Interferon(IFN)responses are central to host defense against coronavirus and other virus infections.Manganese(Mn)is capable of inducing IFN production,but its applications are limited by nonspecific distributions and ...Interferon(IFN)responses are central to host defense against coronavirus and other virus infections.Manganese(Mn)is capable of inducing IFN production,but its applications are limited by nonspecific distributions and neurotoxicity.Here,we exploit chemical engineering strategy to fabricate a nanodepot of manganese(nanoMn)based on Mn2+.Compared with free Mn2+,nanoMn enhances cellular uptake and persistent release of Mn2+in a pH-sensitive manner,thus strengthening IFN response and eliciting broad-spectrum antiviral effects in vitro and in vivo.Preferentially phagocytosed by macrophages,nanoMn promotes M1 macrophage polarization and recruits monocytes into inflammatory foci,eventually augmenting antiviral immunity and ameliorating coronavirus-induced tissue damage.Besides,nanoMn can also potentiate the development of virus-specific memory T cells and host adaptive immunity through facilitating antigen presentation,suggesting its potential as a vaccine adjuvant.Pharmacokinetic and safety evaluations uncover that nanoMn treatment hardly induces neuroinflammation through limiting neuronal accumulation of manganese.Therefore,nanoMn offers a simple,safe,and robust nanoparticle-based strategy against coronavirus.展开更多
Endogenous substance such as nucleotide as a drug carrier has been proposed as a novel drug delivery system.The nucleotide guanosine-5’-monophosphate(GMP) is used to transport an anticancer drug pemetrexed disodium h...Endogenous substance such as nucleotide as a drug carrier has been proposed as a novel drug delivery system.The nucleotide guanosine-5’-monophosphate(GMP) is used to transport an anticancer drug pemetrexed disodium heptahydrate(PMX) via specific base pairing.The endogenous nature of GMP helps to avoid biocompatibility issues that are generally accompanied with nanocarriers including cytotoxicity,immunogenicity and blood compatibility.Furthermore,the low-molecular weight of the GMP nucleotide carrier significantly boosts the drug loading capacity compared to traditional liposomes and high-molecular weight carriers.Hydrogen-bonding interaction between the carrier and drug realizes the controlled release of loaded drug,and also facilitates large scale manufacture since no additional chemical synthesis is required.More importantly,in vivo experiments reveal that the base-paired GMP:PMX nanovesicles improve the target specificity and pharmacokinetic properties of PMX,and exhibit remarkably enhanced anticancer abilities compared to standalone PMX without any carriers.We envision that this strategy could be extended to other endogenous substances and drugs bearing functional groups capable of specific interaction,and promote the construction of drug delivery systems with inherent biocompatibility,enhanced drug delivery efficacy,and a simplified preparation method.展开更多
In this paper,the interaction between hydrogen peroxide(HP)and water were systemically studied by atom-bond electronegativity equalization method fused into molecular mechanics(ABEEM/MM)and ab initio method.The result...In this paper,the interaction between hydrogen peroxide(HP)and water were systemically studied by atom-bond electronegativity equalization method fused into molecular mechanics(ABEEM/MM)and ab initio method.The results show that the optimized geometries,interaction energies and dipole moments of hydrated HP clusters HP(H_(2)O)_(n)(n=1–6)calculated by ABEEM/MM model are fairly consistent with the MP2/aug-cc-pVTZ//MP2/aug-cc-pVDZ results.The ABEEM/MM results indicate that n=4 is the transition state structure from 2D planar structure to 3D network structure.The variations of the average hydrogen bond length with the increasing number of water molecules given by ABEEM/MM model agree well with those of ab initio studies.Moreover,the radial distribution functions(RDFs)of water molecule around HP in HP aqueous solution have been analyzed in detail.It can be confirmed that HP is a good proton donor and poor proton acceptor in aqueous solution by analysis of the RDFs.展开更多
During the past decades,nonlinear optical(NLO)materials have attracted special interest because of their potential applications in photonic devices,such as optical switching,frequency conversion and electro-optic mo...During the past decades,nonlinear optical(NLO)materials have attracted special interest because of their potential applications in photonic devices,such as optical switching,frequency conversion and electro-optic modulators.Among the finding ways to obtain excellent NLO materials with both large NLO response and short response time,展开更多
基金This work was supported by grants including the National Natural Science Foundation of China(Nos.82022032 and 81991505 to D.L.)Clinical Medicine Plus X-Young Scholars Project,Peking University,the fundamental Research funds for the Central Universities(No.PKU2020LCXQ014 to D.L.)+1 种基金the Fundamental Research Funds for the Central Universities(No.BMU2018YJ003 to D.L.,No.BMU2017YJ001 to Z.L.)the Foundation from Science and Technology Bureau of Xinjiang production and Construction Corps(No.2019BC006 to W.L.).
文摘Interferon(IFN)responses are central to host defense against coronavirus and other virus infections.Manganese(Mn)is capable of inducing IFN production,but its applications are limited by nonspecific distributions and neurotoxicity.Here,we exploit chemical engineering strategy to fabricate a nanodepot of manganese(nanoMn)based on Mn2+.Compared with free Mn2+,nanoMn enhances cellular uptake and persistent release of Mn2+in a pH-sensitive manner,thus strengthening IFN response and eliciting broad-spectrum antiviral effects in vitro and in vivo.Preferentially phagocytosed by macrophages,nanoMn promotes M1 macrophage polarization and recruits monocytes into inflammatory foci,eventually augmenting antiviral immunity and ameliorating coronavirus-induced tissue damage.Besides,nanoMn can also potentiate the development of virus-specific memory T cells and host adaptive immunity through facilitating antigen presentation,suggesting its potential as a vaccine adjuvant.Pharmacokinetic and safety evaluations uncover that nanoMn treatment hardly induces neuroinflammation through limiting neuronal accumulation of manganese.Therefore,nanoMn offers a simple,safe,and robust nanoparticle-based strategy against coronavirus.
基金supported by the Shanghai Municipal Government(18JC1410800)the National Natural Science Foundation of China(51690151,21774077)
文摘Endogenous substance such as nucleotide as a drug carrier has been proposed as a novel drug delivery system.The nucleotide guanosine-5’-monophosphate(GMP) is used to transport an anticancer drug pemetrexed disodium heptahydrate(PMX) via specific base pairing.The endogenous nature of GMP helps to avoid biocompatibility issues that are generally accompanied with nanocarriers including cytotoxicity,immunogenicity and blood compatibility.Furthermore,the low-molecular weight of the GMP nucleotide carrier significantly boosts the drug loading capacity compared to traditional liposomes and high-molecular weight carriers.Hydrogen-bonding interaction between the carrier and drug realizes the controlled release of loaded drug,and also facilitates large scale manufacture since no additional chemical synthesis is required.More importantly,in vivo experiments reveal that the base-paired GMP:PMX nanovesicles improve the target specificity and pharmacokinetic properties of PMX,and exhibit remarkably enhanced anticancer abilities compared to standalone PMX without any carriers.We envision that this strategy could be extended to other endogenous substances and drugs bearing functional groups capable of specific interaction,and promote the construction of drug delivery systems with inherent biocompatibility,enhanced drug delivery efficacy,and a simplified preparation method.
基金supported by the grant from the National Natural Science Foundation of China(Nos.21133005 and 20703022)the Foundation of Education Bureau of Liaoning Province of China(No.2009T057).
文摘In this paper,the interaction between hydrogen peroxide(HP)and water were systemically studied by atom-bond electronegativity equalization method fused into molecular mechanics(ABEEM/MM)and ab initio method.The results show that the optimized geometries,interaction energies and dipole moments of hydrated HP clusters HP(H_(2)O)_(n)(n=1–6)calculated by ABEEM/MM model are fairly consistent with the MP2/aug-cc-pVTZ//MP2/aug-cc-pVDZ results.The ABEEM/MM results indicate that n=4 is the transition state structure from 2D planar structure to 3D network structure.The variations of the average hydrogen bond length with the increasing number of water molecules given by ABEEM/MM model agree well with those of ab initio studies.Moreover,the radial distribution functions(RDFs)of water molecule around HP in HP aqueous solution have been analyzed in detail.It can be confirmed that HP is a good proton donor and poor proton acceptor in aqueous solution by analysis of the RDFs.
基金supported by the National Natural Science Foundation of China(Grant No.11474046)Program for New Century Excellent Talents in University(Grant No.NCET-13-0702)+3 种基金Fundamental Research Funds for the Central Universities(Grant Nos.DC201502080202,and DC201502080203)Program for Liaoning Excellent Talents in University(LNET)(Grant No.LR2015016)Science and Technique Foundation of Dalian(Grant Nos.2014J11JH134,and 2015J12JH201)Education Department of Liaoning Province of China.
文摘During the past decades,nonlinear optical(NLO)materials have attracted special interest because of their potential applications in photonic devices,such as optical switching,frequency conversion and electro-optic modulators.Among the finding ways to obtain excellent NLO materials with both large NLO response and short response time,