Monitoringα-glucosidase(α-Glu)activity is of great significance for the early diagnosis of typeⅡdiabetes.Here the blue fluorescent carbon dots(CDs)were integrated with two different recognizing molecules,β-cyclode...Monitoringα-glucosidase(α-Glu)activity is of great significance for the early diagnosis of typeⅡdiabetes.Here the blue fluorescent carbon dots(CDs)were integrated with two different recognizing molecules,β-cyclodextrin and phenylboronic acid,for assembling a multifunctional CDs(mCDs)nanoplatform for sensitively analyzingα-Glu and its inhibitors.The hydrolyzed product of 4-nitrophenyl-α-D-glucopyranoside(α-Glu substrate),p-nitrophenol,could efficiently quench the fluorescence of mCDs due to its cooperative molecular recognition withβ-cyclodextrin and phenylboronic acid.The mCDs could be utilized for the detection ofα-Glu activity with the limit of detection of 0.030 U/L.Moreover,the presentα-Glu detection platform revealed a high selectivity,and other natural enzymes showed scarcely any effect on the present mCDs system.The proposed method could be facilely used to screenα-Glu inhibitors with satisfying performance.The rational mCDs is expected to supplement more comprehensive biosensing platforms for highly sensitive and specific recognition of disease-relevant biomarkers with clinical importance.展开更多
There are five hot springs named separately SHANGT,ZHONGT,WENT,XIAT and SHENT in Lushan County,Pingdingshan City,Henan Province.The archaeal diversity of the five hot springs was investigated and analyzed.16 S rD NA v...There are five hot springs named separately SHANGT,ZHONGT,WENT,XIAT and SHENT in Lushan County,Pingdingshan City,Henan Province.The archaeal diversity of the five hot springs was investigated and analyzed.16 S rD NA v4-5 genes of archaea were sequenced by Illumina Hisiq2500 PE250 technology.The numbers of sample sequences and OTUs were sorted by using Uparse,Mothur,SILVA,MUSCLE and Qiime software.Finally,the archaeal abundance and diversity in the five hot springs were analyzed.87993,67326,44400,48611 and 48495 effective reads have been obtained from SHANGT,ZHONGT,WENT,XIAT and SHENT respectively,and 520,280,678,451 and 437 OTUs have been acquired.The analysis of archaeal classification showed that the archaea from the five hot springs could be classified into 11 phyla,in which Thaumarchaeota accounted for 95.25%and was the dominant archaea.In the genera level,the dominant archaea of the SHANGT,ZHONGT and WENT was Candidatus-Nitrosocaldus,and unidentified-Thaumarchaeota was the dominant archaea in XIAT and SHENT.The results showed that the five hot springs in Lushan are rich in microbial resources.The research provided basic data for further research and utilization of the archaea resources in the five hot springs of Lushan.展开更多
Purpose: to discuss the practice pattern and application effect of PAD class in the practice and training course of Fundamental of Nursing Science for the nursing students in medical school. Method: PAD class is appli...Purpose: to discuss the practice pattern and application effect of PAD class in the practice and training course of Fundamental of Nursing Science for the nursing students in medical school. Method: PAD class is applied in the practice and training course of Fundamental of Nursing Science for 111 nursing students of the school, and after it is implemented, the recognition and achievement of the learning objectives during the implementation of "PAD class" are evaluated for the students, and the recognition of the students of nursing specialty on "PAD class" and their learning attitude and exam results before and after its implementation. Results: After implementation of PAD class, the recognition, learning attitude and exam results of the students of nursing specialty are higher those of them before its implementation (P < 0.05). Conclusions: The application of PAD class in the practice and training course of Fundamental of Nursing Science for the nursing students in the medical schools is conductive to the improvement of the learning enthusiasm of the students and their exam results.展开更多
Objective Discuss and reform community nursing practice teaching mode, and improve effects of community nursing teaching. Method Students are grouped into experimental group and control group randomly. Students in the...Objective Discuss and reform community nursing practice teaching mode, and improve effects of community nursing teaching. Method Students are grouped into experimental group and control group randomly. Students in the experimental group manage individualized health of diabetes patients in the observation group, and students in the control group conduct group health education and management for diabetes patients, no individualized health management. Results Students in the two groups compare cognition about this course and community nursing before teaching, no remarkable difference (all P values are ? 0.05), and compare diabetes knowledge and living behaviors of the old in the two groups, no remarkable difference (all P values are ? 0.05). After teaching, students in the two groups compare recognition of this course and community nursing as well as test performance, and there are remarkable differences (all P values are ? 0.05). And comparison of diabetes knowledge and living behaviors of the old in the two groups shows remarkable differences (all P values are ? 0.05). The implementation of individualized health management mode in community nursing practice teaching can improve students' professional knowledge and competence, and help diabetes patients to form good behaviors and life styles. The combination of community nursing practice teaching and individualized health management for diabetes patients can improve students' professional knowledge and competence, and help diabetes patients to control illness state and improve their physical conditions.展开更多
Metal catalysts pioneer new paradigms in biomedical studies for their intrinsic physiochemical and biocatalyst features.However,their therapeutic potential is still constrained by uncontrollable activation and deficie...Metal catalysts pioneer new paradigms in biomedical studies for their intrinsic physiochemical and biocatalyst features.However,their therapeutic potential is still constrained by uncontrollable activation and deficient theranostic ability.Herein,we developed a microRNA-programmed single AuI catalyst(RSA)for the spatiotemporally on-demand activation of photodynamic therapy.Specifically,the DNA-caged AuI catalyst was encapsulated in a folic acid-functionalized nanocarrier that enabled its specific accumulation in tumor tissue through folate receptor-mediated endocytosis.Then endogenous microRNA triggers the catalyzed assembly/activation of AuI catalyst that subsequently catalyzes the successive hydroamination of photosensitizer precursor(BDPI)with the efficient generation of an amplified fluorescence readout and abundant singlet oxygen therapeutic agent.This multiply-guaranteed cascade RSA platform offered a versatile toolbox for probing these complex biocatalytic transformations and biochemical processes.展开更多
Oxidative stress significantly contributes to secondary damage after spinal cord injury.Despite its importance,research on oxidative stress in spinal cord injury remains limited.Investigating the expression and regula...Oxidative stress significantly contributes to secondary damage after spinal cord injury.Despite its importance,research on oxidative stress in spinal cord injury remains limited.Investigating the expression and regulation of oxidative stress-related genes could enhance the diagnosis and treatment of spinal cord injury.In this study,we analyzed the sequencing data of human blood samples and injured mouse spinal cord tissue that were sourced from GEO databases and identified diagnostic biomarkers associated with the severity of spinal cord injury.We also explored the expression patterns of oxidative stress-related genes,potential regulatory mechanisms,and therapeutic drugs.To validate our findings,we performed immunofluorescence and quantitative polymerase chain reaction to assess gene expression in the injured spinal cord.Our results revealed biomarkers associated with oxidative stress and immune responses across different levels of spinal cord injury in humans.We identified differentially expressed oxidative stress-related genes and key hub genes in injured mouse spinal cord tissue and revealed their temporal expression patterns at both the tissue and single-cell levels.We also clarified the signaling pathways associated with oxidative stress and identified ligand-receptor pairs among various cell types at different time points after injury.Furthermore,we discovered microRNAs,long non-coding RNAs,and transcription factors that regulate these hub genes and revealed their roles in modulating gene expression at various stages after spinal cord injury.We also identified drugs targeting these hub genes.The findings from this study not only aid in identifying diagnostic biomarkers that reflect the severity of spinal cord injury,but also provide insights into the expression dynamics of oxidative stress-related genes.In addition,the study reveals potential regulatory mechanisms and identifies potential drugs to treat patients with spinal cord injury.展开更多
Metastasis remains the primary cause for mortality of breast cancer.Despite advances in current therapeutic agents,patients with metastatic breast cancer still have poor prognoses.Tumor hypoxia,a key microenvironment ...Metastasis remains the primary cause for mortality of breast cancer.Despite advances in current therapeutic agents,patients with metastatic breast cancer still have poor prognoses.Tumor hypoxia,a key microenvironment factor,is emerging as an attractive target to prevent metastasis and is also involved with resistance to phototherapy.Here,we show an effective nanotherapeutic approach based on manganese dioxide-coated polydopamine nanocarriers to trigger robust anti-tumor and anti-metastasis responses against metastatic breast cancer by supplemental oxygenation and multimodal imaging-guided phototherapies.In cancer cells,the produced oxygen by the developed nanoplatform decreases the expression of hypoxia-inducible factors 1 a to inhibit tumor metastasis,and enhances the efficacy of photodynamic therapy.This nanotherapeutic approach enables the combined photodynamic/photothermal treatments with great inhibition on cell migration and invasion in vitro.Moreover,the nanotherapeutics effectively suppresses primary tumor progress and inhibits lung metastasis in v ivo in a breast cancer mouse model with satisfying biosafety.This study suggests that the tumor hypoxia-targeting nanotherapeutics have great potential for preventing and treating metastatic cancers.展开更多
Enzyme-free autocatalytic nucleic acidmachinery has been widely used to engineer various self-assembled nanostructures as well as high-performance bioanalysis,yet has rarely been realized in live cells for complicated...Enzyme-free autocatalytic nucleic acidmachinery has been widely used to engineer various self-assembled nanostructures as well as high-performance bioanalysis,yet has rarely been realized in live cells for complicated design,low robustness,and limited reliability.Herein,we constructed simple yet versatile enthalpy-driven autocatalytic hybridization chain reaction(AHCR)machinery with high reliability and robustness for in situ microRNA analysis in live cells.The homogeneous AHCR machine was composed of two differently designed HCR modules,the lead-in HCR-1 amplification module,and the reverse HCR-2 feedback module.After the AHCR amplification system was delivered into live cells,target microRNA stimulated the autonomous cross-invasion of the HCR-1 module and the HCR-2 module for assembling hyperbranched dsDNA nanostructures with synergistically amplified Förster resonance energy transfer readout,thus enabling accurate intracellular micro-RNA imaging.The synergistic AHCR execution was systematically investigated by a series of experimental studies and computer-aided theoretical simulations.The multiple recognition capacity of HCR constituents and the successive signal amplification of the AHCR machine enabled the accurate intracellular microRNA imaging with precise signal localization inside living cells.Based on its intriguing and modular design,the AHCR machinery can be extended for analyzing diverse biomarkers,thus supplementing a powerful toolbox for clinical diagnosis and therapeutic assessment.展开更多
DNA devices that can recognize molecular inputs and transform them into functional outputs in an autonomous manner have been actively pursued as versatile toolkits for controlled nanofabrication,molecular network regu...DNA devices that can recognize molecular inputs and transform them into functional outputs in an autonomous manner have been actively pursued as versatile toolkits for controlled nanofabrication,molecular network regulation,biosensing and cellular function modulation.The introduction of external stimuli-responsive units not only ensures the programmability and functionality of DNA devices themselves,but also confers rapid,remote and reversible dynamic regulation capabilities.This facilitates on-demand activation and expands the application scope of dynamic DNA devices.Herein,an overview of recent advances in the construction of stimuli-responsive DNA devices that respond to different exogenous triggers,including physical stimuli(e.g.,light,thermal,magnetic field,and electric field),chemical stimuli(e.g.,supermolecules,pH,redox,and metal ions),and biological cues(e.g.,protein,biomolecule,and nucleic acid),and their controllable nanofabrication and biomedical application have been provided.The current challenges and potential solutions of these externally responsive DNA devices for their future advancements in this emerging field are also discussed.展开更多
A label-free deoxyribozyme(DNAzyme)biosensor for m^(6) demethylase activity detection is developed.When demethylase FTO(Fat mass and obesity-associated protein),an important m^(6) demethylase of ALKBH demethylase fami...A label-free deoxyribozyme(DNAzyme)biosensor for m^(6) demethylase activity detection is developed.When demethylase FTO(Fat mass and obesity-associated protein),an important m^(6) demethylase of ALKBH demethylase family is present,the m^(6) group is specifically demethylated,and the cleavage activity of DNAzyme is restored.This allows the cleavage product that contains G-quadruplex sequence to bind to thioflavin T(ThT)and generate fluorescence signals.The biosensor shows high specificity and sensitivity,and fast reaction speed.Our study demonstrates a new design of allosteric DNAzyme for sensing.This method represents the first label-free nucleic acid biosensor for FTO assay,providing a feasible route towards inhibitors screening.展开更多
Synthetic DNA motors have spurred considerable research interest as a way to interrogate biochemical processes that can further facilitate disease diagnosis.However,current direct sense-on-demand DNA motors are hamper...Synthetic DNA motors have spurred considerable research interest as a way to interrogate biochemical processes that can further facilitate disease diagnosis.However,current direct sense-on-demand DNA motors are hampered by undesired signal leakage originating from their nonspecific stimulation prior to their arrival at target sites.Herein,we propose a DNAzyme-guided DNA amplification motor through the facile built-in of a stimuli-responsive DNAzyme brake to facilitate the in vivo sensitive imaging of biomarkers by minimizing the off-site signal leakage in living systems.To realize the on-site activation,the inactive DNAzyme DNA motor was encapsulated into the folate(FA)-modified zeolitic imidazolate framework-8(ZIF-8)/poly(D,L-lactic-co-glycolic acid(PLGA)nanovesicles.The FA interaction-promoted tumor-cell-selective delivery and the pH-responsive disassembly of ZIF-8/PLGA permitted sufficient release of DNAzyme cofactors to achieve on-site stimulation of DNAzyme for restoring the temporally caged DNA amplification motor in tumor cells where the endogenous miRNA target was thus specifically and sensitively analyzed.By integration of the cellselective delivery and the site-specific stimulation,our DNAzyme-guided DNA motor can realize the reliable imaging of tumor cells and provide a new toolbox for disease diagnosis.展开更多
基金supported by National Natural Science Foundation of China(Nos.32202171,22274121 and 22274123)。
文摘Monitoringα-glucosidase(α-Glu)activity is of great significance for the early diagnosis of typeⅡdiabetes.Here the blue fluorescent carbon dots(CDs)were integrated with two different recognizing molecules,β-cyclodextrin and phenylboronic acid,for assembling a multifunctional CDs(mCDs)nanoplatform for sensitively analyzingα-Glu and its inhibitors.The hydrolyzed product of 4-nitrophenyl-α-D-glucopyranoside(α-Glu substrate),p-nitrophenol,could efficiently quench the fluorescence of mCDs due to its cooperative molecular recognition withβ-cyclodextrin and phenylboronic acid.The mCDs could be utilized for the detection ofα-Glu activity with the limit of detection of 0.030 U/L.Moreover,the presentα-Glu detection platform revealed a high selectivity,and other natural enzymes showed scarcely any effect on the present mCDs system.The proposed method could be facilely used to screenα-Glu inhibitors with satisfying performance.The rational mCDs is expected to supplement more comprehensive biosensing platforms for highly sensitive and specific recognition of disease-relevant biomarkers with clinical importance.
基金Supported by the Key Scientific Research Project of Colleges and Universities in Henan Province(16B180004)Science and Technology Public Relations Project from Department of Science and Technology in Henan Province(172102310211,172102310529)+1 种基金Scientific Research Start-up Foundation of High-level Talents in Pingdingshan University(PXY-BSQD-2015006)National Natural Fund Cultivation Project of Pingdingshan University(PXYPYJJ2016004)
文摘There are five hot springs named separately SHANGT,ZHONGT,WENT,XIAT and SHENT in Lushan County,Pingdingshan City,Henan Province.The archaeal diversity of the five hot springs was investigated and analyzed.16 S rD NA v4-5 genes of archaea were sequenced by Illumina Hisiq2500 PE250 technology.The numbers of sample sequences and OTUs were sorted by using Uparse,Mothur,SILVA,MUSCLE and Qiime software.Finally,the archaeal abundance and diversity in the five hot springs were analyzed.87993,67326,44400,48611 and 48495 effective reads have been obtained from SHANGT,ZHONGT,WENT,XIAT and SHENT respectively,and 520,280,678,451 and 437 OTUs have been acquired.The analysis of archaeal classification showed that the archaea from the five hot springs could be classified into 11 phyla,in which Thaumarchaeota accounted for 95.25%and was the dominant archaea.In the genera level,the dominant archaea of the SHANGT,ZHONGT and WENT was Candidatus-Nitrosocaldus,and unidentified-Thaumarchaeota was the dominant archaea in XIAT and SHENT.The results showed that the five hot springs in Lushan are rich in microbial resources.The research provided basic data for further research and utilization of the archaea resources in the five hot springs of Lushan.
文摘Purpose: to discuss the practice pattern and application effect of PAD class in the practice and training course of Fundamental of Nursing Science for the nursing students in medical school. Method: PAD class is applied in the practice and training course of Fundamental of Nursing Science for 111 nursing students of the school, and after it is implemented, the recognition and achievement of the learning objectives during the implementation of "PAD class" are evaluated for the students, and the recognition of the students of nursing specialty on "PAD class" and their learning attitude and exam results before and after its implementation. Results: After implementation of PAD class, the recognition, learning attitude and exam results of the students of nursing specialty are higher those of them before its implementation (P < 0.05). Conclusions: The application of PAD class in the practice and training course of Fundamental of Nursing Science for the nursing students in the medical schools is conductive to the improvement of the learning enthusiasm of the students and their exam results.
文摘Objective Discuss and reform community nursing practice teaching mode, and improve effects of community nursing teaching. Method Students are grouped into experimental group and control group randomly. Students in the experimental group manage individualized health of diabetes patients in the observation group, and students in the control group conduct group health education and management for diabetes patients, no individualized health management. Results Students in the two groups compare cognition about this course and community nursing before teaching, no remarkable difference (all P values are ? 0.05), and compare diabetes knowledge and living behaviors of the old in the two groups, no remarkable difference (all P values are ? 0.05). After teaching, students in the two groups compare recognition of this course and community nursing as well as test performance, and there are remarkable differences (all P values are ? 0.05). And comparison of diabetes knowledge and living behaviors of the old in the two groups shows remarkable differences (all P values are ? 0.05). The implementation of individualized health management mode in community nursing practice teaching can improve students' professional knowledge and competence, and help diabetes patients to form good behaviors and life styles. The combination of community nursing practice teaching and individualized health management for diabetes patients can improve students' professional knowledge and competence, and help diabetes patients to control illness state and improve their physical conditions.
基金supported by the National Natural Science Foundation of China(grant nos.22274123,22274121,and 22074112)the Translational Medicine and Interdisciplinary Research Joint Fund of Zhongnan Hospital of Wuhan University(grant no.ZNJC202231)+1 种基金Shenzhen Science and Technology Program(grant nos.JCYJ20220530140609021 and JCYJ20230807090210020)support from the Postdoctoral Fellowship Program of China Postdoctoral Science Foundation(grant no.GZC20231974).
文摘Metal catalysts pioneer new paradigms in biomedical studies for their intrinsic physiochemical and biocatalyst features.However,their therapeutic potential is still constrained by uncontrollable activation and deficient theranostic ability.Herein,we developed a microRNA-programmed single AuI catalyst(RSA)for the spatiotemporally on-demand activation of photodynamic therapy.Specifically,the DNA-caged AuI catalyst was encapsulated in a folic acid-functionalized nanocarrier that enabled its specific accumulation in tumor tissue through folate receptor-mediated endocytosis.Then endogenous microRNA triggers the catalyzed assembly/activation of AuI catalyst that subsequently catalyzes the successive hydroamination of photosensitizer precursor(BDPI)with the efficient generation of an amplified fluorescence readout and abundant singlet oxygen therapeutic agent.This multiply-guaranteed cascade RSA platform offered a versatile toolbox for probing these complex biocatalytic transformations and biochemical processes.
基金supported by Shenzhen Science and Technology Program,No.JCYJ20230807110259002(to JL)and The Seventh Affiliated Hospital ofSun Yat-sen University,No.ZSQYRSFPD0050(to JL)The Postdoctoral Fellowship Program of CPSF,No.GZC20242074(to KT).
文摘Oxidative stress significantly contributes to secondary damage after spinal cord injury.Despite its importance,research on oxidative stress in spinal cord injury remains limited.Investigating the expression and regulation of oxidative stress-related genes could enhance the diagnosis and treatment of spinal cord injury.In this study,we analyzed the sequencing data of human blood samples and injured mouse spinal cord tissue that were sourced from GEO databases and identified diagnostic biomarkers associated with the severity of spinal cord injury.We also explored the expression patterns of oxidative stress-related genes,potential regulatory mechanisms,and therapeutic drugs.To validate our findings,we performed immunofluorescence and quantitative polymerase chain reaction to assess gene expression in the injured spinal cord.Our results revealed biomarkers associated with oxidative stress and immune responses across different levels of spinal cord injury in humans.We identified differentially expressed oxidative stress-related genes and key hub genes in injured mouse spinal cord tissue and revealed their temporal expression patterns at both the tissue and single-cell levels.We also clarified the signaling pathways associated with oxidative stress and identified ligand-receptor pairs among various cell types at different time points after injury.Furthermore,we discovered microRNAs,long non-coding RNAs,and transcription factors that regulate these hub genes and revealed their roles in modulating gene expression at various stages after spinal cord injury.We also identified drugs targeting these hub genes.The findings from this study not only aid in identifying diagnostic biomarkers that reflect the severity of spinal cord injury,but also provide insights into the expression dynamics of oxidative stress-related genes.In addition,the study reveals potential regulatory mechanisms and identifies potential drugs to treat patients with spinal cord injury.
基金This work is supported by the National Natural Science Foundation of China(Nos.81602610,21874103)Fundam ental Research Funds for the Central Universities(Nos.2042018kf1006,2042018kf0210).
文摘Metastasis remains the primary cause for mortality of breast cancer.Despite advances in current therapeutic agents,patients with metastatic breast cancer still have poor prognoses.Tumor hypoxia,a key microenvironment factor,is emerging as an attractive target to prevent metastasis and is also involved with resistance to phototherapy.Here,we show an effective nanotherapeutic approach based on manganese dioxide-coated polydopamine nanocarriers to trigger robust anti-tumor and anti-metastasis responses against metastatic breast cancer by supplemental oxygenation and multimodal imaging-guided phototherapies.In cancer cells,the produced oxygen by the developed nanoplatform decreases the expression of hypoxia-inducible factors 1 a to inhibit tumor metastasis,and enhances the efficacy of photodynamic therapy.This nanotherapeutic approach enables the combined photodynamic/photothermal treatments with great inhibition on cell migration and invasion in vitro.Moreover,the nanotherapeutics effectively suppresses primary tumor progress and inhibits lung metastasis in v ivo in a breast cancer mouse model with satisfying biosafety.This study suggests that the tumor hypoxia-targeting nanotherapeutics have great potential for preventing and treating metastatic cancers.
基金This work is supported by the National Natural Science Foundation of China(nos.21874103 and 22074112).
文摘Enzyme-free autocatalytic nucleic acidmachinery has been widely used to engineer various self-assembled nanostructures as well as high-performance bioanalysis,yet has rarely been realized in live cells for complicated design,low robustness,and limited reliability.Herein,we constructed simple yet versatile enthalpy-driven autocatalytic hybridization chain reaction(AHCR)machinery with high reliability and robustness for in situ microRNA analysis in live cells.The homogeneous AHCR machine was composed of two differently designed HCR modules,the lead-in HCR-1 amplification module,and the reverse HCR-2 feedback module.After the AHCR amplification system was delivered into live cells,target microRNA stimulated the autonomous cross-invasion of the HCR-1 module and the HCR-2 module for assembling hyperbranched dsDNA nanostructures with synergistically amplified Förster resonance energy transfer readout,thus enabling accurate intracellular micro-RNA imaging.The synergistic AHCR execution was systematically investigated by a series of experimental studies and computer-aided theoretical simulations.The multiple recognition capacity of HCR constituents and the successive signal amplification of the AHCR machine enabled the accurate intracellular microRNA imaging with precise signal localization inside living cells.Based on its intriguing and modular design,the AHCR machinery can be extended for analyzing diverse biomarkers,thus supplementing a powerful toolbox for clinical diagnosis and therapeutic assessment.
基金supported by the National Natural Science Foundation of China(22104116,22209045,22274121,22274123)the Translational Medicine and Interdisciplinary Research Joint Fund of Zhongnan Hospital of Wuhan University(ZNJC202231)。
文摘DNA devices that can recognize molecular inputs and transform them into functional outputs in an autonomous manner have been actively pursued as versatile toolkits for controlled nanofabrication,molecular network regulation,biosensing and cellular function modulation.The introduction of external stimuli-responsive units not only ensures the programmability and functionality of DNA devices themselves,but also confers rapid,remote and reversible dynamic regulation capabilities.This facilitates on-demand activation and expands the application scope of dynamic DNA devices.Herein,an overview of recent advances in the construction of stimuli-responsive DNA devices that respond to different exogenous triggers,including physical stimuli(e.g.,light,thermal,magnetic field,and electric field),chemical stimuli(e.g.,supermolecules,pH,redox,and metal ions),and biological cues(e.g.,protein,biomolecule,and nucleic acid),and their controllable nanofabrication and biomedical application have been provided.The current challenges and potential solutions of these externally responsive DNA devices for their future advancements in this emerging field are also discussed.
基金supported by the Natural Science Foundation of Jiangsu Province(BK20221258)the National Natural Science Foundation of China(22274121 and 22274123).We thank Prof.Xiang Zhou at Wuhan University for CD measurement.
文摘A label-free deoxyribozyme(DNAzyme)biosensor for m^(6) demethylase activity detection is developed.When demethylase FTO(Fat mass and obesity-associated protein),an important m^(6) demethylase of ALKBH demethylase family is present,the m^(6) group is specifically demethylated,and the cleavage activity of DNAzyme is restored.This allows the cleavage product that contains G-quadruplex sequence to bind to thioflavin T(ThT)and generate fluorescence signals.The biosensor shows high specificity and sensitivity,and fast reaction speed.Our study demonstrates a new design of allosteric DNAzyme for sensing.This method represents the first label-free nucleic acid biosensor for FTO assay,providing a feasible route towards inhibitors screening.
基金This work was supported by the National Natural Science Foundation of China(grant nos.21874103 and 22074112)the Fundamental Research Funds for the Central Universities(grant no.2042022kf1175)the Central Funds Guiding the Local Science and Technology Development of Shenzhen(grant no.2021Szvup101).
文摘Synthetic DNA motors have spurred considerable research interest as a way to interrogate biochemical processes that can further facilitate disease diagnosis.However,current direct sense-on-demand DNA motors are hampered by undesired signal leakage originating from their nonspecific stimulation prior to their arrival at target sites.Herein,we propose a DNAzyme-guided DNA amplification motor through the facile built-in of a stimuli-responsive DNAzyme brake to facilitate the in vivo sensitive imaging of biomarkers by minimizing the off-site signal leakage in living systems.To realize the on-site activation,the inactive DNAzyme DNA motor was encapsulated into the folate(FA)-modified zeolitic imidazolate framework-8(ZIF-8)/poly(D,L-lactic-co-glycolic acid(PLGA)nanovesicles.The FA interaction-promoted tumor-cell-selective delivery and the pH-responsive disassembly of ZIF-8/PLGA permitted sufficient release of DNAzyme cofactors to achieve on-site stimulation of DNAzyme for restoring the temporally caged DNA amplification motor in tumor cells where the endogenous miRNA target was thus specifically and sensitively analyzed.By integration of the cellselective delivery and the site-specific stimulation,our DNAzyme-guided DNA motor can realize the reliable imaging of tumor cells and provide a new toolbox for disease diagnosis.
