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1.
Acc Chem Res ; 2024 Jan 25.
Article in English | MEDLINE | ID: mdl-38271669

ABSTRACT

ConspectusThe pursuit of in-depth studying the nature and law of life activity has been dominating current research fields, ranging from fundamental biological studies to applications that concern synthetic biology, bioanalysis, and clinical diagnosis. Motivated by this intention, the spatiotemporally controlled and in situ analysis of living cells has been a prospective branch by virtue of high-sensitivity imaging of key biomolecules, such as biomarkers. The past decades have attested that deoxyribonucleic acid (DNA), with biocompatibility, programmability, and customizable features, is a competitive biomaterial for constructing high-performance molecular sensing tools. To conquer the complexity of the wide extracellular-intracellular distribution of biomarkers, it is a meaningful breakthrough to explore high-efficiently amplified DNA circuits, which excel at operating complex yet captivating dynamic reaction networks for various bioapplications. In parallel, the multidimensional performance improvements of nucleic acid circuits, including the availability, detection sensitivity, and reliability, are critical parameters for realizing accurate imaging and cell regulation in bioanalysis.In this Account, we summarize our recent work on enzyme-free dynamic DNA reaction networks for bioanalysis from three main aspects: DNA circuitry functional extension of molecular recognition for epigenetic analysis and regulation, DNA circuitry amplification ability improvement for sensitive biomarker detection, and site-specific activation of DNA circuitry systems for reliable and accurate cell imaging. In the first part, we have designed an epigenetically responsive deoxyribozyme (DNAzyme) circuitry system for intracellular imaging and gene regulation, which enriches the possible analyzed species by chemically modifying conventional DNAzyme. For example, an exquisite N6-methyladenine (m6A)-caged DNAzyme was built for achieving the precise FTO (fat mass and obesity-associated protein)-directed gene regulation. In addition, varieties of DNAzyme-based nanoplatforms with self-sufficient cofactor suppliers were assembled, which subdued the speed-limiting hardness of DNAzyme cofactors in live-cell applications. In the second part, we have developed a series of hierarchically assembled DNA circuitry systems to improve the signal transduction ability of traditional DNA circuits. First, the amplification ability of the DNAzyme circuit has been significantly enhanced via several heterogeneously or homogeneously concatenated circuitry models. Furthermore, a feedback reaction pathway was integrated into these concatenated circuits, thus dramatically increasing the amplification efficiency. Second, considering the complex cellular environment, we have simplified the redundancy of multicomponents or reaction procedures of traditional cascaded circuits, relying on the minimal component complexity and merely one modular catalytic reaction, which guaranteed high cell-delivering uniformity while fostering reaction kinetics and analysis reliability. In the third part, we have constructed in-cell-selective endogenous-stimulated DNA circuitry systems via the multiply guaranteed molecular recognitions, which could not only eliminate the signal leakage, but could also retain its on-site and multiplex signal amplification. Based on the site-specific activation strategy, more circuitry availability in cellular scenarios has been acquired for reliable and precise biological sensing and regulation. These enzyme-free dynamic DNA reaction networks demonstrate the purpose-to-concreteness engineering for tailored multimolecule recognition and multiple signal amplification, achieving high-gain signal transduction and high-reliability targeted imaging in bioanalysis. We envision that the enzyme-free dynamic DNA reaction network can contribute to more bioanalytical layouts, which will facilitate the progression of clinical diagnosis and prognosis.

2.
Small ; 20(2): e2305672, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37670211

ABSTRACT

The sensing performance of DNAzymes in live cells is tremendously hampered by the inefficient and inhomogeneous delivery of DNAzyme probes and their incontrollable off-site activation, originating from their susceptibility to nuclease digestion. This requires the development of a more compact and robust DNAzyme-delivering system with site-specific DNAzyme activation property. Herein, a highly compact and robust Zn@DDz nanoplatform is constructed by integrating the unimolecular microRNA-responsive DNA-cleaving DNAzyme (DDz) probe with the requisite DNAzyme Zn2+ -ion cofactors, and the amplified intracellular imaging of microRNA via the spatiotemporally programmed disassembly of Zn@DDz nanoparticles is achieved. The multifunctional Zn@DDz nanoplatform is simply composed of a structurally blocked self-hydrolysis DDz probe and the inorganic Zn2+ -ion bridge, with high loading capacity, and can effectively deliver the initially catalytic inert DDz probe and Zn2+ into living cells with enhanced stabilities. Upon their entry into the acidic microenvironment of living cells, the self-sufficient Zn@DDz nanoparticle is disassembled to release DDz probe and simultaneously supply Zn2+ -ion cofactors. Then, endogenous microRNA-21 catalyzes the reconfiguration and activation of DDz for generating the amplified readout signal with multiply guaranteed imaging performance. Thus, this work paves an effective way for promoting DNAzyme-based biosensing systems in living cells, and shows great promise in clinical diagnosis.


Subject(s)
Biosensing Techniques , DNA, Catalytic , MicroRNAs , Nanoparticles , DNA
3.
Chem Sci ; 14(8): 2159-2167, 2023 Feb 22.
Article in English | MEDLINE | ID: mdl-36845932

ABSTRACT

The accurate identification of multiple biomarkers involved in disease plays a vital role in effectively distinguishing cancer cells from normal cells, facilitating reliable cancer diagnosis. Motivated by this knowledge, we have engineered a compact and clamped cascaded DNA circuit for specifically discriminating cancer cells from normal cells via the amplified multi-microRNA imaging strategy. The proposed DNA circuit combines the traditional cascaded DNA circuit with multiply localized responsive character through the elaboration of two super-hairpin reactants, thus concurrently streamlining the circuit components and realizing localization-intensified cascaded signal amplification. In parallel, the multiple microRNA-stimulated sequential activations of the compact circuit, combined with a handy logic operation, significantly elevated the cell-discriminating reliability. Applications of the present DNA circuit in vitro and in cellular imaging experiments were executed with expected results, therefore illustrating that our DNA circuit is useful for precise cell discrimination and further clinical diagnosis.

4.
Chem Commun (Camb) ; 59(10): 1345-1348, 2023 Jan 31.
Article in English | MEDLINE | ID: mdl-36647734

ABSTRACT

Herein, we developed a reliable and portable biosensor (TDR-PGM nanomachine) for the sensitive detection of microRNA by integrating an efficient toehold-mediated strand displacement reaction module (TDR) and a personal glucose meter (PGM). The system provides a versatile methodology for microRNA detection in real samples and holds broad prospects in point-of-care diagnosis.


Subject(s)
Biosensing Techniques , MicroRNAs , MicroRNAs/genetics , Glucose , Entropy , DNA/genetics , Biosensing Techniques/methods , Limit of Detection
5.
Small ; 19(17): e2207961, 2023 04.
Article in English | MEDLINE | ID: mdl-36717281

ABSTRACT

Trace analyte detection in complex intracellular environment requires the development of simple yet robust self-sufficient molecular circuits with high signal-gain and anti-interference features. Herein, a minimal non-enzymatic self-replicate DNA circuitry (SDC) system is proposed with high-signal-gain for highly efficient biosensing in living cells. It is facilely engineered through the self-stacking of only one elementary cascade hybridization reaction (CHR), thus is encoding with more economic yet effective amplification pathways and reactants. Trigger (T) stimulates the activation of CHR for producing numerous T replica that reversely motivate new CHR reaction cycles, thus achieving the successive self-replication of CHR system with an exponentially magnified readout signal. The intrinsic self-replicate circuity design and the self-accelerated reaction format of SDC system is experimentally demonstrated and theoretically simulated. With simple circuitry configuration and low reactant complexity, the SDC amplifier enables the high-contrast and accurate visualization of microRNA (miRNA), ascribing to its robust molecular recognition and self-sufficient signal amplification, thus offering a promising strategy for monitoring these clinically significant analytes.


Subject(s)
Biosensing Techniques , MicroRNAs , MicroRNAs/genetics , Nucleic Acid Amplification Techniques/methods , DNA , Nucleic Acid Hybridization , Diagnostic Imaging , Biosensing Techniques/methods
6.
Chem Sci ; 13(35): 10428-10436, 2022 Sep 14.
Article in English | MEDLINE | ID: mdl-36277649

ABSTRACT

Constructing artificial domino nanoarchitectures, especially dynamic DNA circuits associated with the actuation of biological functions inside live cells, represents a versatile and powerful strategy to regulate the behaviors and fate of various living entities. However, the stepwise operation of conventional DNA circuits always relies on freely diffusing reactants, which substantially slows down their operation rate and efficiency. Herein, a self-adaptive localized catalytic circuit (LCC) is developed to execute the self-sustained bioorthogonal assembly of DNA nanosponges within a crowded intracellular environment. The LCC-generated DNA scaffolds are utilized as versatile templates for realizing the proximity confinement of LCC reactants. Single-molecule-detecting fluorescence correlation spectroscopy (FCS) is used to explore the reaction acceleration of the catalytic circuit. This self-adaptive DNA circuit facilitates the bioorthogonal assembly of highly branched DNA networks for robust and accurate monitoring of miRNA targets. Based on its intriguing and modular design, the LCC system provides a pivotal molecular toolbox for future applications in early disease diagnosis.

7.
Environ Res ; 215(Pt 2): 114364, 2022 12.
Article in English | MEDLINE | ID: mdl-36126692

ABSTRACT

BACKGROUND AND AIM: Experimental studies show that short-term exposure to air pollution may alter cytokine concentrations. There is, however, a lack of epidemiological studies evaluating the association between long-term air pollution exposure and inflammation-related proteins in young children. Our objective was to examine whether air pollution exposure is associated with inflammation-related proteins during the first 2 years of life. METHODS: In a pooled analysis of two birth cohorts from Stockholm County (n = 158), plasma levels of 92 systemic inflammation-related proteins were measured by Olink Proseek Multiplex Inflammation panel at 6 months, 1 year and 2 years of age. Time-weighted average exposure to particles with an aerodynamic diameter of <10 µm (PM10), <2.5 µm (PM2.5), and nitrogen dioxide (NO2) at residential addresses from birth and onwards was estimated via validated dispersion models. Stratified by sex, longitudinal cross-referenced mixed effect models were applied to estimate the overall effect of preceding air pollution exposure on combined protein levels, "inflammatory proteome", over the first 2 years of life, followed by cross-sectional protein-specific bootstrapped quantile regression analysis. RESULTS: We identified significant longitudinal associations of inflammatory proteome during the first 2 years of life with preceding PM2.5 exposure, while consistent associations with PM10 and NO2 across ages were only observed among girls. Subsequent protein-specific analyses revealed significant associations of PM10 exposure with an increase in IFN-gamma and IL-12B in boys, and a decrease in IL-8 in girls at different percentiles of proteins levels, at age 6 months. Several inflammation-related proteins were also significantly associated with preceding PM10, PM2.5 and NO2 exposures, at ages 1 and 2 years, in a sex-specific manner. CONCLUSIONS: Ambient air pollution exposure influences inflammation-related protein levels already during early childhood. Our results also suggest age- and sex-specific differences in the impact of air pollution on children's inflammatory profiles.


Subject(s)
Air Pollutants , Air Pollution , Air Pollutants/analysis , Air Pollutants/toxicity , Air Pollution/adverse effects , Air Pollution/analysis , Child, Preschool , Cross-Sectional Studies , Cytokines , Environmental Exposure/analysis , Female , Humans , Infant , Inflammation/chemically induced , Inflammation/epidemiology , Interleukin-8/analysis , Male , Nitrogen Dioxide/analysis , Nitrogen Dioxide/toxicity , Particulate Matter/analysis , Particulate Matter/toxicity , Proteome
8.
Eur Respir Rev ; 31(165)2022 Sep 30.
Article in English | MEDLINE | ID: mdl-35948392

ABSTRACT

Previous studies have explored the relationships of air pollution and metabolic profiles with lung function. However, the metabolites linking air pollution and lung function and the associated mechanisms have not been reviewed from a life-course perspective. Here, we provide a narrative review summarising recent evidence on the associations of metabolic profiles with air pollution exposure and lung function in children and adults. Twenty-six studies identified through a systematic PubMed search were included with 10 studies analysing air pollution-related metabolic profiles and 16 studies analysing lung function-related metabolic profiles. A wide range of metabolites were associated with short- and long-term exposure, partly overlapping with those linked to lung function in the general population and with respiratory diseases such as asthma and COPD. The existing studies show that metabolomics offers the potential to identify biomarkers linked to both environmental exposures and respiratory outcomes, but many studies suffer from small sample sizes, cross-sectional designs, a preponderance on adult lung function, heterogeneity in exposure assessment, lack of confounding control and omics integration. The ongoing EXposome Powered tools for healthy living in urbAN Settings (EXPANSE) project aims to address some of these shortcomings by combining biospecimens from large European cohorts and harmonised air pollution exposure and exposome data.


Subject(s)
Air Pollutants , Air Pollution , Adult , Air Pollutants/adverse effects , Air Pollution/adverse effects , Child , Cross-Sectional Studies , Environmental Exposure/adverse effects , Humans , Particulate Matter
9.
Angew Chem Int Ed Engl ; 61(45): e202206529, 2022 11 07.
Article in English | MEDLINE | ID: mdl-35775154

ABSTRACT

The wide extracellular-intracellular distribution of microRNA requires the on-site, robust and efficient activation of catalytic DNA circuits inside live cells. Herein, we develop an efficient non-enzymatic circuitry activation strategy to realize the orthogonally controlled catalytic DNA (CCD) circuit for achieving high-fidelity in vivo microRNA imaging through multiply guaranteed molecular recognition and progressively accelerated signal amplification. For predictable on-site activation and useful catalytic efficiency, the dominating circuitry fuel strand was initially split into inactive fuel subunits that were grafted into an auxiliary catalytic circuit. There, the in-cell-specific mRNA triggered the orthogonal amplification of the active fuel strands for sensitive target detection through the chief entropy-driven catalytic DNA circuit. We believe that the on-site orthogonal circuitry activation method can contribute to clinical diagnosis and prognosis.


Subject(s)
Biosensing Techniques , DNA, Catalytic , MicroRNAs , MicroRNAs/genetics , Entropy , Biosensing Techniques/methods
10.
Small ; 18(32): e2203341, 2022 08.
Article in English | MEDLINE | ID: mdl-35843889

ABSTRACT

DNA amplification machines show great promise for intracellular imaging, yet are always constrained by off-site machinery activation or signal leakage, originating from the inherent thermodynamically driven hybridization between machinery substrates. Herein, an entropy-driven catalytic DNA amplification machine is integrated with the on-site amplified substrate exposure procedure to realize the high-contrast in vivo imaging of microRNA (miRNA). The key machinery substrate (fuel strands) is initially split into substrate subunits that are respectively grafted into an auxiliary DNA polymerization amplification accessory for eliminating the undesired signal leakage. Meanwhile, in target cells, the auxiliary polymerization accessory can be motivated by cell-specific mRNA for successively restoring their intact machine-propelling functions for guaranteeing the on-site amplified imaging of miRNA with high specificity. This intelligent on-site multiply guaranteed machinery can improve the specificity of catalytic DNA machines for discriminating different cell types and, thus, can provide a remarkable prospect in biomedical diagnosis.


Subject(s)
Biosensing Techniques , DNA, Catalytic , MicroRNAs , Biosensing Techniques/methods , Catalysis , DNA, Catalytic/metabolism , MicroRNAs/metabolism , Nucleic Acid Amplification Techniques/methods , Nucleic Acid Hybridization
11.
Small ; 18(21): e2200983, 2022 05.
Article in English | MEDLINE | ID: mdl-35460185

ABSTRACT

Probing endogenous molecular profiles in living entities is of fundamental significance to decipher biological functions and exploit novel theranostics. Despite programmable nucleic acid-based aptasensing systems across the breadth of molecular imaging, an aptasensing system enabling in vivo imaging with high sensitivity, accuracy, and adaptability is highly required yet is still in its infancy. Artificial catalytic DNA circuits that can modularly integrate to generate multiple outputs from a single input in an isothermal autonomous manner, have supplemented powerful toolkits for intracellular biosensing research. Herein, a multilayer nonenzymatic catalytic DNA circuits-based aptasensing system is devised for in situ imaging of a bioactive molecule in living mice by assembling branched DNA copolymers with high-molecular-weight and high-signal-gain based on avalanche-mimicking hybridization chain reactions (HCRs). The HCRs aptasensing circuit performs as a general and powerful sensing platform for precise analysis of a series of bioactive molecules due to its inherent rich recognition repertoire and hierarchical reaction accelerations. With tumor-targeting capsule encapsulation, the HCRs aptasensing circuit is specifically delivered into tumor cells and allowed the high-contrast imaging of intracellular adenosine triphosphate in living mice, highlighting its potential for visualizing these clinically important biomolecules and for studying the associated physiological processes.


Subject(s)
Biosensing Techniques , DNA, Catalytic , Animals , Biosensing Techniques/methods , DNA/genetics , DNA, Catalytic/metabolism , DNA, Concatenated , Mice , Nucleic Acid Hybridization
12.
Anal Chem ; 94(10): 4495-4503, 2022 03 15.
Article in English | MEDLINE | ID: mdl-35234458

ABSTRACT

Abnormal DNA methylation contributes to the annoying tumorigenesis and the elevated expression of methylation-related methyltransferase (MTase) is associated with many diseases. Hence DNA MTase could serve as a promising biomarker for cancer-specific diagnosis as well as a potential therapeutic target. Herein, we developed an isothermal autocatalytic hybridization reaction (AHR) circuit for the sensitive detection of MTase and its inhibitors by integrating the catalytic hairpin assembly (CHA) converter with the hybridization chain reaction (HCR) amplifier. The initiator-mediated HCR amplifier could generate amplified fluorescent readout, as well as numerous newly activated triggers for motivating the CHA converter. The CHA converter is designed to expose the identical sequence of HCR initiators that reversely powered the HCR amplifier. Thus, the trace amount of target could produce exponentially amplified fluorescent readout by the autocatalytic feedback cycle between HCR and CHA systems. Then an auxiliary hairpin was introduced to mediate the assay of Dam MTase via the well-established AHR circuit. The Dam MTase-catalyzed methylation of auxiliary hairpin leads to its subsequent efficient cleavage by DpnI endonuclease, thus resulting in the release of HCR initiators to initiate the AHR circuit. The programmable nature of the auxiliary hairpin allows its easy adaption into other MTase assay by simply changing the recognition site. This proposed AHR circuit permits a sensitive, robust, and versatile analysis of MTase with the limit of detection (LOD) of 0.011 U/mL. Lastly, the AHR circuit could be utilized for MTase analysis in real complex samples and for evaluating the cell-cycle-dependent expression of MTase. This developed MTase-sensing strategy holds promising potential for biomedical analysis and clinical diagnosis.


Subject(s)
Biosensing Techniques , Biosensing Techniques/methods , DNA , DNA Methylation , DNA Modification Methylases , Methyltransferases , Nucleic Acid Hybridization
13.
Nanomaterials (Basel) ; 12(3)2022 Feb 06.
Article in English | MEDLINE | ID: mdl-35159901

ABSTRACT

Motivated by the recent successful synthesis of Janus monolayer of transition metal (TM) dichalcogenides, MXenes with Janus structures are worthy of further study, concerning its electronic structure and magnetic properties. Here, we study the effect of different transition metal atoms on the structure stability and magnetic and electronic properties of M'MCO2 (M' and M = V, Cr and Mn). The result shows the output magnetic moment is contributed mainly by the d orbitals of the V, Cr, and Mn atoms. The total magnetic moments of ferromagnetic (FM) configuration and antiferromagnetic (AFM) configuration are affected by coupling types. FM has a large magnetic moment output, while the total magnetic moments of AFM2's (intralayer AFM/interlayer FM) configuration and AFM3's (interlayer AFM/intralayer AFM) configuration are close to 0. The band gap widths of VCrCO2, VMnCO2, CrMnCO2, V2CO2, and Cr2CO2 are no more than 0.02 eV, showing metallic properties, while Mn2CO2 is a semiconductor with a 0.7071 eV band gap width. Janus MXenes can regulate the size of band gap, magnetic ground state, and output net magnetic moment. This work achieves the control of the magnetic properties of the available 2D materials, and provides theoretical guidance for the extensive design of novel Janus MXene materials.

14.
ACS Appl Mater Interfaces ; 14(4): 5080-5089, 2022 Feb 02.
Article in English | MEDLINE | ID: mdl-35044153

ABSTRACT

Aptasensors with high specificity have emerged as powerful tools for understanding various biological processes, thus providing tremendous opportunities for clinical diagnosis and prognosis. However, their applications in intracellular molecular imaging are largely impeded due to the low anti-interference capacity in biological environments and the moderate sensitivity to targets. Herein, a robust enzyme-free autocatalysis-driven feedback DNA circuit is devised for amplified aptasensing, for example, adenosine triphosphate (ATP) and thrombin, with a significantly improved sensitivity in living cells. This initiator-replicated hybridization chain reaction (ID-HCR) circuit was acquired by integrating the HCR circuit with the DNAzyme biocatalysis. Also, the autocatalysis-driven aptasensor consists of a recognition element and an amplification element. The recognition unit can specifically identify ATP or thrombin via a versatile conformational transformation, resulting in the exposure of the initiator to the autocatalysis-driven circuit. The ID-HCR element integrates the charming self-assembly characteristics of the HCR and the remarkable catalytic cleavage capacity of DNAzyme for realizing the continuously self-sustained regeneration or replication of trigger strands and for achieving an exponential signal gain. The autocatalysis-driven aptasensor has been validated for quantitative analysis of ATP and thrombin in vitro and for monitoring the corresponding aptamer substrates with various expressions in live cells. More importantly, the autocatalysis-driven aptasensor, as a versatile amplification strategy, holds enormous potential for analysis of other less abundant biomarkers by changing only the recognition element of the system.


Subject(s)
Adenosine Triphosphate/analysis , Aptamers, Nucleotide/chemistry , Biosensing Techniques/methods , DNA, Catalytic/chemistry , Thrombin/analysis , Adenosine Triphosphate/chemistry , Biocatalysis , Humans , Limit of Detection , MCF-7 Cells , Nucleic Acid Amplification Techniques , Thrombin/chemistry
15.
Angew Chem Int Ed Engl ; 60(19): 10766-10774, 2021 05 03.
Article in English | MEDLINE | ID: mdl-33599385

ABSTRACT

DNAzyme-based gene therapy holds immense prospects for effectively treating severe diseases, yet is constrained with inefficient delivery and unconditional activation. Herein, we designed a bioinspired self-catabolic DNA nanocapsule for sustaining tumor-specific cascade activation of therapeutic DNAzyme. The exquisite DNAzyme was temporarily masked by the self-excising DNAzyme in the hierarchical rolling circle replication (RCR) nanostructures, thus stayed in an inactive state in physiological fluids. Through the multivalent tumor-anchoring aptamer strands, the RCR nanocapsule was specifically accumulated in cancer cells and was sequentially activated for motivating the ultimate DNAzyme-mediated gene silencing via the intelligent stimuli-responsive cascade DNAzyme activation. By virtue of the programmable RCR assembly strategy, our compact DNAzyme nanoplatform shows great promise for developing versatile smart gene therapeutics and personalized nanomedicines.


Subject(s)
DNA, Catalytic/chemistry , Drug Delivery Systems , Nanocapsules/chemistry , DNA, Catalytic/metabolism , Gene Silencing , Genetic Therapy , Humans
16.
Chem Sci ; 12(47): 15710-15718, 2021 Dec 08.
Article in English | MEDLINE | ID: mdl-35003602

ABSTRACT

Catalytic DNA circuits represent a versatile toolbox for tracking intracellular biomarkers yet are constrained with low anti-interference capacity originating from their severe off-site activation. Herein, by introducing an unprecedented endogenous DNA repairing enzyme-powered pre-selection strategy, we develop a sequential and specific on-site activated catalytic DNA circuit for achieving the cancer cell-selective imaging of microRNA with high anti-interference capacity. Initially, the circuitry reactant is firmly caged by an elongated stabilizing duplex segment with a recognition/cleavage site of a cell-specific DNA repairing enzyme, which can prevent undesired signal leakage prior to its exposure to target cells. Then, the intrinsic DNA repairing enzyme of target cells can liberate the DNA probe for efficient intracellular microRNA imaging via the multiply guaranteed molecular recognition/activation procedures. This bioorthogonal regulated DNA circuit presents a modular and programmable amplification strategy for highly reliable assays of intracellular biomarkers, and provides a pivotal molecular toolbox for living systems.

17.
Eur J Breast Health ; 16(4): 255-261, 2020 Oct.
Article in English | MEDLINE | ID: mdl-33062965

ABSTRACT

OBJECTIVE: This study aimed to compare the screening rate trends of mammography among New York State's lower-income women and the higher-income women from 1988 to 2010, and evaluate the potential influence of New York State's Breast Cancer Early Detection Program (introduced in 1994) on the mammography use rates of lower-income women. MATERIALS AND METHODS: Lower-income women are defined as women aged 40 and over whose household income is lower than 250% of the single member household federal poverty level (FPL) in the year that they participated in the survey. Higher-income women are defined as women aged 40 and over whose income is greater than 250% of the five-person household FPL. Data were obtained from the Behavioral Risk Factor Surveillance System. Interrupted time series analysis was conducted to examine screening rates before and after the launch of the Breast Cancer Early Detection program. RESULTS: Among the lower-income women, the pre-intervention mammography screening rate significantly increased by an average of 15.21% every two years. However, after implementation of the Breast Cancer Early Detection Program, this rate of increase significantly slowed (slope change=-13.67, p=0.00016). The lower-income women and the higher-income women experienced a similar trend change after the intervention started. CONCLUSION: This study found limited evidence that the Breast Cancer Early Detection Programme significantly contributed to the state-wide increase in mammography screening rate among lower-income women from 1988 to 2010. Future studies should examine the influence of structural and individual barriers inhibiting uptake of mammography screening among lower-income women.

18.
Chem Commun (Camb) ; 56(77): 11410-11413, 2020 Sep 29.
Article in English | MEDLINE | ID: mdl-32940259

ABSTRACT

The autocatalytic HCR-DNAzyme platform was constructed as a versatile amplification platform for intracellular microRNA imaging by integrating hybridization chain reaction (HCR) circuit with DNAzyme biocatalysis. The HCR-assembled multifunctional DNAzyme nanowires produce new HCR triggers and numerous transducer DNAzyme amplifier, and thus shows great promise in earlier cancer diagnosis.


Subject(s)
Biosensing Techniques , DNA, Catalytic/metabolism , MicroRNAs/analysis , Neoplasms/diagnosis , Nucleic Acid Amplification Techniques , Biocatalysis , DNA, Catalytic/chemistry , Humans , MicroRNAs/metabolism
20.
ACS Nano ; 13(5): 5852-5863, 2019 05 28.
Article in English | MEDLINE | ID: mdl-31042356

ABSTRACT

The development of self-assembled DNA nanomedicine requires a facile and accurate DNA degradation strategy for precisely programmable drug release. Conventional DNA catabolic strategies are restrained with the fragile and unclear enzymatic reactions that might lead to inefficient and uncontrollable digestion of DNA scaffolds and thus might bring undesirable side effects to the sophisticated biosystems. Herein we reported a versatile self-sufficient DNAzyme-driven drug delivery system consisting of the rolling circle polymerized DNAzyme-substrate scaffolds and the encapsulated pH-responsive ZnO nanoparticles (NPs). The full DNAzyme nanosponges (NSs) were also encoded with multivalent tandem aptamer sequences to facilitate their efficient delivery into cancer cells, where the acidic endo/lysosomal microenvironment stimulates the dissolution of ZnO into Zn2+ ions as DNAzyme cofactors and therapeutic reactive oxygen species generators. The supplement Zn2+ cofactors mediated the nonviolent DNAzyme-catalyzed cleavage of DNA scaffolds for precise and efficient drug administrations with synergistically enhanced therapeutic performance. The facile design of DNAzyme, together with their cost-effective and intrinsic robust features, is anticipated to provide extensive insights for the development of DNA-based therapeutic platforms by activating the specific intracellular biocatalytic reactions. As an intelligent and nonviolent self-driven drug delivery platform, the present DNAzyme NS system could be engineered with more therapeutic sequences and agents and was anticipated to show exceptional promise and versatility for applications in biomedicine and bioengineering.


Subject(s)
DNA, Catalytic/metabolism , DNA/metabolism , Drug Delivery Systems , Nanomedicine , Antineoplastic Agents/chemistry , Antineoplastic Agents/metabolism , Antineoplastic Agents/pharmacology , Biosensing Techniques , DNA/drug effects , DNA/genetics , DNA, Catalytic/chemistry , DNA, Catalytic/genetics , Humans , Metabolism/genetics , Nanoparticles/therapeutic use , Nanostructures , Neoplasms/drug therapy , Neoplasms/genetics , Neoplasms/pathology
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