In the cold regions of northern China, incidents of municipal underground gas pipeline rupture and leakage occur quite fi-equently, aaost often in winter. To prevent harm to citizen safety and property, analysis of th...In the cold regions of northern China, incidents of municipal underground gas pipeline rupture and leakage occur quite fi-equently, aaost 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 dttring winter are clarified. Fhe effects of vehicle loadings above buried pipelines are calculated and compared with the effects and calculations of frost heaving forces. We demonstrate thtit 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 9y 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
Background:We systematically searched and summarized clinical studies on traditional Chinese medicine(TCM)for age-relatedmacular degeneration(AMD)with the method of evidence map.We aimed to provide evidence and resear...Background:We systematically searched and summarized clinical studies on traditional Chinese medicine(TCM)for age-relatedmacular degeneration(AMD)with the method of evidence map.We aimed to provide evidence and research direction for the prevention or treatment of AMD with TCM in the future.Materials and methods:We searched PubMed,Web of Science,EMBASE,and Chinese databases including CNKI(Chinese National Knowledge Infrastructure),WanFang and VIP,ClinicalTrials.gov,and ChineseClinical Trial Registry Center studies on the prevention or treatment of TCMfor AMD from January 2000 to November 2022.We showed distribution features of these studies in the form of text description,graphs,and tables.Results:The final 258 articles included 245 clinical studies,9 systematic reviews ormeta-analyses,and 4 guidelines,expert consensus,or clinical pathway.After analyzing the articles with a focus on the stage of AMD,study type,sample size,intervention measures,outcome indicators,and the quality of evidence,we found that the studies were increasing,most of which were wet AMD,the main study type was randomized controlled trials,and the sample size was mostly fewer than 100 cases.Different interventions of TCM,such as Chinese medicine,Chinese patentmedicine,or acupuncture,showed the potential benefits of improving vision,reducing fundus lesions,and alleviating some uncomfortable symptoms.However,the sample size of these studies was small.The outcome indicators were not unified,and the stage of AMD was unclear.The quality of articles was lower,and there were few studies on early AMD.The advantages of TCM for the prevention or treatment of AMD remained unclear.Conclusions:Early intervention will be the focus and direction of AMD in the prevention or treatment of TCM,and more standardized clinical studies of TCM for early AMD need to be designed and carried out in the future.展开更多
Amphiphilic aminated fullerenes have a broad margin of safety and significant antitumor effects.Herein,we develop a simple and versatile synthesis strategy for tetraamino-[60]fullerene epoxide(C_(60)(NR^(1)R^(2))_(4)O...Amphiphilic aminated fullerenes have a broad margin of safety and significant antitumor effects.Herein,we develop a simple and versatile synthesis strategy for tetraamino-[60]fullerene epoxide(C_(60)(NR^(1)R^(2))_(4)O)using C_(60)Cl_(6)as a precursor,which notably reduces the reaction time to less than 1 h while retaining a high yield of over 80%with both cyclic and linear secondary amine substrates even at the gram level.The molecular structure of C_(60)(NR^(1)R^(2))_(4)O is first validated by single-crystal diffraction,and a two-step reaction mechanism comprising nucleophilic substitution of Cl and the oxidative elimination of Cl_(2)is proposed based on experimental verification and density functional theory simulation.A set of water-soluble aminated C_(60)(NR^(1)R^(2))_(4)O was prepared in large quantities,and in vitro antitumor evaluation unveiled the critical role that terminal primary amino moieties of C_(60)(NR^(1)R^(2))_(4)O play in their antineoplastic effects.This work provides an effective synthesis method for aminated C_(60)(NR^(1)R^(2))_(4)O,facilitating the development of fullerene-derived tumor-targeted drugs.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 fi-equently, aaost 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 dttring winter are clarified. Fhe effects of vehicle loadings above buried pipelines are calculated and compared with the effects and calculations of frost heaving forces. We demonstrate thtit 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 9y 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This studywas supported by China Center for Evidence Based Traditional ChineseMedicine(2020YJSZX-2)Capital Health Research and Development of Special Fund(2020-2-4183)+2 种基金National Natural Science Foundation of China(no.81973912,no.82274589)China Academy of Chinese Medical Sciences Innovation Fund(CI2021A02602)the Fundamental Research Funds for the Central Public Welfare Research Institutes(no.ZZ16-XRZ-063).
文摘Background:We systematically searched and summarized clinical studies on traditional Chinese medicine(TCM)for age-relatedmacular degeneration(AMD)with the method of evidence map.We aimed to provide evidence and research direction for the prevention or treatment of AMD with TCM in the future.Materials and methods:We searched PubMed,Web of Science,EMBASE,and Chinese databases including CNKI(Chinese National Knowledge Infrastructure),WanFang and VIP,ClinicalTrials.gov,and ChineseClinical Trial Registry Center studies on the prevention or treatment of TCMfor AMD from January 2000 to November 2022.We showed distribution features of these studies in the form of text description,graphs,and tables.Results:The final 258 articles included 245 clinical studies,9 systematic reviews ormeta-analyses,and 4 guidelines,expert consensus,or clinical pathway.After analyzing the articles with a focus on the stage of AMD,study type,sample size,intervention measures,outcome indicators,and the quality of evidence,we found that the studies were increasing,most of which were wet AMD,the main study type was randomized controlled trials,and the sample size was mostly fewer than 100 cases.Different interventions of TCM,such as Chinese medicine,Chinese patentmedicine,or acupuncture,showed the potential benefits of improving vision,reducing fundus lesions,and alleviating some uncomfortable symptoms.However,the sample size of these studies was small.The outcome indicators were not unified,and the stage of AMD was unclear.The quality of articles was lower,and there were few studies on early AMD.The advantages of TCM for the prevention or treatment of AMD remained unclear.Conclusions:Early intervention will be the focus and direction of AMD in the prevention or treatment of TCM,and more standardized clinical studies of TCM for early AMD need to be designed and carried out in the future.
基金supported by the major research project of the National Natural Science Foundation of China(grant no.52272049)the National Key Research and Development Program of China(grant no.2022YFA1205900).
文摘Amphiphilic aminated fullerenes have a broad margin of safety and significant antitumor effects.Herein,we develop a simple and versatile synthesis strategy for tetraamino-[60]fullerene epoxide(C_(60)(NR^(1)R^(2))_(4)O)using C_(60)Cl_(6)as a precursor,which notably reduces the reaction time to less than 1 h while retaining a high yield of over 80%with both cyclic and linear secondary amine substrates even at the gram level.The molecular structure of C_(60)(NR^(1)R^(2))_(4)O is first validated by single-crystal diffraction,and a two-step reaction mechanism comprising nucleophilic substitution of Cl and the oxidative elimination of Cl_(2)is proposed based on experimental verification and density functional theory simulation.A set of water-soluble aminated C_(60)(NR^(1)R^(2))_(4)O was prepared in large quantities,and in vitro antitumor evaluation unveiled the critical role that terminal primary amino moieties of C_(60)(NR^(1)R^(2))_(4)O play in their antineoplastic effects.This work provides an effective synthesis method for aminated C_(60)(NR^(1)R^(2))_(4)O,facilitating the development of fullerene-derived tumor-targeted drugs.
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.