In the cold regions of northern China, incidents of municipal underground gas pipeline rupture and leakage occur quite frequently, most often in winter. To prevent harm to citizen safety and property, analysis of the ...In the cold regions of northern China, incidents of municipal underground gas pipeline rupture and leakage occur quite frequently, most often in winter. To prevent harm to citizen safety and property, analysis of the causes of such cracking and leakage is therefore valuable. Two incident analyses are discussed here and the reasons why most of these types of cases occur during winter are clarified. The effects of vehicle loadings above buried pipelines are calculated and compared with the effects and calculations of frost heaving forces. We demonstrate that when the soil layer above a pipeline freezes rapidly, the soil generates repeated frost heaving, which exerts heaving forces on the pipeline that can result in fatigue crack propagation and ultimate pipeline failure. Therefore, the incident induced by frost heaving is one of the primary reasons of gas pipeline failure. Based on these analyses, we present some recommendations pertaining to the proper design, construction, and management of gas pipelines.展开更多
Generation-based linguistic steganography is a popular research area of information hiding.The text generative steganographic method based on conditional probability coding is the direction that researchers have recen...Generation-based linguistic steganography is a popular research area of information hiding.The text generative steganographic method based on conditional probability coding is the direction that researchers have recently paid attention to.However,in the course of our experiment,we found that the secret information hiding in the text tends to destroy the statistical distribution characteristics of the original text,which indicates that this method has the problem of the obvious reduction of text quality when the embedding rate increases,and that the topic of generated texts is uncontrollable,so there is still room for improvement in concealment.In this paper,we propose a topic-controlled steganography method which is guided by graph-to-text generation.The proposed model can automatically generate steganographic texts carrying secret messages from knowledge graphs,and the topic of the generated texts is controllable.We also provide a graph path coding method with corresponding detailed algorithms for graph-to-text generation.Different from traditional linguistic steganography methods,we encode the secret information during graph path coding rather than using conditional probability.We test our method in different aspects and compare it with other text generative steganographic methods.The experimental results show that the model proposed in this paper can effectively improve the quality of the generated text and significantly improve the concealment of steganographic text.展开更多
Lipid nanoparticle(LNP)-based drug delivery systems have become the most clinically advanced non-viral delivery technology.LNPs can encapsulate and deliver a wide variety of bioactive agents,including the small molecu...Lipid nanoparticle(LNP)-based drug delivery systems have become the most clinically advanced non-viral delivery technology.LNPs can encapsulate and deliver a wide variety of bioactive agents,including the small molecule drugs,proteins and peptides,and nucleic acids.However,as the physicochemical properties of small-and macromolecular cargos can vary drastically,every LNP carrier system needs to be carefully tailored in order to deliver the cargo molecules in a safe and efficient manner.Our group applied the combinatorial library synthesis approach and in vitro and in vivo screening strategy for the development of LNP delivery systems for drug delivery.In this Review,we highlight our recent progress in the design,synthesis,characterization,evaluation,and optimization of combinatorial LNPs with novel structures and properties for the delivery of small-and macromolecular therapeutics both in vitro and in vivo.These delivery systems have enormous potentials for cancer therapy,antimicrobial applications,gene silencing,genome editing,and more.We also discuss the key challenges to the mechanistic study and clinical translation of new LNP-enabled therapeutics.展开更多
Lipid nanoparticles are promising carriers for oral drug delivery.For bioactive cargos with intracellular targets,e.g.gene-editing proteins,it is essential for the cargo and carrier to remain complexed after crossing ...Lipid nanoparticles are promising carriers for oral drug delivery.For bioactive cargos with intracellular targets,e.g.gene-editing proteins,it is essential for the cargo and carrier to remain complexed after crossing the epithelial layer of intestine in order for the delivery system to transport the cargos inside targeted cells.However,limited studies have been conducted to verify the integrity of cargo/carrier nanocomplexes and their capability in facilitating cargo delivery intracellularly after the nanocomplex crossing the epithelial barrier.Herein,we used a traditional 2D transwell system and a recently developed 3D tissue engineered intestine model and demonstrated the synthetic lipid nanoparticle(carrier)and protein(cargo)nanocomplexes are able to cross the epithelial layer and deliver the protein cargo inside the underneath cells.We found that the EC16-63 LNP efficiently encapsulated the GFP-Cre recombinase,penetrated the intestinal monolayer cells in both the 2D cell culture and 3D tissue models through temporarily interrupting the tight junctions between epithelial layer.After transporting across the intestinal epithelia,the EC16-63 and GFP-Cre recombinase nanocomplexes can enter the underneath cells to induce gene recombination.These results suggest that the in vitro 3D intestinal tissue model is useful for identifying effective lipid nanoparticles for potential oral drug delivery.展开更多
Facing the high incidence of skin diseases,it is urgent to develop functional materials with high bioactivity for wound healing,where reactive oxygen species(ROS)play an important role in the wound healing process mai...Facing the high incidence of skin diseases,it is urgent to develop functional materials with high bioactivity for wound healing,where reactive oxygen species(ROS)play an important role in the wound healing process mainly via adjustment of immune response and neovasculation.In this study,we developed a kind of bioabsorbable materials with ROS-mediation capacity for skin disease therapy.Firstly,redox-sensitive poly(N-isopropylacrylamide-acrylic acid)(PNA)nanogels were synthesized by radical emulsion polymerization method using a disulfide molecule as crosslinker.The resulting nanogels were then incorporated into the nanofibrous membrane of poly(L-lactic acid)(PLLA)via airbrushing approach to offer bioabsorbable membrane with redox-sensitive ROS-balance capacity.In vitro biological evaluation indicated that the PNA-contained bioabsorbable membrane improved cell adhesion and proliferation compared to the native PLLA membrane.In vivo study using mouse wound skin model demonstrated that PNA-doped nanofibrous membranes could promote the wound healing process,where the disulfide bonds in them were able to adjust the ROS level in the wound skin for mediation of redox potential to achieve higher wound healing efficacy.展开更多
基金supported by the National Natural Science Foundation of China (NNSF) (No. 10472020)the Special Foundation of Dalian University of Technology (DUT) (DUTTX2009-103)
文摘In the cold regions of northern China, incidents of municipal underground gas pipeline rupture and leakage occur quite frequently, most often in winter. To prevent harm to citizen safety and property, analysis of the causes of such cracking and leakage is therefore valuable. Two incident analyses are discussed here and the reasons why most of these types of cases occur during winter are clarified. The effects of vehicle loadings above buried pipelines are calculated and compared with the effects and calculations of frost heaving forces. We demonstrate that when the soil layer above a pipeline freezes rapidly, the soil generates repeated frost heaving, which exerts heaving forces on the pipeline that can result in fatigue crack propagation and ultimate pipeline failure. Therefore, the incident induced by frost heaving is one of the primary reasons of gas pipeline failure. Based on these analyses, we present some recommendations pertaining to the proper design, construction, and management of gas pipelines.
基金supported in part by the National Natural Science Foundation of China [62102136]the 2020 Opening Fund for Hubei Key Laboratory of Intelligent Vision Based Monitoring for Hydroelectric Engineering [2020SDSJ06]the Construction Fund for Hubei Key Laboratory of Intelligent Vision Based Monitoring for Hydroelectric Engineering [2019ZYYD007].
文摘Generation-based linguistic steganography is a popular research area of information hiding.The text generative steganographic method based on conditional probability coding is the direction that researchers have recently paid attention to.However,in the course of our experiment,we found that the secret information hiding in the text tends to destroy the statistical distribution characteristics of the original text,which indicates that this method has the problem of the obvious reduction of text quality when the embedding rate increases,and that the topic of generated texts is uncontrollable,so there is still room for improvement in concealment.In this paper,we propose a topic-controlled steganography method which is guided by graph-to-text generation.The proposed model can automatically generate steganographic texts carrying secret messages from knowledge graphs,and the topic of the generated texts is controllable.We also provide a graph path coding method with corresponding detailed algorithms for graph-to-text generation.Different from traditional linguistic steganography methods,we encode the secret information during graph path coding rather than using conditional probability.We test our method in different aspects and compare it with other text generative steganographic methods.The experimental results show that the model proposed in this paper can effectively improve the quality of the generated text and significantly improve the concealment of steganographic text.
基金supported by the National Institutes of Health(NIH)Grants R01 EB027170-04 and UG3 TR002636-01,USA。
文摘Lipid nanoparticle(LNP)-based drug delivery systems have become the most clinically advanced non-viral delivery technology.LNPs can encapsulate and deliver a wide variety of bioactive agents,including the small molecule drugs,proteins and peptides,and nucleic acids.However,as the physicochemical properties of small-and macromolecular cargos can vary drastically,every LNP carrier system needs to be carefully tailored in order to deliver the cargo molecules in a safe and efficient manner.Our group applied the combinatorial library synthesis approach and in vitro and in vivo screening strategy for the development of LNP delivery systems for drug delivery.In this Review,we highlight our recent progress in the design,synthesis,characterization,evaluation,and optimization of combinatorial LNPs with novel structures and properties for the delivery of small-and macromolecular therapeutics both in vitro and in vivo.These delivery systems have enormous potentials for cancer therapy,antimicrobial applications,gene silencing,genome editing,and more.We also discuss the key challenges to the mechanistic study and clinical translation of new LNP-enabled therapeutics.
基金Q.X.acknowledges the funding support by NIH Grant R01 EB027170-01D.L.K.acknowledges the funding support by NIH grant 5U19AI131126-04.
文摘Lipid nanoparticles are promising carriers for oral drug delivery.For bioactive cargos with intracellular targets,e.g.gene-editing proteins,it is essential for the cargo and carrier to remain complexed after crossing the epithelial layer of intestine in order for the delivery system to transport the cargos inside targeted cells.However,limited studies have been conducted to verify the integrity of cargo/carrier nanocomplexes and their capability in facilitating cargo delivery intracellularly after the nanocomplex crossing the epithelial barrier.Herein,we used a traditional 2D transwell system and a recently developed 3D tissue engineered intestine model and demonstrated the synthetic lipid nanoparticle(carrier)and protein(cargo)nanocomplexes are able to cross the epithelial layer and deliver the protein cargo inside the underneath cells.We found that the EC16-63 LNP efficiently encapsulated the GFP-Cre recombinase,penetrated the intestinal monolayer cells in both the 2D cell culture and 3D tissue models through temporarily interrupting the tight junctions between epithelial layer.After transporting across the intestinal epithelia,the EC16-63 and GFP-Cre recombinase nanocomplexes can enter the underneath cells to induce gene recombination.These results suggest that the in vitro 3D intestinal tissue model is useful for identifying effective lipid nanoparticles for potential oral drug delivery.
基金The research was supported by National Key R&D Program of China(2018YFE0201500,2017YFB0309300)National Natural Science Foundation of China(81772317,51973060,82072051,81771964)+5 种基金National Natural Science Foundation of China for Innovative Research Groups(51621002)Natural Science Foundation of Heilongjiang Province(LH2020H076)Shanghai International Cooperation Program(15520721200)Central Universities(WD1714002)The funding grants from Joint research project of important diseases in Xuhui District(XHLHGG201802)Fundamental Research Funds for the Shanghai Municipal Commission of Health and Family Planning(201740034)were also acknowledged.
文摘Facing the high incidence of skin diseases,it is urgent to develop functional materials with high bioactivity for wound healing,where reactive oxygen species(ROS)play an important role in the wound healing process mainly via adjustment of immune response and neovasculation.In this study,we developed a kind of bioabsorbable materials with ROS-mediation capacity for skin disease therapy.Firstly,redox-sensitive poly(N-isopropylacrylamide-acrylic acid)(PNA)nanogels were synthesized by radical emulsion polymerization method using a disulfide molecule as crosslinker.The resulting nanogels were then incorporated into the nanofibrous membrane of poly(L-lactic acid)(PLLA)via airbrushing approach to offer bioabsorbable membrane with redox-sensitive ROS-balance capacity.In vitro biological evaluation indicated that the PNA-contained bioabsorbable membrane improved cell adhesion and proliferation compared to the native PLLA membrane.In vivo study using mouse wound skin model demonstrated that PNA-doped nanofibrous membranes could promote the wound healing process,where the disulfide bonds in them were able to adjust the ROS level in the wound skin for mediation of redox potential to achieve higher wound healing efficacy.
