Immunization has long played essential roles in preventing diseases.However,the desire for precision delivery of vaccines to boost a robust immune response remains largely unmet.Here,we describe the use of acupoint de...Immunization has long played essential roles in preventing diseases.However,the desire for precision delivery of vaccines to boost a robust immune response remains largely unmet.Here,we describe the use of acupoint delivery of nanovaccines(ADN)to elicit dual-niche immunological priming.ADN can simultaneously stimulate mast cell-assisted maturation of dendritic cells at the acupoint and enable direct delivery of nanovaccines into the draining lymph nodes.We demonstrate that ADN not only provokes antigen presentation by lymph node-resident CD8α^(+)dendritic cells,but also induces the accumulation of nanovaccines in B-cell zones,amplifying antigen-specific cytotoxic T lymphocyte responses and immunoglobulin G antibody expression in draining lymph nodes.ADN also generates systemic immune responses by causing immune memory and preventing T-cell anergy in the spleen.Further supported by evoking effective antitumor responses and high-level antiviral antibodies in mice,ADN provides a simple yet versatile platform for advanced nanovaccination.展开更多
Osteocytes, the most abundant bone cells, form an interconnected network in the lacunar-canalicular pore system （LCS） buried within the mineralized matrix, which allows osteocytes to obtain nutrients from the blood ...Osteocytes, the most abundant bone cells, form an interconnected network in the lacunar-canalicular pore system （LCS） buried within the mineralized matrix, which allows osteocytes to obtain nutrients from the blood supply, sense external mechanical signals, and communicate among themselves and with other cells on bone surfaces. In this study, we examined key features of the LCS network including the topological parameter and the detailed structure of individual connections and their variations in cortical and cancellous compa~ tments, at different ages, and in two disease conditions with altered mechanosensing （perlecan deficiency and diabetes）. LCS network showed both topological stability, in terms of conservation of connectivity among osteocyte lacunae （similar to the ＂nodes＂ in a computer network）, and considerable variability the pericellular annular fluid gap surrounding lacunae and canaliculi （similar to the ＂bandwidth＂ of individual links in a computer network）. Age, in the range of our study （15-32 weeks）, affected only the pericellular fluid annulus in cortical bone but not in cancellous bone. Diabetes impacted the spacing of the lacunae, while the perlecan deficiency had a profound influence on the pericellular fluid annulus. The LCS network features play important roles in osteocyte signaling and regulation of bone growth and adaptation.展开更多
In biological systems, conformational transformations of nucleic acids play critical roles in genetic regulation. However, it remains a tricky task to design and optimize specific labeling strategies to track these ch...In biological systems, conformational transformations of nucleic acids play critical roles in genetic regulation. However, it remains a tricky task to design and optimize specific labeling strategies to track these changes.In this study, we exploited an intercalating fluorescent dye,GelRed, to characterize different DNA structures. We studied the correlation between fluorescence intensity and DNA structural properties. We showed that single-stranded DNAs with predicted self-folded secondary structures show much stronger fluorescence than those without such structures. For double-stranded DNAs, we observed that fluorescence intensity is positively correlated to their GCcontent. We also demonstrated that GelRed can be used to monitor DNA conformational changes upon temperature variations in real time. Based on these findings, we concluded that the fluorescence intensity of a GelRed-stained DNA structure has a good correlation with its thermostability in the form of a change in Gibbs free energy.展开更多
In this review,the history and outlook of gas-phase CO_(2)activation using single electrons,metal atoms,clusters(mainly metal hydride clusters),and molecules are discussed on both of the experimental and theoretical f...In this review,the history and outlook of gas-phase CO_(2)activation using single electrons,metal atoms,clusters(mainly metal hydride clusters),and molecules are discussed on both of the experimental and theoretical fronts.Although the development of bulk solid-state materials for the activation and conversion of CO_(2)into value-added products have enjoyed great success in the past several decades,this review focuses only on gas-phase studies,because isolated,well-defined gas-phase systems are ideally suited for high-resolution experiments using state-of-the-art spectrometric and spectroscopic techniques,and for simulations employing modern quantum theoretical methods.The unmatched high complementarity and comparability of experiment and theory in the case of gas-phase investigations bear an enormous potential in providing insights in the reactions of CO_(2)activation at the atomic level.In all of these examples,the reduction and bending of the inert neutral CO_(2)molecule is the critical step determined by the frontier orbitals of reaction participants.Based on the results and outlook summarized in this review,we anticipate that studies of gas-phase CO_(2)activations will be an avenue rich with opportunities for the rational design of novel catalysts based on the knowledge obtained on the atomic level.展开更多
Electrochemical logical operations utilizing biological molecules(protein or DNA), which can be used in disease diagnostics and bio-computing, have attracted great research interest. However, the existing logic operat...Electrochemical logical operations utilizing biological molecules(protein or DNA), which can be used in disease diagnostics and bio-computing, have attracted great research interest. However, the existing logic operations, being realized on macroscopic electrode, are not suitable for implantable logic devices. Here, we demonstrate DNA-based logic gates with electrochemical signal as output combined with gold flower microelectrodes. The designed logic gates are of fast response, enzyme-free, and micrometer scale. They perform well in either pure solution or complex matrices, such as fetal bovine serum,suggesting great potential for in vivo applications.展开更多
In this study, we designed and applied proteinmimicking nanoparticles(Protmin) as an intracellular nanosensor for in vivo detection of lead ions(Pb^(2+)).Monodispersed gold nanoparticles(Au NPs) of 13 nm in diameter w...In this study, we designed and applied proteinmimicking nanoparticles(Protmin) as an intracellular nanosensor for in vivo detection of lead ions(Pb^(2+)).Monodispersed gold nanoparticles(Au NPs) of 13 nm in diameter were modified using poly-adenine-tailed Pb^(2+)-specific 8–17 DNAzyme to form a spherical and functional Protmin. Substrate strands modified with a fluorophore at the 50 end and a quencher at the 30 end were bound to DNAzyme. Pb^(2+) facilitated cleavage of DNAzyme to release the fluorophore-modified short strands to generate fluorescence. We observed rapid kinetics of the Protmin nanosensor, for which the typical assay time was 10 min.Further, we demonstrated the Protmin nanosensor could readily enter living cells and respond to Pb^(2+) in the intracellular environment. The broad of range of Protmindesigns will be useful for advancing biological and medical applications.展开更多
As a robust platform for genome editing,CRISPR/Cas9 is currently being explored for engineering biology or therapeutics,yet means for quantitative detection of Cas9 proteins remain to be fully realized.Here,we express...As a robust platform for genome editing,CRISPR/Cas9 is currently being explored for engineering biology or therapeutics,yet means for quantitative detection of Cas9 proteins remain to be fully realized.Here,we expressed Cas9 proteins and developed a novel detection method that traced Cas9 based on radiolabeled iodine.Through optimizing the reaction conditions of reaction time,temperature and cycles,we obtained ^(125)I-Cas9 of high labeling yield.The prepared ^(125)I-Cas9 was stable in various media and preserved excellent genome editing efficiency.Thus,our strategy provides a convenient and efficient tool for further tracing biological behaviors of Cas9 proteins in living systems.展开更多
Rett syndrome is a progressive neurodevelopmental disorder that lacks effective treatments.Although deep-brain stimulation can alleviate some symptoms in Rett model mice,this interventional manipula-tion requires deli...Rett syndrome is a progressive neurodevelopmental disorder that lacks effective treatments.Although deep-brain stimulation can alleviate some symptoms in Rett model mice,this interventional manipula-tion requires deliberate surgical operations.Here,we report that electro-acupuncture stimulation(EAS)can ameliorate symptoms of an Mecp2-knockout rat model of Rett syndrome from the remote acupoints Baihui(GV 20),Yongquan(KI 1),and Shenmen(HT 7).We find that EAS not only prolongs the survival time of Rett rats,but also improves their behavior ability,including locomotion,motor coordination,and social interaction.Neural activation was observed in the substantia nigra of the midbrain,corpus striatum,and cerebral cortex of wild-type and Rett model rats,as reflected by the increased expression of the c-Fos protein.Hence,EAS provides a potential promising therapeutic tool for treating neurodevel-opmental diseases.展开更多
Bismuth vanadate(BiVO_4) is a promising semiconductor material for solar energy conversion via photoelectrochemical(PEC) water splitting,whereas its performance is limited by surface recombination due to trapping stat...Bismuth vanadate(BiVO_4) is a promising semiconductor material for solar energy conversion via photoelectrochemical(PEC) water splitting,whereas its performance is limited by surface recombination due to trapping states.Herein,we developed a new method to passivate the trapping states on BiVO_4 surface using ultrathin aluminum oxide(Al_2O_3) overlayer by atomic layer deposition.The coated ultrathin Al_2O_3 film on BiVO_4 significantly enhanced photocurrent densities of the BiVO_4 anodes under standard illumination of AM1.5 G(100 mW/cm2).The electrochemical impedances and photoluminescence spectra were studied to confirm that the improved PEC water splitting performance of BiVO_4 was due to the decreased surface recombination state on BiVO_4,which effectively enhanced the charge separation.展开更多
Compared with other imaging techniques,fluorescence microscopy has become an essential tool to study cell biology due to its high compatibility with living cells.Owing to the resolution limit set by the diffraction of...Compared with other imaging techniques,fluorescence microscopy has become an essential tool to study cell biology due to its high compatibility with living cells.Owing to the resolution limit set by the diffraction of light,fluorescence microscopy could not resolve the nanostructures in the range of<200 nm.Recently,many techniques have been emerged to overcome the diffraction barrier,providing nanometer spatial resolution.In the course of development,the progress in fluorescent probes has helped to promote the development of the high-resolution fluorescence nanoscopy.Here,we describe the contributions of the fluorescent probes to far-field super resolution imaging,focusing on concepts of the existing super-resolution nanoscopy based on the photophysics of fluorescent nanoprobes,like photoswitching,bleaching and blinking.Fluorescent probe technology is crucial in the design and implementation of super-resolution imaging methods.展开更多
Uniform silver-containing metal nanostructures with well-defined nanogaps hold great promise for ultrasensitive surface-enhanced Raman scattering （SERS） analyses. Nevertheless, the direct synthesis of such nanostruc...Uniform silver-containing metal nanostructures with well-defined nanogaps hold great promise for ultrasensitive surface-enhanced Raman scattering （SERS） analyses. Nevertheless, the direct synthesis of such nanostructures with strong and stable SERS signals remains extremely challenging. Here, we report a DNA-mediated approach for the direct synthesis of gold-silver nano-mushrooms with interior nanogaps. The SERS intensities of these nano-mushrooms were critically dependent on the area of the nanogap between the gold head and the silver cap. We found that the formation of nanogaps was finely tunable by controlling the surface density of 6-carboxy-X-rhodamine （ROX） labeled single-stranded DNA （ssDNA） on the gold nanoparticles. We obtained nano-mushrooms in high yield with a high SERS signal enhancement factor of -1.0×109, much higher than that for Au-Ag nanostructures without nanogaps. Measurements for single nano- mushrooms show that these structures have both sensitive and reproducible SERS signals.展开更多
Graphene-based nanomaterials have emerged as a novel type of materials with exceptional physicochemical properties and numerous applications in various areas. In this review, we summarize recent advances in studying i...Graphene-based nanomaterials have emerged as a novel type of materials with exceptional physicochemical properties and numerous applications in various areas. In this review, we summarize recent advances in studying interactions between graphene and biosystems. We first provide a brief introduction on graphene and its derivatives, and then discuss on the toxicology and biocompatibility of graphene, including the extracellular interactions between graphene and biomacromolecules, cellular studies of graphene, and in vivo toxicological effects. Next, we focus on various graphene-based practical applications in antibacterial materials, wound addressing, drug delivery, and water purification.We finally present perspectives on challenges and future developments in these exciting fields.展开更多
In this paper, we report a highly sensitive chemiluminescence(CL) sensor for Hg2+ ions based on thymine-Hg2+-thymine(T-Hg2+-T) coordination chemistry. We designed a thymine rich oligonucleotide as a capture probe and ...In this paper, we report a highly sensitive chemiluminescence(CL) sensor for Hg2+ ions based on thymine-Hg2+-thymine(T-Hg2+-T) coordination chemistry. We designed a thymine rich oligonucleotide as a capture probe and a signal probe that includes two functional domains: a horseradish peroxidase-mimicking DNAzyme domain for the generation of CL, and a recognition domain. Graphene oxide(GO) was introduced to adsorb the signal probe via π-π interaction, which brought the DNAzyme domain and GO into close proximity and quenches CL. In the presence of Hg2+ ions, the coordination of Hg2+ with the capture probe yielded a hairpin complex, triggers cascaded strand displacement reactions and Exonuclease III-assisted signal amplifications. As a result, accumulated amounts of DNAzyme were generated and released from GO, leading to an enhanced CL signal. This strategy combines enzyme-based signal amplification and GO as a background reducer, leads to a limit of detection(LOD) of 2 nmol/L. This simple detection system provides a label-free yet sensitive approach for detection of Hg2+ ions.展开更多
Autophagy is a basic cellular process that decomposes damaged organelles and aberrant proteins. Dysregulation of autophagy is implicated in pathogenesis of neurodegenerative disorders, including Parkinson's diseas...Autophagy is a basic cellular process that decomposes damaged organelles and aberrant proteins. Dysregulation of autophagy is implicated in pathogenesis of neurodegenerative disorders, including Parkinson's disease(PD). Pharmacological compounds that stimulate autophagy can provide neuroprotection in models of PD. Nanoparticles have emerged as regulators of autophagy and have been tested in adjuvant therapy for diseases. In this present study, we explore the effects of quantum dots(QDs) that can induce autophagy in a cellular model of Parkinson's disease. Cd Te/Cd S/Zn S QDs protect differentiated rat pheochromocytoma PC12 cells from MPP+-induced cell damage, including reduced viability, apoptosis and accumulation of α-Synuclein, a characteristic protein of PD. The protective function of QDs is autophagy-dependent. In addition, we investigate the interaction between quantum dots and autophagic pathways and identify beclin1 as an essential factor for QDs-induced autophagy. Our results reveal new promise of QDs in the theranostic of neurodegenerative diseases.展开更多
A fluorescent turn-on probe for specifically targeting γ-glutamyltranspeptidase （GGT） was designed and synthe- sized by integrating boron-dipyrromethene （BODIPY） as a chromophore and glutathione （GSH） as the GG...A fluorescent turn-on probe for specifically targeting γ-glutamyltranspeptidase （GGT） was designed and synthe- sized by integrating boron-dipyrromethene （BODIPY） as a chromophore and glutathione （GSH） as the GGT sub- strate. GGT-catalyzed the cleavage of the γ-glutamyl bond and generated the aromatic hydrocarbon transfer between the sulfur and the nitrogen atom in BODIPY, leading to distinct optical changes. Such specific responsiveness pro- vides an easily distinguishable fluorescence signal to visualize the GGT activity in living cells and differentiate GGT-positive cancer cells from GGT-negative cells.展开更多
Magnetite nanoparticles （Fe3O4 NPs） are a well proven biocompatible nanomaterial, which hold great promise in various biomedical applications. Interestingly, unlike conventional biocompatible materials （e.g., polye...Magnetite nanoparticles （Fe3O4 NPs） are a well proven biocompatible nanomaterial, which hold great promise in various biomedical applications. Interestingly, unlike conventional biocompatible materials （e.g., polyethylene glycol （PEG）） that are chemically and biologically inert in nature, Fe3O4 NPs are known to be catalytically active and exhibit prominent physiological effects. Herein, we report an ＂active＂, dynamic equilibrium mechanism for maintaining the cellular amenity of Fe3O4 NPs. We examined the effects of two types of iron oxide （magnetite and hematite） NPs in rat pheochromocytoma （PC12） cells and found that both induced stress responses. However, only Fe2O3 NPs caused significant programmed cell death; whereas Fe3O4 NPs are amenable to cells. We found that intrinsic catalase-like activity of Fe3O4 NPs antagonized the accumulation of toxic reactive oxygen species （ROS） induced by themselves, and thereby modulated the extent of cellular oxidative stress, autophagic activity, and programmed cell death. In line with this observation, we effectively reversed severe autophagy and cell death caused by Fe2O3 NPs via co-treatment with natural catalase. This study not only deciphers the distinct intrinsic antagonism of Fe3O4 NPs, but opens new routes to designing biocompatible theranostic nanoparticles with novel mechanisms.展开更多
DNA tetrahedral nanostructures are considered to be uew nanocarriers because they can be precisely controlled and hold excellent penetration ability to the cellular membrane. Although the DNA tetrahedral nanostructure...DNA tetrahedral nanostructures are considered to be uew nanocarriers because they can be precisely controlled and hold excellent penetration ability to the cellular membrane. Although the DNA tetrahedral nanostructure is extensively studied in biology and medicine, its behavior in the cells with nanoscale resolution is not understood clearly. In this letter, we demonstrate superrcsolution fluorescence imaging of the distribution of DNA tetrahedral nanostructures in the cell with a simulated emission depletion （STED） microscope, which is built based on a conventional eonfocal microscope and can t）rovide a resolution of 70 nm.展开更多
Visualization of the spatiotemporal organization of chromatin is highly desirable in the study of genome function regulations.Clustered regularly interspa-ced short palindromic repeats(CRISPR)/CRISPR-associated endonu...Visualization of the spatiotemporal organization of chromatin is highly desirable in the study of genome function regulations.Clustered regularly interspa-ced short palindromic repeats(CRISPR)/CRISPR-associated endonuclease system has shown great promise for application in real-time chromatin imag-ing due to its DNA targeting ability in living cells.Previous studies typically used fluorescent proteins to generate fluorescent signals which,however,have trade-offs among signal intensity,multiplexibility,and simplicity.展开更多
Since the discovery of the double-helix structure in 1953,nucleic acids have been developed from natural genetic codes into functional building blocks in a wide range of biotechnology and materials sciences.Taking adv...Since the discovery of the double-helix structure in 1953,nucleic acids have been developed from natural genetic codes into functional building blocks in a wide range of biotechnology and materials sciences.Taking advantage of their design diversity and biocompatibility,functional nucleic acids facilitate the“bottom-up”fabrication of nanomaterials that are highly potential for molecular medicine to treat different diseases,such as cancers.The present perspective article introduces recent advances in the use of these unique properties of nucleic acid biopolymers for biomedical applications.Specifically,nanomaterial/nucleic acid hybrid structures for sensing,controlled drug release,programmable intracellular imaging,and apoptosis,as well as logic calculation,are discussed.Furthermore,the detailed operation for both extracellular and intracellular bioactivity regulation with these new design functional nucleic acid nanostructures are fully illustrated.展开更多
Stimulated emission depletion(STED) microscope is one of the most prominent super-resolution bio-imaging instruments, which holds great promise for ultrahigh-resolution imaging of cells. To construct a STED microscope...Stimulated emission depletion(STED) microscope is one of the most prominent super-resolution bio-imaging instruments, which holds great promise for ultrahigh-resolution imaging of cells. To construct a STED microscope, it is challenging to realize temporal synchronization between the excitation pulses and the depletion pulses. In this study, we present a simple and low-cost method to achieve pulse synchronization by using a condensed fluorescent dye as a depletion indicator. By using this method, almost all the confocal microscopes can be upgraded to a STED system without losing its original functions. After the pulse synchronization,our STED system achieved sub-100-nm resolution for fluorescent nanospheres and single-cell imaging.展开更多
基金supported by the National Key Research and Development Program of China(2021YFA0909400)the National Natural Science Foundation of China(22425505,32301099,and 21834007)+2 种基金the Shanghai Sailing Program(22YF1424200)the Interdisciplinary Program of Shanghai Jiao Tong University(YG2022QN032)the Xiangfu Lab Research Project(XF012022E0100).
文摘Immunization has long played essential roles in preventing diseases.However,the desire for precision delivery of vaccines to boost a robust immune response remains largely unmet.Here,we describe the use of acupoint delivery of nanovaccines(ADN)to elicit dual-niche immunological priming.ADN can simultaneously stimulate mast cell-assisted maturation of dendritic cells at the acupoint and enable direct delivery of nanovaccines into the draining lymph nodes.We demonstrate that ADN not only provokes antigen presentation by lymph node-resident CD8α^(+)dendritic cells,but also induces the accumulation of nanovaccines in B-cell zones,amplifying antigen-specific cytotoxic T lymphocyte responses and immunoglobulin G antibody expression in draining lymph nodes.ADN also generates systemic immune responses by causing immune memory and preventing T-cell anergy in the spleen.Further supported by evoking effective antitumor responses and high-level antiviral antibodies in mice,ADN provides a simple yet versatile platform for advanced nanovaccination.
基金supported partially by funds from the NIH (RO1AR054385, P30GM103333)
文摘Osteocytes, the most abundant bone cells, form an interconnected network in the lacunar-canalicular pore system （LCS） buried within the mineralized matrix, which allows osteocytes to obtain nutrients from the blood supply, sense external mechanical signals, and communicate among themselves and with other cells on bone surfaces. In this study, we examined key features of the LCS network including the topological parameter and the detailed structure of individual connections and their variations in cortical and cancellous compa~ tments, at different ages, and in two disease conditions with altered mechanosensing （perlecan deficiency and diabetes）. LCS network showed both topological stability, in terms of conservation of connectivity among osteocyte lacunae （similar to the ＂nodes＂ in a computer network）, and considerable variability the pericellular annular fluid gap surrounding lacunae and canaliculi （similar to the ＂bandwidth＂ of individual links in a computer network）. Age, in the range of our study （15-32 weeks）, affected only the pericellular fluid annulus in cortical bone but not in cancellous bone. Diabetes impacted the spacing of the lacunae, while the perlecan deficiency had a profound influence on the pericellular fluid annulus. The LCS network features play important roles in osteocyte signaling and regulation of bone growth and adaptation.
基金supported by the National Natural Science Foundation of China(Nos.U1532119,21775157,21675167,and 31571014)the Instrument Developing Project of the Chinese Academy of Sciences(Develop the Microsystems for Single Particle Tracking)
文摘In biological systems, conformational transformations of nucleic acids play critical roles in genetic regulation. However, it remains a tricky task to design and optimize specific labeling strategies to track these changes.In this study, we exploited an intercalating fluorescent dye,GelRed, to characterize different DNA structures. We studied the correlation between fluorescence intensity and DNA structural properties. We showed that single-stranded DNAs with predicted self-folded secondary structures show much stronger fluorescence than those without such structures. For double-stranded DNAs, we observed that fluorescence intensity is positively correlated to their GCcontent. We also demonstrated that GelRed can be used to monitor DNA conformational changes upon temperature variations in real time. Based on these findings, we concluded that the fluorescence intensity of a GelRed-stained DNA structure has a good correlation with its thermostability in the form of a change in Gibbs free energy.
基金National Key R&D Program of China(2018YFE0115000)the National Natural Science Foundation of China(22003027 and 22174073)+2 种基金the NSF of Tianjin City(19JCYBJC19600)the Frontiers Science Center for New Organic Matter of Nankai University(63181206)supported by the Air Force Office of Scientific Research(AFOSR)under grant number,FA9550-19-1-0077(KHB)。
文摘In this review,the history and outlook of gas-phase CO_(2)activation using single electrons,metal atoms,clusters(mainly metal hydride clusters),and molecules are discussed on both of the experimental and theoretical fronts.Although the development of bulk solid-state materials for the activation and conversion of CO_(2)into value-added products have enjoyed great success in the past several decades,this review focuses only on gas-phase studies,because isolated,well-defined gas-phase systems are ideally suited for high-resolution experiments using state-of-the-art spectrometric and spectroscopic techniques,and for simulations employing modern quantum theoretical methods.The unmatched high complementarity and comparability of experiment and theory in the case of gas-phase investigations bear an enormous potential in providing insights in the reactions of CO_(2)activation at the atomic level.In all of these examples,the reduction and bending of the inert neutral CO_(2)molecule is the critical step determined by the frontier orbitals of reaction participants.Based on the results and outlook summarized in this review,we anticipate that studies of gas-phase CO_(2)activations will be an avenue rich with opportunities for the rational design of novel catalysts based on the knowledge obtained on the atomic level.
基金supported by the National Natural Science Foundation of China(Nos.31470960 and 21422508)
文摘Electrochemical logical operations utilizing biological molecules(protein or DNA), which can be used in disease diagnostics and bio-computing, have attracted great research interest. However, the existing logic operations, being realized on macroscopic electrode, are not suitable for implantable logic devices. Here, we demonstrate DNA-based logic gates with electrochemical signal as output combined with gold flower microelectrodes. The designed logic gates are of fast response, enzyme-free, and micrometer scale. They perform well in either pure solution or complex matrices, such as fetal bovine serum,suggesting great potential for in vivo applications.
基金supported by the National Natural Science Foundation of China(Nos.21390414 and 21605087)the Chinese Academy of Sciences(No.QYZDJ-SSW-SLH031)+2 种基金the China Postdoctoral Science Foundation funded project(No.BX201700123)the Scientific Research Foundation of Nanjing University of Posts and Telecommunications(No.NY215058)the Natural Science Fund for Colleges and Universities in Jiangsu Province(16KJB150032)
文摘In this study, we designed and applied proteinmimicking nanoparticles(Protmin) as an intracellular nanosensor for in vivo detection of lead ions(Pb^(2+)).Monodispersed gold nanoparticles(Au NPs) of 13 nm in diameter were modified using poly-adenine-tailed Pb^(2+)-specific 8–17 DNAzyme to form a spherical and functional Protmin. Substrate strands modified with a fluorophore at the 50 end and a quencher at the 30 end were bound to DNAzyme. Pb^(2+) facilitated cleavage of DNAzyme to release the fluorophore-modified short strands to generate fluorescence. We observed rapid kinetics of the Protmin nanosensor, for which the typical assay time was 10 min.Further, we demonstrated the Protmin nanosensor could readily enter living cells and respond to Pb^(2+) in the intracellular environment. The broad of range of Protmindesigns will be useful for advancing biological and medical applications.
基金supported by the National Key Research and Development Program(No.2016YFA0400902)the Ministry of Science and Technology of China(Nos.2012CB825805,2012CB932600)+3 种基金the National Natural Science Foundation of China(Nos.11675251 and 11275251)Shanghai Rising-Star Program(No.14QA1404400)Distinguished Scientist Fellowship Program of King Saud Universitythe Youth Innovation Promotion Association of CAS(No.2016236)
文摘As a robust platform for genome editing,CRISPR/Cas9 is currently being explored for engineering biology or therapeutics,yet means for quantitative detection of Cas9 proteins remain to be fully realized.Here,we expressed Cas9 proteins and developed a novel detection method that traced Cas9 based on radiolabeled iodine.Through optimizing the reaction conditions of reaction time,temperature and cycles,we obtained ^(125)I-Cas9 of high labeling yield.The prepared ^(125)I-Cas9 was stable in various media and preserved excellent genome editing efficiency.Thus,our strategy provides a convenient and efficient tool for further tracing biological behaviors of Cas9 proteins in living systems.
基金supported by the Ministry of Science and Technology of China (2016YFA0400902)the National Science Foundation of China (11575278, 21675167, 81690263, 21227804, 21505148, and U1632125)+2 种基金the Project of State Key Laboratory of Radiation Medicine and Protection, Soochow University (GZK1201813)the Key Research Program of Frontier Sciences (QYZDJ-SSW-SLH031)the Open Large Infrastructure Research of Chinese Academy of Sciences (CAS) and Youth Innovation Promotion Association, CAS (2012205 and 2016236)
文摘Rett syndrome is a progressive neurodevelopmental disorder that lacks effective treatments.Although deep-brain stimulation can alleviate some symptoms in Rett model mice,this interventional manipula-tion requires deliberate surgical operations.Here,we report that electro-acupuncture stimulation(EAS)can ameliorate symptoms of an Mecp2-knockout rat model of Rett syndrome from the remote acupoints Baihui(GV 20),Yongquan(KI 1),and Shenmen(HT 7).We find that EAS not only prolongs the survival time of Rett rats,but also improves their behavior ability,including locomotion,motor coordination,and social interaction.Neural activation was observed in the substantia nigra of the midbrain,corpus striatum,and cerebral cortex of wild-type and Rett model rats,as reflected by the increased expression of the c-Fos protein.Hence,EAS provides a potential promising therapeutic tool for treating neurodevel-opmental diseases.
基金supported by the National Natural Science Foundation of China(21473236,21227804)the Shanghai Municipal Commission for Science and Technology(13NM1402300)+1 种基金the Chinese Academy of Sciencessupport by the Deanship of Scientific Research,College of Science Research Center at King Saud University
文摘Bismuth vanadate(BiVO_4) is a promising semiconductor material for solar energy conversion via photoelectrochemical(PEC) water splitting,whereas its performance is limited by surface recombination due to trapping states.Herein,we developed a new method to passivate the trapping states on BiVO_4 surface using ultrathin aluminum oxide(Al_2O_3) overlayer by atomic layer deposition.The coated ultrathin Al_2O_3 film on BiVO_4 significantly enhanced photocurrent densities of the BiVO_4 anodes under standard illumination of AM1.5 G(100 mW/cm2).The electrochemical impedances and photoluminescence spectra were studied to confirm that the improved PEC water splitting performance of BiVO_4 was due to the decreased surface recombination state on BiVO_4,which effectively enhanced the charge separation.
基金supported by the National Basic Research Pro-gram of China(973 program,2012CB825805,2013CB933800,2012CB-932603)the National Natural Science Foundation of China(10975179,61008056,and 61078016)
文摘Compared with other imaging techniques,fluorescence microscopy has become an essential tool to study cell biology due to its high compatibility with living cells.Owing to the resolution limit set by the diffraction of light,fluorescence microscopy could not resolve the nanostructures in the range of<200 nm.Recently,many techniques have been emerged to overcome the diffraction barrier,providing nanometer spatial resolution.In the course of development,the progress in fluorescent probes has helped to promote the development of the high-resolution fluorescence nanoscopy.Here,we describe the contributions of the fluorescent probes to far-field super resolution imaging,focusing on concepts of the existing super-resolution nanoscopy based on the photophysics of fluorescent nanoprobes,like photoswitching,bleaching and blinking.Fluorescent probe technology is crucial in the design and implementation of super-resolution imaging methods.
基金We thank the National Basic Research Program of China （973 program） （Nos. 2013CB932802 and 2012CB932600）,Alexander von Humboldt Foundation, and the National Natural Science Foundation of China （Nos. 91127037 and 91123037） for financial support.
文摘Uniform silver-containing metal nanostructures with well-defined nanogaps hold great promise for ultrasensitive surface-enhanced Raman scattering （SERS） analyses. Nevertheless, the direct synthesis of such nanostructures with strong and stable SERS signals remains extremely challenging. Here, we report a DNA-mediated approach for the direct synthesis of gold-silver nano-mushrooms with interior nanogaps. The SERS intensities of these nano-mushrooms were critically dependent on the area of the nanogap between the gold head and the silver cap. We found that the formation of nanogaps was finely tunable by controlling the surface density of 6-carboxy-X-rhodamine （ROX） labeled single-stranded DNA （ssDNA） on the gold nanoparticles. We obtained nano-mushrooms in high yield with a high SERS signal enhancement factor of -1.0×109, much higher than that for Au-Ag nanostructures without nanogaps. Measurements for single nano- mushrooms show that these structures have both sensitive and reproducible SERS signals.
基金the National Key Research and Development Program (No. 2016YFA0201200)the Shanghai Municipal Natural Science Foundation (No. 17ZR1412100)+1 种基金the Key Laboratory of Interfacial Physics and Technology, the Chinese Academy of Sciences (No. CASKL-IPT1603)the Talent Program of Shanghai University of Engineering Science, the Startup Foundation for Doctors of Shanghai University of Engineering Science, and the National Natural Science Foundation of China (Nos. 81870749, 21373260, 31470960 and 51375294).
文摘Graphene-based nanomaterials have emerged as a novel type of materials with exceptional physicochemical properties and numerous applications in various areas. In this review, we summarize recent advances in studying interactions between graphene and biosystems. We first provide a brief introduction on graphene and its derivatives, and then discuss on the toxicology and biocompatibility of graphene, including the extracellular interactions between graphene and biomacromolecules, cellular studies of graphene, and in vivo toxicological effects. Next, we focus on various graphene-based practical applications in antibacterial materials, wound addressing, drug delivery, and water purification.We finally present perspectives on challenges and future developments in these exciting fields.
基金supported by the National Natural Science Foundation of China(21222508,21375073)the Shanghai Municipal Commission for Science and Technology(13QH1402300)+1 种基金the State Ethnic Affairs Commission(10ZY02)the 111 Project of Minzu University(B08044)
文摘In this paper, we report a highly sensitive chemiluminescence(CL) sensor for Hg2+ ions based on thymine-Hg2+-thymine(T-Hg2+-T) coordination chemistry. We designed a thymine rich oligonucleotide as a capture probe and a signal probe that includes two functional domains: a horseradish peroxidase-mimicking DNAzyme domain for the generation of CL, and a recognition domain. Graphene oxide(GO) was introduced to adsorb the signal probe via π-π interaction, which brought the DNAzyme domain and GO into close proximity and quenches CL. In the presence of Hg2+ ions, the coordination of Hg2+ with the capture probe yielded a hairpin complex, triggers cascaded strand displacement reactions and Exonuclease III-assisted signal amplifications. As a result, accumulated amounts of DNAzyme were generated and released from GO, leading to an enhanced CL signal. This strategy combines enzyme-based signal amplification and GO as a background reducer, leads to a limit of detection(LOD) of 2 nmol/L. This simple detection system provides a label-free yet sensitive approach for detection of Hg2+ ions.
基金supported by the National Natural Science Foundation of China (U1332119, 31371015, 31470970)the Youth Innovation Promotion Association, CAS (2015211)Visiting Professor Program at King Saud University and the Shanghai Municipal Commission for Science and Technology (13NM1402300)
文摘Autophagy is a basic cellular process that decomposes damaged organelles and aberrant proteins. Dysregulation of autophagy is implicated in pathogenesis of neurodegenerative disorders, including Parkinson's disease(PD). Pharmacological compounds that stimulate autophagy can provide neuroprotection in models of PD. Nanoparticles have emerged as regulators of autophagy and have been tested in adjuvant therapy for diseases. In this present study, we explore the effects of quantum dots(QDs) that can induce autophagy in a cellular model of Parkinson's disease. Cd Te/Cd S/Zn S QDs protect differentiated rat pheochromocytoma PC12 cells from MPP+-induced cell damage, including reduced viability, apoptosis and accumulation of α-Synuclein, a characteristic protein of PD. The protective function of QDs is autophagy-dependent. In addition, we investigate the interaction between quantum dots and autophagic pathways and identify beclin1 as an essential factor for QDs-induced autophagy. Our results reveal new promise of QDs in the theranostic of neurodegenerative diseases.
基金We gratefully acknowledge the financial support by the National Natural Science Foundation of China （Nos. 21372083. 21672062）.
文摘A fluorescent turn-on probe for specifically targeting γ-glutamyltranspeptidase （GGT） was designed and synthe- sized by integrating boron-dipyrromethene （BODIPY） as a chromophore and glutathione （GSH） as the GGT sub- strate. GGT-catalyzed the cleavage of the γ-glutamyl bond and generated the aromatic hydrocarbon transfer between the sulfur and the nitrogen atom in BODIPY, leading to distinct optical changes. Such specific responsiveness pro- vides an easily distinguishable fluorescence signal to visualize the GGT activity in living cells and differentiate GGT-positive cancer cells from GGT-negative cells.
基金We would like to dedicate this article to Professor Qing Huang. This work was supported by National Natural Science Foundation of China （Nos. 31771102, 31371015, 21675167, U1532119, 31470970, 31371493, and 31571498）, the National Basic Research Program of China （Nos. 2013CB932803, 2013CB933802, 2016YFA0400900, and 2016YFA0201200）, the Youth Innovation Promotion Association from Chinese Academy of Sciences （No. 2015211）, Key Research Program of Frontier Sciences, CAS （Nos. QYZDJ-SSW-SLH019 and QYZDJ-SSW-SLH031）.
文摘Magnetite nanoparticles （Fe3O4 NPs） are a well proven biocompatible nanomaterial, which hold great promise in various biomedical applications. Interestingly, unlike conventional biocompatible materials （e.g., polyethylene glycol （PEG）） that are chemically and biologically inert in nature, Fe3O4 NPs are known to be catalytically active and exhibit prominent physiological effects. Herein, we report an ＂active＂, dynamic equilibrium mechanism for maintaining the cellular amenity of Fe3O4 NPs. We examined the effects of two types of iron oxide （magnetite and hematite） NPs in rat pheochromocytoma （PC12） cells and found that both induced stress responses. However, only Fe2O3 NPs caused significant programmed cell death; whereas Fe3O4 NPs are amenable to cells. We found that intrinsic catalase-like activity of Fe3O4 NPs antagonized the accumulation of toxic reactive oxygen species （ROS） induced by themselves, and thereby modulated the extent of cellular oxidative stress, autophagic activity, and programmed cell death. In line with this observation, we effectively reversed severe autophagy and cell death caused by Fe2O3 NPs via co-treatment with natural catalase. This study not only deciphers the distinct intrinsic antagonism of Fe3O4 NPs, but opens new routes to designing biocompatible theranostic nanoparticles with novel mechanisms.
基金supported by the National Natural Science Foundation of China under Grand Nos.61008056,21227804,61078016,and 61378062)
文摘DNA tetrahedral nanostructures are considered to be uew nanocarriers because they can be precisely controlled and hold excellent penetration ability to the cellular membrane. Although the DNA tetrahedral nanostructure is extensively studied in biology and medicine, its behavior in the cells with nanoscale resolution is not understood clearly. In this letter, we demonstrate superrcsolution fluorescence imaging of the distribution of DNA tetrahedral nanostructures in the cell with a simulated emission depletion （STED） microscope, which is built based on a conventional eonfocal microscope and can t）rovide a resolution of 70 nm.
基金This work was supported by the National Key R&D Program of China(2016YFA0400900)National Natural Science Foundation of China(21775157,21390414,61475181,and U1632125)Key Research Program of Frontier Sciences,Chinese Academy of Sciences(QYZDJ-SSW-SLH031).
文摘Visualization of the spatiotemporal organization of chromatin is highly desirable in the study of genome function regulations.Clustered regularly interspa-ced short palindromic repeats(CRISPR)/CRISPR-associated endonuclease system has shown great promise for application in real-time chromatin imag-ing due to its DNA targeting ability in living cells.Previous studies typically used fluorescent proteins to generate fluorescent signals which,however,have trade-offs among signal intensity,multiplexibility,and simplicity.
基金The authors thank the NSFC(21788102 and 21878086)Shanghai Municipal Science and Technology Major Project(2018SHZDZX03)+1 种基金the international cooperation program of Shanghai Science and Technology Committee(17520750100)the Shanghai Rising-Star Program(19QA1402500 to J.Z.).
文摘Since the discovery of the double-helix structure in 1953,nucleic acids have been developed from natural genetic codes into functional building blocks in a wide range of biotechnology and materials sciences.Taking advantage of their design diversity and biocompatibility,functional nucleic acids facilitate the“bottom-up”fabrication of nanomaterials that are highly potential for molecular medicine to treat different diseases,such as cancers.The present perspective article introduces recent advances in the use of these unique properties of nucleic acid biopolymers for biomedical applications.Specifically,nanomaterial/nucleic acid hybrid structures for sensing,controlled drug release,programmable intracellular imaging,and apoptosis,as well as logic calculation,are discussed.Furthermore,the detailed operation for both extracellular and intracellular bioactivity regulation with these new design functional nucleic acid nanostructures are fully illustrated.
基金supported by the National Natural Science Foundation of China (21227804, 21390414, 61378062, 21505148)National Key Research and Development Program (2016YFA0400902)the Natural Science Foundation of Shanghai (15ZR1448400, 14ZR1448000)
文摘Stimulated emission depletion(STED) microscope is one of the most prominent super-resolution bio-imaging instruments, which holds great promise for ultrahigh-resolution imaging of cells. To construct a STED microscope, it is challenging to realize temporal synchronization between the excitation pulses and the depletion pulses. In this study, we present a simple and low-cost method to achieve pulse synchronization by using a condensed fluorescent dye as a depletion indicator. By using this method, almost all the confocal microscopes can be upgraded to a STED system without losing its original functions. After the pulse synchronization,our STED system achieved sub-100-nm resolution for fluorescent nanospheres and single-cell imaging.
