regulate their biological functions with non-viral gene vectors, mainly due to the low cellular uptake and endosomal escape of polyplexes. Herein, to improve the interactions of polyplexes with cellular membranes, we design and synthesize highly branched poly(β-amino ester)(HPAE) via an “A2 + B4 + C2” Michael addition strategy.Results show that branching significantly increases DNA condensation of HPAE, cellular uptake and endosomal escape of HPAE/DNA polyplexes. In mast cells(MCs), HPAE exhibits up to 80-fold higher gene transfection efficiency compared to the corresponding linear poly(β-amino ester)(LPAE) and the leading commercial gene transfection reagents PEI25k, jetPEI, and Lipofectamine 3000, without causing obvious cytotoxicity. Our study establishes a reliable non-viral platform for efficient gene transfection of suspension cells.
基金funded by the National Natural Science Foundation of China(NSFC,No.51903202)Hainan Provincial Natural Science Foundation of China(No.521RC1058)+3 种基金the Key R&D Program of Shaanxi Province(No.2020GXLH-Y-016)the Natural Science Foundation of Shaanxi Province(No.2020JM-055)the Fundamental Research Funds for the Central Universities(No.xtr042019020)the Young Talents Support Plan of Xi’an Jiaotong University(No.HG6J002)。
文摘Highly branched poly(β-amino ester)s(HPAEs) have shown their great promise in gene delivery. However, their broad molecular weight distribution(MWD) poses an additional challenge to the mechanistic understanding of the influence of molecular weight(MW) on their gene transfection activity. Using a stepwise precipitation strategy, HPAEs were fractionated. It is shown that MW has a significant effect on the transfection activity and cytotoxicity of HPAEs. The intermediate MW mediates higher transfection efficiency while maintaining high cell viability. Mechanistic studies show that the intermediate MW confers stronger DNA binding affinity to HPAEs, leading to the formulation of polyplexes with a relatively smaller size and more positive zeta potential. This study not only suggests a simple strategy to fractionate HPAEs with narrow MWD but also provides new insights into understanding the structure-property relationship, which would facilitate the clinical translation of HPAEs in gene therapy.
基金financially supported by the Science and Technology Project of State Grid Customer Service Center(research on access control and searchable encryption technology of attribute encryption for data value-added service)(SGKF0000DFQT2200030).
文摘Smart grid enhances the intelligence of the traditional power grid,which allows sharing varied data such as consumer,production,or energy with service consumers.Due to the untrustworthy networks,there exist potential security threats(e.g.,unauthorized access and modification,malicious data theft)hindering the development of smart grid.While several access control schemes have been proposed for smart grid to achieve sensitive data protection and fine-grained identity management,most of them cannot satisfy the requirements of decentralizing smart grid environment and suffer from key escrow problems.In addition,some existing solutions cannot achieve dynamic user management for lacking the privilege revocation mechanism.In this paper,we propose a decentralizing access control system with user revocation to relieve the above problems.We design a new multiple-authority attribute-based encryption(MABE)scheme to keep data confidentiality and adapt decentralizing smart grid applications.We also compare our proposal with the similar solution from both security and performance.The comparing results show that our access control system can achieve a trade-off among confidentiality,authentication,distribution and efficiency in smart grid.
基金This work is financially supported by National Natural Science Foundation of China(Nos.51735001 and 11472046).
文摘The triboelectric nanogenerator(TENG)is a new mechanical energy harvesting technology in which the typical viscoelastic material polydimethylsiloxane(PDMS)is widely used.Micro-/nano-textures are often fabricated on the PDMS surface to enhance the electrical performance of TENG.As the contact region decreases to micro/nano scale,the adhesive forces become dominant.However,there is still a lack of contact mechanics model considering both material viscoelasticity and the adhesive forces to guide the surface texture design.In this paper,the explicit data-fitting formulas based on the fractional derivative Zener model are firstly derived to identify the viscoelastic constitutive parameters,which can not only avoid the influence of the initial contact point,but also ensure the accurate conversion between the creep compliance and the relaxation modulus function.Then a viscoelastic-adhesive contact model based on the fitted constitutive parameters is established,and the numerical algorithms such as bi-conjugate stabilized(Bi-CGSTAB)method and fast Fourier transform(FFT)technique are employed to analyze the effects of material viscoelasticity and texture sizes on the contact and electrical performance.It is shown that,compared with results from the elastic-adhesive contact model,the contact area ratio based on the viscoelastic-adhesive contact model is significantly larger,which is much closer to the experimental results.Among the selected sizes of pyramid texture,the higher electrical performance can be obtained from the textures with a smaller pitch and a larger width under the heavier applied load.This study can provide a theoretical reference for the design of viscoelastic surface texture of TENG.
基金This work was financially supported by the National Natural Science Foundation of China(Nos.21804072 and 82071838)the Natural Science Foundation of Jiangsu Province(No.BK20180941)+3 种基金China Postdoctoral Science Foundation(No.2018M642297)Science and technology Project of Nantong City(No.MS12019022)the Postgraduate Research&Practice Innovation Program of Jiangsu Province(Nos.KYCX19-2080 and KYCX19-2078)Jiangsu Students’Program for Innovation and Entrepreneurship Training(No.201910304031Z).
文摘Periodontitis is recognized as the major cause of tooth loss in adults, posing an adverse impact on systemic health. In periodontitis, excessive production of reactive oxygen species (ROS) at the inflamed site culminates in periodontal destruction. In this study, a novel ROS-responsive drug delivery system based on polydopamine (PDA) functionalized mesoporous silica nanoparticles was developed for delivering minocycline hydrochloride (MH) to treat periodontitis. The outer PDA layer and the inner MH of the nanoparticles acted as ROS scavengers and anti-inflammatory agents, respectively. Under the synergistic action of PDA and MH, macrophages were polarized from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype. The in vitro experiments provided convincing evidence that PDA could scavenge ROS effectively, and the expression of pro-inflammatory cytokines was attenuated and the secretion of anti-inflammatory cytokines was enhanced through M1 to M2 polarization of macrophages with the cooperation of MH. In addition, the results obtained from the periodontitis rat models demonstrated that the synergetic effect of PDA and MH prevented alveolar bone loss without causing any adverse effect. Taken together, the results from the present investigation provide a new strategy to remodel the inflammatory microenvironment by inducing the polarization of macrophages from M1 toward M2 state for the treatment of periodontitis.
